Vol 11

Information
THE BANGKOK
February 2016
MEDICAL JOURNAL Volume 11
Editor in Chief: Chirotchana Suchato, MD

Co-Editor: Rergchai Varatorn, MD
Deputy Editors: Paithoon Boonma, MD
Montri Saengpattrachai, MD
English Language Editor: Ms. Jessica Pelham, MA (Oxon)
Executive Consultation Editors

Prasert Prasarttong-Osoth, MD
Arun Pausawadi, MD Chuladej Yossundharakul, MD Chatree Duangnet, MD
Trin Charumilind, MD Krittavith Lertutsahakul, MD Poramaporn Prasarttong-Osoth, MD
Editorial Board
Frans J Van de Werf, MD Karl E Hammemeister, MD
(University Hospitals Leuven, Belgium) (University of Texas Medical Branch, Galveston)
Robert A. Balk, MD Septimiu Dan Murgu MD
(Rush University Critical Care Specialists, USA) (University of California Irvine, Orange, CA)
Gumpanart Veerakul, MD Koonlawee Nademanee, MD
(Chandrubeksa hospital, Thailand) (Pacific Rim Electrophysiology Research Institute, USA)
Wilaiporn Bhothisuwan, MD Prasert Lertsanguasinchai, MD
(Siriraj Piyamaharajkarun Hospital, Thailand) (Wattanosoth Hospital, Thaiiland)
Wirote Lausoontornsiri, MD Kongkiat Kulkantrakorn, MD
(The National Cancer Institute, Thailand) (Thammasat University, Thailand)
Swang Saenghirunvattana, MD Phurdlerd Piyaraj, MD, MHS, PhD
(Bangkok Hospital, Thailand) (Phramongkutklao College of Medicine, Thailand)
Shanop Shuangshoti, MD Varocha Mahachai, MD
(Chulalongkorn University, Thailand) (Bangkok Hospital, Thailand)
Tanupol Virunhagarun, MD Surajit Suntorntham, MD
(Bangkok Hospital, Thailand) (National Health Security Office, Thailand)
Vijtr Boonpucknavig, MD Yunyong Thongcharoen, MD
(Nhealth pathology, Thailand) (Bangkok Hospital, Thailand)
Chaiyos Kunanusort, MD, PhD Boonsong Ongphiphadhanakul, MD, PhD
(Bangkok Hospital, Thailand) (Ramathibodi Hospital, Thailand)
Staff - Production and Circulation

Ms. Pasuta Sangprasert Ms. Rita Juneja, PhD
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The Bangkok Medical Journal Vol. 11; February 2016 A

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ISSN 2287-0237 (online)/2228-9674 (print)
D The Bangkok Medical Journal Vol. 11; February 2016

Editorial
Esteemed readers,
We are proud to share Volume 11 of the Bangkok Medical Journal with you. This volume
contains excellent original articles, case studies, review articles from guest writers and medical
images capturing the wide range of innovative and cutting edge procedures and time-saving
measures taken by our medical colleagues to improve patients clinical outcomes and to
diagnose and treat potentially fatal conditions in time.
We recommend readers, particularly young radiologists at the beginning of their profes-
sional careers, to take an interest in learning some of the practical tips in the diagnosis of acute
appendicitis using CT and or ultrasound. This very common ailment, usually presenting with
the classic symptom of abdominal pain, can be difficult to diagnose in some cases. We present
a clear account of some of the things to look out for to make an accurate and potentially
life-saving diagnosis.
We are very proud to share that the first renal interhospital CPC was held at Bangkok
Hospital in 2016, with more than 60 fellow nephrologists attending. Prof Vijitr reported a case
study that demonstrated a kidney biopsy presenting a rare instance of AA amyloidosis in SLE
(see front cover).
Early cholangiocarcinoma can be confused in diagnosis with a nonspecific liver abscess
caused by Klebsiella pneumoniae. We report a case of a hepatic venous thrombophlebitis
captured in a CT image with identified elevation of presepsin in serum. Presepsin is useful in
diagnosis of bacterial infection and follow-up after treatment.
The special feature on Dengue Fever explores how this disease is increasing the burden
on healthcare providers worldwide. In addition, we include a short Memoriam to Professor
Natth Bhamarapravati whose pioneering work in the early stages of developing a vaccine for
DENV has been taken forward by Professor Sutee Yoksan who has been carrying on his work
and legacy. Mahidol University is at the forefront of developing a vaccine that is effective
for all four serotypes of Dengue. Professor Usa Thisyakorn represents the Dengue Project
Banpong-Photharam, Faculty of Tropical Medicine, Mahidol University study group for
clinical efficacy and safety of a novel tetravalent dengue vaccine in healthy children in Asia: a
phase 3, randomised, observer-masked, placebo-controlled trial.
We encourage you to read the Handbook of Targeted Cancer Therapy as an excellent
summary for modern cancer treatments, up to 2015. This handbook is highly recommended to
clinical oncologists, radio oncologists and general medical practitioners.
Finally, we note that this issue of the Bangkok Medical Journal comes to you in February,
the month traditionally associated with love with the celebration of St. Valentines Day on the
14th. We share a medical image with you of an ultrasound image with a heart configuration in
the spirit of this season.
Chirotchana Suchato, MD
Editor in Chief
Rergchai Varatorn, MD
Co-Editor
The Bangkok Medical Journal Vol. 11; February 2016 E

Content
THE BANGKOK
February 2016
MEDICAL JOURNAL Volume 11
Editorial
E The Bangkok Medical Journals Editor
Original Article
1 Diagnosing Obstructive Sleep Apnea by Performing Fiberoptic Bronchoscopy and PEEP Titration of Mask
Continuous Positive Airway Pressure
Saenghirunvattana P, Saenghirunvattana C, Napairee C, Pupipat P, Christina Gonzales M, Sutthisri K, Siangpro C
6 Innovative Intracapsular Tonsillectomy: How we do it.

Kiatsurayanon S, Thitithapana P
11 Evaluation of Liver and Kidney Toxicity in Rats Receiving Proteoglycans from Fish Cartilage for the Acceleration
of Burn Wound Healing
Bunman S, Dumavibhat N, Larbcharoensub N
17 Perceived Social Isolation, Self-Care Behaviors and Health Status among Community Dwelling Older Adults
Living Alone
Phatharapreeyakul L, Kraithaworn P, Piaseu N
24 Effect of Participation in Type 2 Diabetes Mellitus (T2DM) Education Pathway on HbA1c

Songsai P, Tungjuk N, Phitchayapiyasak K, Tantinukul Y
Case Report
28 MRI Findings in Transient Global Amnesia

Chansakul C
32 Reversible Stress-induced Cardiomyopathy (Takotsubo) Mimics Acute Anterior Wall ST Segment Elevation
Myocardial Infarction: A Case Report with Review of Literature
Veerakul G, Kiattipoom B, Tawatchai N, Issaraporn C, Supatcha W, Natharinee S, Amornrat S, Krongthong P,
Watchira S, Nattawut P, Palakorn S
39 Liver Abscess caused by Klebsiella pneumoniae: A Case Report

Jongwutiwes U, Suchato C
42 EUS-Guided Rendezvous Pancreatic Duct Stenting in Symptomatic Chronic Pancreatitis Patient

Siripun A
47 Practical Points in Diagnosis of Acute Appendicitis by CT Image and/or Pelvic Ultrasonic Scan: A Case Report
Suchato C
F The Bangkok Medical Journal Vol. 11; February 2016

Content
Review Article
52 Outpatient Total Joint Arthroplasty-Can It Be Done Safely?: A Review

Hongvilai S, Narkbunnam R, S. Mow C
57 Erectile Dysfunction
Leungwattanakij S
73 Part 1: Balloon and principle of Balloon Angioplasty in Peripheral Arterial Disease (PAD)
Tanisaro K
Medical Images
79 Demonstration of Ingested Fish Bone Embedding at Upper Esophagus by CT 3D Reconstruction

Pattamakajonpong P, Suphareokthaweechai R, Wongwarntana A
81 Valentines Day
Mongkolpanya C
Special Feature
82 AA Amyloidosis in Systemic Lupus Erythematosus: Case Presentation Interhospital Renal Clinicopathological

Conference (1/2016)
Boonpucknavig V, Worawichwong S, Jarukitsopa S, Sangsiraprapha W
85 Live-Attenuated Tetravalent Dengue Vaccine Development at Mahidol University

Yoksan S
86 In Memoriam - Professor Natth Bhamarapravati (1928-2004)

Yoksan S
Book Review
87 Handbook of Targeted Cancer Therapy

Kluwer W
The Bangkok Medical Journal Vol. 11; February 2016 G

H The Bangkok Medical Journal Vol. 11; February 2016
Original Article
Diagnosing Obstructive Sleep Apnea by Performing

Fiberoptic Bronchoscopy and PEEP Titration of
Mask Continuous Positive Airway Pressure
Abstract
OBJECTIVE: This study was conducted to pioneer a new technique of diagnosing
obstructive sleep apnea using fiberoptic bronchoscopy (FOB) and mask continuous
positive airway pressure (CPAP), supported by sleep questionnaires and a portable
sleep study procedure.
MATERIALS AND METHODS: Ten patients suspected of obstructive sleep apnea
(OSA) who needed to undergo FOB for other reasons aside from sleep apnea were
diagnosed with OSA by using FOB and CPAP.
RESULTS: From the sleep study, the mean apnea-hypopnea index (AHI) was 21
events per hour. All the patients had been using CPAP, and tolerated how the machine
operates. Nobody reported any difficulty during the follow-up checkup.
Saenghirunvattana S, MD CONCLUSION: This new technique is not only practical, cost-efficient, time-saving
and beneficial for both patient and physician but it may also be considered as the new
gold standard in diagnosing OSA.
Keywords: obstructive sleep apnea, fiberoptic bronchoscopy, mask continuous
positive airway pressure
F
Sawang Saenghirunvattana, MD1 iberoptic bronchoscopy (FOB) is a procedure that pulmo-
Chao Saenghirunvattana, MD2 nologists perform to investigate the airway passages for
Chittisak Napairee, MD1 diagnostic or therapeutic purposes. Patients undergoing FOB
Pakorn Pupipat, MD1 are either under local anesthesia or moderate sedation. The type
Maria Christina Gonzales, RN1 of sedation will depend either on the complexity of the procedure
Kritsana Sutthisri, BSc1 or the time needed by the physician to complete the assessment
Chitchamai Siangpro, BSc1 and or treatment. During moderate sedation, several patients were
observed in Bangkok Hospital manifesting snoring and hypopneas
or apneas. This prompted our team to carry out further investiga-
tions in the diagnosis of sleep apnea.
Obstructive sleep apnea (OSA) is described as the repeated

instability of the upper airway during sleep which results in
hypopnea or apnea. It is a serious condition that can affect an
individuals activities which in turn can also cause long term health
problems. Polysomnography or sleep study has been the gold
standard in diagnosing sleep apnea. It typically records the brain
wave changes, eye movements, muscle motion, breathing and
heart rate and rhythm.1 Once diagnosed, the management of OSA
depends on the severity of the condition. Some patients may
resort to a mandibular advancement splint, continuous positive
airway pressure (CPAP), or surgery. Although sleep studies have
1
Bangkok Hospital, Bangkok Hospital Group, Bangkok, Thailand. been effective, the cost and lack of available sleep laboratories and
2
Naresuan University, Phitsanulok, Thailand. trained technicians has been a major concern in screening patients
* Address Correspondence to author: suspected of sleep apnea. To compensate, methods such as sleep
Sawang Saenghirunvattana, MD endoscopy and portable polysomnographic devices supported by
Bangkok Hospital,
2 Soi Soonvijai 7, New Petchburi Rd.,
sleep questionnaires are used in the diagnosis of sleep apnea.
Bangkok 10310, Thailand.
e-mail: sawang.sa@bangkokhospital.com Materials and Methods
Received: January 8, 2016
Revision received: January 10, 2016 Over a period of twelve months, from January 2014 to December
Accepted after revision: January 18, 2016
Bangkok Med J 2016;11:1-5.
2014, a total of ten patients suspected of having OSA and who needed
E-journal: http://www.bangkokmedjournal.com to undergo FOB for other reasons aside from sleep apnea were
diagnosed with OSA using FOB and CPAP at the Bangkok Hospital .
The Bangkok Medical Journal Vol. 11; February 2016 1

Saenghirunvattana S, et al.
Pre-procedure assessment Post-FOB and PEEP titration of mask CPAP
Each patient received a thorough physical examination When a patient displayed upper airway collapse or
with particular attention given to the status of the upper obstruction during FOB and PEEP titration of the CPAP,
airway. This examination was followed by radiographic an ambulatory sleep study was performed to confirm the
imaging (either a chest x-ray or computed tomography diagnosis of obstructive sleep apnea. A full portable poly-
scan). When the patient was already required to undergo somnography was completed and mask CPAP with specif-
bronchoscopy for further investigation and or treatment, ic PEEP for treatment was prescribed as treatment. Three
he or she was then further evaluated for a possible months after using CPAP, subjects were asked to come
diagnosis of obstructive sleep apnea. The Berlin back for evaluation.
Questionnaire and the Epworth Sleepiness Scale were
used to measure the patients risk of sleep apnea. If both
the physical assessment and the questionnaire score
pointed to a high likelihood of sleep apnea, the patient
was informed, and consent was obtained to perform FOB
and positive end-expiratory pressure (PEEP) titration of
mask CPAP.
FOB and PEEP titration of mask CPAP
The FOB allowed direct visualization of the oropah-

rayngeal airways with the patient under moderate seda-
tion. This view provided the physician with a clear and
direct picture of whether the upper airway was collapsed
or if any obstruction were present thus confirming sleep
apnea. The FOB was then inserted via the mask CPAP
to help titrate and adjust PEEP providing the accurate
measurement needed when using CPAP. Post-FOB with
mask CPAP, the pulmonologist was then able to perform
FOB, diagnose OSA and provide CPAP management with
specific PEEP levels. Figure 1: The patient with CPAP mask is diagnosed
with obstructive sleep apnea.
Figure 2: A direct visualization of closed airway of a Figure 3: The airway dilates when CPAP was applied
moderately sedated patient seen via FOB. to the patient.
2 The Bangkok Medical Journal Vol. 11; February 2016

Diagnosing Obstructive Sleep Apnea by Performing Fiberoptic Bronchoscopy and
PEEP Titration of Mask Continuous Positive Airway Pressure

Saenghirunvattana S, et al.
Results is 2 months, and in Australia between 3 and 16 months.

In the United States waiting time is between 2 and 10
Fiberoptic bronchoscopy and PEEP titration of mask months and in Canada 4 to 36 months. The waiting time
continuous positive airway pressure (CPAP) was performed varies widely depending on several factors such as the
on ten consenting patients, six of whom were male and patients condition and demographics. This shows that
four female. The patients ages ranged from 35 to 72 years even in more developed countries, there is still a lack of
old with a mean age of 51. The mean body weight was 72.8 facilities available for patients suspected of having sleep
kilograms (kgs) ranging from 52 kgs to 89.5 kgs. The body problems. In Asia it is expected that waiting times are
mass index (BMI) ranged from 27 to 35 and the mean neck even longer, given that the population density is higher,
circumference was 18.2 inches. The average PEEP was healthcare resources are limited and sleep disorders are
found to be 7 cmH20 (ranging from 5 to 12 cmH20). No not given priority. Furthermore, if a sleep laboratory is
untoward complications were noted from the procedure used for every presumed case of sleep apnea, waiting
and moderate sedation. From the sleep study, the mean times will be longer still.
apnea-hypopnea index (AHI) was 21 events per hour. All
the patients had been using CPAP, and tolerated how the The study of sleep and the use of CPAP for treatment
machine operates. Nobody reported any difficulty during have evolved in past decades. Recently, sleep study
the follow-up checkup. monitoring has been categorized into 4 types. Type I
monitors are facility-based with 7 channels; they are
Discussion run by a sleep laboratory technician, and evaluated by
a sleep specialist. Type II monitors are portable, with 7
Obstructive sleep apnea (OSA) is a serious disorder channels to allow for the identification of different sleep
characterized by repeated collapse of the upper airway stages and AHI. Type III monitors have 3 to 7 channels
when asleep, resulting in reduced airflow or brief absolute but do not assess sleeping and waking stages. Type IV
airflow cessation when asleep.2 It can present as nocturnal monitors have 1 to 2 channels and do not detect sleep
symptoms such as snoring, gasping and apneas observed stages nor do they identify the type of apnea, but oxygen
by bed partners. This condition can also manifest morning saturation is measured.11 To our knowledge, there has
symptoms like excessive daytime sleepiness, fatigue, not been a complete and comprehensive study to measure
morning headaches, personality changes and other more the efficacies of each type of sleep study. However,
serious problems such as hypertension, cardiovascular in research published by Dr. Stephanie Su12 comparing
disease, type 2 diabetes mellitus and vehicular accidents.3-8 PSG and portable home sleep study, it was concluded
that there was a significant correlation of respiratory
Diagnostic evaluations play a major role in provid- disturbance index (RDI) between the PSG in the labora-
ing the best treatment options for sleep apnea. A thorough tory and ambulatory sleep study. Although mobile sleep
physical examination is very important in diagnosing tests have their limitations, accompanying reports and
OSA particularly the BMI, neck and waist circumferences. physical examination with medical history could prove
These clinical features should be integrated with information to be a good alternative for PSG in diagnosing OSA.
obtained from sleep questionnaires such as the Epworth
Sleepiness Scale and or the Berlin Questionnaire and Sleep nasendoscopy was introduced by Croft and
especially the polysomnography report to accurately Pringle in 1991, and requires the patient to be sedated so
diagnose sleep apnea.9 direct visualization of the airways can be performed while
the patient is asleep. This method allows the physician to
Polysomnography (PSG) or sleep study is a standard assess the levels of snoring and or obstruction. Maneuvers
diagnostic test that requires the patient to stay in a sleep and mandibular splints are also applied for further
laboratory to be monitored by a sleep technician8 and assessment. In a study conducted by Dr. Hohenhorst,13 he
may or may not try using CPAP to determine treatment. stated that drug-induced sleep endoscopy has no known
This method has been considered the gold standard record of severe side effects or life threatening compli-
for diagnosing OSA but due to an increase in demand cations. It is a reliable and safe procedure to help diagnose
coupled by a lack of facilities and human resources, OSA and determine the individual therapeutic choice
several techniques have been developed to meet the which could be either surgery or mandibular repositioning
demands of patients who want to get tested for OSA. appliances. However, polysomnography is still necessary
for a complete diagnosis of OSA. In another published
Flemons W et al.10 published a study on the duration study by Dr. Salama,1 it was concluded that sleep endos-
of waiting times for the diagnosis of sleep apnea and copy is a practical procedure in diagnosing OSA. It can
treatment with CPAP in five countries. Patients from the also aid in a pre-operative evaluation of patients suspected
United Kingdom wait on average from 7 to 60 months for of OSA.
diagnosis and treatment, whereas in Belgium, the wait

Diagnosing Obstructive Sleep Apnea by Performing Fiberoptic Bronchoscopy and
PEEP Titration of Mask Continuous Positive Airway Pressure
Sleep nasendoscopy has some points in common with course of action is that it has only been tested on 10
our procedure. Both studies use pharmacological agents in patients, all of whom have responded well to CPAP
inducing patients to sleep; both visualize the airway using treatment. Further studies that are more wide scale should
a scope to further investigate the anatomical structure and now be made to show if FOB with CPAP PEEP titration
level of obstruction of patients suspected of OSA. Both alone can adequately diagnose OSA without recourse to
procedures do not have records of emergency side effects other studies.
(considering our study was conducted on patients with
comorbidities) and both procedures still require a physical Conclusion
examination, medical history and sleep study results.
Several research findings proving the effectiveness and The evolution and widespread availability of inter-
practicality of this procedure have been published. The ventional bronchoscopy has played a great role in the
main difference however, is that after assessment of the development of diagnosing certain conditions such as
airways, CPAP PEEP titration is used to determine if OSA. This new technique is not only practical, cost-
the equipment will function and be useful in dilating the efficient, time-saving and beneficial for both patient and
obstruction or narrowed airway of the subjects or if physician but it may also be considered as the new gold
surgery is still deemed necessary. The limitation of this standard in diagnosing OSA.
References
1. Salama S, Kamel E, Omar A, et al. Role of sleep endos- 8. Qaseem A, Dallas P, Owens DK, et al. Diagnosis of
copy in obstructive sleep apnea syndrome. Egypt J Tuberc obstructive sleep apnea in adults: a clinical practice
Lung Dis 2013:62;467-73. guideline from the American College of Physicians. Ann
2. Johal A, Battagel JM, Kotecha BT. Sleep nasendos- Intern Med 2014;161:210-20.
copy: a diagnostic tool for predicting treatment success 9. DE Corso E, Fiorita A, Rizzotto G, et al. The role of
with mandibular advancement splints inobstructive sleep drug-induced sleep endoscopy in the diagnosis and
apnoea. Eur J Orthod 2005;27:607-14. management of obstructive sleep apnoea syndrome: our
3. McNicholas WT. Diagnosis of Obstructive Sleep Apnea personal experience. Acta Otorhinolaryngol Ital 2013;
in Adults. Proc Am Thorac Soc 2008:5:154-60. 33:405-13.
4. Lavie P, Herer P, Hoffstein V. Obstructive sleep apnoea 10. Flemons WW, Douglas NJ, Kuna ST, et al. Access to
syndrome as a risk factor for hypertension: population diagnosis and treatment of patients with suspected sleep
study. BMJ 2000;320:479-82. apnea. Am J Respir Crit Care Med 2004;169:668-72.
5. Shahar E, Whitney WC, Redline S, et al Sleep-disordered 11. Zancanella E, Haddad FM, Oliveira LAMP et al.
breathing and cardiovascular disease: cross-sectional Obstructive sleep apnea and primary snoring: diagnosis.
results of the Sleep Heart Health Study. Am J Respirw Braz J Otorhinolaryngol 2014; 80 (Sup1):S1-S16.
Crit Care Med 2001;163:19-25. 12. Su S, Baroody FM, Kohrman M, et al. A comparison
6. Ip MS, Lam B, Ng MM, et al. Obstructive sleep apnea is of polysomnography and a portable home sleep study in
independently associated with insulin resistance. Am J the diagnosis ofobstructive sleep apnea syndrome.
Respir Crit Care Med 2002;165:670-6. Otolaryngol Head Neck Surg 2004;131:844-50.
7. Powell NB, Schechtman KB, Riley RW, et al. Sleepy 13. Hohenhorst W, Ravesloot MJL, Kezirian EJ, et al.
driving: accidents and injury. Otolaryngol Head Neck Drug-induced sleep endoscopy in adults with sleep-
Surg 2002;126:217-27. disordered breathing: Technique and the VOTE Classifi-
cation system. Oper Tech Otolaryngol 2012:23:11-8.

Original Article
Innovative Intracapsular Tonsillectomy: How we do it.
Abstract
OBJECTIVE: To present a new technique of intracapsular tonsillectomy using
carbondioxide CO2 lasers, aiming to increase visibility by providing a better view of the
tonsil and related structures in the obscure area by using the technique of rotating the
operating table, 20-30 instead of using a 30 endoscope.
MATERIALS AND METHODS: From October 23, 2014 to October 23, 2015, 124
patients underwent an intracapsular tonsillectomy using a CO2 laser with the technique
of rotating the operating table 20-30 to have a clearer view of the tonsil tissue and the
related structure. Absorbable suture material (3-0 vicryl) is also used to tie 6-8 areas of
each side of the tonsillar capsule to prevent post-tonsillectomy bleeding.
RESULTS: Rotating the operating table 20-30 to the left and to the right while
Kiatsurayanon S, MD operating the intracapsular tonsillectomy using a CO2 laser helps the surgeons see the
tonsillar tissue and the related structures in the obscure part clearer. That makes the
intracapsular tonsillectomy using a CO2 laser safer and more precise due to improved
ability to preserve healthy tonsillar tissue and vaporize the infected tonsillar tissue.
Moreover, surgeons can also see the bleeding area (if any) and can precisely control the
Saranchai Kiatsurayanon, MD1 bleeding by using the electric cautery or suture ligation.
Paweena Thitithapana, MD1 CONCLUSION: Rotating the operating table 20-30 in intracapsular tonsillectomy
using a CO2 laser helps the surgeon not only to identify the upper, lower, and the side edges
of the tonsillar capsule clearer but also makes the surgery safer and easier. Suture ligation
of tonsillar capsule using 3-0 vicryl helps reduce the chance of post-tonsillectomy
bleeding effectively.
Keywords: innovation intracapsular tonsillectomy, CO2 laser intracapsular tonsil-

lectomy, CO2 laser minimally invasive tonsillectomy
I
ntracapsular Tonsillectomy that preserves small amounts of
the healthy tonsillar tissue has been performed since the 20th
century but this technique was stopped due to arguments put
forward by ear, nose and throat (ENT) surgeons. They were
concerned with diseases that might still reside in the remaining
tissues and cases of severe infection. Some diseases such as
rheumatism and scarlet fever will still remain even after surgery.1,2
Nevertheless, this surgery technique was brought back into use at
the start of the 21st century and it has been more and more popular
due to the development of surgical instruments and modern
knowledge that surgery can save the healthy tonsillar tissue (about
5-10% of the tonsil).3 It is generally known now that this new
1
Otorhinolaryngology Clinic, Phyathai 3 Hospital,
technique of surgery helps reduce post-tonsillar pain after the
Bangkok Hospital Group, Bangkok, Thailand.
surgery and it helps reduce the post-tonsillectomy bleeding 3 times
* Address Correspondence to author: less than the traditional tonsillectomy.1,4 Moreover, there is no
Saranchai Kiatsurayanon, MD
Otorhinolaryngology Clinic, Phyathai 3 Hospital,
problem in tonsils diseases not being completely cured. The
Bangkok 10160, Thailand. findings from research centers around the world show that this
e-mail: saranchaikia@gmail.com
new surgical technique is as good as cutting off the tonsil like the
Received: January 5, 2016 traditional technique does; the difference is the new technique
Revision received: January 8, 2016 helps protect the lateral walls of the throat to remain intact because
Bangkok Med J 2016;11:6-10. it preserves the tonsillar capsule which provides the strength to the
E-journal: http://www.bangkokmedjournal.com lateral walls of the throat.

Recently, this new intracapsular tonsillectomy has Discussion

become more popular than the traditional tonsillectomy,
especially in patients younger than 4 years old that have Laser stands for light amplification by stimulated
enlarged tonsils or who have sleep apnea. Moreover, emission of radiation, and the CO2 laser is the most used
children who weigh less than 15 kilograms or who are at laser in otorhinolaryngology. CO2 laser has been brought
risk of bleeding can also benefit. However, the problem of into use in the medical field since the 1970s. CO2 laser
this surgical technique is that it always has obscure parts. is a laser caused by amplification and stimulation of CO2
Obscure parts are located around the tonsillar capsule to release energy in the form of light. CO2 laser is widely
which cannot easily be seen clearly if the oral cavity is in used in the medical field supported by well understood
a straight position just like in general tonsil surgery. This scientific studies and in-depth studies of medical laser
similar issue can be solved by using a 30 endoscope to and its uses. Moreover, the CO2 is the first laser used in
help during the operation in order to see clearer through the otorhinolaryngology. The wavelength of CO2 laser is 10.6
obscure areas. Nevertheless, using such a tool in a surgery microns which is the peak that the CO2 laser has a strong
costs a lot of money since the tool itself is expensive. affinity with water, and the tissues of the mouth and throat
Moreover, it takes a long time to have one surgery done. can absorb the CO2 laser energy very well because this
Given these constraints, this report is going to discuss the area of tissues contains 80-90% water. CO2 laser has
new technique of operation, rotating the operating bed excellent cutting and ablating properties especially with
through 20-30. This new technique will make the intra- soft tissue. When the CO2 laser beams, it is not reflected
capsular tonsillectomy easier, cheaper, and faster and it or scattered in mucosa tissue. The absorption of the laser
will help the surgeon to identify the structure in the energy by water rapidly causes heat to increase within the
tonsilliar capsule and to preserve the healthy tonsillar tissue, which carbonizes the tissue. CO2 laser can be set to
tissue and to control the bleeding more effectively. pulsed mode or continuous wave (CW) mode. CW mode is
suitable for oral cavity and oropharynx. CO2 laser energy
Material and Method enters the target tissue by using the non-contact technique.
The data is collected from 124 patients who had CO2 laser intracapsular tonsillectomy will preserve the
intracapsular tonsillectomy using CO2 laser from October tonsillar capsule to avoid injury of the pharyngeal muscles
23, 2014 to October 23, 2015. The technique of rotating the and to keep 5-10%, attached with tonsillar capsule, of
operating table 20-30 is used with all patients during the the healthy tonsillar tissue to act as a form of biological
surgery for the surgeons to see the side edges, the upper dressing. This biological dressing will protect the neck
parts, and the lower parts of the tonsillar capsule clearer muscles from contacting the external environment such
and thoroughly. The CO2 laser is used to vaporize all as saliva and food. It is the prevention of injury and the
unwanted tonsils tissues and vicryl 3-0 is also used to tie infection of the neck muscle wall that can reduce pain
the outer surface of the tonsillar capsule (about 6-8 areas after the surgery and helps the patients to recover faster.5
each side) to prevent bleeding after the surgery. After the
surgery, the record of the pain score including the primary The absence of post tonsillectomy bleeding both im-
post-operative tonsillectomy bleeding and the secondary mediate post-operative bleeding and delayed post-opera-
post-operative tonsillectomy bleeding of all the patients tive bleeding, in patients who used CO2 laser intracapsular
is recorded. tonsillectomy might occur because the surgeons preserve
the tonsil tissue and tonsillar capsule along with suture
The patients can be discharged the following day with ligation the tonsillar capsule using vicryl 3-0. This vicryl
the follow up appointments at 1 week and 5 weeks after 3-0 will come off by itself within 3-5 weeks. This tech-
surgery. The results detailed below show that there is no nique of tonsil surgery by removing tonsillar tissue from
primary and secondary post-operative bleeding. The pain the outside in, where no large vessels but only small arteri-
score is at level 1-3 (mild pain). There is no residual and oles are affected greatly reduces the occurrence of delayed
recurrent tonsil stone, no recurrent infection and no re- hemorrhage.
growth of the tonsil after the operation.
The rotation of operating table to the left and to the
Results right through a range of 20-30 during surgery allows
the surgeon to see the tonsillar capsule clearer, especially
A total of 124 patients aged between 3 and 70 years in the obscure part, namely the upper pole, lower pole,
of age underwent CO2 laser intracapsular tonsillectomy. and anteromedial aspect of tonsillar capsule. This allows
The average amount of bleeding is 10 cc. In this group the surgeon to vaporize infected tissue, keep the healthy
of patients shows neither immediate post-operative bleed- tonsillar tissue, and preserve tonsillar capsule more
ing, nor delayed post-operative bleeding. None of these effectively.
patients has come for readmission due to dehydration. The
average of the pain score is 1-3 for all patients.

Kiatsurayanon S and Thitithapana P
Conclusion Rotating the operating table about 20-30 will help the
doctors see the tonsillar tissue that is adhered to the
Intracapsular tonsillectomy is the new technique of tonsillar capsule, thus, the doctors will be able to determine
tonsillectomy surgery. It is a minimally invasive intracap- whether to vaporize the infected tonsillar tissue or to
sular tonsillectomy. It causes less pain than the traditional preserve the tonsil tissue. The intracapsular tonsillectomy
tonsillectomy and it signifiantly reduces the chance of using CO2 laser, the suture ligation of the tonsillar
bleeding. However, this new surgery technique is still capsule surface area using vicryl 3-0 to control the bleeding
difficult in seeing the tonsillar capsule structure thoroughly. and the use of rotating operating table 20-30 can help
Seeing through the tonsillar capsule will help increase the surgeons perform the surgery neatly. The surgeons can
success of the operation. save the capsule of the tonsil without cutting through
the muscles beneath. The preserving of the tonsillar
capsule and the suture ligation of the tonsillar capsule
using vicryl 3-0 will help reduce the incidence of post
tonsillectomy bleeding and maintain the strength of the
side lateral walls of the throat.
References
1. King JJ. Tonsillar infections as a source of systemic 4. Krespi YP, Ling EH. Laser-assisted serial tonsillectomy.
disease. Trans Am Acad Ophthalmol Otolaryngol J Otolaryngol 1994;23:325-7.
1917/1918;22:306-24. 5. Koltai PJ, Solares CA, Koempel JA, et al. Intracapsular
2. Kaiser AD, Results of tonsillectomy: a comparative tonsillar reduction (partial tonsillectomy): reviving a
study of twenty-two hundred tonsillectomized children historical procedure for obstructive sleep disordered
with an equal number of controls three and ten years after breathing in children. Otolaryngol Head Neck Surg
operation. JAMA 1930;95:837-42. 2003;129:532-8.
3. Koempel JA, Solares CA, Koltai PJ. The evolution
of tonsil surgery and rethinking the surgical approach to
obstructive sleep-disordered breathing in children.
J Laryngol Otol 2006;120:993-1000.

Appendix (Pictures)
When using the Boyle-Davis gag to hold the mouth open nor right and that prevents the surgeons, when doing the
in general tonsil surgery, the tongue blade handle will be intracapsular tonsillectomy, from getting a clear view of
attached to the edge of mayo table. In that position, the the upper, lower and the side edges of the tonsillar capsule
oral cavity will not be able to flip or tilt either to the left through the obscure part.
Figure 1 Figure 2
Figure 3 Figure 4
Figure 5 Figure 6 Figure 7

Kiatsurayanon S and Thitithapana P
The new technique is developed to use the rotating

operating table without attaching the tongue blade handle
to the table. Instead, attach it with the L-square anesthetists
screen frame. One of the L-squares anesthetists screen
frame will be attached to the right side of the bed, another
one will be placed across the patients body and that will
be used to attach to the tongue blade handle (Figure 1-4).
This technique will allow the surgeons to rotate the bed to
the left and to the right and the head side of the operating
table is also adjustable to a higher or lower level during
the operation (Figure 5-8). Rotating the operating table
through 20-30 and being able to adjust the head side of
the table up and down allows the doctors to see the upper
and the lower parts of the obscure area, including the side
edges of the tonsillar capsule clearly and thoroughly
Figure 8
without (Figure 8) using 30 endoscope. (Figure 9, 10)
Figure 9 Figure 10

Original Article
Evaluation of Liver and Kidney Toxicity in Rats Receiving

Proteoglycans from Fish Cartilage for the Acceleration
of Burn Wound Healing
Abstract
OBJECTIVE: The aim of this study was to evaluate the toxicity of proteoglycan
extracted from fish cartilage for the acceleration of wound healing.
MATERIAL AND METHODS: Second degree burn wounds were induced by an
electrical hot plate measuring 2 cm in diameter and set at a temperature of 90 oC and
placed on the back of rats for 10 seconds. Rats were randomly assigned to receive 1 gram
of cream base (control group), 1% silver sulfadiazine (SSD), 1% proteoglycans (PG),
2% PG, a combination of 1% SSD + 1% PG, or a combination of 1% SSD + 2% PG
applied to burn wounds to accelerate wound healing immediately after burning and
once daily until day 27 post-burn. The toxicity of the rats liver and kidney functions
were evaluated on day 7, 14, 21 and 28.
Bunman S, MSc RESULTS: An evaluation of liver function tests showed on day 28 that the level
of aspartate aminotransferase, alanine transaminase, and alkaline phosphatase of
rats treated with 1% SSD, 1% PG, 2% PG, combination of 1% SSD + 1% PG and
combination of 1% SSD + 2% PG were not significantly different when compared to
the control group. An evaluation of blood urea nitrogen and creatinine levels, on day 28
Sitthiphon Bunman, MSc1 showed the level of blood urea nitrogen and creatinine of rats treated with 1% SSD, 1%
Narongpon Dumavibhat, MD, PhD1 PG, 2% PG, combination of 1% SSD + 1% PG and combination of 1% SSD + 2% PG
Noppadol Larbcharoensub, MD2 were not significantly different when compared to the control group.
CONCLUSION: This study demonstrated that PG extracted from fish cartilage is safe
without causing toxic effects to the liver and kidney for long term use.
Keywords: proteoglycans, toxicity, liver, kidney, fish cartilage, burn wounds
A
burn wound is a type of skin injury caused by tissue damage
after exposure to heat, chemicals, electrical, or radiation.
A burn is one of the most common types of wound found
in patients. There are up to 250,000 burn patients each year. Burns
can occur in all age groups, from babies to the elderly, and are
a problem in both developed and developing countries. The
major causes of burn injury are classified as follows: flame exposure
(55%), hot water exposure (scalds; 40%), and chemical and electrical
exposure (5%). The incidence of burn injury is classified by age as
follows: 16-64 years old (60%), 1-4 years old (20%), 5-14 years old
(10%), and over 65 years old (10%).1 The severity of burn injury
depends on the percentage of the total body surface area damage
(%TBSA) and depths of skin layer damage (degree of burn depth).
It has been indicated that more than 30% of total body surface
1
Department of Preventive and Social Medicine, Faculty of area damage could influence a change in physical systems such as
Medicine Siriraj Hospital, Mahidol University, Bangkok, cardiovascular, respiratory, and immune systems.1
Thailand.
2
Department of Pathology, Faculty of Medicine, Ramathibodi
Hospital, Mahidol University, Bangkok 10400, Thailand. Current treatment of burn wound depends on the severity of
the burn: for example, drug therapy or surgery is applied to severe
* Address Correspondence to author: burn cases, but new approaches such as amniotic membrane,
Sitthiphon Bunman MSc
Department of Preventive and Social Medicine, Faculty of Medicine Siriraj cytokine and gene therapy are increasingly used.1-4 Medication is
Hospital, Mahidol University, Bangkok 10700, Thailand. the most common and easiest way to treat burns, and 1% of silver
e-mail: acetaminophen55@gmail.com
sulfadiazine (SSD) cream is used as a gold standard for the treatment
Received: January 12, 2016 of burn wounds. When SSD is exposed to the wound, it will ionize to
Revision received: January 13, 2016
Ag+ and inhibit the enzymes involved in the electron transport chain
Bangkok Med J 2016;11:11-16. and bacterial DNA replication process, resulting in the killing of
E-journal: http://www.bangkokmedjournal.com bacteria. SSD is absorbed through the skin to the blood vessels and

Bunman S, et al.
then transported to liver, where metabolism occurs and Cream base preparation: Stearic acid, glyceryl mono-
more than 50% is eliminated via the kidney system in the stearate, isopropyl myristate, sodium lauryl sulfate, glycerin,
original chemical form.5 A previous study showed that triethanolamine, uniphen P-23 and germaben II-E were
Ag+ of SSD is toxic to bone marrow, which leads to dissolved in warm water and then mixed with other ingre-
abnormal blood synthesis5 and also affects liver and dients during the cream-forming process.
kidney.6,7 Thus, the use of this drug in the patients with
hepatic or renal impairment should be avoided.6-8 SSD and PG cream preparation: SSD powder, PG
solution, stearic acid, glyceryl monostearate, isopropyl
PG is a hybrid molecule composed of a central core myristate, sodium lauryl sulfate, glycerin, triethanol-amine,
protein by bonding it with polysaccharides (glycosamino- uniphen P-23 and germaben II-E were used to formulate
glycans or GAGs) with a covalent bond.9 PG is the major PG, SSD or SSD+PG creams. SSD powder and/or PG
component of cartilage, and makes up approximately 90% solution were dissolved in warm water and then mixed
of dry weight.10-12 It has been found that PG plays an with other ingredients during the cream-forming process.
important role in the wound-healing process.2,13-14 Neelam
et al.13 studied the effect of PG extract of fish cartilage Electrical hotplate inducing second-degree burn
on L929 fibroblast cells. The results showed that PG wounds: The method to induce burn wounds was inves-
extract promoted fibroblast cell activation by increasing tigated using the method of Somboonwong,15 which was
cell proliferation and migration and increasing collagen modified from Zawacki.16 Rats were randomly divided
synthesis, which is involved in wound healing13 but this into 6 groups of 10 rats each: control rats were treated
study is not an evaluation of toxicity. Bunman et al.2 with cream base; positive controls were treated with
recently studied PG extract from fish cartilage for the 1% SSD cream; and 4 treatment groups received 1% PG
acceleration of burn wound healing. The results suggested cream, 2% PG cream, 1% SSD + 1% PG cream, and
that PG extracted from fish cartilage can accelerate and 1% SSD + 2% PG cream. Rats were anesthetized by
facilitate wound healing in rats. The combination of 1% intraperitoneal injection with sodium pentobarbital (60
SSD and 1% or 2% PG seem to have high efficacy in miligrams per kilograms body weight). The hair on the
accelerating and facilitating wound healing in rats. back was shaved. Second-degree burn wounds were
Further investigation of the safety profile of PG and the induced by placing an electrical hot plate, of a diameter
combination of 1% SSD and PG in detail is required.2 of 2 cm, set at a temperature of 90 C on a selected skin area
of the back for 10 seconds. All wounds were cleaned and
The aim of this study is to evaluate the toxicity of liver and treated with 1 gram of cream base, 1% SSD cream, 1% PG
kidney function in rats receiving PG from fish cartilage for cream, 2% PG cream, 1% SSD + 1% PG cream, or 1%
the acceleration of burn wound healing in an in vivo model. SSD + 2% PG cream once daily and covered with sterile
gauzes.
Materials and Methods
Evaluation toxicity
Drugs and chemicals: PG solution (Garguar Lab,
Co., Ltd., Thailand), SSD powder (Sigma, USA.), Sodium Blood collection and Preparation of plasma: Collect
pentobarbital (Nembutal; Tariqbrian Ltd, USA.). 0.5 ml of blood from lateral tail vein at 5 time points;
baseline, on day 7, 14, 21, and 28.17,18 The whole blood
Animals: Male Wistar (age 8 weeks, weighing 250-300 in the test tube was centrifuged at 3,000 revolutions
gram) were purchased from the National Laboratory per minute (rpm) for 10 minutes. The whole blood was
Animal Centre, Mahidol University, Salaya, Thailand. separated into two layers: the upper layer which contains
The animals were housed in the Laboratory Animal Unit plasma (approximately 55% of whole blood) and the
of the Faculty of Pharmaceutical Sciences, Chulalongkorn lower layer which contains erythrocytes (approximately
University under standard conditions of temperature 45% of whole blood). Plasma was stored at 2-8 oC and
25 2 C, 50 - 60 % humidity, and a 12 hours/12 hours used within 24 hours for further analysis.19, 20
light/dark cycle. The rats were kept under laboratory
conditions for one week prior to the start of the experiments Evaluation of liver function tests: The liver function
and allowed food and water ad libitum. At the end of test of rats was evaluated by measuring three hepatic
each experiment, the animals were sacrificed with carbon enzyme levels including aspartate aminotransferase,
dioxide asphyxiation. Animal experiments in this study alanine transaminase and alkaline phosphatase. Twenty
were carried out in accordance with the Ethical Principles microliters of plasma were used for measurement of each
and Guidelines for the Use of Animals for Scientific enzyme level. The activities of aspartate aminotransferase,
Purposes of the National Research Council of Thailand. alanine transaminase and alkaline phosphatase were
The animal use protocol was approved by the Institutional determined using assay kits which are commercially
Animal Care and Use Committee of the Faculty of available diagnostic laboratory tests and light a ultraviolet
Pharmaceutical Sciences, Chulalongkorn University, (UV) spectrophotometer (I lab 150, Instrumentation
Bangkok, Thailand (Protocol Approval No. 13-33-011). laboratory, Italy).

Evaluation of Liver and Kidney Toxicity in Rats Receiving Proteoglycans from Fish Cartilage
for the Acceleration of Burn Wound Healing
Evaluation of renal function tests: The renal func- Results

tion test of rats was evaluated by measuring levels of blood
urea nitrogen and creatinine. Twenty microliters of plasma The level of aspartate aminotransferase enzyme:
were used for measurement of each parameter. The On day 7, 14 and 28 post-burn the levels of aspartate
concentrations of blood urea nitrogen and creatinine were aminotransferase enzyme of rats treated with 1% SSD,
determined using the assay kits and a UV spectrophotometer 1% PG, 2% PG, combination of 1% SSD + 1% PG and
(I lab 150, Instrumentation laboratory, Italy). combination of 1% SSD + 2% PG were not significantly
different when compared to the control group. On day 21
Statistical analysis post-burn, the levels of aspartate aminotransferase enzyme
of rats treated with 1% SSD, 1% PG, combination of 1% SSD
Results are expressed as meansSD. Data were + 1% PG and combination of 1% SSD + 2% PG were not
analyzed using one-way analysis of variance (ANOVA), significantly different when compared to levels in the control
followed by a Bonferroni post hoc test using SPSS for group but were significantly lower than their own baselines
Windows, ver. 17. Values of p < 0.05 were considered to (p < 0.001, p < 0.001, p < 0.01 and p < 0.001, respectively)
be significant. (Table 1).
Table 1: The level of aspartate aminotransferase enzyme on day 7, 14, 21 and 28 post-burn.
The level of aspartate aminotransferase enzyme (U/L)
Groups
Baseline Day 7 Day 14 Day 21 Day 28
Control (Cream base) 119.10 8.94 118.80 17.52 97.20 21.19 98.10 14.91 139.11 43.38
***
1% SSD 126.30 16.57 101.90 15.09 100.80 24.10 84.60 12.94 164.20 86.28
***
1% PG 129.70 19.47 114.30 29.08 101.60 18.37 91.80 12.98 151.10 35.32
2% PG 134.40 21.34 114.30 30.74 124.70 26.80 108.90 27.84 146.11 46.59
**
1% SSD + 1% PG 123.10 9.12 115.00 27.90 110.70 32.28 90.50 9.95 143.20 30.85
***
1% SSD + 2% PG 137.30 28.51 99.70 14.71 126.20 46.04 99.90 15.36 180.87 92.51
n = 10 for all groups, Data are shown as means SD.
**p < 0.01, ***p < 0.001 significantly different compared to baselines.
Table 2: The level of alanine transaminase enzyme on day 7, 14, 21 and 28 post-burn.
The level of alanine transaminase enzyme (U/L)
Groups
Control (Cream base) *

33.80 9.07 52.10 16.91 34.90 8.46 43.40 8.25 52.30 24.33
1% SSD 32.80 10.11 43.80 4.61 42.40 11.08 38.60 5.21 56.00 23.45
1% PG 39.30 10.91 52.60 20.06 43.30 9.12 37.00 2.36 57.22 27.61
+
2% PG 41.20 11.79 45.60 8.85 50.50 11.28 45.40 15.43 46.90 19.53
1% SSD + 1% PG 38.00 8.86 50.80 10.36 42.80 9.34 39.30 7.48 41.40 14.68
1% SSD + 2% PG 39.60 6.47 43.80 10.85 44.00 9.50 40.50 6.55 47.42 10.93
*p < 0.05 significantly different compared to baseline.
+p < 0.05 significantly different compared to cream base.

Bunman S, et al.
The level of alanine transaminase enzyme: On day Discussion

14 post-burn, the level of alanine transaminase enzyme
of rats treated with 2% PG was significantly higher (p < In addition, the liver enzymes including aspartate
0.05) than the baseline. However, on day 7, 21 and 28 post- aminotransferase and alanine transaminase in the blood
burn, the levels of alanine transaminase enzyme of rats increase when the liver is damaged, injured or inflamed
treated with 1% SSD, 1% PG, 2% PG, combination of 1% from alcohol or drugs. Aspartate aminotransferase has
SSD + 1% PG and combination of 1% SSD + 2% PG were also been found in other cells besides liver cells such as
not significantly different when compared to the control cardiac cells and striated muscle cells. Thus, the level
group (Table 2). of this enzyme is not specific to liver dysfunction but
can also be attributed to a disease like acute myocardial
The level of alkaline phosphatase enzyme: On day infarction. Therefore, alanine transaminase level is more
7 post-burn, the levels of alkaline phosphatase enzyme specific than aspartate aminotransferase level as an
of rats treated with 1% SSD, 1% PG, combination of 1% indicator for the liver function test.21 On day 21, the level
SSD + 1% PG and combination of 1% SSD + 2% PG were of aspartate aminotransferase in rats treated with 1% SSD
not significantly different when compared to the control and PG increased significantly compared to baselines but
group but the levels of alkaline phosphatase enzyme of all were still within the normal range (82-127 U/L).22 The
groups were significantly higher than their own baselines level of alanine transaminase only in rats treated with
(p < 0.01, p < 0.001, p < 0.001, p < 0.001 and p < 0.01, 2% PG increased significantly compared to baselines but
respectively). On day 14 post-burn, the levels of alkaline were still within the normal range (36-64 U/L).22
phosphatase enzyme of rats treated with 1% SSD, 1% PG,
combination of 1% SSD + 1% PG and combination of 1% Alkaline phosphatase is an enzyme in the epithelial
SSD + 2% PG were significantly higher compared to the cells of the gall bladder. This enzyme increases when the
control group (p < 0.05, p < 0.05, p < 0.05 and p < 0.001, patient has an obstruction of the bile duct, small biliary
respectively). Moreover, the level of alkaline phosphatase tract, stones, and some liver diseases. Alkaline phosphatase
enzyme of rats treated with combination of 1% SSD + 2% is also found in other organs such as bone, placenta and
PG cream was significantly higher than baseline (p < 0.05). intestine.23 On day 7, the level of alkaline phosphatase in
On day 21 post-burn, the level of alkaline phosphatase rats treated with cream base increased significantly
enzyme of rats treated with cream base and combination compared to baselines which may be due to dehydration
of 1% SSD + 2% PG were significantly higher than their from the second degree burn. The level of alkaline
baselines (p < 0.001 and p < 0.05, respectively). phosphatase of rats treated with 1% SSD and PG also
increased on day 14 and 21 post-burn and decreased to
However, on day 28 post-burn, the levels of alkaline normal range (82-112 U/L) on day 28.22 The increase of all
phosphatase enzyme of rats treated with 1% SSD, 1% PG, three liver enzymes levels (of less than three fold) are
2% PG, combination of 1% SSD + 1% PG and combina- indicated as acceptable levels in clinical settings.24-26
tion of 1% SSD + 2% PG were not significantly different
when compared to the control group (Table 3). Blood urea nitrogen (BUN) and creatinine are the
waste products from the metabolism process which are
Blood urea nitrogen: On day 7 post-burn, the levels of excreted by the kidney to maintain the homeostasis. High
blood urea nitrogen of rats treated with 1% PG and combi- level of BUN and creatinine indicates an impairment of
nation of 1% SSD + 2% PG were significantly higher than renal function. The baseline levels of BUN of all groups
the control group (p < 0.05 and p < 0.01, respectively). were higher than normal levels (15.6-20.1 mg/dl) reported
Moreover, on day 7 and day 14 post-burn, the level of by Diloke B etal.22 which was probably due to different
blood urea nitrogen of rats treated with combination of housing environment of the animals. The level of BUN
1% SSD + 2% PG were also significantly (p < 0.05) higher of rats treated with SSD appeared to decrease, while the
than 1% SSD. On day 21 post-burn, the levels of blood BUN level of rats treated with PG appeared to increase
urea nitrogen of rats treated with cream base and 1% PG compared to baselines on the early stages of wound
were significantly higher than their own baselines (p < healing (day 7). On day 7 post-burn, the level of BUN
0.01 and p < 0.01, respectively) (Table 4). in rats treated with 1% PG was significantly higher
compared to cream base and in rats treated with 1%
Creatinine: On day 7 post-burn, the levels of creatinine SSD + 2% PG was significantly higher compared to
of rats treated with 1% PG and combination of 1% SSD + 1% cream base and 1% SSD. The levels of BUN of all
PG were significantly higher than the control group (p < groups reached their maximum levels on day 21 or 28
0.05 and p < 0.05, respectively). However, on day 14, 21 and dropped back to baselines at the end stage of wound
and 28 post-burn, the levels of creatinine of rats treated healing (day 28). The decrease in BUN levels after day
with 1% SSD, 1% PG, 2% PG, combination of 1% SSD + 21 post-burn was in accordance with other studies. The
1% PG and combination of 1% SSD + 2% PG were not sig- results indicated that the increase levels of BUN may
nificantly different compared to the control group (Table 5). partly be due to PG.

Evaluation of Liver and Kidney Toxicity in Rats Receiving Proteoglycans from Fish Cartilage
for the Acceleration of Burn Wound Healing
Table 3: The level of alkaline phosphatase enzyme on day 7, 14, 21 and 28 post-burn.
The level of alkaline phosphatase enzyme (U/L)
Groups
Control (Cream base) ** **

138.30 20.30 202.10 50.65 183.00 53.43 219.50 53.66 153.80 25.57
*** *
1% SSD 137.30 25.52 220.70 24.89 194.80 40.19 200.80 50.71 160.90 44.17
*** *
1% PG 152.20 28.96 231.50 29.89 211.50 44.02 200.40 64.95 156.30 33.01
2% PG 154.10 36.75 206.40 46.25 200.00 32.00 198.10 61.64 148.80 27.12
*** *
1% SSD + 1% PG 146.30 26.68 221.10 46.45 205.90 35.00 208.10 37.93 158.70 20.47
*** + *
1% SSD + 2% PG 143.60 32.99 244.30 35.15 ***, 210.60 27.68 160.20 55.91
237.30 43.38
*p < 0.05, **p < 0.01, ***p < 0.001 significantly different compared to baseline.
Table 4: The level of blood urea nitrogen on day 7, 14, 21 and 28 post-burn.
The level of blood urea nitrogen (mg%)
Groups
Control (Cream base) **

21.50 2.07 22.50 4.25 23.40 1.96 37.34 3.76 26.50 3.66
1% SSD 34.10 6.14 24.51 6.73 29.90 3.35 41.13 12.91 27.80 3.74
+ **
1% PG 24.40 7.20 35.32 9.79 27.90 3.35 38.89 7.37 27.70 3.74
2% PG 32.00 5.66 33.81 10.10 27.20 4.32 36.55 8.26 26.70 2.26
1% SSD + 1% PG 30.40 5.64 29.46 10.51 28.20 2.25 38.31 9.09 26.60 2.67
++, # #
1% SSD + 2% PG 30.20 5.07 37.59 10.94 27.90 2.81 28.35 10.55 29.90 3.35
**p < 0.01 significantly different compared to baseline.
+p < 0.05, ++p < 0.01 significantly different compared to cream base.
#p < 0.05 significantly different compared to 1% SSD.
Table 5: The level of creatinine on day 7, 14, 21 and 28 post-burn.

The level of creatinine (mg%)
Groups
Control (Cream base) 0.54 0.05 0.48 0.04 0.50 0.05 0.53 0.05 0.54 0.16
1% SSD 0.51 0.05 0.50 0.07 0.57 0.05 0.60 0.12 0.57 0.13
+
1% PG 0.54 0.05 0.58 0.05 0.56 0.05 0.59 0.05 0.51 0.51
2% PG 0.54 0.05 0.53 0.05 0.55 0.05 0.54 0.05 0.53 0.08
+
1% SSD + 1% PG 0.55 0.05 0.57 0.05 0.55 0.05 0.55 0.05 0.49 0.07
1% SSD + 2% PG 0.53 0.07 0.55 0.05 0.55 0.05 0.52 0.04 0.72 0.07

Bunman S, et al.
Baseline levels of creatinine in all groups were higher Conclusion

than normal levels (0.37-0.47 mg/dl) reported by Diloke
et al.22 which was also probably due to a different housing This study demonstrated that PG extracted from fish
environment. In the early stages of wound healing (day cartilage accelerated and facilitated wound healing as
7 post-burn), the levels of creatinine in rats treated with Bunman2 and Neelam13 studied without causing toxic
1% PG and combination of 1% SSD + 1% PG cream were effects to the liver and kidney in rats in long term use.
significantly higher compared to cream base. However, the Further investigation of the safety profile of PG and the
levels of creatinine of both groups decreased to baselines combination of 1% SSD, 1% PG and 2% PG in detail is
at the end stage of wound healing (day 28). The results required in clinical settings.
indicated that the increased levels of creatinine may partly
be due to PG. Altogether, these results indicated that the
increase in BUN and creatinine levels were partly due
to PG.
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Original Article
Perceived Social Isolation, Self-Care Behaviors and Health

Status among Community Dwelling Older Adults Living Alone
Abstract
OBJECTIVE: To study and analyze the links among basic conditioning factors,
perceived social isolation, self-care behaviors and health status of community dwelling
older adults living alone.
MATERIAL AND METHOD: This study was a descriptive correlational research.
The samples were 212 community dwelling older adults living alone in Sa Kaeo
Province, Thailand. The data were collected by structured interviews and were
analyzed using descriptive statistics, Pearsons Product Moment Correlation statistics
and Chi-square test.
RESULTS: The perceived social isolation of the samples was at a moderate level
(62.7%) while that of the self-care behaviors was at a fair level (55.2%). Also, both
Phatharapreeyakul L, RN, MNS perceived physical status and mental health status were both at a high level (50.5%
and 60.8%, respectively). The perceived social isolation had statistically significant
negative correlation with self-care behaviors (r = -0.518, p < 0.001) and the perceived
physical health status (r = -0.249, p < 0.001) and the perceived mental health
(r = -0.364, p < 0.001). The basic factors which were statistically significant correlated
with the perceived social isolation was education (2= 6.194, p = 0.045) and income
Lithong Phatharapreeyakul, RN, MNS1,2 (2 = 17.489, p < 0.001). Self-care behaviors were statistically significant associated
Phachongchit Kraithaworn, RN, PhD2 with age (r = -0.236, p < 0.001), gender (2 = 9.288, p = 0.01), education (2 = 10.255,
Noppawan Piaseu, RN, APN, PhD2 p = 0.006) and income 2 = 21.414, p < 0.001). The perceived physical health status
was statistically significant associated with age (r = -0.328, p < 0.001), income
(2 = 14.584, p = 0.001) and health problems (2 = 9.726, p = 0.008). The perceived
mental health status was statistically significant associated with age (r = -0.238,
p < 0.001) and income (2 = 23.309, p < 0.001).
CONCLUSION: It can be concluded that there were links among basic conditioning
factors, the perceived social isolation, self-care behaviors and health status of the
community dwelling older adults living alone. Thus, in assessing the health status and
promoting self-care behaviors that are appropriate for this group of older adults, these
factors should be taken into account, especially the older adults who have a low income
and are poorly educated.
Keywords: community dwelling older adults living alone, perceived social isolation,
self-care behaviors, health status
S
ince the Thai economy and society changed from an
agricultural society to an industrial society, workers have
made their migration into the cities to work and earn a
living. As a result, the older adults and children are abandoned to
stay at home, or the older adults have to stay home alone.1 Moreover,
1
SaKaeo Crown Prince Hospital, SaKaeo Province, Thailand the family structure has also changed from the extended family to
2
Ramathibodi School of Nursing, Faculty of Medicine Ramathibodi Hospital, the nuclear family.2 This leads to an increasing number of older
Mahidol University, Bangkok, Thailand.
adults living alone. The current trend of older adults living alone
* Address Correspondence to author: increased from 3.6% in 1994 to 6.3%, 7.7%, and 8.6% in 2002,
Phachongchit Kraithaworn, RN, PhD. (Nursing) 2007, and 2011, respectively.3 Older adults living alone at home are
Ramathibodi School of Nursing, Faculty of Medicine,
Ramathibodi Hospital, Bangkok, 10400, Thailand. considered to be a major risk group to have health problems, both
e-mail: phachongchit.kra@mahidol.ac.th, physical and mental. Common physical health problems in older
phachong@hotmail.com adults are mostly chronic diseases such as hypertension, diabetes,
Received: November 26, 2015 bone and joint problems and heart disease.4 It also leads to a risk
Revision received: November 26, 2015 of infection, falls and death at home.5,6 For mental health problems,
Accepted after revision: December 29, 2015
Bangkok Med J 2016;11:17-23. it was found that many older adults feel lonely, desperate7 and
E-journal: http://www.bangkokmedjournal.com discouraged. The perceived mental health was lower than those

Phatharapreeyakul L, et al.
who live with family members.8 They also have dementia, The research instruments included 4 questionnaires as
depression, and even suicidal thoughts.9-11 In terms of follows:
social issues, this group of older adults runs a high risk of
social isolation as they have less interaction with others, Part 1: The demographic characteristics questionnaire.
less power, low self-esteem,12 and experience a lack of This was used to gather the general information of the
social support and networks. This can lead to inappropriate samples. The questionnaire was in the form of multiple
behaviors which can cause physical and mental health choices and open-ended questions. It consisted of 20
problems.13,14 questions, including the information of gender, age, marital
status, education, income, health problems and information
Since leaving older adults to live alone may cause about living alone.
many of the health problems mentioned above, self-care
behavior is very important to this group because they have Part 2: The perceived social isolation questionnaire.
no family members to provide care and assistance. Al- The test created by Cornwell and Waite14 was used. The
though the results of the research in other countries have test was translated into Thai and the back translation
mainly revealed that living alone as an older adult does process was used. The test consisted of 9 questions with
not mean facing loneliness there is more of a risk of health two aspects: the aspect of the feeling of isolation which
problems than older adults who live with their families.15-17 was 3 negative questions and the perceived social support
Yet, this group of older adults living alone feel that they which was 6 positive questions. A three-point Likert
have a better health status than those who live with Scale was used for the answers. In terms of scoring, for
others.17 It is clear, therefore, that there are some inconsis- a negative question the points were distributed as: never
tencies in the studies. Also, most research and studies are (1 point), sometimes (2 points) and often (3 points). For
studied in other countries which have different cultures. a positive question the points were distributed as: never
In some western countries, living alone for older adults is (3 points), sometimes (2 points) and often (1 points). The
more commonplace and the government plays a major scores ranged from 9-27 points. The interpretation of the
role in providing welfare for older adults. However, in scores was divided into three levels: low perceived social
Thailand, taking care of an older adult is the responsibility isolation (score < 14), moderate perceived social isolation
of the family. But, at present, the trend of taking care of (15-20 points) and high perceived social isolation (score
older adults has been decreasing,1 and from the reviews of > 21).
research in Thailand, there have been no studies associated
with social isolation and the links among the perceived Part 3: The questionnaire of self-care behaviors. The
social isolation, self-care behaviors and health status of self-care behaviors were assessed by using the self-care
older adults living alone in the community. Therefore, behaviors assessment in older adults which was created
in order to prepare for Thailands aging society and the according to the concept of Orem by Waraporn Thingerd.19
increasing number of older adults living alone in the country, It consisted of 22 items, including:
the researchers were interested in this issue in order to 1. 15 items of general self-care.
provide guidelines for the development of improved health 2. 4 items of developmental self-care.
care and quality of life for older adults living alone. 3. 3 items of health deviation self-care.
Material and methods A five-level Likert Scale was used. Seventeen items
were positive questions. In terms of scoring, the points
This study was a descriptive correlational analysis ranged from: not performing at all (0 point), to regularly
research. The samples were the community dwelling older performing (4 points). There were 5 items of negative
adults aged 60 and over living alone in Muang District, questions, and in terms of scoring, the points ranged from:
Sa Kaeo Province, Thailand. The study was conducted not performing at all (4 points), to regularly performing
from April to June 2015. The inclusion criteria included: (0 point). The score ranged from 0-88 points. The inter-
1) living alone for at least six months, 2) being able to pretation of the scores was divided into three levels: poor
speak and understand Thai language and not having self-care behaviors (score 52), fair self-care behaviors
communication problems, and, 3) no impairments in (53-69 points) and good self-care behaviors (score 70).
thinking and memory, based on Chula Mental Test.18 The
score obtained from the test must be equal to or greater Part 4: The questionnaire of perceived health status
than 15 points. Through purposive sampling, samples of assessment. The Short Form -36 Health Survey (SF 36)
212 participants were recruited to the study. (Version 2) which was developed by Ware et al.,20 and
translated into Thai by Jirarattanaphochai et al.21 was
The sample size of the study was calculated with the used. There were 36 questions with two health dimensions:
level of significance () equal to 0.05, the power of test 21 items of physical health and 15 items of mental health.
equal to 0.80, and the effect size equal to 0.20, which was a The interpretation of the score depended on the types of
small effect size. The two-tailed test was used to calculate questions in each subscale. For example, for the questions
the sample size using the G* Power 3.0.10 Program. on physical functioning, the points ranged from: greatly

Perceived Social Isolation, Self-Care Behaviors and Health Status among Community Dwelling Older Adults Living Alone
reduced (0), slightly reduced (50), and not reduced (100). Data analysis
For mental health, the points ranged from: always (0),
mostly (25), sometimes (50), once in a while (75), and The data were analyzed by a Statistical Package.
never (100). Then the points were put together and the Descriptive statistics, including the frequency, percentage,
average point of each subscale was calculated. After that, mean and standard deviation were analyzed. Pearsons
the average point of each subscale was put together as the Product Moment Correlation and chi-square were utilized
component. The scores ranged from 0-400 points. The to determine the relationships of the variables.
interpretation of the scores was divided into three levels:
low perceived health status (0 -133.33 points), moderate Results
perceived health status (133.34-266.67 points) and high
perceived health status (266.68- 400 points). The contents It was found that most of the samples were females
of the questionnaires were verified by 3 experts, namely (76.4%), and almost half of them aged 70-79 years (41.5%).
2 experts in geriatric care and an expert in community The average age was 72.34 years (Min = 60, Max = 93,
health and family nursing. The questionnaires were SD = 7.78). The samples were mostly Buddhists (98.2%).
improved before piloting with 15 subjects whose charac- They were widowed (72.6%), and single (8.5%). More than
teristics were similar to those of the subjects in the main half of them completed primary school level (69.8%) and
study. After that, the reliability of the perceived social did not work (64.6%). The average income was 3991.48
isolation, self-care behaviors and perceived health status Thai baht. The source of income was from their children
questionnaires were analyzed by using Cronbach alpha (51.4%). Most of them had health problems (76.9%).
coefficient. The reliability of the questionnaires was 0.83,
0.84 and 0.94 respectively. The first top three health problems were hypertension
(57.7%), arthritis / joint problems (55.8%) and hyper-
Protecting the rights of the samples: The researcher lipidemia (38.0%), respectively. For the period of living
submitted the consent to do research on people to the alone, it was 5-10 years (35.4%). Regarding the reasons
Human Research Ethics Committee of the Faculty of for living alone, more than half of them were living alone
Medicine, Ramathibodi Hospital, Mahidol University. after the death of their spouses, and their children worked
It was approved with Approval No. 2015/118 to protect in other areas and had their own families (69.3%). Half
the rights of the samples from the process of gathering of the samples had negative feelings towards living alone
data to the presentation of the findings. Participants were (53.3%), including feeling lonely and bored, followed
informed of the purpose of the research and given details by feeling neutral (25.0%). However, 21.7% of them had
about the activities as were the samples. The samples were a positive feeling towards living alone as they felt free
also informed that they could leave the study at any time. and had privacy, and they also were proud to take care of
themselves. Most of them were not worried about being
Data collection alone (75.0%), whilst a smaller proportion of them were
concerned about it (25%). The matters of concerns
Muang District, Sa Kaeo Province was selected included fear of illness without close supervision, fainting,
specifically as it is the largest and the most populated falling, and crime. Most of them did not have difficulties
district in the province. Stratified random sampling was living alone (75.9%).
used to identify potential partipants as there are 8 sub-
districts in Sa Kaeo and the Sa Kaeo Sub-district is the More than half of the samples perceived social isolation
largest the most populated sub-district. So it was chosen as medium (62.7%) while 12.7% of them perceived it as
as a representative sample of a big sub-district to study. high. Half of the samples had a fair level of self-care
Also, one small sub-district was selected from seven behaviors (55.2%) and a perceived physical health status
sub-districts by simple random sampling: drawing lots. that was relatively high (50.5%), and more than half of
Khok Pi Khong sub-district was selected. So, there were them perceived their mental health status as high (60.8%).
two sub-districts in total. The name lists of 315 older Education and income were correlated with the perceived
adults living alone were categorized, and divided into social isolation and were statistically significant. The
three groups based on age: 60-69 years, 70-79 years and chi-square was equal to 6.194, p = 0.045 and 17.489,
80 years and over. After that the numbers of samples p < 0.001, respectively as shown in Table 1. Gender,
required based on the ratio for each group was calculated. education and income were associated with self-care
The numbers of the older adults in each group were 84, 88 behaviors and were statistically significant. The chi-square
and 40 people, respectively. Then a simple random sample was equal to 9.288, p = 0.01, 10.255, p = 0.006 and 21.414,
by drawing lots was administered and 212 samples were p < 0.001, respectively, while income and health problems
obtained. Also, the process of data collection was done. associated with physical health status were statistically
significant. The chi-square was 14.584, p = 0.001, 9.726,
p = 0.008, respectively. Finally, income linked to mental
health status was statistically significant with a chi-square
of 23.309, p < 0.001.

Table 1: The links among basic factors (gender, marital status, education, income and health problems) and
perceived social isolation of older adults living alone in the community by chi-square (n = 212).
Perceived social isolation
Basic factors
Low Medium High 2
p
n (%) n (%) n (%)
Gender
Male 11 (22.0) 33 (66.0) 6 (12.0)

1.111 0.574
Female 48 (29.6) 96 (59.3) 18 (11.1)
Marital status
Single 3 (16.7) 12 (66.6) 3 (16.7)

1.487 0.475
Widowed/Separated 56 (28.9) 117 (60.3) 21 (10.8)
Education
Uneducated 8 (19.0) 25 (59.5) 9 (21.5)

6.194 0.045
Educated 51 (30.0) 104 (61.2) 15 (8.8)
Income
Low income 21 (26.9) 39 (50) 18 (23.1)

17.489 <0.001
Moderate income 38 (28.4) 90 (67.2) 6 (4.5)
Health problems
Less health problems 46 (24.3) 119 (63.0) 24 (12.7) 0.042 0.979

A lot of health problems 6 (26.1) 14 (60.9) 3 (13.0)
Table 2: The links among age, perceived social isolation, self-care behaviors, physical health status and mental
health status among older adults living alone in the community using statistical Pearsons Product Moment
Correlation (n = 212).
Variables 1 2 3 4 5
1. Age -
2. Perceived social isolation 0.063 -
3. Self-care behaviors -0.236** -0.518** -
4. Physical health status -0.328** -0.249** 0.342** -
5. Mental health status -0.238** -0.364** 0.467** 0.783** -
The perceived social isolation of negative links with Discussion

self-care behaviors, physical health status and mental
health status were statistically significant: r = -0.518 (p < The results of the study revealed that more than half
0.001), r = -0.249 (p < 0.001) and r = -0.364 (p < 0.001), of the samples had moderate perceived social isolation.
respectively. Self-care behaviors were positively associated This can in part be explained because some of them were
with physical health status and mental health status and supported by their children in terms of needed resources,
were statistically significant: r = 0.342 (p < 0.001) and especially money although their children did not live with
r = 0.467 (p < 0.001), respectively. Age was negatively them. Moreover, the samples also received psychological
associated with self-care behaviors, physical health status and emotional support from the persons who were close
and mental health status and were statistically significant: to them. They still had relatives and friends / neighbors.
r = -0.236 (p < 0.001), r = -0.328 (p < 0.001) and r = -0.238 So, they might not feel very lonely. Half of the samples
(p < 0.001), respectively, as shown in Table 2. had self-care behaviors at a fair level and more than half

of them had perceived physical health status and mental elderly had adequate social support from their children,
health status at a high level. It might be because most of relatives and friends / neighbors. This was consistent with
them were early and middle older adults, whose physical the study of Hawthorne.28
and mental health, awareness and intelligence was not in
bad condition. So, they had the capacity for self-care and Gender was associated with self-care behaviors and
were still healthy.22 this was statistically significant. In this study, the majority
of the samples which were females had better self-care
It was also found that basic conditioning factors behaviors than males. This was because the role of the
were associated with perceived social isolation, self-care females was determined as the persons providing care to
behaviors and health status. Income had a negative corre- others. So, they had experience and skills in self-care. They
lation with the perceived social isolation and was statisti- were also sensitive to changes and tried to keep themselves
cally significant. This can be partly explained as income in a healthy condition.29 This was consistent with the study
was a factor that allowed older adults to access resources of Khwandao Klamrat30 in 2011. Nevertheless, gender was
without having to rely on others. So, they were proud of not associated with perceived social isolation. This may
themselves. This was in accordance with the study of be because most of the female respondents were early and
Parkotwong W.12 in 2008 which found that income was middle older adults who had the ability to participate in
associated with loneliness among older adults living social activities, so they can gain social supports and work
alone. It was also found that income was associated with for a living. This allowed them to have better self-esteem
self-care behaviors and health status and this was statisti- and they felt less lonely and isolated.12 This was consistent
cally significant since having sufficient income or a good with the study of Hawthorne28 in 2008, which was found
economic status allowed individuals to access more health that gender was not associated with perceived social isolation.
resources, and they were likely to be healthier than those
who earned less.23 This was consistent with the findings Marital status was not associated with perceived
of the study of Zhou et al.24 in 2015 which revealed that social isolation, self-care behaviors and health status. This
the elderly with low incomes were associated with poor was probably because most of the samples were widowed
health status. as their spouses passed away and some of them were single.
So, they were all considered as not having spouses. This
Regarding education, it was associated with perceived was consistent with the study of Dale et al.31 in 2011, which
social isolation and this was statistically significant. Those found that marital status was not associated with self-care
who were educated obviously had communication channels behaviors and health status of older adults living alone.
and social networks. They had social support to ascertain
needed information to be applied as a solution or relief Health problems and perceived health status were
of the problem that people were facing.25 Therefore that correlated and were statistically significant. Illnesses
could result in those who were better educated to have a caused difficulties to individuals, families and society,
lower perceived social isolation than those who did not and health status and perceived health status of individuals
get education. It was also found education was associated influenced management of illnesses.22 Thus, health problems
with self-care behaviors and this was statistically signifi- of the samples were obviously associated with perceived
cant since education gave individuals the skills and oppor- health status. This was consistent with the study of Caetano
tunities to communicate with others and have increased et al.32 in 2013. However, their health problems were not
access to health information. As a result, they had good associated with the perceived social isolation. This was
self-care behaviours.23 In this study, older adults who had probably because health problems did not impede social
received education had better self-care behaviors than activities. The samples were treated at the Health
those who did not, which was in accordance with the study Promoting Hospital near their homes, so they met with
of Bai et al.26 in 2009. friends who had similar health problems, and they could
exchange experiences.8,15 This allowed the samples to
Age was negatively associated with self-care behaviors perceive that having chronic diseases or health problems
and this was significant statistically as an increasing of was common with older adults.
age was an indication of the deterioration of physical
health, resulting in the reduction of the ability in taking The links among perceived social isolation, self-care
care of themselves without support from others. The results behaviors and health status and perceived social isolation
of the study also revealed that age was negatively associated and self-care behaviors were negatively correlated and
with perceived health status and this was statistically this was statistically significant. It can be explained
significant. This was consistent with the study of Smith according to the theory of Orem that those who have
and Goldman27 in 2006 which was found that age was interactions with society will be supported in the future,
negatively correlated with the perceived health of the so they can take care of themselves the way that society
elderly. However, there was no correlation between age does. If people, however, have a sense of isolation and lack
and perceived social isolation. This may be because the the ability to socially interact with others, they will lack

the ability to care for themselves and have inappropriate revealed that self-care behaviors were correlated with
self-care behaviors.22 This was in accordance with study health status.
of Bai et al.26 in 2009, which revealed that self-care behav-
iors were negatively correlated with feelings of loneliness Conclusion
and depression, but there was a positive correlation with
social support. According to the results of this study, it can be concluded
that there were links among perceived social isolation,
Perceived social isolation and health status were self-care behavior and health status of older adults living
negatively associated with each other with a statistical alone in the community. Thus, in assessing the health
significance. This is best described by the concept of status of older adults, these factors should be taken into
Cornwell and Waite14 in 2009 that the causes of social account, especially in older adults who have low income
isolation of persons are chronic diseases and physical, and are uneducated. The access to health services and
mental, social and intellectual deterioration, which lead social services should be increased and offered served
to the lack of social networks and less social support. This to reduce perceived social isolation. Encouraging older
will affect the physical and mental health of individuals.14 adults to have good self-care behaviors based on an
This was in accordance with the studies of Cornwell and individual basis will help older adults living alone in the
Waite14 in 2009, and Hawthorne28 in 2008, which found community to have both good physical and mental health.
that older adults with high perceived social isolation This will result in a better quality of life.
usually had links with poor physical and mental health.
Acknowledgement
Self-care behaviors and health status were positively
correlated. It can be explained by the concept of Orem that We would like to express our gratitude to the director
promoting and maintaining health status are the results of of Sa Kaeo Crown Prince Hospital, the community nurses,
ongoing care. This is done deliberately with a targeted and the health care officers, the community leaders and the
structured process. When it is done effectively, it will sample participants who facilitated, cooperated and gave
contribute to well-being and health and people can perform their time to take part in this study.
their duties effectively. It can be said that health status
is a result of self-care.24 The results of this study were
consistent with the study of Sunsli et al.33 in 2012, which
References
1. Sasipat Yodpet. Long - term care system for older persons 9. Fratiglioni L, Paillard-Borg S, Winblad, B. An active and
in family. Bangkok: Mister Copy; 2006. (in Thai). socially integrated lifestyle in late life might protect
2. National Statistical Office. Executive summary for against dementia: A community-based longitudinal study.
administrator 2013.(Accessed October 25, 2014 at http:// Lancet Neurol 2004;35:343-53.
service.nso.go.th/nso/nsopublish/) 10. Cacioppo JT, Hughes ME, Waite LJ, et al. Loneliness as a
3. National Statistical Office. Health care behaviors 2011. specific risk factor for depressive symptoms: cross-sec-
(Accessed October 30, 2011 at http://service.nso.go.th/ tional and longitudinal analyses. Psychol Aging 2006;
nso/daata/02/woe_article47.html) 21:140 -51.
4. Martsut R. Health status and self-care behavior of the 11. Alpass, FM, Neville S. Loneliness, health and depression
elderly living alone at Kalasin Municipalty, Kalasin in older males. Aging Ment Health 2003;7:212-6.
Province (Thesis Master of Nursing Science). Chonburi: 12. Prakotwong W. Factors predicting feeling of loneliness
Burapha University;2011. among living alone (Thesis Master of Nursing Science).
5. Faulkner KA, Cauley JA, Zmuda JM, et al. Is social Phitsanulok: Naresuan University; 2009.
isolation integration associated with the risk of falling in 13. Berkman LF, Glass T, Brissette I, et al. From social
older community-dwelling women? J Gerontol A Biol Sci integration to health: Durkheim in the new millennium.
Med Sci 2003;58:954-9. Soc Sci Med 2000;51:843-57.
6. Gurley RJ, Lum N, Sande M, et al. Persons found in their 14. Cornwell EY, Waite LJ. Social disconnectedness, per-
homes helpless or dead. N Eng J Med 2001;334:1710-6. ceived isolation, and health among older adults. J Health
7. Routasalo PE, Savikko N, Tilvis RS, et al. Social contacts Soc Behav 2009;50;31-48.
and the relationship to loneliness among aged people-A 15. Yeh SL, Lo SK. Living alone, social support, and feeling
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8. Chou KL, Chi I. Comparison between Chinese living 32:129-38.
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appraisal in older people2: The implications for clinicians Welsley; 1981.
and commissioners of social isolation risk in older 26. Bai YL, Chiou CP, Chang YY. Self- care behavior and
people. Br J Gen Prac 2007;57:277-82. related factors in older people with type2 diabetes.
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elderly persons living alone and those living with others. 27. Smith KV, Goldman N. Socioeconomic differences in
J Gerontol Soc Wor 1994;21:5-26. health among older adults in Mexico. Soc Sci Med
18. Jitapunkul S, Lailert C. Mini-Mental Status Examination: 2007;65:1372-85.
is it appropriate for screening in Thai elderly? J Med 28. Hawthorne G. Perceived social isolation in a community
Assoc Thai 1997 ;80:116-20. sample: its prevalence and correlates with aspects peoples
19. Thinkerd W. Effects of self-care behavior promotion lives. Soc psychiatr and psychiatr epidemiol 2008;43:140-50.
program for the elderly (Thesis Master of Education). 29. Burnette D, Mui AC, Zodikoff BD. Gender, self-care and
Chonburi: Burapha University; 2002. functional status among older persons with coronary heart
20. Ware JE, Sherbourne CD. The MOS 36-item short form disease: A national perspective. Women Health 2004;
health survey(SF-36): I. conceptual framework and item 39:65-84.
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21. Jirarattanaphochai K, Jung S, Sumananont C, et al. Western region of Thailand (Thesis of Doctoral of
Reliability of the medical outcomes study short-form Education). Bangkok: Silapakorn University; 2011.
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back pain patients. J Med Assoc Thai 2005;88:1355-61. among home- dwelling older people in rural area in
22. Orem DE. Nursing: Concept of Practice. 5th ed. St. Louis: southern Norway. Scand J Car Sci 2012;26:113-22.
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24. Zhou Y, Zhou L, Fu C, et al. Socio- economic factors lation- based study in Brazil, BMC Geriatr 2013;13:122-36.
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people living indepently in China. Int J Equity Health self- care in urban living older people in southern
2015;14:5. Norway. J Multidiscip Healthc 2012;5:85-95.

Original Article
Effect of Participation in Type 2 Diabetes Mellitus (T2DM)

Education Pathway on HbA1c
Abstract
OBJECTIVE: To examine glycemic control in diabetic patients who participated in
a T2DM education pathway.
MATERIAL AND METHODS: The study was a retrospective study on diabetic
patients who participated in a T2DM education pathway at the Diabetes, Thyroid and
Endocrine Center, Bangkok Hospital from January 2012 to December 2013. The data
assessment included: 1) Demographic data, 2) Data of self-care behaviors including
exercise behavior, self-monitoring blood glucose and drug related problems (DRP)
and, 3) Hemoglobin A1c (HbA1c) data obtained from the electronic medical record
(EMR).
RESULTS: A total of 163 diabetic patients took part and 105 of these (64.4%) were
Songsai P, RN, MSN males. The average age was 53.7 11.5 years. The average HbA1c decreased from
9.6 2.0% to 7.6 1.6% after one year of joining the pathway (p < 0.01). With
regards to the links between the related factors and HbA1c after participating in
the pathway, it was found that self-monitoring blood glucose (SMBG) was associated
with a decrease in HbA1c which was statistically significant (p < 0.01). For other
factors, including exercise and drug related problems (DRPs), although there was no
Pannee Songsai, RN, MSN1
statistical correlation, the patients who did exercise had lower HbA1c levels than
Nucharin Tungjuk, RN1
those who did not exercise.
Kitithat Phitchayapiyasak2
CONCLUSION: The study revealed that SMBG allowed the diabetic patients to be
Yuwadee Tantinukul3
able to better control their blood glucose level. The research team will apply these
results with the diabetic patients by encouraging them to do SMBG in order to allow
them to adjust their eating habits and do appropriate exercises.
Keywords: DM education pathway, type 2 diabetes, HbA1c
D
iabetes mellitus (DM) is a chronic disease that affects
millions of people around the world. Management of
DM requires comprehensive and ongoing care. To achieve
the goal of diabetes care, the patient needs both input from their
healthcare provider and their own life style modification. An
appropriate patients behavior and self-management of DM is
one of the main keys of success. DM education is a very
important part of DM care and usually the outcome is better
if the patient is compliant to the educators recommendation. The
American association of Diabetes Educator (AADE)1 has defined
1
Diabetes, Thyroid and Endocrine Center, Bangkok Hospital, the areas to assess and evaluate the effectiveness of the
Bangkok Hospital Group, Bangkok, Thailand. education on diabetes self-management of each individual. This
2
Nutrition Therapeutic, Bangkok Hospital, Bangkok Hospital Group,
Bangkok, Thailand. involves seven self-care behaviors which include: being active
3
OPD Pharmacy, Bangkok Hospital, Bangkok Hospital Group, (exercise), healthy eating, taking medicine, monitoring blood
Bangkok, Thailand.
sugar, problem-solving especially for blood glucose, reducing risk
* Address Correspondence to author: of diabetes complications, and psychosocial adaptation.
Pannee Songsai, RN, MSN
Diabetes, Thyroid and Endocrine Center, Bangkok Hospital,
2 Soi Soonvijai 7, New Petchaburi Rd.,
Several studies have shown that few patients follow multiple
Bangkok 10310, Thailand. self-care behaviors at the recommenced levels.2 Therefore, an
e-mail: pannee.so@bangkokhospital.com
educational program is considered to be essential in controlling
Received: November 10, 2015 diabetes or reaching a good glycemic control. Many studies found
Revision received: November 15, 2015 that a DM education program can increase not only knowledge but
Bangkok Med J 2016;11:24-27.
also self-management to achieve target glycemic control.3-5 The
E-journal: http://www.bangkokmedjournal.com Diabetes, Thyroid and Endocrine center at Bangkok Hospital has

Effect of Participation in Type 2 Diabetes Mellitus (T2DM) Education Pathway on HbA1c
developed a DM education pathway in order to serve as patients on compliance issues with drug related problems
a guideline to ensure the same high quality standard of (DRP) including: 1) taking too little medication, 2) take
diabetes care is offered to all patients. This pathway also too much medication, 3) difficulty using the dosage form,
includes patients multidisciplinary visits. In the pathway, and 4) other common compliance problems associated
other than seeing only the doctor, the patient will also with drug use which are frequently found in patients with
see a DM educator, a dietician and a pharmacist. This type 2 diabetes mellitus.
pathway helps to encourage patients to do their part to
control their blood sugar, which means to follow The inclusion criteria for participants were: 1) those
recommended self-care behavior modification at home. who had been diagnosed with type 2 diabetes, 2) aged
The aim of this study was to evaluate the effects of the between 15 and 80 years old and, 3) with a level of HbA1c
diabetes education pathway in glycemic control repre- 7%. The exclusion criteria were patients who had been
sented by a decrease in HbA1c levels among people with diagnosed with stage 4 cancer, end stage renal disease or
diabetes exposed to this pathway. severe medical problems or bedridden condition.
Material and Methods Data collected from electronic medical record (EMR)
included: 1) Demographic data including age and gender,
The study was a retrospective study to evaluate glycemic 2) data of self-care behaviors including exercise behavior,
control of diabetes patients who participated in a DM self-monitoring blood glucose and drug related problems
education pathway at the Diabetes, Thyroid and Endocrine (DRP) and, 3) HbA1c level at before and after participating
Center, Bangkok Hospital from January, 2012 to December, in the education pathways.
2013. The DM education pathway is delivered over 12
months for diabetes self-management instructed by a Data collection started after receiving approval form
multidisciplinary team on different topics or problems at the Institutional Review Board and Ethics Committee
each visit for 12 months (Figure 1). All subjects involved at Bangkok Hospital. The data used questionnaires and
in this pathway were interviewed by the nurse coordinator data record forms from the electronic medical records
about performing exercise and self-monitoring blood to include: general information, eating habits, drug use,
glucose (SBMG). In addition, pharmacists interviewed the exercise, SMBG, and levels of HbA1c.
Figure 1: Type 2 Diabetic Mellitus Education Pathway.

Songsai P, et al.
Statistical analysis from 9.6 2.0% to 7.6 1.6% after participating in the DM
education pathway for one year (p < 0.01). For behavior
A descriptive analysis was used to analyze the number, modification, when it came to exercise, it was found
percentage, mean and standard deviation of demographic that the number of participants who performed exercise
data. A chi Square test was used to analyze the categorical increased from 33.1% to 52.2% and participants who
data and a pair t-test was utilized to analyze the continuous performed SMBG increased from 41.7% to 66.9% after
data to compare HbA1c between before and after participating in the education pathway for one year
participating in the education pathway and the relation (Table 1).
between the factors and HbA1c was analyzed by odds ratio
(OR) with a 95% confidence interval (95% CI) and logistic When the related factors were analyzed to find out
regression. the relationship with HbA1c after participating in the
education pathway, it was revealed that using a SMBG
Results device was associated with a decrease in HbA1c which
was statistically significant (p < 0.01). For other factors
Of the 163 diabetic patients participating in the study, including exercise, although there was no statistical relation,
the majority of participants were male (64.4%). The average the patients who did exercise had lower HbA1c levels than
age was 53.7 11.5 years. The average HbA1c decreased those who did not exercise (Table 2).
Table 1: Changes in mean HbA1c, exercise behavior and Self-Monitoring Blood Glucose before and after
participating the education pathway (n=163).
Before After
Data p
n (%) n (%)
Total patient (n) 163 (100)
HbA1c (%) (meanSD) 9.6 2.0 7.6 1.6 < 0.01
Exercise < 0.05
Yes 54 (33.1) 85 (52.2)
No 109 (66.9) 78 (47.8)
Self-Monitoring Blood Glucose (SMBG) < 0.05
Yes 68 (41.7) 109 (66.9)
No 21 (12.9) 19 (11.6)
Table 2: The relation of the decrease in HbA1c after participating in the pathway (n = 163).
HbA1c
Adjusted OR3
Activity Improved 1
Not Improved2 OR (95%CI) p
(95%CI)
(n) (n)
Exercise
Yes 65 20 1.72 (0.87 3.41) 1.35 (0.62 2.92) 0.44
No 51 27
Self-Monitoring Blood Glucose (SMBG)
Yes 80 8 3.79 (1.39 10.36) 3.74 (1.36 10.27) <0.01
No 29 11
Drug related problems (DRPs)
No 73 31 0. 71 (0.36 1.43) 0.81 (0.36 1.80) 0.06
Yes 43 16
1
refers to the difference in HbA1c values between before and after joining the pathway of more than 0.5%.
2
refers to the difference in HbA1c values between before and after joining the pathway less than or equal to 0.5%.
3
refers to the analysis combined with exercise, self-monitoring blood glucose and the DRPs

Effect of Participation in Type 2 Diabetes Mellitus (T2DM) Education Pathway on HbA1c
Discussion who did not have drug related problems, it was found that
the exercise increased (from 33% to 52%) and drug related
The present study aimed to assess the effect of DM problems decreased after participating in the education
education pathway in controlling HbA1c levels among pathway for one year.
adults with type 2 diabetes. The primary outcome of the
study is improved glycemic levels (in terms of reduced It is acknowledged that improvements in HbA1c levels
HbA HbA1c) of patients after participating in the education in diabetes patients cannot be attributed solely to par-
pathway. The study results showed a significant decrease ticipating in the DM education pathway. However, the
in HbA1c levels in participants by the end of the education pathway may have helped people with diabetes
program (from 9.6 2.0% at before to 7.6 1.6% and multi-disciplinary team members to guide and focus
after participating in the pathway). It showed the patients on the recommended topics relating to diabetes and this
who participated in the education pathway can improve tended to have a good effect on self-care behavior and
their self-care behaviors and can help patients to control glycemic control.
their blood glucose. The findings of this study are similar
with the results from a previous study by Keeratiyutawong6 Conclusion
that showed a significant decrease in HbA1c levels in the
intervention group after attending the program. This study found that SMBG allowed the patients with
diabetes mellitus to be able to better control their blood
In addition, the results demonstrated that a number glucose level. The research team will share these results
of patients who performed SMBG regularly showed with diabetes mellitus patients and encourage them to
significant improvement of levels of HbA1c. The findings perform SMBG to help them to adjust their eating habits
of this study are similar to the results from previous and to exercise appropriately.
studies7-12 Therefore, SMBG can help diabetic patients
to control their blood glucose level and can be used as a Acknowledgements
tool to learn appropriate self-care behaviors in line with
recommendation guidelines.13 However, although there We are deeply grateful to the Bangkok Health Research
was no statistically significant difference in the number Center at Bangkok Hospital and our research consultant,
of participants who showed an improvement in HbA1c for their assistance in data analysis.
levels among those who performed exercise regularly and
References
1. American Diabetes Association. (2004a). Standards of 8. Laguna DM, Morro I Pla. J, Rodigo SM, et al. Recommended
medical care in diabetes. Diabetes Care 2014;37 (Suppl. 1): self-monitoring of blood glucose, better metabolic control
514-80. with different monitoring intervals. Primary Care Diabetes
2. Gavgani RM, Poursharifi H, Aliasgarzadeh A. Effectiveness 2013;7:71-89.
of Information-Motivation and Behavioral skill (IMB) 9. Garcia de la N, Duran A, Del Valle L. et al. Early management
model in improving self-care behaviors & Hba1c measure of type2 diabetes based on a SMBG strategy: the way to
in adults with type2 diabetes in Iran-Tabriz. Procedia-Social diabetes regression-the St Carlos study: 3year, Prospective,
and Behavioral Sciences 2010;5:1868-73. randomized, clinic-based, interventional study with parallel
3. Spollett, G. Promoting continuing education in diabetes group. Acta Diabetol 2013;50:607-14.
management. Endocrine Practice 2006;12 (Suppl. 3):68-71. 10. Kunkla A. The assessment of the ability to control diabetes.
4. Wongsunopparat B, Ngarmukos C, Saibuathong N. Glycemic Regional Med J 6/2 1999;7:429-39.
control in persons with diabetes after attending a group 11. Cramer JA. A systematic review of adherence with
educational program for diabetes self-management. Rama medications for diabetes. Diabetes Care 2004;27:1218-24.
Nurs J 2008;14:289-97. 12. Scavini M, Bosi E, Ceriello A, et al. Prospective, randomized
5. Unger, J. Practical strategies for achieving targeted trial on intensive SMBG management added value in
glycemic control in patients with type 2 diabetes. Journal non-insulin-treated T2DM patients (PRISMA): a study to
of Family Practice 2006;55:25S-32S. determine the effect of a structured SMBG intervention.
6. UK Prospective Diabetes Study 7: Response of fasting Acta Diabetol 2013;50:663-72.
plasma glucose to diet therapy in newly presenting type II 13. Diabetes Association of Thailand. Clinical Practice
diabetic patients. Metabolism 1990;39:905-12. Guideline in DM, 2014. Bangkok: Arun Printing; 2014.
7. Keeratiyutawong P, Hanucharurnkul S , Panpakde O, et al.
Effectiveness of a Self-Management Program for Thais
with Type 2 Diabetes. Thai J Nurs Res 2006;1085-97.

Case Report
MRI Findings in Transient Global Amnesia
Abstract
Transient global amnesia (TGA) is characterized by an attack of temporary antero-
grade amnesia without other focal neurological deficits. Characteristic magnetic
resonance imaging (MRI) findings include small, punctate, unilateral or bilateral
diffusion restriction in the lateral aspect of the hippocampus, which mostly occurs
within 48 hours after symptoms onset. The outcome of TGA is usually excellent. The
pathophysiology of TGA remains uncertain, but recent evidence suggests that this
disorder may result from the inability to generate new memory in the hippocampus due
to vulnerability of CA-1 neurons to metabolic stress.
Keywords: transient global amnesia; MRI, hippocampus

Chansakul C, MD
T
ransient global amnesia (TGA) is a disorder characterized
by a sudden attack of severe anterograde amnesia, where
patients are unable to learn and recall novel information
during the event. Although first described at least 60 years ago,1
Chakorn Chansakul, MD1
the etiology and pathophysiology of TGA remain unclear and have
been a matter of debate among clinicians and researchers. In this
paper, we present a case of TGA with typical MRI findings and the
review of literature.
Case Report
A 38-year-old, right-handed, Thai lady, without significant past

medical history, presented to the Neuroscience Center of Bangkok
Hospital Medical Center with a sudden onset of transient memory
loss. Her symptoms occurred on the morning of the same day of the
hospital visit. After sending her daughter to school and driving back
home, the patient suddenly could not remember what was going on,
and repeatedly asked the same questions. She was able to remember
her name and her husband. Her language was not disturbed during
the event. She denies headache, dizziness, or vertigo associated with
this spell. There were no other focal neurological deficits. There
were no witnessed abnormal movements of the face, lip smacking,
or fidgeting of the hands and feet. The symptoms lasted for
1
Neuroscience Center, Bangkok Hospital, Bangkok Hospital Group, approximately two hours before her memory gradually came back.
Bangkok, Thailand.
The patient could not remember the entire spell. She denies prior
* Address Correspondence to author: similar symptoms. She denies the history of recent head injury or
Chakorn Chansakul, MD any stressful events.
Neuroscience Center, Bangkok Hospital
Bangkok 10310, Thailand. On examination, the patient was alert, awake, and oriented to
e-mail: chakorn.chansakul@gmail.com
time, place, and person. She appeared anxious and frustrated as she
Received: January 12, 2016 could not remember what happened during the event. Her concen-
Revision received: January 12, 2016 tration, memory, repetition, naming, reasoning and executive func-
Bangkok Med J 2016;11:28-31. tions were all intact. There was otherwise no focal neurological
E-journal: http://www.bangkokmedjournal.com deficit. Her vital signs were all within normal ranges.

Figure 1: The MRI diffusion weighted imaging (DWI) showed small punctuate hyper-intense lesions in the CA1
area of the bilateral hippocampi. (b value = 1000 s/mm2, 2-mm slice through the hippocampus, performed at
approximately 12 hours after symptom onset).
Figure 2: The MRA of the brain was unremarkable.

Chansakul C
Figure 3: The MRV of the brain revealed hypoplasia of the left transverse and sigmoid
sinuses, which could be a normal variation.
Blood chemistry revealed fasting blood glucose of 6. Attacks must resolve within 24 hours
81 mg/dL, HbA1c of 4.9%, total cholesterol of 195 mg/ 7. Patients with recent head injury or active epilepsy
dL, triglyceride of 107 mg/dL, HDL-C of 90 mg/dL, and (that is, remaining on medication or one seizure in
LDL-C of 96 mg/dL. 12-lead EKG showed a normal sinus the past 2 years) are excluded.
rhythm of 67 beats per minute without other pathological
findings. When the patient fulfills the definite diagnosis for
TGA, the outcome is usually excellent. The rate of subse-
The patient underwent electroencephalography (EEG) quent major vascular event is less than 1% per year,2 and in
which was within normal limits. MRI, MRA, and MRV most patients (more than 90% of cases), TGA occurs only
of the brain were obtained (Figures 1-3), which revealed once in their lifetime.3
two small foci of restricted diffusion at the bilateral
hippocampal bodies; otherwise the studies were unremark- Given the temporary nature of this disorder, TGA
able. is often hypothesized to be caused by transient cerebral
ischemia, epilepsy, migraine,4 as well as venous congestion
Discussion due to retrograde venous cerebral blood flow.5 However,
none of these pathophysiological theories is convincing as
The patient in our case meets the strict diagnostic the relapse rate of such conditions are significantly higher
criteria for transient global amnesia, which was proposed than that of TGA.6 Additionally, most of the initial studies
by Hodges and Warlow as follows:2 found no significant difference between the brain imaging
1. Attacks must be witnessed and information avail- of TGA patients and normal control.2,7
able from a capable observer who was present for
most of the attack An MRI study in 1999 by Grass and colleague8 in
2. There must be a clear-cut anterograde amnesia patients with acute TGA (performed within 8 hours of
during the attack symptoms resolution) found no evidence of hyperintensity
3. Clouding of consciousness and loss of personal on diffusion-weighted (DW) images or hypointensity on
identity must be absent, and the cognitive impairment apparent diffusion coefficient (ADC) maps that would
limited to amnesia (that is, no aphasia, apraxia, etc) imply decreases of water mobility or acute T2 changes.
4. There should be no accompanying focal neurological However, when the study by the same group was modified
symptoms during the attack and no significant in order to serially investigate TGA patients using DW
neurological signs afterwards images performed on the day of symptom onset through
5. Epileptic features must be absent days 1 and 2, more than 80% of the patients developed

a small, punctate, unilateral or bilateral DW MRI lesion found that TGA patients scored significantly higher than
in the lateral aspect of the hippocampal formation (pes the control group on a scale that measured phobic attitude.13
and fimbria hippocampi).9 Such findings have been According to an analysis by Quinette et al, TGA episodes
confirmed by several subsequent studies.10-12 Since lesions in women are associated with an emotional precipitating
were rarely detected in the hyperacute phase, and most event, a history of anxiety and pathological personality
became noticeable within 48 hours, this may explain why traits, suggesting that psychological factors are of particular
many prior studies did not reveal significant abnormalities importance in TGA.14 Griebe and colleagues showed
in neuroimaging of TGA patients.9 Follow up brain MRI that patients with prior TGA has a hypersensitivity of the
is recommended several days later when no lesion is hypothalamicpituitaryadrenal (HPA) axis, which can
detected by DW images within 24 hours after onset.11 result in a significant elevation of the glucocorticoid level
during an acute stress event, affecting the function of the
Although diffusion restriction is often associated with hippocampus on a cellular level.15 Thus, recent hypothesis
ischemic stroke representing a zone of irreversible damage, suggests that TGA might result from a stress-related
several studies showed that hippocampal lesions in TGA temporary inhibition of memory formation in the hippo-
patients completely resolve without structural sequelae.10,12 campus by means of a selective vulnerability of CA-1
In addition, there is no significant difference in long-term neurons to metabolic stress.16
cognitive performance and psychological outcomes
between patients with and without DW restriction as Conclusion
well as compared to healthy control.6 Moreover, the
frequently delayed onset of the lesions is not consistent Transient global amnesia is a disorder characterized by
with the abrupt nature of cerebral ischemic events. There- an attack of temporary anterograde amnesia with no other
fore, the DWI restriction in TGA may not result from focal neurological symptoms. Recent studies showed that
similar pathophysiology to that of an acute cerebrovascular the characteristic MRI findings of this disorder are small
accident. punctuate diffusion restricted lesions in the CA1 area of
the hippocampal formation. The onset of such findings
There are certain personality traits and psychological can be delayed up to 48 hours after the symptom onset:
comorbidities that have been suggested to be more therefore, serial MRI may be helpful.
common in TGA. For example, Inzitari and colleagues
References
1. Hauge T. Catheter vertebral angiography. Acta Radiol 10. Bartsch T, Alfke K, Stingele R, et al. Selective affection
Suppl 1954;109:1-219. of hippocampal CA-1 neurons in patients with transient
2. Hodges JR, Warlow CP. Syndromes of transient amnesia: global amnesia without long-term sequelae. Brain 2006;
towards a classification. A study of 153 cases. J Neurol 129:2874-84.
Neurosurg Psychiatry 1990;53:834-43. 11. Weon YC, Kim JH, Lee JS, et al. Optimal diffusion-
3. Agosti C, Akkawi NM, Borroni B, et al. Recurrency in weighted imaging protocol for lesion detection in transient
transient global amnesia: a retrospective study. Eur J global amnesia. Am J Neuroradiol 2008;29:1324-8.
Neurol 2006;13:986-9. 12. Ueno H1, Naka H, Ohshita T, et al. Serial changes in
4. Tong DC, Grossman M. What causes transient global delayed focal hippocampal lesions in patients with tran-
amnesia? New insights from DWI. Neurology 2004 sient global amnesia. Hiroshima J Med Sci 2010;59:77-81.
22;62:2154-5. 13. Inzitari D, Pantoni L, Lamassa M, et al. Emotional
5. Baracchini C, Tonello S, Farina F, et al. Jugular veins arousal and phobia in transient global amnesia. Arch
in transient global amnesia: innocent bystanders. Stroke Neurol 1997;54:866-73.
2012;43:2289-92. 14. Quinette P, Guillery-Girard B, Dayan J, et al. What does
6. Uttner I, Prexl S, Freund W, et al. Long-term outcome in transient global amnesia really mean? Review of the
transient global amnesia patients with and without focal literature and thorough study of 142 cases. Brain 2006;
hyperintensities in the CA1 region of the hippocampus. 129:1640-58.
Eur Neurol 2012;67:155-60. 15. Griebe M, Nees F, Gerber B, et al. Stronger pharmacological
7. Crowell GF, Stump DA, Biller J, et al. The transient global cortisol suppression and anticipatory cortisol stress
amnesia-migraine connection. Arch Neurol 1984;41:75-9. response in transient global amnesia. Front Behav Neurosci
8. Gass A, Gaa J, Hirsch J, et al. Lack of evidence of acute 2015;9:63.
ischemic tissue change in transient global amnesia on 16. Bartsch T, Deuschl G. Transient global amnesia: functional
single-shot echo-planar diffusion-weighted MRI. Stroke anatomy and clinical implications. Lancet Neurol 2010;
1999;30:2070-2. 9:205-14.
9. Sedlaczek O, Hirsch JG, Grips E, et al. Detection of
delayed focal MR changes in the lateral hippocampus in
transient global amnesia. Neurology 2004;62:2165-70.

Case Report
Reversible Stress-induced Cardiomyopathy (Takotsubo)

Mimics Acute Anterior Wall ST Segment Elevation Myocardial
Infarction: A Case Report with Review of Literature
Abstract
We reported a transient stress-induced cardiomyopathy (SIC) in a 73-year-old woman
who manifested with the setting of ST segment elevation myocardial infarction
condition. She was initially complicated by heart failure from both systolic and
diastolic dysfunction but had a fast recovery within 3 days. The trigger in this case
was pneumonia of the right lower lung which responded well to medical therapy. The
proposed pathophysiologic mechanisms and outcome had been reviewed. Currently,
SIC was no longer considered a benign condition since the in-hospital complication
rates were not different from those of ACS patients.
Keywords: takotsubo, stress-induced cardiomyopathy, acute reversible heart failure,

Veerakul G, MD systolic and diastolic left ventricular dysfunction, pneumonia, anterior ST segment
elevation myocardial infarction
U
Gumpanart Veerakul, MD1 nder severe mental or physical stress, elderly patients can
Buranawanich Kiattipoom, MD2 present with chest pain and ST segment elevation despite
Ngamwong Tawatchai, MD3 having no significant coronary artery obstruction. This
Chuaychoowong Issaraporn, BSc3 condition was described in early 1990s, known as stress induced
Wongkasai Supatcha, RN2 cardiomyopathy (SIC), but its underlying pathophysiologic
Srathongpim Natharinee, BSc2 mechanism remains unknown.1,7 Owing to a reversible course,
Sangwan Amornrat, RN3 SIC used to be viewed as a benign form of left ventricular (LV)
Pornchaiyasithi Krongthong, RN3 dysfunction but more recent study indicates that SIC victims shared
Suwannasri Watchira, RN3 the same risk of death and complication with acute coronary
Rakprom Nattawut, TN3 syndrome (ACS) patients.7 We reported a 73-year-old lady who
Sirirat Palakorn, TN3 had pneumonia of right lower lung that triggered SIC and
manifested with acute anterior ST segment elevation myocardial
infarction-like condition. The clinical presentation, ECG changes,
pathophysiologic mechanisms, treatment and prognosis have been
discussed in detail.
Case Report
A 73-year-old lady, presented with no known underlying disease,

and experienced low grade fever, dyspnea and non-productive
cough for two days. She was treated at a local clinic with some
improvement but the treatment detail was not available. At
1
Directorate of Medical Office, Royal Thai Air Force, Bangkok, Thailand. 03.00 am of December, 21, 2015, she developed shortness of
2
Chandrubeksa Heart Center, Chandrubeksa Hospital, Kampaengsaen,
Nakhonpathom, Thailand. breath and arrived at Chandrubeksa hospital at 05.20 am. It
3
Cardiovascular Preventive Center, Bhumibol Adulyadej Hospital, was found that she was tachypneic (respiration rate of 36/min),
Bangkok, Thailand.
hypoxic (room air O2sat was 89%) so she was later intubated.
* Address Correspondence to author: Blood pressure was high, 188/95 mmHg, and heart rate was 100/
Gumpanart Veerakul, MD
Chandrubeksa Heart Center, Chandrubeksa Hospital,
min. Crepitation and rhonchi were audible at both lower lungs.
Kampaengsaen 73180, Nakhonpathom, Thailand. Supine chest film showed parenchymal infiltration at right lower
e-mail: gumcardio@gmail.com lung field and calcified aortic knob with mild pulmonary conges-
Received: January 22, 2016 tion (Figure 1). Her temperature was 37.5 degree Celsius, white
Revision received: January 22, 2016 blood cell count was 9.8 K/unit with predominant neutrophil of
Bangkok Med J 2016;11:32-38.
88%. The platelet count was slightly low, hemoglobin was 11.6 mg/
E-journal: http://www.bangkokmedjournal.com dl and the MCV was 65.9 Fl.

Mimics Acute Anterior Wall ST Segment Elevation Myocardial Infarction: A Case Report with Review of Literature
1A 1B
Figure 1A-B: 1A: The first chest film showed some degree of body rotation, calcified aortic knob and infiltration at right lower lung
field with mild pulmonary congestion. 1B: Chest film after endotracheal intubation showed improves lung expansion, proper tube
position and unchanged right lower lung lesion.
Figure 2A-B: 2A: The 1st ECG showed sinus rhythm with ST segment elevation (STE) in leads V2-3, aVL and tall T in V4, 5.
It should be noted that there was no STE in lead V1 which is common in the setting of acute anterior STE myocardial infarction.
2B: Serial ECG, 7 hours after symptom onset, showed more STE in V1-4, tall T in V5-6 and the serum potassium level was normal.

Veerakul G, et al.
3A 3B 3C
Figure 3A-C: The first echocardiogram showed an akinetic wall beginning from distal septum to apical region, causing depressed
left ventricular systolic function, LVEF of 0.35. Figure 3B: Serial echocardiogram on day 4 showed markedly improved apical wall
and LVEF increased to 0.45. Figure 3C: On day-30, all wall motion appeared normal and LVEF was 0.60.
4A 4B 4C
Figure 4A-C: Coronary angiogram showed no significant luminal stenosis along the left main, left anterior descending, circumflex
arteries, and the dominant right coronary arteries (4C).
The first ECG at 06.22 am showed sinus tachycardia ischemic area, the team referred her to the emergent
with ST segment elevation (STE) in muliple leads (V2,3,I, cardiac catheterization laboratory at Bhumibol Adulyadej
aVL), and relative tall T in leads V4-5. ST depression hospital. Aspirin, clopidogrel, intravenous heparin and
in leads III, aVF and T wave inversion in lead aVR were ceftriazone were given before transfer.
also noted (Figure 2A). The fi rst troponin T (cTnT)
remained within normal range. Echocardiogram showed After risks and benefits were explained and informed
akinesia of mid septal, apical walls and depressed left consent was obtained, coronary angiography was per-
ventricular (LV) systolic ejection function, LVEF of 0.36 formed through right femoral artery, under local anes-
(Figure 3A). These findings suggested the diagnosis thetic drug. It was found that the LM trunk, circumflex
of an acute evolving anterior wall ST segment elevation and right dominant coronary arteries were all unob-
myocardial infarction, in addition to pneumonia and structed and the contrast flow was normal. The left an-
possible iron deficiency anemia. Owing to the large terior descending artery was patent and had only mild

Figure 5A, B: Serial ECG showed and resolution of precordial ST segment elevation and T inversion on day-7 and
day-30 with no Q wave development.
6A 6B 6C
Figure 6A, B, C: left ventricular diastole of another case. Figure 6B: apical ballooning during systole. Figure 6C: Japanese octopus pot.4
luminal irregularity with no significant lesion (Figure ECGs illustrated resolution of elevated ST segment with
4). The left ventricular diastolic pressure (LVEDP) was no Q wave development (Figures 5A,B). Serial echocardio-
high, 32 mmHg and was compatible with an elevated gram on day 4, showed improved LV systolic function and
serum NT-PRO BNP, 3,520 pg/ml. The diagnosis was then apical wall motion with LVEF of 0.45 (Figure 3B). She
changed to stress-induced cardiomyopathy (Takotsubo) was discharged in one week and did well. On follow-up,
causing heart failure and the patient was medically treated day-30, all wall motion appeared normal and LVEF was
in the coronary care unit. 0.60 and there was no apical thrombus noted, see Figure 3C.
With antibiotic and diuretic treament the patient was Discussion

clinically improved and was extubated within 72 hours.
Although blood culture remained with no growth observed, Takotsubo, reversible stress-induced cardiomyopathy (SIC)
sputum culture was positive for pseudomonas aeruginosa
and the sensitive drug, ceftazidime, was started. The thyroid In 1990, Sato and colleagues reported a group of
function test was within normal range. Despite the second Japanese patients, mostly post-menopausal women, who
rise of hs-cTnT to 236.7 (normal < 14 ng/L), subsequent had emotional stress and developed transient apical

Veerakul G, et al.
akinesia without significant coronary obstruction.1 The p < 0.001) and diastolic dysfunction (LVEDP 22.1 vs
term Tako-tsubo (fishing pot to capture octopus) was 20.1 mmHg, p = 0.001).7 Despite having the worse
used to describe the shape of left ventricular (LV) apex that systolic (LVEF of 0.35) and diastolic dysfunction (LVEDP of
balloons out during systole, relative to normal contractile 32 mmHg), our case recovered well within 72 hours.
basal part, see Figure 6B. Since then, this unique syndrome
has been recognized worldwide under various names, Pathophysiology
including transient apical ballooning syndrome, stress-
induced cardiomyopathy (SIC), broken heart syndrome, The underlying mechanism of SIC has remained
adrenergic cardiomyopathy, Takotsubo cardiomyopathy.2-6 unclear for the past 25 years. Three major mechanisms have
Although apical ballooning is the most common finding been proposed: 1) vasospasm of epicardial artery, 2) acute
(81.7%), other forms of wall motion such as mid ventricle coronary microvascular dysfunction causing ischemic
(14.6%), basal (2.2%) and focal type (91.5%) are also reported.7 myocardial stunning and, 3) cathecholamine mediated
direct myocardial injury and stunning.9 Multi-vessel
Because of its reversible nature, SIC was initially coronary spasm had been reported in 5 apical ballooning
considered a benign condition. SIC predominantly cases but this finding was quite rare, only 1.2% among
affected female (80%) elderly patients (age ranges from 415 ACS cases.10 In addition, spasm could be a secondary
61-76 years), who had prior emotional or physical stress.2-6 symptom resulting from administration of epinephrine
Recent data from the international registry of 1,750 in SIC patient who presented with bradycardic arrest.11
takotsubo cases (collecting from 25 heart centers of 9 Although abnormal myocardial perfusion defects have
countries, during 2011-2014), confirms the same age and been reported in the affected wall of SIC cases,12,13 the
sex distribution. The majority of SIC patients are still precise role of coronary microvascular dysfunction is not
women (89.8%) with a mean age of 668 years and the two yet established.9
most common presentations are chest pain (75.9%) and
dyspnea (46.9%).7 Recent data suggested the role of stress-induced
cathecholamine mediated myocardial injury. First, data
Stress-induced cardiomyopathy (SIC) vs acute coronary from an international study7 indicated that two-thirds
syndrome (ACS) (63%) of SIC cases had physical (36%) or emotional
stress (27.7%) and only one third had no stress (28.5%).
Data from the sex and age matched cohort study of 455 Second, SIC was associated with several stress condi-
SIC and 455 ACS cases shows no statistical difference in tions including pheochromocytoma,14 sepsis, non-cardiac
age, sex distribution, median troponin level, systolic blood surgery, bronchial asthma exacerbation, Guillain-Barre
pressure, cathecholamine use, cardiopulmonary resusci- syndrome,15 subarachnoid hemorrhage (SAH),16 acute
tation, cardiogenic shock and death, between these two ischemic stroke,17 head injury,18 psychiatric illness19 and
syndromes.7 Owing to the overlapping age range, presenting electro-convulsive therapy.20 For example, 20-30% of
symptoms, ECG changes, abnormal wall motion and SAH victims had reversible LV wall motion abnormalities
troponin T leakage, it is quite challenging to differentiate in the absence of coronary obstruction.21 In addition,
SIC from acute coronary syndrome (ACS) cases.2-7 In SIC victims had higher prevalence of psychological or
addition, SIC is not a benign syndrome since its complication neurological disorders than ACS cases, 55.8% vs 25.7%,
and mortality rates are not different from ACS cases.7 p < 0.001.7. Of those, 27% of SIC cases had either acute
or chronic neurological disorders, 42.3% had psychiatric
By analyzing ECG, ACS cases trends to have more illnesses and half of these were affective disorders.7 All of
STE (51.2% vs 44%, p = 0.03), and ST depression (31.1% these stress conditions might create a significant amount
vs 8.3%, p < 0.001). Konsuge and colleagues observed that of stress hormone such as cathecholamine for the develop-
the ST depression in lead aVR and the absence of STE in ment of SIC. In our reported case, the most likely physical
lead V1 supported the diagnosis of SIC, with the sensitivity stress that triggered SIC was pneumonia.
and specificity of 91% and 96% respectively.8 Our case did
not have ST depression in aVR but there was no STE in Third, high levels of the stress hormone and devel-
V1 (Figure 1A) and no Q wave development on the serial opment of SIC has been documented. Wittstein and
ECG (Figure 5A, B) which would be expected in acute colleagues found that the level of cathecholamine and its
anterior wall myocardial infarction cases. metabolites in SIC victims from sudden emotional stress
were 2-3 times higher than those of acute myocardial
In practice, like our case, performing a coronary infarction cases who had a similar degree of heart fail-
angiography is mandatory to diagnose SIC and to exclude ure.22 Cherian J and colleagues23 reported the first fatal
ACS. However, concomitant but not relevant coronary apical ballooning during dobutamine stress test in an
artery disease can be found in 21% of SIC patients.7 In 85-year-old lady who had planned hip surgery. After given
comparison to ACS cases, SIC victims had more abnormal 40 g/min of dobutamine, her heart rate reached 91% of
left ventricular systolic function (LVEF 40.7 vs 51.5%, age predicted maximal heart rate. During recovery, the

patient developed chest pain, STE in inferior and lateral complications. Older age and emotional stress are good
wall and apical ballooning with systolic anterior motion prognostic predictors, while younger age, male gender,
of anterior mitral valve leaflet, causing LV outflow track physical stress either neurological or psychiatric disor-
obstruction and low cardiac output. Coronary angiogram ders, high initial cTnT above 10 times of upper limit and
showed no evidence of coronary obstruction. Despite low LVEF < 0.45 were associated with high complication
administration of beta-blocker, the patient developed rates.7 The 30 days major adverse outcomes of SIC including
pulseless electrical activity and expired.23 Lastly, the death, stroke or TIA were 7.1% and men had more adverse
histology from cardiac biopsy in SIC victims and patients events than women, 13.7% vs 6.3%, p = 0.002).7 Although
died from epilepsy and subarachnoid hemorrhage shared our case had some bad predictors such as physical stress
the common feature of contraction band necrosis (myocy- (pneumonia) and lower LVEF (0.35), she also received
tolysis) which was known as cathecholamine toxicity.9,24 ACEI late (on day 3) but recovered well. The good prog-
Molecular mechanisms of SIC was studied in rat nostic factors in this case were an elderly female patient
models.25 After induced emotional stress, rapid activation with an initial negative troponin.
of p44/p42 mitogen-activated protein kinase was observed
in the heart, followed by transient up-regulation of genes Conclusion
in smooth muscle and endothelium cells of coronary
arteries, induction of heat shock protein 70 in the aorta, Stress-induced cardiomyopathy (Takotsubo, SIC) is a
coronary arteries, myocardium and up-regulation of transient ventricular systolic and diastolic dysfunction in
natriuretic peptides gene. The author concluded that the absence of relevant coronary artery obstruction. With
activation of alpha and beta adrenoreceptors were the the overlapping age range, STE, apical akinesia, depressed
primary trigger of emotional stress-induced molecular LV systolic and diastolic function, it is mandatory to
changes in the heart.25 perform coronary angiography to rule out ACS. We
reported a 73-year-old woman who developed SIC after
Treatment and prognosis having pneumonia of the right lower lung. Although our
case recovered well within 72 hours, most SIC patients
Data from the latest SIC registry7 showed that only from the registry study shared the same in-hospital
angiotensin converting enzyme inhibitors (ACEI) and complications as ACS cases including cardiogenic shock,
angiotensin receptor blockers, but not beta-blockers, were ventricular dysrhythmia, stroke and death. Current data
associated with good outcomes. In addition, SIC victims has suggested the role of stress-induced catecholamine
shared similar in-hospital complications with ACS mediated myocardial injury. We hope that this case will
patients, including cardiogenic shock (12.4 % vs 10.5%, raise clinical attention among colleagues to promote the
p = 0.39) and death (3.7% vs 5.3%, p = 0.26). Other early detection and successful treatment of this potentially
severe SIC complications were ventricular tachycardia fatal condition.
(3%), intra-ventricular thrombus (1.3%) and ruptured
ventricle (0.2%).7 The types of SIC had no influence on
References
1. Sato H, Taiteishi H, Uchida T. Takotsubo-type cardiomy- 5. Akashi YJ, Goldstein DS, Barbaro G, et al. Takotsubo
opathy due to multivessel spasm. In: Clinical aspect of cardiomyopathy: a new form of acute, reversible heart
myocardial injury: From ischemia to heart failure/ failure. Circulation 2008;118:2754-62.
Kodama K, Haze K, Hon M (eds), Kagakuhyouronsha, 6. Lapanun W. Stress-induced cardiomyopathy in Veerakul
Tokyo 1990:56-64. G, Kositchaiwat J (eds): 7R Ways to reduce mortality in
2. Tsuchihashi K, Ueshima K, Uchida T, et al. Transient left acute coronary syndrome patients, Srinakorn design
ventricular apical ballooning without coronary artery printing, January 2014 (ISBN 978-616-348-612-7):197-203.
stenosis: a novel heart syndrome mimicking acute 7. Templin C, Ghadri JR, Diekmann J,et al. Clinical Features
myocardial infarction. Angina Pectoris-Myocardial and Outcomes of Takotsubo (Stress) Cardiomyopathy. N
Infarction Investigations in Japan. J Am Coll Cardiol Engl J Med 2015;373:929-38.
2001;38:11-8. 8. Konsuge M, Ebina T, Hibi K, et al. Simple and acurate
3. Bybee KA, Kara T, Prasad A, et al. Systematic review: electrographic criteria to differentiate Takotsubo cardio-
transient left ventricular apical ballooning: a syndrome myopathy from anterior acute myocardial infarction.
that mimics ST-segment elevation myocardial infarction. JACC 2010;55:2514-7.
Ann Intern Med 2004;141:858-65. 9. Bybee KA, Prasad A. Stress-related cardiomyopathy
4. Sharkey SW, Lesser JR, Zenovich AG, et al. Acute and syndromes. Circulation 2008;118:397-409.
reversible cardiomyopathy provoked by stress in women 10. Dote K, Sato H, Uchinda T, Ishihara M. Myocardial
from the United States. Circulation 2005;111:472-9. stunning due to simultaneous multivessel coronary
spasms: a review of 5 cases. J Cardiol 1991:21;203-14.

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11. Haghi D, Suselbeck T, Wolpert C. Severe Multivessel 19. Summers MR, Lennon RJ, Prasad A. Pre-morbid psychi-
Coronary Vasospasm and Left Ventricular Ballooning atric and cardiovascular diseases in apical ballooning
Syndrome. Circ Cardiovasc Interv 2009;2:268-9. syndrome (tako-tsubo/stress induced cardiomyopathy):
12. Kurisu S, Inoue I, Kawagoe T, et al. Myocardial perfusion potential predisposing factors? J Am Coll Cardiol
and fatty acid metabolism in patients with tako-tsubo-like 2010;55:700-1.
left ventricular dysfunction. J Am Coll Cardiol 2003; 20. Sharp RP, Welch EB, Takotsubo cardiomyopathy as a
41:743-8. complication of electro-convulsive therapy. Ann Pharma-
13. Bybee KA, Murphy J, Wright RS, et al. Acute impairment cother 2011;45:1559-65.
of regional myocardial glucose utilization in the apical 21. Banki N, Kopelnik A, Tung P, et al. Prospective analysis
ballooning (Takotsubo) syndrome. J Nuc Cardiol 2006; of prevalence, distribution and rate of recovery of left
13:244-50. ventricular systolic dysfunction in patients with sub-
14. Quezado ZN, Keiser HR, Parker MM. Reversible arachnoid hemorrhage. J Neurosurg 2006;105:15-20.
myocardial depression after massive catecholamine 22. Wittstein IS, Thiemann DR, Lima JAC, et al. Neurohor-
release from a pheo-chromocytoma. Crit Care Med moral features of myocardial stunning due to sudden
1992;20:54951. emotional stress. N Engl J Med 2005;352:539-48.
15. Park JH, Kang SJ, Song JK, et al. Left ventricular apical 23. Cherian J, Kothari S, Angelis D, et al. Atypical
ballooning due to severe physical stress in patients admitted takotsubo cardiomyopathy: dobutamine-precipitated apical
to the medical ICU. Chest 2005;128:296-302. ballooning with left ventricular outflow tract obstruction.
16. Lee VH, Connolly HM, Fulgham JR, et al. Tako-tsubo Tex Heart Inst J 2008;35:73-5
cardiomyopathy in aneurysmal subarachnoidal hemor- 24. Samuels MA. The brain-heart connection. Circulation
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J Neurosurg 2006; 105:264-70. 25. Ueyama T, Senba E, Kasamatsu K, et al. Molecular
17. Yoshimura S, Toyoda K, Ohara T, et al. Takotsubo cardio- mechanism of emotional stress-induced and catecholamine-
myopathy in acute ischemic stroke. Ann Neurol induced heart attack. J Cardiovasc Pharmacol 2003;41
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18. Riera M, Llompart-Pou JA, Carrillo A, et al. Head injury
and inverted Takotsubo cardiomyopathy. J Trauma 2010;
68:E13-15.

Case Report
Liver Abscess caused by Klebsiella Pneumoniae:

A Case Report
Abstract
We report a case of a 51-year-old Thai patient with Klebsiella-associated liver abscess
evaluated at our institution with acute febrile illness and no other specific clinical
symptoms. Presepsin, a novel sepsis biomarker was used to aid in rapid diagnosis of
bacterial sepsis. The patient was treated successfully with antibiotics. Percutaneous
drainage was not performed due to the size of the abscess.
Keywords: Klebsiella pneumoniae, liver abscess, hepatic venous thrombophlebitis,

presepsin
K
lebsiella related liver abscesses can occur at a primary site
Jongwutiwes U, MD and are most likely monomicrobial.1-3 The virulent strains
of K. pneumoniae are able to invade a normal liver paren-
chyma without underlying hepatobiliary diseases, intra-abdominal
infections, surgery, trauma or colorectal diseases.4 Most cases have
been reported from Asian countries.5 A polymicrobial liver abscess
Ubonvan Jongwutiwes, MD1 is usually secondary to other intra-abdominal infections.1,6 We
Chirotchana Suchato, MD2 report a case of a Klebsiella-associated liver abscess, presenting
only with high fever.
Case Report
A 51-year old Thai male presented to the emergency depart-

ment with high fever and chills six hours prior to admission. His
past medical history was significant for only hyperlipidemia and
hypertension. Physical examination revealed mild scleral icterus
and a temperature of 40oC. Other findings were unremarkable.
Laboratory tests were pertinent for a leukocytosis (11,630 cells/
mm3), neutrophil predominance (86%), hyperbilirubinemia (2.2
mg/dL), aspartate transferase 121 U/L, and alanine transferase
176 U/L. Dengue NS-1 antigen and influenza screening test were
negative. Presepsin levels were found to be elevated at 1,831.0 pg/
mL (< 300.0 pg/mL) and this aided in the differentiation between
bacterial versus non-bacterial infection.
The patient was started on intravenous ceftriaxone. Hemoculture

grew Klebsiella pneumonia (K. pneumonia) sensitive to all antibiotics
1
Infectious Disease, Medical Department, Bangkok Hospital,
except amoxicillin-clavulinate. Computed tomography (CT) of the
Bangkok Hospital Group, Bangkok, Thailand. whole abdomen was performed to evaluate the primary source of
2
Imaging Center, Bangkok Hospital, Bangkok Hospital Group, bacteremia. Localized hypoattenuation at the hepatic angle with no
Bangkok, Thailand.
linear appearance was seen in the non-contrast study (Figure A),
* Address Correspondence to author: while contrast study revealed a localized hypoattenuation lesion
Ubonvan Jongwutiwes, MD 2x3 cm with rim enhancement associated with linear hypoattenuation
Infectious Disease, Medical Department, Bangkok Hospital
2 Soi Soonvijai 7, New Petchaburi Rd., appearance proximally (Figure B, C). This finding was suggestive
Bangkok 10310, Thailand. of liver abscess. Percutaneous drainage was not performed due to
e-mail: ubonvan.jo@bangkokhospital.com
the size of the lesion. His fever gradually subsided and the patient
Received: December 12, 2015 was clinically improved after the first few days of antibiotic treatment.
Revision received: December 14, 2015 Presepsin levels subsequently declined to 498.0 pg/mL. The
Bangkok Med J 2016;11:39-41. antibiotic was later switched to oral levofloxacin after 14 days of
E-journal: http://www.bangkokmedjournal.com IV ceftriaxone. At the 28 day-follow up, the presepsin level had

Jongwutiwes U and Suchato C
A B
C D
Figure A: CT coronal section without contrast enhancement reveals localized hypoattenuation near hepatics only.
Figure B-C: CT coronal and sagiital sections with contrast enhancement reveals rim contrast enhancement and linear hypoattenuation
radiating towards medially on delay phase with is due to hepatic venous thrombophlebitis (see arrows).
Figure D: CT coronal section on delay phase 28 days after treatment reveals disappearance of all mass and linear hypoattenuation.
further dropped to 235.0 pg/mL. The follow-up CT scan urgently. The novel sepsis biomarker that has recently
(Figure D) revealed complete resolution of the previously been made available is presepsin. Soluble (sCD14) or
seen lesion. The disappearance of the linear attenuation presepsin is the free fragment of a glycoprotein expressed
observed on the initial CT study is due to hepatic venous on monocytes and macrophages. As a receptor of the
thrombophlebitis, which is simulated as a small dilated lipopolysaccharide-lipopolysaccharide binding protein
intrahepatic duct. (LPS-LBP) complex, CD14 can activate a series of signal
transduction pathways and inflammatory cascades in the
Discussion setting of bacterial infection (sepsis), and leads to systemic
inflammatory response. If the level is higher than 300 pg/
Monomicrobial pyogenic liver abscess caused by mL, systemic bacterial infection (sepsis) should be consid-
K. pneumoniae occurs in a patient without underlying ered. In the range of 500-1000 pg/mL, moderate and severe
hepatobiliary tract diseases, colorectal diseases or sepsis is suggestive. For this patient, presepsin was 1,831.0
pre-existing intra-abdominal pathology. It has been found pg/mL on the first day of admission. Presepsin was superior
to be associated with Asian ethnicity, diabetes and middle- to procalcitonin (PCT) in early diagnosis of bacterial
to-older-aged patients. The common presenting symptom sepsis. Compared with PCT, presepsin increased earlier
is acute febrile illness, while only one-half of cases and faster in patients with sepsis, at 2 hours after infec-
presents with more specific clinical clues such as right tion in the cecal ligation and puncture (CLP) sepsis model,
upper quadrant pain, jaundice and hepatomegaly. peaked at 3 hours, and declined at 4-8 hours.7,8 However,
there was no difference between levels of presepsin and
The symptom of high fever may be due to bacterial or sepsis severity.
non-bacterial infection, which needs to be differentiated

Liver Abscess caused by Klebsiella pneumoniae: A Case Report
To identify the source of infection, it is important to Conclusion

perform an abdominal CT with contrast enhancement as
this shows the hepatic mass with rim contrast enhancement K. pneumoniae causing pyogenic liver abscesses are now
and linear hypoattenuation radiating towards medially only seen as an emerging pathogen with clinical significance.
on delay phase. This finding is likely to occur due to a liver The risk factors are diabetes, cancer, impaired host
abscess with hepatic venous thrombophlebitis. This finding defenses, and glucocorticoid therapy. This syndrome
is not a dilated intrahepatic duct because in non-contrast occurs almost exclusively in Asia, possibly due to a
enhancement there was no demonstrable; hence cholan- distinctive virulent strain. The chief complaints usually
giocarcinoma peripheral type is excluded. include high fever, nausea, vomiting, and right-sided upper
abdominal pain. This report presents this case to increase
awareness among physicians for accurate management
and investigation of this condition. We suggest the use of
presepsin to aid in early diagnosis of bacterial sepsis.
References
1. Wang JH, Liu YC, Lee SS, et al. Primary liver abscess 5. Yu WL, Chuang YC, et al. Invasive liver abscess syndrome
due to Klebsiella pneumoniae in Taiwan. Clin Infect Dis caused by Klebsiella pneumoniae. (Accessed October 6,
1998;26:1434. 2015 at http://www.uptodate.com/contents/invasive-liver-
2. Yang CC, Yen CH, Ho MW, et al. Comparison of pyogenic abscess-syndrome-caused-by-klebsiella-pneumoniae).
liver abscess caused by non- Klebsiella pneumoniae 6. Yu WL, Ko WC, Cheng KC, et al. Association between
and Klebsiella pneumoniae. J Microbiol Immunol Infect rmpA and magA genes and clinical syndromes caused by
2004;37:176. Klebsiella pneumoniae in Taiwan. Clin Infect Dis 2006;
3. Chan KS, Chen CM, Cheng KC, et al. Pyogenic liver 42:1351.
abscess: a retrospective analysis of 107 patients during a 7. Zou Q, Wen W, Zhang XC. Presepsis as a novel sepsis
3-year period. Jpn J Infect Dis 2005;58:366. biomarker. World J Emerg Med 2014;5:16-9.
4. Fang CT, Lai SY, Yi WC, et al. Klebsiella pneumoniae 8. Endo S, Suzuki Y, Takahashi G, et al. Presepsin as a
genotype K1: an emergening pathogen that causes septic powerful monitoring tool for the progenosis and treatment
ocular or central nervous system complications from of sepsis: a multicenter prospective study. J Infect Che-
pyogenic liver abscess. Clin Infect Dis 2007;45:284. mother 2014;20:30-4.

Case Report
EUS-Guided Rendezvous Pancreatic Duct Stenting in

Symptomatic Chronic Pancreatitis Patient
Abstract
Chronic pancreatitis (CP) is a progressive disease with irreversible changes in the
pancreas. Patients commonly present with pain. All therapeutic efforts in CP are
directed towards the relief of pain. Endoscopic therapy either endoscopic retrograde
pancreatography (ERP) or endoscopic ultrasound (EUS) guided pancreatic drainage,
offers pain relief in patients with CP who present with ductal calculi and/or main
pancreatic duct strictures with upstream dilation with a high rate of success with low
morbidity in properly selected patients.
Interventional Endoscopic ultrasound (EUS) is an emerging technology to provide

pancreatic duct drainage to patients when conventional ERP technique fails or in the
Siripun A, MD case of inaccessible pancreatic ducts. Endotherapy should be offered as the first line
of therapy in properly selected patients with CP who have failed to respond to medical
therapy and require intervention.
Keywords: chronic pancreatitis, endoscopic ultrasound, EUS, endoscopic retrograde

cholangiopancreatography, ERCP, pancreatic duct stricture
Aroon Siripun, MD 1
E
ndoscopic ultrasound (EUS)-guided main pancreatic duct
(MPD) access is an available option (step approach) after
failed endoscopic retrograde cholangiopancreatography
(ERCP) from various reasons such as difficult MPD cannulation
from tight stenosis, large stone, pancreas diversum or post-surgical
stricture.1,2
There are two major EUS-guided MPD interventions, namely,

rendezvous technique and antegrade technique (pancreatico-
gastrostomy). In general, the EUS-guided rendezvous approach
is preferred if the guidewire can be placed across the papilla.3
Success rates are between 77% and 92%, and reported complications
range between 0% to 44% of cases, and include pain, bleeding,
perforation and hematoma.3-6
Case Report
1
Gastrointestinal and Liver center, Bangkok Hospital, A 36-year-old man presented with recurrent acute to chronic
Bangkok Hospital Group, Thailand. pancreatitis at an outside hospital. ERCP was performed but the
pancreatic stent placement was unsuccessful. Computed tomo-
graphy (CT) abdomen demonstrated multiple large MPD stones at
the head of the pancreas accompanied by upstream MPD dilatation
measuring 4-6 mm in diameter (see CT scan as shown in Figure
* Address Correspondence to author: 1A and 1B). He was referred to our center for further management.
Aroon Siripun, MD
Gastrointestinal and Liver center, Bangkok Hospital,
2 Soi Soonvijai 7, New Petchaburi Rd., At our center, ERCP was repeated and deep cannulation via the
e-mail: aroon1979@gmail.com
major papilla and minor papilla was unsuccessful as well (Figure
2A, 2B), and the procedure was terminated. After discussion
Received: November 11, 2015 regarding the success rates of procedures and complications with
Revision received: November 15, 2015
the patient, we decided to perform a EUS-guided pancreatic duct
Bangkok Med J 2016;11:42-46. drainage, preferably rendezvous procedure to access MPD for
E-journal: http://www.bangkokmedjournal.com stone removal and MPD stent placement.

EUS-Guided Rendezvous Pancreatic Duct Stenting in Symptomatic Chronic Pancreatitis Patient
Procedure for EUS-guided rendezvous pancreatic The standard exchange technique was performed.
duct stenting Once the needle device had been detached and withdrawn
completely from the echoendoscope, the scope was gradu-
The procedure was performed under general anesthesia, ally pulled out while performing fluoroscopy to ensure that
and the patient received prophylactic antibiotics with the distal end of the wire remained within the 2nd part of
fluoroquinolone. EUS was performed using a linear array the duodenum. When the scope was completely removed,
echoendoscope (EG-3870UTK, Pentax and Hi Vision the wire was grasped and secured at the oral orifice.
Avius, HITACHI, JAPAN). EUS showed evidence of
chronic pancreatitis and main pancreatic duct dilatation, The ERCP therapeutic duodenoscope (TJF 160;
4-6 mm in diameter at body to tail. The puncture site was Olympus Medical, Japan) was subsequently inserted
chosen after careful endosonographic assessment of the alongside the wire in through the 2nd part of the duodenum
pancreatic duct (Figure 3A). Puncture was achieved using (Figure 4B). The distal end of the wire was detected via
a 19-gauge needle (Echo tip 19; Cook Endoscopy, Winston a minor ampulla (Figure 4C). Sphincterotome 30 mm
Salem, North Carolina). Pancreatic duct access was (Boston scientific, USA) and the angled-tip 0.035-inch
confirmed by pancreatic fluid aspiration and contrast hydrophilic wire (Jag wire Boston scientific, USA) were
instillation under fluoroscopy (Figure 3B). Subsequently, used to cannulate the minor ampulla along with an angled-
a 450 cm long and angled-tip 0.025-inch hydrophilic tip 0.025-inch hydrophilic wire (Visiglide, Olympus, Japan)
wire (Visiglide, Olympus, Japan) was introduced through (rendezvous wire) successfully. After this, a hurricane
the needle and direct downstream advancement in an dilator balloon 6mm in dilator (Boston scientific, USA)
anterograde manner. Finally the guide wire was passed was inserted properly into the minor ampulla over the
through the 2nd part of the duodenum, with several loops guide wire. The hurricane balloon was inflated up to
of the wire placed in the duodenum to maintain wire 6 mm in dilator diameter for 60 seconds across the
stability during needle and scope withdrawal (Figure 4A). stricture site (Figure 4D to Figure 4F).

Siripun A
Gall bladder
Common
bile duct
Pancreas
Pancreatic duct
Duodenum

EUS-Guided Rendezvous Pancreatic Duct Stenting in Symptomatic Chronic Pancreatitis Patient
Gall bladder
Common bile duct
Pancreas
Pancreatic duct
Duodenum

Siripun A
However, the waist line did not disappear, and the case since the MPD was dilated enough to puncture
Soehendra stent retriever (Wilson Cook Medical, Winston- (6 mm). Fatal complications have never been reported
Salem, N.C.) was used to dilate the stricture site (Figure with this procedure, while a few complications such
4G and 4H). A pancreatic stent 7 Fr x 12 cm (Wilson Cook as abscess, mild pancreatitis or transient fever were
Medical, Winston-Salem, N.C.) was subsequently placed reported, and these complications mostly happened to
successfully into the main pancreatic duct over a jagwire patients with pancreatic ducts of normal diameter.8,9
via minor ampulla (Figure 4I and 4J). Accordingly, for the EUS-guided rendezvous techniques
we should select patients who satisfy these conditions.
Discussion EUS-guided pancreaticogastrostomy was a second
treatment option in this case, as EUS-guided pancreati-
Interventional EUS has recently become more cogastrostomy has the risk of stent dysfunctions such as
advanced in terms of available devices and techniques. obstruction and migration.
Bataille et al.7 first reported a pancreatic duct drainage
with EUS-guided rendezvous technique in 2002. This Conclusion
procedure is technically challenging and has an approxi-
mately 70% success rate. The reasons for failure include We demonstrated the usefulness of pancreatic duct
the impossibility of puncturing the pancreatic duct without drainage using endoscopic ultrasonography-guided
dilatation, and the inability to pass through the stenotic rendezvous technique for pancreatic duct stricture after
due to its tightness and less than ideal orientation of the failed multiple attempts of ERCP cannulation in pancreas
puncture. divisum patient. However, this procedure requires advanced
technical skill. In our case, guidewire manipulation
The diameter of the pancreatic duct is an important and Soehendra stent retrieve for dilating tight stricture
factor in avoiding complications as well as success. We were the keys of success.
achieved a successful pancreatic duct drainage in this
References
1. Dumonceau JM, Delhaye M, Tringali A, et al. Endoscopic 6. Brauer BC, Chen YK, Fukami N, et al. Single-operator
treatment of chronic pancreatitis: European Society of EUS-guided cholangiopancreatography for difficult
Gastrointestinal Endoscopy (ESGE) Clinical Guideline. pancreaticobiliary access (with video). Gastrointest
Endoscopy 2012;44:784-800. Endosc 2009;70:471-9.
2. Tringali A, Boskoski I, Costamagna G. The role of endoscopy 7. Bataille L, Deprez P. A new application for therapeutic
in the therapy of chronic pancreatitis. Best Pract Res Clin EUS: main pancreatic duct drainage with a pancreatic
Gastroenterol 2008;22:145-65. rendezvous technique. Gastrointest Endosc 2002;55: 740-3.
3. Itoi T, Kasuya K, Sofuni A, et al. Endoscopic ultrasonog- 8. Mallery S, Matlock J, Freeman ML. EUS-guided rendez-
raphy-guided pancreatic duct access: techniques and vous drainage of obstructed biliary and pancreatic ducts:
literature review of pancreatography, transmural drainage Report of 6 cases. Gastrointest Endosc 2004;59:100-7.
and rendezvous techniques. Dig Endosc 2013;25:241-52. 9. Barkay O, Sherman S, McHenry L, et al. Therapeutic
4. Kahaleh M, Hernandez AJ, Tokar J, et al. EUS-guided EUS-assisted endoscopic retrograde pancreatography
pancreaticogastrostomy: analysis of its efficacy to drain after failed pancreatic duct cannulation at ERCP.
inaccessible pancreatic ducts. Gastrointest Endosc Gastrointest Endosc 2010;71:1166-73.
2007;65:224-30.
5. Tessier G, Bories E, Arvanitakis M, et al. EUS-guided
pancreatogastrostomy and pancreatobulbostomy for the
treatment of pain in patients with pancreatic ductal
dilatation inaccessible for transpapillary endoscopic
therapy. Gastrointest Endosc 2007;65:233-41.

Case Report
Practical Points in Diagnosis of Acute Appendicitis by

CT Image and/or Pelvic Ultrasonic Scan: A Case Report
Abstract
Acute appendicitis is one of the most common causes of abdominal pain. CT image and
/or pelvic ultrasonic scan are excellent resources to assist in diagnosis. The common
locations to examine are retroceacal, pelvic and retroileum. The size of a normal
appendix is less than 6 mm in diameter and the wall is less than 2 mm thick.
The associated findings are periappendiceal edema with or without fluid collection
and/ or calcified fecalith in the lumen. In pregnancy and pediatric groups, ultrasound
should be performed. The differential diagnosis is diverticulitis.
Keywords: locations of appendix, acute appendicitis
Suchato C, MD
A
cute appendicitis is one of the most common causes of
acute abdominal pain. Some cases present as classical right
lower quadrant pain and tenderness. Serum blood test
findings include elevation of white blood cells (WBC), neutrophil
and C-reactive protein test. However other cases may present with
Chirotchana Suchato, MD1
other more unusual symptoms and in these situations a computed
.
tomography (CT) image and/or pelvic ultrasonic scan is recom-
meded to provide additional support to the diagnosis.
The normal appendix diameter size is not more than 6 mm, and
the mural wall is 2 mm thick. The common locations are retroceacal,
pelvic and retroileum, and other locations are subceacal, preileal,
and extraperitoneal (in 5% of reported cases). The other associated
findings are periappendiceal edema with or without fluid collection.
Fecalith in situ is most likely reported in the diagnosis. This
case report gives details of three cases of acute appendicitis with
differing presentations.
Case # 1: Pelvic Appendicitis
A 9-year-old male presented with the chief complaint of fever,

abdominal pain for 3 days, vomiting for 8 hours and one bout of
diarrhea prior to admission. Physical examination (PE) revealed
1
Imaging Center, Bangkok Hospital, Bangkok Hospital Group, lower abdominal pain and decreased bowel sounds. Total WBC
Bangkok, Thailand. 55.96*10^3/mm3 (normal range 4.5-13.0 *10^3/mm3), neutrophil
* Address Correspondence to author:
is 87.2% (normal range 46.5-75.0%). CT image without contrast
Chirotchana Suchato, MD enhancement and oblique reconstruction at right lower abdomen
Imaging Center, Bangkok Hospital reveals an enlarged appendix 2 cm in diameter with an edematous
Bangkok 10310, Thailand. mural wall with periappendiceal edema (Figure 1A). A single,
e-mail: chirotchana@bangkokhospital.co.th small fecalith is seen at the root of the appendix. The tip of the
Received: January 8, 2016
appendix points to the pelvic cavity. Pelvic ultrasonic scan reveals
Revision received: January 10, 2016 an enlarged appendix 2 cm in diameter with thickening mural
Accepted after revision: January 20, 2016 wall (Figure 1B). Pathological diagnosis is acute necrotizing
Bangkok Med J 2016;11:47-51.
E-journal: http://www.bangkokmedjournal.com appendicitis, ruptured (Figure 1C).

Suchato C
Figure 1A: CT image reveals markedly enlarged appendix Figure 1B: ultrasonic scan finding reveals enlarged appendix
with thickening wall (see red arrows). with thickening wall (see arrows).
Figure 1C: Gross specimen of appendix.

Practical Points in Diagnosis of Acute Appendicitis by CT Image and/or Pelvic Ultrasonic Scan: A Case Report
Case # 2: Retroceacal Appendicitis
A 41-year-old male presented with the chief complaint CT image without contrast enhancement on the sagittal
of abdominal pain with diarrhea for 2 days and one day of section reveals swelling of the appendix with a thickening
fever and persistent abdominal pain. (PE) reveals marked mural wall containing a fecalith, located at the retrocecal
tenderness at the right lower quadrant (RLQ), otherwise region (Figure 2A). There is periappendiceal edema
findings are unremarkable. Total WBC is 11.22 *10^3/ surrounding the body of the appendix. Pathological
mm3 (normal range 4.0-10.0*10^3/mm3), neutrophil is diagnosis is acute suppurative appendicitis with severe
86% (normal range 46.5-75.0%). serositis, with presence of a fecalith (Figure 2B).
Figure 2A: CT image reveals enlarged appendix (see white arrows) containing
calcified fecalith (see red arrows).
Figure 2B: Gross specimen of appendix with fecalith.

Suchato C
Case # 3: Retroileal Appendicitis
A 22-year-old female presented with the chief complaint Pelvic ultrasonic scan reveals enlarged appendix with
of acute colicky abdominal pain, no fever or diarrhea is a thickening mural wall and minimal free fluid near the
observed. PE tenderness at epigastrium and mid abdomen tip of the appendix, the terminal ileum lies anteriorly
otherwise findings appear unremarkable. Total WBC 9.1 (Figure 3B). Pathological diagnosis show acute suppurative
*10^3/mm3 (normal range 4.0-10.0 *10^3/mm3), neutrophil appendicitis with periappendicitis (Figure 3C).
is 76.43 (normal range 46.5-75.0%). CT image reveals
an enlarged appendix behind the terminal ileum (Figure 3A).
Figure 3A: CT image reveals enlarged appendix behind terminal ileum (see red arrows).
Figure 3B: Ultrasonic scan reveals enlarge appendix Figure 3C: Microscopic scan shows acute suppurative
with a thickened mural wall (see red arrows) appendicitis with periappendicitis

Practical Points in Diagnosis of Acute Appendicitis by CT Image and/or Pelvic Ultrasonic Scan: A Case Report
Discussion In case of suspected pregnancy, ultrasonic scan should

be the first diagnostic tool employed, and in some cases, it
These three cases of acute appendicitis are presented may be complicated to detect an enlarged appendix. On an
with CT image findings, and in some cases diagnosis was ultrasonic scan we have to strictly identify each element,
obtained in combination with a pelvic ultrasonic scan to especially the ceacum and ileum. The other possibility is
show the common locations of appendicitis to include the colonic diverticulitis. The CT image plays an important
pelvic, retroceacal and retroileal regions. It is important role here mainly at the ceacum and ascending colon. In
to know the precise appendiceal location for surgical diverticulitis, opaque density at the colonic wall may be
planning. The use of CT image and ultrasound are excel- depicted and is associated with evidence of pericolonic
lent in diagnosis with high sensitivity and specificity. The edematous changes.
appendix can be found by tracing the tubular structure
that arises from the tip of the ceacum. There are some Conclusion
evidence-based issues about the optimization of using im-
age modalities in this condition. A recent meta-analysis3 CT image and /or pelvic ultrasonic scan should examine
reveals CT examination in adult patients has high sensitiv- the appendiceal locations and size of appendix with
ity and specificity for acute appendicitis and is superior to clinical correlation as well as laboratory findings in the
ultrasound with graded compression. But in the pediatric diagnosis of acute appendicitis. Samples are presented
group, graded compression ultrasound is highly sensitive with imaging and gross specimen/microscopic scans.
and specific in detecting acute appendicitis.
Ultrasonic scan is the first priority in case of pregnancy,
In equivocal cases, ultrasound followed by CT exami- and the identification of the ceacum and ileum are an
nation has a higher sensitivity but lower specificity than important consideration. The other possibility to investigate
ultrasound alone because of increased false positives. is colonic diverticulitis with shown the depiction of opaque
density at the colonic wall and evidence of pericolonic
edematous changes may also be observed.
References
1. Jaffar A. Position of the appendix. Filmed at University of 2. Dhnert W. Radiology Review Manual/Wolfgang Dhnert 6th
Sharjah, College of Medicine, United Arab Emirates, edition. Lippincott Willium& Wilkins, 2007:804.
February 2013. (Accessed at August 10, 2015 at https:// 3. Blackmore C.C.et al, Imaging in acute abdominal pain:
www.youtube.com/watch?v=gEH-9CXIb5g). evidence-based Imaging. Springer, 2006:457-74.

Review Article
Outpatient Total Joint Arthroplasty-Can It Be Done Safely?

: A Review
Abstract
Total knee arthroplasty and total hip arthroplasty are one of the most successful
procedures treating patients with later stage of osteoarthritis. With an improvement
of patient care, in every step from pre-operation, intra-operation and post operation,
the length of hospital stay is decreasing to a few days and lastly, in outpatient service.
We reviewed the current literatures about outpatient arthroplasty, to determine what
you should know before doing an outpatient total joint arthroplasty, results and
complications.
Keywords: outpatient, day-surgery, total knee arthroplasty, total hip arthroplasty
T
Hongvilai S, MD otal knee arthroplasty (TKA) and total hip arthroplasty
(THA) are among the most successful orthopedic pro-
cedures with a 15 year-survival rate of more than 90% in
most studies.1,2 They have traditionally been considered as inpatient
surgical procedures. Historically, the inpatient stay exceeded
several weeks. With multiple improvements including surgical
Sarit Hongvilai, MD1
techniques, anesthesia and implementation of clinical pathways, the
Rapeepat Narkbunnam, MD2
length of stay (LOS) in the hospital has substantially decreased to
Christopher S. Mow, MD3
a few days.3,4 The reasons that keep patients in hospital care
postoperatively include patient and physician concerns about
uncontrolled pain, delayed mobilization and possibility of peri-
operative complications.5,6 However, more recent studies7 indicate
that there are no differences between longer hospital stays, short
hospital stays and outpatient surgery. Berger et al have reported
successful outpatient total knee arthroplasty without an increase in
perioperative and early postoperative complications.8 The studies
which reported the outpatient arthroplasty results defined an out-
patient as a patient discharged within 23 hours.8,9
Why outpatient arthroplasty?

1
Hip and Knee center, Bangkok Hospital, Bangkok Hospital Group,
Bangkok, Thailand.
2
Department of Orthopaedic Surgery, Mahidol University, Historically, it was thought that an extended acute hospital
Siriraj Hospital, Bangkok, Thailand. stay for several weeks was the best way for patients to recover and
3
Department of Orthopaedic Surgery, Stanford University Medical achieve a good outcome after total joint arthroplasty. However,
Center, Stanford California USA.
there are studies that show with early discharge protocols,10,11
* Address Correspondence to author: patients can recover safely and faster than previously thought, and
Sarit Hongvilai, MD
Hip and Knee center, Bangkok Hospital, Bangkok Hospital Group,
this decreases inpatient workload and subsequent cost. Moreover,
2 Soi Soonvijai 7, New Petchaburi Rd., patients discharged quickly have comparable outcomes to patients
Bangkok 10310, Thailand. who remain admitted for the standard hospital stay of 5-10 days.
e-mail: sarit_hongvilai@hotmail.com
Bertin12 has reported that outpatient THA costs average 4,000 USD
Received: October 10, 2015 less than inpatient surgery. Lovald et al.7 have compared the incre-
Revision received: October 16, 2015
Accepted after revision: December 8, 2015 mental payment for osteoarthritis and attributable costs at 2 years
Bangkok Med J 2016;11:52-56. and reported that costs were approximately 8,527 USD lower for
E-journal: http://www.bangkokmedjournal.com
the outpatient group.

Outpatient Total Joint Arthroplasty-Can It Be Done Safely?: A Review
Key to success in outpatient arthroplasty Pre-arthroplasty rehabilitation further educates

patients about what is expected from them after the
To initiate and accomplish outpatient arthroplasty operation, such as how patients are going to move the
surgery, the roadblocks need to be understood. Studies13-15 operated extremity, how to use a cane or crutches, and
show that patient fear or anxiety about the unknown, not what to expect in the perioperative phase. Patients who
knowing what is going to happen, and fear of pain are receive pre-arthroplasty rehabilitation education have
major obstacles as well as patient co-morbidities. For the been shown to have significantly better post-operative
surgeon, the side effects of the treatment from narcotics outcomes regarding strength, recovery and function26 and
or anesthesia, blood loss or surgical trauma are concern- also tend to save on hospital-related expenditure and have
ing and indications for keeping the patient in hospital care a shorter length of stay in the hospital.22,27,28
under observation.10,16 For all of these reasons, good
clinical pathways and protocols are crucial. Perioperative care
Preoperative care The main perioperative goals are prevention and

prompt treatment of pain, nausea, and hypovolemia.
Patient selection is the first and most important step It is better to manage these issues before symptoms arise.
to success in outpatient arthroplasty. In addition to the Premedication and perioperative protocols are varied
history and physical examination by the surgeon, the in details between published studies, but all try to
patients home status should be also assessed to determine avoid using narcotics and aim to keep the patient well
whether the patient has any support to help them move hydrated.8,9,29-31
around the house safely after surgery.17 Patients with a
history of diabetes, myocardial infarction, stroke, con- The choice of anesthesia for outpatient arthroplasty
gestive heart failure, venous thromboembolism, cardiac varies according to surgeon, anesthesiologist, and insti-
arrhythmia, respiratory failure, chronic pain requiring tution. Multimodal pain management including spinal
regular opioid medications or patients who are on anti- anesthesia, local nerve block, intravenous narcotics
coagulation therapy should not be considered candidates and anti-inflammatory drugs have been shown to have
for outpatient total joint surgery as they were excluded significantly better post-operative pain management
from some of the studies.8,9 Lovald et al.18 has reported results.32-37
increased risk of revision, infection, accidental falls,
wound complications, and death in patients with poorer Tranexamic acid administration has also been dem-
health status (i.e. with a higher Charlson score). However, onstrated to safely reduce perioperative blood loss in hip
patients with ischemic heart disease or diabetes were and knee arthroplasty38-41 and to reduce blood transfusion
not associated with increased risk for re-hospitalization, requirements which are one of the main problems that
death, revision, infection, or DVT. Courtney et al.19 have keep patients in the hospital.
reviewed 1,012 consecutive patients undergoing elective
primary hip and knee arthroplasties and reported the The operative intervention itself should be smooth
independent multivariate risk factors for developing late and efficient, but not hurried. Less invasive approaches
(> 24 hours) complications included COPD (adjusted OR and techniques have been reported to have significantly
4.16), CHF (adjusted OR 9.71), CAD (adjusted OR 2.80), decreased pain and improve outcomes especially in the
and cirrhosis (adjusted OR 8.43). short term.42-44
Co-morbidities and any surgical risks of the patient Post-operative care

should be evaluated carefully and cleared by a team of
internal medicine specialists who are familiar with out Physical therapy is usually started a few hours after
-patient procedures and aware of factors that would make surgery, soon after patients are assessed for vital signs and
an outpatient procedure undesirable.5,20 nausea. If any signs of hypovolemia or nausea are present,
these should be treated promptly.8,45 The draining tube can
There are studies21-25 that confirm that a significant be used in an effort to reduce wound complications8 and is
aspect to consider is patient education which involves typically removed 4 hours post-operation in the recovery
giving the patient appropriate goals and expectations, room. However, there is a study9 that did not use the
education about the surgical procedure and potential draining tube and reported no wound complication.
complications, the entire expected hospital course and
postoperative care especially for pain control and am- Patients will be discharged to return home only if
bulation. Reviewing the patients questions and particu- all discharge criteria are met satisfactorily. To meet the
larly addressing the patients needs are necessary steps to criteria, patients must have stable vital signs, be able
improve postoperative patient satisfaction and outcome. to eat regular diet and oral medication, and complete a
formal physical therapy protocol. This protocol requires

Hongvilai S, et al.
that patients can independently transfer out of bed to Current published results
standing and into bed from standing, rise from a chair
to standing and sit from standing, ambulate 100 feet in Most of the out-patient total joint arthroplasty studies
distance, and ascend and descend a full flight of stairs. have reported more than 90% success in discharging
patients home within 23 hours without postoperative short
After being discharged, patients will follow the care term complications and less than 1% readmission due to
plan explained preoperatively. Pain is managed with oral pain, nausea or hypotension (Table 1).8,9,29,30 Lovald et al.7
narcotics and anti-inflammatory agents. Patients are seen have reported significantly less pain (31.7% vs 43.5%) in
by a home health nurse and therapist on the first post- the outpatient group compared to the standard stay (3-4
operative day. Patients will be seen by the surgeon 1 week days) group, but had higher 90 days infection (2% vs
post operation and thereafter as a usual follow up. 1.9%), dislocation (0.4% vs 0.3%) and readmission rates
(0.9% vs 0.5%). However, none of these differences are
considered significant.
Table 1: Results of outpatient arthroplasty.
Study Year Operation Patient Follow up Result

Berger et al.8 2005 TKA 50 3 months 48 (96%) discharged within 23 hours
5 (10%) readmission within 30 days
Kolisek et al.9 2009 TKA 64 24 months12-41 62 (100%) discharged within 23 hours

1 peroneal nerve dysfunction
1 genu recurvatum 10 months post op
1 tibial plateau fracture 1 year post op
2 manipulations
Berger et al.30 2009 THA 150 Minimum 3 months 150 (100%) discharged within 23 hours
7 (4.67%) emergency visits
Dorr et al.29 2010 THA 69 6 months 53(77%) discharged within 23 hours

TKA Total knee arthroplasty, THA Total hip arthroplasty
Conclusion Those interested in performing outpatient arthroplasty

should initially aim to reduce the length of stay to 2 days.
A trend of outpatient arthroplasty is emerging. It has After a successful protocol and clinical pathway imple-
already been established for orthopedic procedures which mentation, once a 1 day discharge can be achieved safely,
were formerly done as inpatient procedures such as upper then a same day discharge may be considered.
extremity surgery, arthroscopy and anterior cruciate
ligament reconstruction. The potential benefit is that With careful patient selection and good clinical path-
patients can recover in their own home with reduced ways, outpatient total joint arthroplasty can be done safely.
inpatient services. Outpatient arthroplasty involves However, current clinical studies have demonstrated only
multiple and specialized protocols for preoperative, peri- short term follow-up outcomes. Further studies with longer
operative and postoperative care. The surgeons role will term follow-up and larger patient number are needed.
change from the physician in the hospital to coordinator of
the entire care experience.

Outpatient Total Joint Arthroplasty-Can It Be Done Safely?: A Review
Diagram shows patient management flow chart summary from Berger et al.8
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Assessment and Prediction Tool Predict Discharge Anaesthesiol 2011;24:331-8.
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arthroplasty. Ann R Coll Surg Engl 2011;93:71-5. and Topical Application of Tranexamic Acid in Primary
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28. Huang SW, Chen PH, Chou YH. Effects of a preoperative 44. Cheng T, Liu T, Zhang G, et al. Does minimally invasive
simplified home rehabilitation education program on surgery improve short-term recovery in total knee arthro-
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Traumatol Surg Res 2012;98:259-64. 45. Tasker A, Hassaballa M, Murray J, et al. Minimally
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Review Article
Erectile Dysfunction
Abstract
Erectile dysfunction (ED) is an important issue in sexual relationships and can affect
family and lead to other problems. Hence, ED treatments are widely acceptable with
high efficacy rates and with low risks of adverse side effects at the present time.
Physicians and healthcare workers should study and understand all mechanisms,
history, family environment, underlying diseases for instance DM, hypertension and
hypercholesterinemia. A better understanding of these underlying factors may help
provide an appropriate consultation. The various treatments on offer include psycho-
therapy and sex therapy. Medical therapy, mechanical devices, vascular surgery,
combined therapy or others including topical PGE, gene therapy and testosterone are
also available. Each case is different and the patient may select one or multiple kinds
Leungwattanakij S, MD of treatment, suitable for them, whilst the physician may suggest or give guidelines to
patients to help ensure the best clinical outcome.
Keywords: penile erection, erection dysfunction (ED) neurotransmitters, phophodi-

esterase type 5 (PDE5) inhibitor, intraurethral medications, intracavernosal injection
therapy, vacuum devices, and penile prosthesis devices
E
Somboon Leungwattanakij, MD1 rectile dysfunction (ED) was previously defined by the term
impotence with a very broad encompassing meaning
including the lack of sexual desire. The definition of erectile
dysfunction was revised in 1993 to be more accurate, pertaining to
individuals who desire but fail to perform sexual activity because
they could not achieve or maintain an erect penis long enough to
obtain satisfactory sexual performance.1
Erectile dysfunction may have a significant impact on relation-

ships with a partner and family. One of the problems that men with
erectile dysfunction experience is shame and discomfort associated
with the discussion of the condition. This discourages these men
from seeking consultation from their physicians and vice versa.
There was no easy and effective treatment for erectile dysfunction
in the past. However, in recent years there has been a significant
advancement in the knowledge concerning the physiology of
erection allowing the mechanisms of penile erection to be better
understood. These advancements have allowed research in erectile
dysfunction management to gain significant development.
Prevalence
1
Professor of Urology, Urology Center, Bangkok Hospital,
Bangkok Hospital Group, Bangkok, Thailand.
An epidemiological study carried out by The Massachusetts
* Address Correspondence to author: Male Aging Study (MMAS) between 1987 and 1989 revealed the
Somboon Leungwattanakij, MD
Urology Center, Bangkok Hospital,
prevalence of erectile dysfunction in US male population to be
2 Soi Soonvijai 7, New Petchburi Rd., as high as 30 million.2 The highest prevalence was found in men
e-mail: somboon.le@bangkokhospital.com
aged between 40 and 70 years old at 52%, with 17%, 25%, and 10%
corresponding to mild, moderate, and severe degree of dysfunction
Received: December 24, 2015 respectively. Mild degree of dysfunction refers to the condition
Revision received: December 28, 2015
where penis erection can be achieved long enough for completion
Bangkok Med J 2016;11:57-72. of sexual intercourse but not always. Moderate degree of dysfunction
E-journal: http://www.bangkokmedjournal.com refers to the condition where penile erection can only be achieved

Leungwattanakij S
and maintained for completion of sexual intercourse some- corpus cavernosa lie parallel to each other and separate
times. Severe degree of dysfunction refers to the condition at the bulb of penis forming the crus of the penis that
where penile erection cannot be achieved and maintained attaches to the pubic arch.
for completion of any sexual intercourse.
2. Anatomy of blood vessels
A Thailand Erectile Dysfunction Epidemiology Study
(TEDES) examined the prevalence of erectile dysfunc- The artery that provides blood supply to the penis is
tion in 1,250 Thai men aged between 40 and 70 years in called the internal pudendal artery that branches from the
1998 and found the prevalence of mild, moderate, and internal iliac artery. The distal portion of the pudendal
severe degree of erectile dysfunction to be 19.1%, 13.7%, artery forms the common penile artery that branches
and 4.7% respectively.3 The overall prevalence estimation into dorsal, bulbourethral, and carvernous arteries. The
from the TEDES study was 37.5% (Figure 1). carvernous arteries further branch into helicine arterioles
with convoluted appearance draining into the sinusoidal
tissue of the penis.
The blood inside the corpus cavernosa is drained into

the emissary veins via tiny subtunica venules perforating
Erectile
dysfunction
the two layers of tunica albuginea. An erection is achieved
37.5% No erectile when the sinusoidal tissue of the penis is filled with blood
dysfunction from the arterial supply causing the tissue to become
62.5% swollen. The erection causes the tunica albuginea layer to
become distended resulting in the mechanical compres-
sion of subtunica venules between the layers of tunica
albuginea that subsequently lower or prevent blood
Severe (4.7%) drainage from the penis.
Moderate (13.7%)
Mild (19.1%) 3. Anatomy of nerve supply
Prevalence of erectile dysfunction in
Thai men aged between 40 and 70 years old. The peripheral nervous system responsible for sensory
(Sample size = 1,250 participants) and erection control can be divided into two groups,
namely autonomic nervous system and somatic nervous
Figure 1: Prevalence of erectile dysfunction (ED) in Thai men. system. Penile erection is regulated mainly by the para-
sympathetic branch of the autonomic nervous system that
contains the control center located at S2-4 known as the
sacral erection center. The nerves that exit the center and
Physiology of penile erection
form a preganglionic plexus are called the pelvic nerve or
nervi erigentes (Figure 2).
Penile erection is achieved when the emissary venous
drainage is impeded due to compression of tunica albu-
The sympathetic branch of autonomic nervous system
ginea caused by an increased in blood flow to the penis
exits the spinal nerves at T10-L2 level. The preganglionic
due to sexual stimulation. In recent years, the neurotrans-
fibers join together to form the sympathetic chain (Figure
mitter critical for achieving an erection was determined to
2) that connects with the inferior mesenteric plexus and
be nitric oxide, previously known as endothelium-derived
superior hypogastric plexus. The preganglionic fibers
relaxing factor (EDRF).4,5 This finding has led to wide-
from the pelvic nerve will join with the postganglionic
spread development of treatments for erectile dysfunction.
fibers from the superior hypogastric plexus forming the
pelvic plexus that gives rise to the cavernous nerve that
1. Anatomy of penis
regulates penile erection.
The penis contains three cylindrical erectile tissues;
The somatic nervous system exits the spinal nerves at
two corpus cavernosa and one corpus spongiosum containing
level S2-4 and innervates the penis via the pudendal nerve.
the urethra.6 The corpus cavernosum is surrounded by a
The nerve contains both sensory and motor neurons. The
thick and tough layer of tunica albuginea. The intercavernous
motor efferent fibers innervate the ischiocarvernosus and
midline septum that separates the two corpus carvernosum
bulbocarvernosus muscles and terminate at the dorsal
contains many tiny spaces on the ventromedial side of
nerve of the penis. The distal end of the dorsal nerve of the
tunica albuginea that may be perforated easily during
penis fans out and is responsible for carrying the sensa-
penile implant surgical procedure. The inside of copus
tion from the skin around the perineum, glans penis, and
cavernosum is filled with sinusoidal tissue surrounded by
tunica albuginea.
a vascular endothelium layer called trabeculae. The two

Figure 2: Peripheral nervous system responsible for controlling penile erection.
4. Mechanisms of penile erection 5. Neurotransmitters and chemicals
The mechanisms involved in penile erection can be 5.1 Central neurotransmitters

divided into three types.
a) Nocturnal erection: A normal male experiences A number of neurotransmitters are involved in regulating
3-5 nocturnal erections per night each lasting around penile erection including prolactin, opioids, and oxytocin.
30-40 minutes.7 Nocturnal erections occur during Studies have shown that dopaminergic stimulation causes
rapid eye movement (REM) sleep. It is still unclear sexual arousal and erection. It is believed that stimulation
how and why nocturnal erection happens. of the D2-like dopamine receptor located at the paraven-
b) Psychogenic erection: The brain is responsible for tricular area causes oxytocin production.9 Oxytocin has
regulating erection following sexual stimulation been shown to be released during sexual intercourse and
(Figure 3). It is still unclear what parts of the brain injection of oxytocin to the paraventricular area in mice
are involved in controlling this response. The signal induced sleepiness and penile erection.10, 11 The mechanism
travels through the medial preoptic area (MPOA) of how oxytocin function in erection remains unclear but it
near the anterior hypothalamus before going to the is believed to be involved with release of nitric oxide (NO).
sacral erection center via lateral funiculus of the
spinal cord.8 5.2 Peripheral neurotransmitters
c) Reflexogenic erection: Reflex erection of the penis
occurs when the signal from direct stimulation of Stimulation of the sacral erection center from either
the penis travels past the dorsal nerve of the penis psychogenic or reflexogenic origins will cause the
to the sacral erection center. The motor pathway nerve impulse to travel through the cavernous nerve via
travels to the penis from the sacral erection center cholinergic neurons releasing acetylcholine (Ach) and
through pelvic nerve, pelvic plexus, and cavernous vasoactive intestinal peptides (VIP) (Figure 4). The end
nerve respectively. of the cavernous nerve also contains axon terminals from

Leungwattanakij S
Figure 3: Mechanisms of psychogenic erection via medial preoptic area (MPOA) and reflexogenic
erection via pudendal nerve are shown in this figure.
another type of neuron that releases nitric oxide, the most (PDE 2, 3) enzymes into inactive adenosine monophos-
important neurotransmitter in regulating penile erection. phate. Other PDE enzymes can be found in other organs
These neurons are called nonadrenergic-noncholinergic such as the brain, cardiac muscle, vascular smooth muscle,
neurons (NANC). Therefore there are two pathways adrenal gland, platelet, and retina.18 There are about 11
that cause erection of the penis following stimulation: PDE isoenzymes that have been identified.48
the nitrergic pathway that releases nitric oxide; and the
vipergic pathway that releases Ach and VIP. Causes
Nitric oxide activates guanylate cyclase that catalyzes Research conducted by Goldstein and members, a study
the production of cyclic guanosine monophosphate of 861 patients with erectile dysfunction, suggested that
(cGMP)13-16 and induces protein kinase G causing a the causes of the disorder are from organic, psychogenic,
reduction in intracellular calcium levels. Meanwhile the or from both origins (mixed ED) with the prevalence per-
binding of VIP to receptors on the cavernous smooth centages of 70%, 11%, and 18% respectively.
muscle cell membrane causes activation of the G protein-
coupled receptor leading to cAMP production through The factors causing erectile dysfunction can be classified
the activity of adenylate cyclase. cAMP functions as as follows:
a secondary messenger capable of activating protein
kinase A and this can also cause the intracellular calcium 1. Arterial disorder
level to decline. The decrease in the calcium level causes
trabecular smooth muscle relaxation. The gap junctions The primary cause of erectile dysfunction, responsible
between the cavernous smooth muscle cells contain a pro- for 60-80% of the cases,20 is atherosclerosis resulting from
tein called connexin 43, 0.25 micron in size. The presence various factors such as hypertension, hyperlipidemia,
of these gap junctions helps the muscular cells to contract diabetes mellitus, radiotherapy, and changes associated
and relax together,17 allowing erection to be achieved. with aging. Treatment of erectile dysfunction due to arterial
disorder by blood vessel surgical procedures cannot
cGMP is broken down by phosphodiesterase type 5 always be carried out because the patients are often elderly
(PDE 5) enzyme into guanosine monophosphate (GMP) with chronic diseases. Localized obstructive arterial
which is inactive. PDE 5 inhibitors, such as sildenafil, can abnormalities that can be treated with a surgery are found
be used to treat erectile dysfunction. Similarly, cAMP in patients who are young and the conditions have resulted
is broken down by phosphodiesterase type 2 and type 3 from an accident.

(From: Leungwattanakij S, Flynn V, Hellstrom WJG. Intracavernous and intraurethral therapy for erectile dysfunction.
Urol Clin of North Am 2001;28(2):343-354.)
Figure 4: The pathways involved in causing a penile erection after stimulation. The nitrergic pathway uses nitric oxide that
induces the production of cGMP and the vipergic pathway uses Ach and VIP that stimulate the production of cAMP. Both
cGMP and cAMP cause a reduction in intracellular calcium level that causes relaxation of the smooth muscle.12
[GTP (guanosine triphosphate), cGMP (cyclic guanosine monophosphate), GMP (guanosine monophosphate), ATP
(adenosine triphosphate), cAMP (cyclic adenosine monophosphate), AMP (adenosine monophosphate), PKG (protein kinase
G), PKA (protein kinase A), Vasoactive intestinal peptide (VIP), VIP-R (VIP receptor), EP-R (prostaglandin receptor),
eNOS (endothelial nitric oxide synthase), nNOS (neural nitric oxide synthase), NANC (nonadrenergic noncholinergic), PDE
(phosphodiesterase), Ach (acetylcholine), E (epinephrine), NE (norepinephrine), Alpha ad R (alpha adrenergic receptor),
NO (nitric oxide)].

Leungwattanakij S
2. Venous and sinusoidal disorder 6. Other risk factors
Erectile dysfunction with impaired veno-occlusive There are a number of other risk factors that can
function of the penis may be caused by fibrosis in the contribute to erectile dysfunction especially many types
corpus cavernosum due to prolonged penile erection or of medications.
Peyronies disease. Castration in mice have resulted in
fibrosis of the corpus cavernosum and venous leakage.21 Clinical Diagnosis
3. Neurogenic disorder 1. Patient history
Erectile dysfunction due to neurological causes can be In practice, a number of patients often consult their
divided into those caused by disorders of the brain, such as physicians concerning erectile dysfunction symptoms
brain tumor, epilepsy, cerebro vascular accidents (CVA), unaware that they also have diabetes mellitus or hyper-
Parkinsons disease, and Alzheimers disease, and those tension. While obtaining the patient medical history, it is
from disorders of the spinal cord, with the most common important to also ask about the sexual history in detail.
cause being spinal cordinjuries that affect the afferent and Moreover, information concerning the socioeconomic
efferent nerve pathways or both. Disorders of the peri- status of the patient should be obtained. Given that the
pheral nervous system including the cavernous nerve of the treatment plan for each patient is unique and must be
autonomic branch and pudendal nerve of the somatic suitable for that particular patient, the doctor may order
branch can also cause erectile dysfunction. The most additional specific diagnostic studies using the patient
common condition of peripheral neuropathy found by goal-direct approach. For example, patients who choose
general practitioners is diabetes mellitus since the disease to treat their erectile dysfunction with oral medications
can cause damage to both vascular and nervous systems. or vacuum erection devices should be diagnosed with
Diabetes mellitus is responsible for 30% of erectile standard procedures. Patients who have chosen to undergo
dysfunction.22 more invasive surgical options should receive diagnostic
tests, such as rigiscan and ultrasonography, to confirm the
4. Hormonal disorder causes of the condition to be truly organic.
Diseases of the endocrine system that may decrease sexual The detailed sexual history of the patient can be used
desire include hypogonadism, hyperthyroidism, Cushings to help distinguish erectile dysfunction from other sexual
syndrome, Addisons disease, and hyperprolactinemia. problems. General practitioners have found a large
number of patients who misunderstood their premature
5. Psychological disorder ejaculation problem for erectile dysfunction. Assessment
of the patients psychological problems and relationships
Psychological processes that can cause erectile dys- with patient sexual partner can help distinguish whether
function are depression and fear of sexual intercourse the erectile dysfunction is psychogenic or organic as shown
commonly seen in men with obsessive and compulsive in Table 1. The physician should inquire about existing
disorder and anxiety. Other psycho logical factors may medical conditions and explain information concerning
be the results from other illnesses or conditions, such as the limitations and risks of each erectile dysfunction
men who suffer from premature ejaculation may experience treatment with the patient. Formalized sexual question-
erectile dysfunction because they constantly fear and worry naires, such as the International Index of Erectile Function
that they will ejaculate prematurely again. (IIEF) especially an abbreviated 5-item version called
Sexual Health Inventory for Men (IIEF-5), can be com-
pleted easily by the patient. However, some physicians
believe that this method is suitable for research purposes
only because the score before and after treatment can be
compared.
Table 1: Characteristics listed in this table can be used to help distinguish psychogenic erectile dysfunction from organic erectile dysfunction.
Psychogenic ED Organic ED
Sudden onset Gradual onset
Normal morning erection No morning erection or morning erection not fully erected
Condition present with some sexual partners only (specific situation) Condition present for all sexual partners (non specific)
Capable of oral intercourse Incapable of oral intercourse
Normal penis erection during masturbation Absent of penile erection during masturbation

2. Physical examination intercourse demands a relatively fit condition. A large

number of patients with erectile dysfunction are elderly
Beside the normal physical examination of erectile who have not engaged in any sexual activity for a long
dysfunction patients, it is beneficial to assess the blood period of time. Therefore it is important for the physician
pressure and pulsation of the limbs, the lower limbs in who will prescribe medications for the treatment of
particular. The presence of bruit may indicate underly- erectile dysfunction to take the risk of ischemic heart
ing vascular conditions such as an aneurysm. Secondary condition into account.
sexual characteristics examination for hair distribution,
gynecomastia, and testicular consistency and size can also 3.4 Additional special examination
be done.
3.4.1 Nocturnal erection examination
Neurological examinations measure the motor and
sensory function of the lower extremities. Evaluation of Examination for the presence of nocturnal erection
the cremasteric reflex (L1-2) can be done by assessing the may help confirm the psychogenic cause for erectile dys-
activity of the anal sphincter muscle upon stimulation of function. This evaluation is very important for patients
glans penis. This evaluation is recommended for patients who will undergo surgical procedures, especially penile
who are older than 50 years old. Examination of the prosthesis implantation, to treat their erectile dysfunction
prostate gland can be carried out while testing for the condition. Rigiscan is a widely used tool that can continu-
cremasteric reflex. Palpation of the penis can be done to ously measure the frequency, size, and rigidity of erection
detect the presence of fibrous plaque or curvature of the throughout the night.24 Normal males will have at least
penis in Peyronies disease. All of these causes for erectile one nocturnal erection with an increase in the diameter
dysfunction should be treated simultaneously. of the penis base exceeding 3 cm and the tip exceeding 2
cm, the rigidity of the penis must be above 70% compared
3. Laboratory examination with flaccid penis, and last for at least 10 minutes.25 The
average number of nocturnal erections is 4-5 times per
3.1 Standard laboratory examinations night lasting over 30 minutes in total.26
The following standard laboratory analysis must be 3.4.2 Penile blood vessel examination
done in all erectile dysfunction patients, regardless of
the cause: complete blood count, urinalysis, fasting blood Examination of the blood vessels in the penis can be
sugar, lipid profile, renal function test, and liver function done using a duplex Doppler ultrasound device with an
test. Diabetes mellitus and hyperlipidemia have been injection of vasoactive agents that can point out causes of
identified as important conditions that can cause erectile erectile dysfunction due to abnormalities of penile arterial
dysfunction. and venous blood vessels. The procedure can also be used
as a screening test before more invasive tests, such as
3.2 Endocrine evaluation of testosterone and prolactin pudendal angiography or cavernosometry and caver-
nosography, are performed. Utilization of color imaging
A study carried out by Buvat and team23 revealed that technique has been incorporated into the procedure (color
the measurement of serum testosterone levels should be Doppler ultra-sonography (CCDU)), and this allows
done for patients who are younger than 50 years old and faster detection of small cavernous arteries.27 A number
have experienced loss of libido or testicular abnormalities, of institutes also recommend simultaneous stimulation of
since a low serum testosterone level was only found in 4% the penis or utilization of audiovisual sexual stimulation
of patients. For patients aged over 50 years, analysis of (AVSS).28 This procedure may cause patients to feel
serum testosterone level is recommended for all patients anxious, therefore the results can only be used to determine
because a low serum testosterone level was found in 9% whether the cause of the erectile dysfunction may be due to
of the patients. The measurement of prolactin level is only the conditions related to the arteries and veins in the penis.
recommended in patients with loss of libido, gynecomastia, For patients who have to undergo vascular surgeries, a
and/or testosterone levels below 400 ng/dl (4 ng/ml) since pudendal angiography must be carried out for patients
the condition of prolactinoma was found only in 1 out of with arterial insufficiency and cavernosometry and phar-
1,022 individuals. macocavernosography in patients with veno-occlusive
dysfunction.
3.3 Examination for risks for ischemic heart disease
3.4.3 Examination of the nervous system regulating penile
The dangers posed by ischemic heart disease during erection
sexual activity do not come from any known medications
for treating erectile dysfunction. Instead these dangers are Examination of the nervous system responsible for
directly related to the sexual activity itself because sexual erection regulation as a diagnostic tool is not widely used

Leungwattanakij S
since erectile dysfunction with a sole neurological cause patients with liver diseases, kidney failure or aged 65 or
accounts for about 10% of cases.29 The majority of cases older where the starting dose should be adjusted to 25 mg
are associated with diabetes mellitus and occur after per day. The dose can be increased to 100 mg where
radical surgery indicating that the condition is caused by the desired effect is not yet obtained and the adverse
multiples factors involving vascular conditions and other effects are absent. However, if the patient is responsive
psychological entities. More importantly, the determination but experiences adverse effects, the dose can be lowered
of erectile dysfunction due to neurological origins is often to 25 mg. In general, a better response is obtained with
obtained from assessing the patients medical history and a higher dose but adverse events are more common. Around
a neurological examination. 75% of patients show response to a 50mg dosage. The
dose that was seen with second highest response rate was
Treatment 100 mg. Sildenafil should be taken 1 hour prior to sexual
activity because the highest level of the drug inside the
The patients sexual partner should also be brought in blood is seen within 30-120 minutes (average 60 minutes).
to visit the doctor where possible since it may improve the In practice, the effects of the medication can be seen as
outcome of the treatment. A positive relationship between early as 30 minutes in some patients, where normal sexual
the physician and patient can be strengthened by educat- arousal can promote an erection and the medication help
ing the patient about the condition. The doctor should sustains it. The drug should be taken while the stomach
also provide other recommendations to promote healthy is empty. When sildenafil is taken with food, especially
behaviors, such as exercising regularly, avoiding or min- with high amount of fats, the absorption time is increased
imizing risks that may worsen the condition or impede thereby lowering the level of the drug in the blood around
treatment success, including hyperlipidemia, hyperten- 29% at 60 minutes time point. The half-life of sildenafil
sion, hyperglycemia, smoking, alcohol consumption, and is approximately 4-5 hours, therefore some patients have
usage of certain medications. reported to be able to complete sexual intercourse after
waking up in the morning despite have taken the drug
Psychotherapy and sex therapy were widely used in before going to sleep.
the past to treat erectile dysfunction, but were expensive,
required long treatment periods, and had a high chance The results from Asian Sildenafil Efficacy and Safety
of reoccurrence. It is now known that a large number of Study (ASSESS), that examined the effects of sildenafil in
cases of erectile dysfunction are due to organic causes. Asian men including Thailand, found an improvement in
Treatments that are easy and convenient to use include erectile function of 81.0-88.5% in the group treated with
oral and intraurethral drugs. In principle, the treatment of the drug compared with 28-38% in the placebo group. A
erectile dysfunction should start from easy to hard, taking significantly higher percentage of the subjects that were
into consideration convenience, cost, and ease of usage. It able to complete sexual intercourse were found around
is important for the physician to always take the patient 67.8-74.0% in the treatment group compared to 27.0-30.5%
and his partner psychological conditions into account from the placebo group. A study that evaluated the safety
when choosing an appropriate treatment. Patients who are of sildenafil in a large number of samples by comparing
struggling with his partner or at work should be advised to the data with the placebo group for 1 year,31 reported the
seek attention from a psychiatrist. adverse effects as summarized in Table 2. Most of the
adverse side effects were temporary and mild. The pres-
1. Treatment with oral medications ence of these effects can be explained by the mechanism
of the drug, for example, vasodilation can also occur in
1.1 Phosphodiesterase type 5 (PDE 5) inhibitors blood vessels inside the brain causing headache. General
vasodilation of blood vessels around the facial and nasal
The class of medication functions by inhibiting the regions may cause the subject to experience flushing
activity of PDE 5 enzyme that is responsible for degrada- and nasal congestion. Relaxation of the smooth muscle
tion of cyclic guanosine monophosphate (cGMP) in corpus surrounding the gastrointestinal tract may cause dyspepsia.
cavernosum and relaxation of smooth muscle around the Abnormal vision, with blurry images, impaired ability
sinusoids (Figure 5). As a result, there is an increased to distinguish green and blue colors, and addition of blue
volume of blood inside the penis leading to the develop- color into vision, may be explained by the fact that silde-
ment of an erection. PDE 5 inhibitors do not directly cause nafil can also inhibit the activity of PDE 6, an enzyme
the relaxation of the smooth muscle, therefore an erection involved in phototransduction inside the retina.30
cannot be achieved without the activities of nitric oxide
and cGMP, both of which are produced in response to Sildenafil must not be taken with any nitrate medications.
sexual stimulation. In other words, the medication can help Nitrates can significantly increase the level of nitric oxide
prolong an erection after sexual stimulation. Sildenafil and cGMP in the blood, therefore when they are taken
(Viagra) was the first drug of this class and is widely with sildenafil, a lethal hypotension condition may ensue.
used. The drug is available in three doses, 25mg, 50 mg, Taking sildenafil with hypertensive medications does not
and 100 mg. The starting dose should be 50 mg, except for have any significant synergistic effects. When sildenafil

Figure 5: Mechanisms of sildenafil.
Table 2: Adverse effects from sildenafil compared with placebo.

Side effects Sildenafil (%) Placebo (%)
Headache 16 4
Flushing 10 1
Dyspepsia 7 2
Nasal congestion 4 2
Abnormal vision 3 0
Table 3: Inhibitory concentrations of sildenafil, tadalafil, and vardenafil.

IC50 (nM)
Isoenzyme Distribution
Sildenafil Tadalafil Vardenafil
PDE 5 Corpus cavernosum, platelets, skeletal muscle, 3.5 6.7 0.1
vascular and visceral smooth muscle
PDE 6 Retina; rod 37 1260 3.5
; cone 34 1030 0.6
PDE 11 Cardiac muscle, testes, corpus cavernosum, 2730 37 1620
pituitary, pancreas
IC50 = inhibitory concentration at 50%

Leungwattanakij S
is taken with cimetidine, ketoconazole, and erythromycin, 1.2 Medications with a central acting mechanism
the level of sildenafil is abnormally high because these
medications inhibit the activity of cytochrome P3A4 in Apomorphine is a D2-like dopamine receptor antagonist
the liver, which inhibits the activity of sildenafil. distributed by Abbott Laboratories (Uprima) and Takeda
(Ixense) in Thailand. It is the first medication that was
Other PDE 5 inhibitors that can be taken orally32 are used to treat erectile dysfunction with its effects on the
Cialis (tadalafil or IC351) by Lily-ICOS and Levitra central nervous system or directly at the hypothalamus
(vardenafil or BAY 38-9456) by Bayer-GSK. The advan- (paraventricular nucleus). The medication is taken orally
tages of tadalafil are that there are no restrictions on the by placing the drug under the tongue to allow fast
type of food that can be consumed, no abnormal vision absorption. The effects can be seen within 10-25 minutes.
because the 50% inhibitory concentration (IC50) of PDE 6 The doses that were used in studies ranged from 2-6mg
is significantly higher than PDE 5 (Table 3).48,49 The half- but most research used a dose ranging from 2-4mg. The
life of tadalafil is 17.5 hours which is significantly longer results showed that completion of sexual activity were
than sildenafil. However, the IC50 of tadalafil is only 5.5 seen in 41.5% and 50.6% of the subjects who received
times higher against PDE 11, an enzyme found in high 2 and 4 mg doses respectively. Only a few mild adverse
amount inside the cardiac muscle, compared with PDE 5. effects, that corresponded to the dosage, were reported
Although the exact functions of PDE 11 inside the cardiac with the most common being nausea that was found in
muscles are still unclear, there are no adverse effects on 2-8% of the subjects. The efficacy of the drug at 3 mg.
the heart in phase III study and tadalafil is considered to dose is very similar to that of 4 mg. but with lower risks
be very safe. It is worth looking out for other adverse ef- of adverse effects, so only 2 and 3 mg dose are available
fects in the future when tadalafil goes to the market and on the market. The main benefit of this drug class is that it
is widely used. Vardenafil has a pharmacokinetic profile can be taken with nitrate medications. However, the drug
very similar to that of sildenafil, with a slightly shorter cannot be used to treat erectile dysfunction caused by
time for peak blood level. The half-life of vardenafil is 4-5 spinal cord injuries and nerve damage. This drug is no
hours. There is also no restriction on taking the medica- longer sold in Thailand.
tion with any food. The efficacy and side effects of these
three drugs are very similar. 1.3 Other oral therapies
Low dosage of tadalafil of 5 mg/ml has been used as a Another erectile dysfunction medication that used to
treatment for patients who have frequent sexual activities. be popular in the past was trazodone,30 an anti-depres-
Studies have indicated that daily administration of the sive drug that works by inhibiting serotonin reuptake
drugs at 5, 10, and 20 mg yielded similar efficacy but the along with peripheral 2-adrenoceptor blocking activity.
5 mg dose had the lowest adverse effects, 51-52 and lower The efficacy profile of trazodone was not very high with
adverse effects compared with taking the drug on demand adverse effects of headache, nausea, sleepiness commonly
with 10-20 mg dose. Treatment daily with 2.5 mg/day had reported. Trazodone should only be used to treat psycho-
a higher response compared with placebo but the efficacy genic erectile dysfunction.
was lower than 5 mg dosage.
2. Intraurethral medications
It was later reported that daily treatment of a low dose
of tadalafil can help treat patients with lower urinary tract The intraurethral medication for treating erectile
symptoms (LUTS). The recommended dosages were 2.5 dysfunction is called intraurethral alprostadil or MUSE
and 5 mg/day, with 5 mg dose giving better response com- (Medicated Urethral System for Erection) distributed by
pared with 2.5 mg, but no significant differences when Vivus (Menlo Park, California) with doses of 125, 250,
compared with 10 mg and 20 mg doses similar to findings 500, and 1,000 micrograms. The medication is to be
from the erectile dysfunction study.53 inserted through the urethra before sexual intercourse
(Figure 6). The license of this medication in Thailand
There are three additional PDE 5 inhibitors that are belongs to Abbott.
available on the market but are not being sold in Thailand.
This is because after the expiration of sildenafil patent, Alprostadil that has been administered via the urethra
other brands have been sold at lower prices, especially will be absorbed into corpus cavernosal tissue via
Sidegra that is manufactured by Thailands Government communicating vessels that link the corpus spongiosum
Pharmaceutical Organization (GPO), making it less prof- and corpus cavernosum.12 After the drug is inserted in
itable for sale in the Thai market. These three drugs are the urethra, it will take approximately 8 minutes for the
Avanafi (Stendra), Udenafil (Zydena) and Mirodenafil effects to be seen with full erection achieved after 20
(Mvix) with similar efficacy profiles compared with older minutes. The effects of the medication will wear off after
PDE 5 inhibitors but with different half-life and adverse about 60 minutes.
effects.54-56

is injected with Invicrop (vasoactive intestinal peptide

+ phentolamine).36 Other medications that can be given
when standard intracavernosal injections are irresponsive
are potassium channel openers which function through
the potassium channel causing muscle relaxation similar
to calcium channel drugs.
The efficacy of this method is around 90% with pro-

longed erection (erection exceeding 4 hours) as the main
side effect found in 1-6.9% of the subjects, with the highest
being papaverine and lowest being PGE1. Long-term
usage may cause fibrosis which has been reported in 4.1-
5% of cases.35
Intracavernosal injection therapy is unpopular since

Figure 6: MUSE applicator stem is inserted into the urethra patients not only have to learn how to correctly perform
often after urination to provide moisture. The button is gently the injection but also are afraid of performing injection
pressed to deposit the pellet inside the urethra. Massage the into their own penises. The medication can also cause pro-
penis with both hands to dissipate the drug and help speed up long pain especially in PGE1 drugs due to lowering of the
absorption. pain threshold receptor or the pH of the medication itself
remains unclear.12
Hellstrom and team found that treatment with MUSE 4. Vacuum devices
at 500 micrograms dosage yielded satisfactory penis
erection in 26.7-39.6% and slightly higher percentages of A vacuum constriction device (VCD) works by using
31.7-48.8% for 1,000 micrograms dosage.34 Lower dosages the vacuum pump to increase the blood flow into the penis
at 125 and 250 micrograms do not provide a satisfactory and application of a constrictor ring to retain the blood
level of erection. Therefore, the starting dose for MUSE and remain erect. The device contains three pieces of
should be 500 micrograms and a higher dose of 1,000 equipment; a cylinder, a vacuum pump, and a constrictor
micrograms can be increased where the patients are not ring (Figure 7). The pump may be manually operated by
yet satisfied with the lower dose. pumping action of the hand or used a battery-operated
automatic vacuum pump. Certain pump models contain a
The most common adverse effect of MUSE is urethral built-in valve that automatically opens when the pressure
burning pain that is experienced in 10-30% of the cases. inside the chamber falls below the safety level and to
Other side effects that are found in small numbers include ensure that the pump does not exceed 250-350 mmHg.38
infection of the urethra and priapism.35 Patients who are at
risks of priapism, have penis curvature, and are allergic to Vacuum constriction devices should not be used in
alprostadil should not use MUSE. patients who have bleeding disorders, are taking antico-
agulants, or have a history of priapism. However, the utili-
A study examining the effects of transurethral PGE1 zation of vacuum constriction devices in patients who are
with prazosin showed a slightly higher response than taking anticoagulants has also been reported to be safe.
PGE1 alone.36 Other medications, including nitric oxide Some men with Peyronies disease cannot use the device
donors, given intraurethrally did not provide a better because the curvature of the penis may cause pain if the
response than those that were taken orally.37 penis is inserted into a small and straight cylinder.
3. Intracavernosal injection therapy 5 Penile prosthetic devices
The most common starting intracavernosal injection There are many types of penile prostheses. For ease of
drug is alprostadil. Other medications include papaverine, understanding, the penile prostheses will be classified into
a non-specific PDE 5 inhibitor, and phentolamine, an two classes, nonhydraulic and hydraulic penile prosthesis.
alpha adrenergic antagonist, are often used as a second-line Each class can be further divided according to the appear-
injection drugs and are mixed with alprostadil36 called ance of the prosthetic shaft.39
tri-mixed therapy.12
5.1 Nonhydraulic penile prostheses
The injection drug that is currently under research is
forskolin which promotes direct adenylate cyclase activa- Nonhydraulic penile prosthetic devices have simple
tion that increases the level of cyclic AMP (Figure 4) and mechanics therefore have lower risk of mechanical failures.

Leungwattanakij S
Figure 7: A vacuum constriction device.
The disadvantages of these devices are abnormal feel Despite high satisfaction above 90% and low risks of
and appearance, hard to conceal, and the size of the complications from the surgical procedure, the high cost
enlargement cannot be controlled. of the device causes some minor complications to become
more severe. The physician must try to minimize the risks
5.2 Hydraulic penile prostheses of complications. Some of the complications are discussed
here.
Hydraulic penile prosthetic devices allow fluid to be
pumped from the reservoir into the penis shaft to obtain an a) Corporal crossover: The distal part of the corpus
erection. The fluid can be returned to the reservoir to allow cavernosum septum is very fragile and can easily be
the penis to return to the flaccid state (Figure 8). This type perforated. The perforation in the medial septum
of device permits better concealment and allows enlarge- side may be minimized by positioning the dilator in
ment during erection. Newer generations of these devices the center to the lateral side.
can also provide penis enlargement of the length during b) Corporal perforation: Perforation across tunica
an erection. The devices can be easily inserted through albuginea may occur at proximal and distal corpus
a small surgical opening of the penoscrotal junction cavernosa and urethra, but is more frequently
(Figure 9). The hydraulic penile prostheses can be further observed with the proximal corpus cavernosa. This
categorized according to the number of equipment. Newer condition is commonly found in patients with fibrosis
pumps are larger and can easily be deflated with one press with unknown cause or those with Peyronies disease.
of a button (AMS 700 momentary squeeze or MS pump).57 c) Perforation of the urethra: This complication is
rare but can be severe and usually occurs at the end
Patients who should be treated with penile prostheses of the urethra.
are those with organic erectile dysfunction who are d) Perforation of penile implant: Erosion and extrusion
not responding to other treatments. For those who have of the penile prostheses usually happens with an
psychogenic erectile dysfunction, penile implants should infection. Patients with compromised tissues, such
only be performed when other treatments have failed as those with diabetes mellitus or patients who have
and advice from psychiatrists regarding the surgical preexisting infections from previous penile implants,
procedure should be provided. Most of the procedures are more susceptible. This complication is more
carried out today use the hydraulic penile devices because common in the semi-rigid rod type which is no
they offer a more normal look and feel. The advantages longer used.
and disadvantages of each device should be thoroughly e) Glans bowing (SST deformity): Deformity of the
explained to patients. It is important to take the limitation glans penis formed during erection that may cause
of dexterity in some patients into consideration, since it pain during erection and sexual intercourse.
may be difficult to operate the pump and return the fluid f) Infection: Although infections caused by penile
to the reservoir. Patients partners should also be educated implants are rare, the condition may be very
about the device and be ask whether they can help assist dangerous. A prevalence of infection with the
the patients with device operation. penile implant of 0.6-3.0% has been reported in

Figure 8: Three-piece hydraulic penile implant- Figure 9: A surgical procedure installing a three-piece
consisting of the cylinders, pump, and a reservoir bag. penile implant at Bangkok Hospital through a small
incision at the penoscrotal junction.
the rod prosthesis group and 0.8-8.9% in the sometimes carried out in patients whose arteries are still
multicomponent inflatable prosthesis group. 40 functioning normally from the test using duplex Doppler
Staphylococcus epidermidis is the most common ultrasound and have confirmed venous leakage from
cause of infection. This type of bacteria can normally cavernosography despite high chance of reoccurrence.
be found on the skin surface. Risk of infection is
higher in patients with diabetes mellitus, impaired 7. Combination therapy
spinal cord, who are immune-deficient, and have
or frequently use a catheter. Some companies now Utilization of multiple medications with different
coat a layer of antimicrobial substance that can properties to simultaneously treat erectile dysfunction has
minimize colonization of bacteria.50 been gaining a lot of attention in recent years. For example,
g) Mechanical malfunction: Newer models of treatment with MUSE and sildenafil in 16 patients
three-piece prostheses have an incidence of with suboptimal response to monotherapy provided
malfunction lower than 5%. Most failures involve satisfactory outcomes for 3 months evaluation period.41
leakage at the junction between the pumps and the A similar study showed that 60 of 65 patients reported
cylinders, bending of the tubing, and problems at satisfactory response using IIEF score assessment.42
junctions. Another study using 4 mg of doxazosin given orally with
h) Autoinflation: This happens when the device is an increased dosage spanning a 3-week period, along with
inflated without the pumping action. intracavernous PGE1 injection therapy, as a form of treat-
ment in 38 patients who had failed to respond to intra-
6. Vascular surgery cavernous injection, showed 60% efficiency evaluated by
IIEF score.44
Vascular surgery is not practiced widely despite the fact
that abnormalities of penile blood vessels are important 8. Other treatments
causes for erectile dysfunction. A long period of treat-
ment and a low success rate has made vascular surgery A number of alternative treatments for erectile dys-
an unpopular method of treatment. This procedure is function are currently being developed. Topical therapy
only carried out when a specific pathology of the vascular by application of topical PGE1 to glans penis has received
system has been identified, for instance a young male who approval from the China Food and Drug Administration
has erectile dysfunction after an accident causing damage and has an efficiency similar to intraurethral PGE1 or
to pelvic blood vessels. Ligation of venous vessels are MUSE but with minor side effects such as a burning

Leungwattanakij S
sensation at glans penis and penile pain. The topical low, because low level testosterone is often not the cause
PDE1 medication that has been preliminarily evaluated is of erectile dysfunction but instead is another symptom
Topiglans by MacroChem. The gel formula consists of 1% that can be found with erectile dysfunction. However,
alprostadil plus 5% SEPA gel (2-n-nonyl-1,3-dioxolane) testosterone therapy can still help increase bone mass,
that act as a transdermal enhancer. McVary and team has muscle tone, erythropoietin production, and synthesis of
reported an effectiveness of 67-75%.45 Another formula some liver proteins.47
containing 4% Alprostadil gel plus NexAct technology
enhancer from NexMed is currently being developed. Conclusion
The dose of 500 mg applied topically was assessed in
10 patients with erectile dysfunction after radical pros- Erectile dysfunction poses as a problem for any sexual
tatectomy by comparing the effects from 10 micrograms relationship and may also affect relationships with
dose of alprostadil that were given via intracavernous family and work. Available treatments for erectile
injection. The measurements of peak systolic, end diastolic dysfunction are widely accepted with high efficacy, low
activity, and resistive index value were similar to intracav- risks of adverse side effects, and not as complicated
ernous injection.46 compared with previous therapies. Doctors and healthcare
workers should learn about the condition in order to be
Treatment using gene therapy is predicted to gain popu- able to provide appropriate consultation to the patients.
larity in the future because of its high effectiveness and Selection of treatment uses patients goal-directed
elimination of oral therapy or intracavernous injections. approach where the patients can select the most suitable
The patients would have to visit the hospital to receive an form of treatment themselves. Physicians should screen
injection of the genes around 3-4 times per year. As the for conditions that may cause erectile dysfunction, for
penis is located external to the body, it has slow blood flow example diabetes mellitus and hypertension, provide
when flaccid, so a constriction ring can be applied prior to recommendations, restrictions, and educate the patients
the injection of the genes, and these factors make the penis about each form of treatment and make suggestions that
a suitable organ for this method of treatment. match the needs of the patients. When treatment fails, the
patients must then be referred to a specialist for further
Treatment with testosterone has only been used in examination and treatment.
patients with low testosterone levels. The effectiveness of
testosterone therapy for treating erectile dysfunction is
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Clin North Am 1991;29:629-45. using oral alpha-blockers and intracavernosal injection in
28. Montorsi F, Guazzoni G, Barbieri L, et al. The effect of men with erectile dysfunction. Urol 1998;52:739-43.
intracorporeal injection plus genital and audiovisual 45. McVary KT, Polepalle S, Riggi S, et al. Topical prosta-
sexual stimulation versus second injection on penile color glandin E1 SEPA gel for the treatment of erectile
Doppler sonography parameters. J Urol 1996;155:536-40. dysfunction. J Urol 1999;162:726-30.
29. Zonszein J. Diagnosis and management of endocrine 46. Becher E, Borghi M, Momesso A, et al. Penile hemody-
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1995;22:789-802. J Urol 1998;159(5)(Suppl):A915.
30. Tantiwong A. Oral therapy for erectile dysfunction. In: 47. Leungwattanakij S, Bryan W, Hellstrom WJG. Androgen
Ratana-Olarn K, Leungwattanakij S, eds. Erectile deficiency in aging male. Mediguide to Urology 2000;13:1-7.
dysfunction. Bangkok: Beyond Enterprise 2001:100-8. 48. Ballard SA, Gingell CJ, Tang K, et al. Effects of sildenafil
31. Morales A, Gingell C, Colllins H, et al. Clinical safety on the relaxation of human corpus cavernosum tissue in
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32. Leungwattanakij S. Future trend of management of erectile 49. Phillips S, Gbekor E, Bethell S et al. Selectivity of Silde-
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Erectile dysfunction. Bangkok: Beyond Enterprise tors against all human phosphodiesterase families. Euro
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33. Claes H, Sorgeloose T, Van Poppel H, et al. Int J Impot 50. Hellstrom WJ, Hyun JS, Human L, et al. Antimicrobial
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double-blind, placebo-controlled evaluation of the erectile 51. Porst H, Giuliano F, Glina S, et al. Evaluation of the
response to transurethral alprostadil. Urol 1996;48:851-6. efficacy and safety of once-a-day dosing of tadalafil 5mg
and 10mg in the treatment of erectile dysfunction: results
of a multicenter, randomized, double-blind, placebo-
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52. Rajfer J, Aliotta PJ, Steidle CP, et al. Tadalafil dosed once 55. Paick JS, Ahn TY, Choi HK, et al. Efficacy and safety of
a day in men with erectile dysfunction: a randomized, mirodenafil, a new oral phosphodiesterase type 5 inhibitor,
double-blind, placebo-controlled study in the US. Int J for treatment of erectile dysfunction. J Sex Med 2008;5:
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53. Roehrborn CG, McVary KT, Elion-Mboussa A, et al. 56. Salem EA, Kendirci M, Hellstrom WJ. Udenafil, a long-
Tadalafil administered once daily for lower urinary tract acting PDE5 inhibitor for erectile dysfunction. Curr Opin
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54. Hellstrom WJ, Kaminetsky J, Belkoff LH, et al. Efficacy satisfaction with the new AMS 700 momentary squeeze
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Dysfunction: A Randomized, Double-Blind, Placebo
Controlled Study. J Urol 2015;194:485-92.

Review Article
Part 1: Balloon and principle of Balloon Angioplasty in

Peripheral Arterial Disease (PAD)
Abstract
Balloon angioplasty has been one of the modalities of choice in the treatment of
peripheral artery disease, or PAD, for many decades. Balloon technology was
developed not only in the form of designs and materials but also as a new application
with the introduction of cutting, cryo, or drug eluted principles. Many clinical trials
have been studied and have changed clinical guidelines in the treatment of peripheral
arterial disease. This content of this article includes the principle of balloon angio-
plasty in atherosclerosis disease, types of balloon, materials, basic balloon selection
with a focus on peripheral artery disease alone.
Keywords: angioplasty, peripheral artery disease, balloon
Tanisaro K, MD
C
harles T. Dotter was the first to describe balloon angioplasty
and Melvin P. Judkins published the angioplasty technique
using a Teflon dilating catheter in the magazine Circulation
in 1964.1 This technique was developed by Andreas Gruentzig to
use in the clinic, especially in the coronary artery, and was published
Komgrit Tanisaro, MD1
in South Germany in 1974. This marked an important change in
the use of balloons in angioplasty and in organs which is still
practiced today.
Anatomic layers in arterial wall
The innermost layer of the artery is called the Intima. It contains

endothelial cells which have only one layer on the basement mem-
brane and are inserted by a connective tissue around the subendo-
thelial area that connects to the media layer. This seam is called the
internal elastic lamina, or IEL. The media layer mostly contains
smooth muscle cells along with some collagen fibers and elastic
fibers. The adjoining media layer, before the outermost layer is
called Adventitia, and is the joint called the external elastic lamina,
or EEL. In the adventitia layer some connective tissues, especially
elastic fibers, distribute loosely. In this layer, there are both vasa
vasorum, nerve plexus and lymphatic vessels. Vasa vasorum
provide nourishment to the media layer.
1
Vascular Center, Bangkok Hospital, Bangkok Hospital Group,
Bangkok, Thailand.
There are three types of arteries; arteriole, muscular arteries
* Address Correspondence to author: and elastic arteries. The aorta and the iliac are the largest elastic
Komgrit Tanisaro, MD arteries in the body. These contain the most elastic fibers while
Vascular Center, Bangkok Hospital,
2 Soi Soonvijai 7, New Petchburi Rd., muscular arteries such as the coronary artery, the arms, legs and
Bangkok 10310, Thailand. abdominal arteries contain more smooth muscles than elastic fibers
e-mail: komgrit.th@ bangkokhospital.com
so they control the circulation and blood pressure. Arterioles, which
Received: December 30, 2015 are the smallest arteries, act as a controller of physiology and secrete
Revision received: January 18, 2016 substances to regulate the operation of coronary endothelial cells
Bangkok Med J 2016;11:73-78.
like endothelin-derived relaxing factor, prostacyclin, tissue plas-
E-journal: http://www.bangkokmedjournal.com minogen activator, heparin sulphate, and prostanoids.

Tanisaro K
Pathology of the arterial wall
General lesions in arteries presenting with artheroscle-

rotic symptoms will have fibro-fatty plaques in the intima
layer. The media layer will also be thinner and will enter a
decline leading to fibrosis.
There are 2 types of plaques; fibrous plaques and

artheromatous plaques. Fibrous plaques are found in
abundance in the intima layer. They are later replaced by
smooth muscle cells and connective muscle cells. The
bold area that extends into the blood vessels is called the
fibrous cap of artheromatous plaques and mostly contain
cholesterol. Both types of plaques can cause stenosis or
obstruction in the blood vessels. If there is a lot of fat
and high cholesterol, and plaques in the fibrous cap, it can
split, break and become ulcerated which can then cause
thrombus. When this occurs in small blood vessels, it
causes an obstruction. If this happens to the larger blood Figure 1: Diagram shows pathophysiology of artery plaques.
vessels, the lesions might have fibrosis or might be calcified
and that can lead to chronic artery stenosis (See Figure 1).
Mechanism and Pathology of Balloon Angioplasty2 adventitia layers. From observation, it is found that there
is a stretching of the smooth muscle cells and a necrosis
Many theories try to explain the mechanism and of some smooth muscle cells. Studying the IVUS, it can
pathology of balloon angioplasty by studying laboratory be seen that arterial stretching happens to 25% of patients
animals, and cadaveric and intravascular ultrasound after having balloon angioplasty.3
(IVUS) studies.
Balloon
In the early days, there was a belief that plaques com-
pression or plaques displacement caused the remodeling Rule of Laplace T=PR
of the endothelial. This theory was refuted when the path-
ological examination found that there was no change in T= Tension or pressure to the artery wall
the interior features of plaques. However, the result of the P= Pressure inside the balloon
study using IVUS in measuring the size and the volume of R= Radius of the balloon used
plaques after balloon angioplasty found that plaques were
squeezed out of the lesions to the top and the bottom of An increase in tension or pressure to the artery can be
the lesions. This proved the existence of plaques compres- achieved by adding inflation pressure into the balloon or
sion and displacement but this is nonetheless not the main by increasing the diameter of the balloon.
mechanism.
The types of balloon are non-complaint, compliant
The most widely accepted theories nowadays are that and special.
plaques fracture and there is localized wall dissection.
After balloon angioplasty, the plaques will split and break A non-compliant type of balloon is used in balloon
especially the thinnest area (in the case of eccentric angioplasty. It means that, when the balloon is enlarged to
plaques). Moreover, the tearing of the artery is also found its limit, it cannot be expanded no matter how much more
in the intima layer and in some parts of the media layer pressure is added inside. Therefore, it is more suitable to
around the IEL line, both circumferential and longitudinal. be used in angioplasty than a compliant balloon. The size
The tearing of the artery especially in the media layer of a compliant balloon changes according to the pressure
causes a dissection flap which can be seen sometimes from applied inside it. The pressure is higher in the area that
the vascular imaging after balloon angioplasty. These are has no obstruction while the stenosis area has lower
shown by the thin stripes in the longitudinal vessels or the pressure. This kind of balloon is mostly used with a balloon
stain of contrast media around the area that has the intimal expandable stent or the balloon that is used in endovascu-
flap (Figure 2,3,4). lar aortic repair (EVAR).
Another mechanism that explains the result of balloon New types of balloon are made from different kinds of
angioplasty is the arterial wall stretching of the media and materials, such as polyvinyl chloride (PVC), polyethylene

Part 1: Balloon and Principle of Balloon Angioplasty in Peripheral Arterial Disease (PAD)
Figure 2: The demonstrated mechanism of balloon angio- Figure 3: The right femoral artery shows an intimal
plasty on plaque. flap after balloon angioplasty.
(PE), polyethylene terephthalate (PET), polylephin

copolymers (POC), nylon derivatives (N), nylon-rein-
forced polyurethane (PU) (which is the most popular
material used), and co-extruded copolymers (CP).
Non-compliant balloons are PET, PU and CP while

PVC and POC are found in highly compliant balloons. The
balloons that withstand High Burst Pressure (HBP) are
PET, N, PU and CP. PU, CP and N can resist a puncture
from sharp calcium or from the wire of a stent. Hydro-
philic polymers or silicone are popularly used because of
their coating effect, as this makes the balloon slippery and
easier to put through the stenosis area.
The design of the balloon used nowadays is mostly true

multiple-lumen (see Figure 5) which is the type of balloon
that is used with guide wires sized 0.035 inch, 0.018 inch,
and 0.014 inch. The same hole is used to inflate or deflate Figure 4: Diagram shows the rule the rule of Laplace.
the balloon. Another type of balloon that is popularly used
in expanding coronary arteries and small blood vessels is
To select the appropriate balloon, the following
called the monorail balloon (see Figure 6). This type of
factors need to be considered:
balloon is special as its hole is located in the catheter that
allows the guide wire to emerge from the side. With this
1. The size of the guide wire, 0.035, 0.018, or 0.014
balloon, a normal size guide wire can be used, and there
inch.
is no need to change to the longer sized guide wire (such
2. The size of the introducing sheath that the balloon
as in the case of the co-axial balloon). The disadvantage
that it will be going through.
of using this kind of balloon is that it is impossible to in-
3. Type of balloon (co-axial or monorail).
ject the contrast media through the tip of the catheter and
4. When the co-axial balloon is used, the length of the
it might be more difficult to put the balloon through the
catheter must be long enough. For instance, in the
stenosis areas.
case of expanding the right side arteries, the length
of the balloon catheter used is 135 cm, the catheter
length must be 300 cm. when accessing the
introducing sheath through the left groin.

Tanisaro K
Figure 5: Diagram of true multiple-lumen balloons. Figure 6: Diagram of monorail balloons.
5. The diameter and the length of the balloon are There are few effects on normal vessel walls and
determined based on the size of the stenosis area. thus the flow-limiting dissection is reduced. This
6. Nominal pressure or suitable pressure in expanding is one of the principles of the focal pressure
the balloon must be known. balloon used more frequently nowadays.
7. Burst pressure or the highest pressure in expanding 2. Cryotherapy balloons are a blend of balloon
the balloon must be known. mechanisms employed with the use of cold caused
8. In the low profile balloon, the size of the diameter by nitrous oxide. A temperature of 10C, has been
of the catheter in the balloon section is smaller than found to reduce plaque inflammation post-angio-
the diameter of the other catheters and that makes it plasty and as a result the elastic recoil and the
easier to go through the stenosis areas. growth of smooth muscle cells decreases. The
9. The higher deflation rate, the faster it can flatten the likelihood of having neo-intimal hyperplasia is
balloon and that can make the procedure quicker to also reduced. However, the treatment results found
complete. that, compared with a normal type balloon, there
10. In general, the contrast media will be mixed in a are still some disadvantages for lesions that are
proportion of 3 with the saline in the inflator used very high in calcium. From the study of in-stent
to expand the balloon. By doing so, the balloon can stenosis and in stenosis of an AV graft, it was found
be seen in the fluoroscope screen. Moreover, it that the use of a cryotherapy balloon to expand
makes the balloon get flat easier and not too the femoral arteries after using a nitinol stent
viscous for using the same balloon for the next (post-dilated balloon angioplasty) in patients with
angioplasties. diabetes, can help reduce the chance of re-stenosis
of the vessels more so than with a normal type
Special types of Balloons balloon.4
3. Focal pressure balloons employ angioplasty by
1. Cutting balloons have long been used to expand using the force exerted on each layer of the artery
the coronary artery with in-stent stenosis and have walls in a longitudinal position, to be able to
been applied more frequently to the peripheral enlarge the arteries to the same size as when
arterial, especially in treating the stenosis area using a normal type balloon. It decreases the
of an AV graft or AV fistula. This type of balloon unnecessary effects to the normal vessel wall,
is designed with 3-4 microsurgical blades or and reduces the chance of dissection and future
atherotomes designed to cut the lesions when the stenosis caused by intimal hyperplasia. In designing
balloon is dilated. The blade will be placed only the balloon, a nitinol coil will be cut in a stripe
0.127 mm. from the balloon. A cutting balloon or spiral shape on a semi-compliant balloon. This
makes a longitudinal incision to create a force on kind of balloon is used more and more in many
the vessel walls which is hard or high tension. countries (but not to the same degree in Thailand).

Part 1: Balloon and Principle of Balloon Angioplasty in Peripheral Arterial Disease (PAD)
4. The drug-eluting stent was in fact developed before 2. In the case of a tandem lesion, the selection of the
the drug-eluting balloon but the problem of lesion to be treated first is based on several
neo-intimal hyperplasia in the strut of the stent was reasons. If there is a lot of stenosis on proximal
still observed. The advantage of coating the drug blood vessels, it is necessary to get expand this
on the surface of the balloon is that the drug can first before doing the distal blood vessel. But if
enter into direct contact with the blood vessel walls there is only partial stenosis on the proximal area,
and there are more contact areas than with a stent. the distal area should be performed first to avoid
But the disadvantage is that the coating drug only any disturbance from the proximal blood vessel.
stays on the blood vessel walls for a short period of But be aware that, during the expansion of the
time. Palitaxel is mostly used in coating as it has distal blood vessel, the equipment including the
the effect of stopping the formation of microtu- balloon catheter will not produce any of the blood
bules in the smooth muscle cells of vessel walls. It clots in the lesion of the proximal blood vessel.
can also stop some growth factors that contribute Heparin should be given in adequate quantities.
to the movement of smooth muscle cells to the
intima layer. Palitaxel contains lipophilic that 3. The length of the balloon should be as short as
prevents the substance from getting into the blood possible to cover the lesions. The length should not
vessel wall. Therefore, a mixture of hydrophilic be longer than the balloon because that can cause
substances, such as iopromide or urea, is needed to unnecessary damage to the normal blood vessel
make the coating stay longer and more effectively wall which can happen by chance during dissection.
on the blood vessel walls. In comparing the use However, if the balloon chosen is too short, especially
of normal type balloon to cure stenosis of the in the stenosis lesions, the balloon may be affected
femoropopliteal arteries, the study found that a by sliding skids. In the case of leg artery lesions,
drug-eluting balloon helps to reduce the chance of however, involving both the femoral artery and the
re-stenosis in both the short and long term when infrapopliteal artery, the femoral artery will
follow-up occurs over the period of 5 years.5 normally be treated first followed by the artery
below knee level.
Principle and basic technique of balloon angioplasty
(Techniques in detail will be presented in Part 2) 4. In choosing the diameter of the balloon, the size of
diameter should be larger than the diameter of the
1. Balloon angioplasty is prohibited or should be used blood vessel by about 10-15% measuring the blood
with caution in the following cases: vessel from the vascular imaging using the available
1.1. The stenosis of the arteries is attached to the tools in the new DSA or by using the sizing catheter.
aneurysm due to the risk of rupture of the vessels. The balloon with a small diameter will be applied
1.2. Atherosclerotic plaque that is too big or is first to give way to the larger diameter balloon
polypoid and located too far from the blood catheter or stents catheter to go through the stenosis.
vessel wall has a significant chance of breaking The techniques of balloon angioplasty are more
and blocking the distal embolization. varied at the present time.
1.3. The stenosis of the arteries that happens all
over the body or the stenosis that is very long. 5. The pressure used in an inflator balloon angioplasty
1.4. Blood vessels that are extended by balloon of arteries is normally around 5-10atm and around
several times or has just extended recently. If 8-24atm in case of veins or artificial veins due to
possible, allow 3 months for the healing of the high chance of recoil (refer above on how to
pathology before the next angioplasty. choose the appropriate balloon for each procedure).
1.5. Blood vessels that have been used to radiate If the balloon used is too big or if there is too much
arteries or veins of the patients who have had pressure inside the balloon, it may cause a rupture
radiation around the iliac area or blood vessel of the arteries. Should a balloon break, this can
that is badly infected in itself or its surrounding sometimes cause the tearing of blood vessels
organs (similar to the case of a patient whose (although the tearing can also happen before the
aorta was infected or in cases of an abdominal balloon breaks).6
aortic of a patient with pancreatitis.)

Tanisaro K
References
1. Dotter CT, Judkins MP, Transluminal treatment of 5. Tepe G, Zeller T, Albrecht T, et al. Local delivery of
artheroscletic obstruction. Circulation 1964;30:654. paclitaxel to inhibit ve stenosis during angioplasty of the
2. Castaneda WR, Amplatz K, Laerum F. Mechanics of leg. N Eng J Meg 2008;358:689.
angioplasty: an experimental approach. Radiographics 6. Zollikofer CL, Salomonowitz E, Castaneda-Zuniga WR,
1981;1(3):1-14. et al. The relation between arterial and balloon rupture in
3. Losordo DW, Rosenfield K, Pieczeck A, How does experimental angioplasty. Am J Roentgenol 1985;144:777.
Angioplasty work? Serial Analysis at human iliac arteries
using intravascular ultrasound. Circulation 1992; 77:1845.
4. Banergee S. Plenary session XXl. Late-breaking clinical
trials and first report investigation lll. Presented at:
Transcatheter Cardiovascular Therapeutics Scientific
Symposium: Nov 7-11, 2011:San Fancisco, USA.

Medical Images
Demonstration of Ingested Fish Bone Embedding at Upper

Esophagus by CT 3D Reconstruction
Piyanuch Pattamakajonpong, MD1, Ruthairat Suphareokthaweechai, MD1, Asadawut Wongwarntana, RT2
1
Ear Nose Throat Center, Bangkok Hospital Hua Hin, Bangkok Hospital Group, Prachuap Khiri Khan, Thailand.
2
Imaging Center, Bangkok Hospital Hua Hin, Bangkok Hospital Group, Prachuap Khiri Khan, Thailand.
Keywords: ingested fish bone, esophagus, CT 3D reconstruction
Received: November 11, 2015, Revision received: November 16, 2015, Accepted after revision: December 1, 2015.
Bangkok Med J 2016;11:79-80.
1A 1B 1C
2A 2B 2C
C
ase 1: A 28-year-old male presenting with odynophagia and dysphagia after swallowing a fish bone. A suspected
opaque elongation of fish bone was seen at the upper esophagus level C5-6 (Fig 1A). CT 3D reconstruction
at upper esophagus revealed a thin elongated opaque foreign body embedding into the upper esophagus
(Fig 1B, 1C). The dislodged fish bone was discovered during the endoscopic examination. The patient recovered after
conservative treatment.
Case 2: 17-year-old female presented with dysphagia after ingesting a fish bone. The plain film lateral neck and
CT 3D reconstruction demonstrated an opaque fish bone embedding at the upper esophagus (Fig. 2A, 2B). Endoscopic
retrieval of the fish bone is shown in Figure 2C. The patient made a full recovery afterwards.

Pattamakajonpong P
An ingested foreign body can penetrate into the esophagus. The most commonly occurring foreign bodies are fish
bones, followed by chicken bones.1 The history of fish bone ingestion with dysphagia symptoms was studied. The most
common cause of dysphagia that physicians need to definitively rule out is usually a fish bone embedded in the
esophagus. In some cases, the foreign body may dislodge before or during the endoscopic procedure (see Case 1).
But sometimes the fish bone remains as an obstruction (see Case 2). This condition may develop into life-threatening
complications if the diagnosis is missed or delayed. In cases of suspected fish bone embedded at the upper esophagus, a
plain film of the neck region may not be adequate or if examined by a less experienced radiologist as the lesion may be
overlooked. Barium swallowing study including barium coating thin cotton also seems to be ineffective in detecting an
ingested fish bone. A neck CT and 3D reconstruction of the upper esophagus is a straightforward and reliable method to
detect foreign bodies.
References
1. DCosta H, Bailey F, McGavigan B, et al. Perforation of the esophagus and aorta after eating fish: An unusual cause of chest
pain. Emerg Med J 2003;20:385-6.

Medical Images
Valentines Day
Chomsuda Mongkolpanya, RT1
1
Imaging Center, Bangkok Hospital Hua Hin, Bangkok Hospital Group, Prachuap Khiri Khan, Thailand.
Keywords: valentines day, enlarged prostate gland
Received: January 18, 2016, Revision received: January 18, 2016, Accepted after revision: January 19, 2016.
Bangkok Med J 2016;11:81.
A
66 year old male presenting with acute urinary retention and hematuria. Pelvic ultrasonic scan reveals
markedly enlarged prostate gland mainly medial lobe projecting through the bladder neck simulating the image as
Heart Configuration.

Speacial Feature
AA Amyloidosis in Systemic Lupus Erythematosus

Case Presentation Interhospital Renal Clinicopathological Conference (1/2016)
Vijitr Boonpucknavig, MD1, Suchin Worawichwong, MD2, Sudumpa Jarukitsopa, MD3, Wiroon Sangsiraprapha, MD4
1
N Health Pathology, Bangkok Hospital Group, Bangkok, Thailand.
2
Department of Pathology, Ramathibodi Hospital, Bangkok, Thailand.
3
Division of Rheumatology, Bumrungrad International Hospital, Bangkok, Thailand.
4
Division of Nephrology, Bumrungrad International Hospital, Bangkok, Thailand.
Keywords: AA Amyloidosis in systemic lupus erythematosus
Received: January 30, 2016, Revision received: January 30, 2016, Accepted after revision: February 2, 2016.
Bangkok Med J 2016;11:82-84.
Abstract
We report on a 62-year-old female with a 10-year history of hypertension and of systemic lupus erythematosus with Sjogrens
syndrome for 5 years. Her current visit showed worsening anemia with severe proteinuria and deterioration of renal function.
Renal biopsy showed deposition of amyloid A as demonstrated by immunohistochemical staining with amyloid A specific
antibody and electron microscopy. Immunofluorescence microscopy revealed deposition of C3, leading to the diagnosis of
AA amyloidosis secondary to SLE. The patient received colchicine for one month and she did not follow-up.
A
62-year-old Ethiopian woman with a 10 year leukocytes. Some nonatrophic tubules show tubulitis with
history of hypertension and cirrhosis of unknown amorphous material in the lumens.
cause. Sjogrens syndrome and systemic lupus
erythematosus (discoid lupus, autoimmune hemolytic Immunofluorescence microscopy (IF) findings (Figure
anemia, positive ANA/SSA/antiribosome P/R052) had 3): six (6) glomeruli are present in each frozen section.
been diagnosed in 2010. She has been on prednisone Two (2) glomeruli are globally sclerosed. Four (4) glom-
10mg per day, hydroxychloroquine 200 mg per day, eruli show nodular deposition of C3 in some mesangial
candesartan 4 mg per day and Ferli-6, 1 tab three areas. There is no deposition of IgG, IgM, IgA, Ciq, fibrin,
times daily. She denied new rashes, joint stiffness or kappa L. C or lambda L. C.
fever. She had a dry mouth. At her visit she was found to
have more severe anemia and and increase of proteinuria. Immunohistochemical (IHC) staining (Figure 4, 5) for
There was no family history of rheumatoid arthritis, SLE amyloid A revealed irregular distribution of amyloid A in
or other autoimmune disease. mesangial areas, along the tubular basement membrane, in
arteriolar walls and interstitial tissue.
Physical examination (PE) revealed a normotensive,
overweight woman with 1+ ankle edema. Laboratory Ultrastructural findings (Figure 6): The kidney tissue
investigation revealed hemoglobin 7.7 mg/dl, normal com- was obtained from the paraffin block and reprocessing for
plement level, negative coombs test, albumin 2.0 mg/dl, transmission electron microscope (TEM) study. Randomly
normal TSH, negative hepatitis virus A and C, proteinuria arranged non-branching fibrils (8 - 12nm), compatible
(1.6 gm/day), creatinine 1.9 mg/dl. The CRP level was with amyloid fibrils are seen in the arteriolar wall and
5.03 mg/dl. Chest radiograph was normal. interstitium, corresponding with the amorphous material
under light microscope. The diagnosis of AA amyloidosis
Bone marrow biopsy revealed normocellular marrow with renal involvement secondary to SLE was established.
without excess blasts or dysplastic change. A renal biopsy The patient received colchicine for 1 month then she no
was performed. longer came in for follow-up visits.
Light microscopy findings (Figure 1, 2): The biopsy is Discussion

a sample of two cores of renal cortex and medulla with 12
glomeruli per section level. All glomeruli reveal variable AA amyloidosis is known to be secondary to chronic
stages of accumulation of eosinophilic extracellular deli- infectious diseases including tuberculosis, bronchiectasis,
cately fibrillar material in the mesangium, arteriolar walls chronic osteomyelitis, and chronic inflammatory diseases
and interstitial tissue. There is extensive tubular atrophy such as Crohns disease, rheumatoid arthritis, ankylosing
with segmentally dense interstitial inflammatory infiltrates spondilitis and has been reported in familial Mediterra-
consisting of lymphocytes, plasma cells, and mononuclear nean fever.1 A small number of cases of AA amyloidosis

AA Amyloidosis in Systemic Lupus Erythematosus
Figure 1: Glomerular deposition of eosinophilic fibrillar Figure 2: Glomerular deposition of eosinophilic fibrillar
material (H&Ex200). material in glomerular structure and periglomerular fibrotic
tissue (H&Ex200).
Figure 3: Deposition of C3 in glomerulus (IFx200). Figure 4: Deposition of amyloid A in glomerulus (IHCx200).
Figure 5: Deposition of amyloid A in peritubular and inter- Figure 6: Electron microcopy demonstrating deposition of
stitium (IHCx200). non-branching 8-12 nm typical of amyloid fibrils in arterio-
lar wall (TEMx40,000).

Boonpucknavig V, et al.
associated with systemic lupus erythematosus (SLE) are The diagnosis of amyloidosis requires a histologic
reported in the literature. Some previous reports state demonstration of amyloid deposits. This is accomplished
that the link between AA amyloidosis and SLE might be by staining with Congo red dye and the presence of
explained by the presence of additional conditions known characteristic fibrils identified by electron microscopy
to cause amyloidosis. The type of amyloid protein involved examination. Types of amyloid are indistinguishable by
has not been clearly established in most of the reported light or electron microscopy. The definitive method used
cases. is immunofluorescence or immunohistochemical staining
of tissue with antibodies that are directed against known
The kidney is the most common site of amyloid fibril amyloidogenic proteins.
deposition with progressive deterioration in renal function.2
Deposition of amyloid fibrils in other organs in patients Renal pathology in previous reported cases revealed
with SLE such as heart,3 gastrointestinal tract,4 and skin5 light microscopy change, compatible only with amyloidosis
have been reported. without immune deposition by immunofluorescence
microscopy. Our case showed also glomerular deposition
Our patient developed two diseases of the immune of C3 in high intensity together with amyloid fibrils with
system, SLE and Sjogren syndrome at the same time. no deposits of gamma globulins. The prognostic factor
An extensive evaluation of clinical history and labora- affecting progression to deterioration of renal function is
tory tests did not reveal any of those abovementioned the concentration of the amyloidogenic precursor SAA.7
causes for the development of secondary amyloidosis.
Both diseases were clinically inactive, yet the C-reactive The amyloidogenic precursor SAA was not tested in
protein was high. Amyloidosis usually develops in patients our case. The relationship between amyloid fibrils and
with long-standing SLE as in our case. Occasionally, two immunoglobulins or complement components is not well
diseases have been discovered at the same time.6 understood. More extensive investigation into these
kinetic alterations of immune complexes and AA protein
is required.
References
1. Gertz MA, Kyle RA. Secondary systemic amyloidosis: 5. Ridley MG, Maddison P J, Tribe CR. Amyloidosis and
response and survival in 64 patients. Medicine (Baltimore) systemic lupus erythematosus. Ann Rheum Dis 1984;43:
1991;70:246-56. 649-50.
2. Dember LM. Amyloidosis-associated kidney disease. J Am 6. Singh NP, Prakash A, Sridhara G, et al. Renal and systemic
Soc Nephrol 2006;17:3458-71. amyloidosis in systemic lupus erythematosus. Ren Fail
3. Yilmaz BA, Dusgun N, Mete T, et al. AA amyloidosis 2003;25:671-5.
associated with systemic lupus erythematosus: impact on 7. Lachmann HJ, Goodman HJB, Gilbertson JA, et al. Natural
clinical course and outcome. Rheumatol Int 2008;28:367-70. history and outcome in systemic AA amyloidosis. N Engl
4. Betsuyaku T, Adachi T, Haneda H, et al. A secondary J Med 2007;356:2361-71.
amyloidosis associated with systemic lypus erythrmatous.
Intern Med 1993; 32:391-4.

Special Feature
Live-Attenuated Tetravalent Dengue Vaccine Development

at Mahidol University
Sutee Yoksan, MD, PhD1
1
Center for Vaccine Development, Institute of Molecular Biosciences, Mahidol University, Salaya Campus, Nakhonpathom, Thailand.
Keywords: dengue, vaccine, live attenuation
Bangkok Med J 2016;11:85.

D
engue virus (DENV) is a mosquito- borne flavivirus endemic to tropical and
subtropical regions of the world. Four antigenically related serotypes of DENV
circulate in nature. While 2/3 of these infections are unapparent and non-symptom-
atic, clinical manifestations range from a self-limited febrile illness to a potentially fatal
disease characterized by hemorrhage and/or shock.
As the immune response elicited by natural DENV infection confers life-long protection
against re-infection by viruses of the same serotype, vaccination and immunologic protec-
tion against DENV should be feasible. The development of a DENV vaccine is complicated
by a requirement to protect simultaneously against the four serotypes of DENV and the
potential for a suboptimal vaccine-induced immune response to exacerbate disease.
Yoksan S, MD, PhD
The development of live attenuated tetravalent DENV vaccine has been actively pursued at Mahidol University
since 1980 using a classical method of attenuation pioneered by Louis Pasteur, the serial passaging of a virulent
organism in a non-natural host. The process selects for mutations that differ between viruses by selection mechanisms
that are not well understood. Every method of producing a viral vaccine candidate results in a biological agent that
must be thoroughly characterized and finally tested in human volunteers. Wild type DENV used for attenuation attempts
at Mahidol had been derived from a population of viruses recovered from infected individuals which composed of
viruses circulated as quasispecies populations of genetically different virions. The discovery of selection pressure on
wild type DENV afforded by Primary Dog Kidney (PDK) cells was made. In this effort all 4 DENV replicated in PDK.
Each of these viruses was tested individually at different passage levels for biological markers. Successful individual
candidate vaccines were identified for all DENV1-4. When combined, the mixture of those viruses resulted in balance of
immune responses among all the 4 serotypes in primates.
Extensive viral biomarker and clinical trial experience at Mahidol University revealed two conclusions concerning
the use of PDK cells to select attenuated DENV vaccines: 1) serial passage in PDK cell uniformly selected for attenu-
ation of all four DENV for human beings and 2) attenuation biomarkers appeared during each set of serial passages at
approximately the same PDK passage level. This latter observation suggested that PDK passage subjected each of the
four DENV with reproducible selective pressure.
As high potential vaccine candidates, such a live attenuated tetravalent DENV vaccine was licensed to vaccine
biopharmaceutical industry for production scale up. After decades of working with live attenuated dengue vaccines,
several objectives could be achieved. The safe and well tolerated vaccines could be identified. Strong and long lasting
immune responses could be obtained as a result of using suitable virions similar to natural viruses which still
could elicit strong stimulation to both the humoral and cell mediated immunities. The prospects for these DENV
vaccine innovations are very promising.

Professor Natth Bhamarapravati. The worlds first immunization of a tetravalent
dengue vaccine in children, 1992
In Memoriam -Professor Natth Bhamarapravati (1928-2004)

reliable dengue vaccines approach to protect children
against wild type dengue viruses circulating in nature.
The university has successfully licensed dengue vaccine
candidates to several vaccine manufactures including
Pasteur Merieux serum et vaccin (now Sanofi Pasteur),
Kaketsuken of Japan and Serum Institute of India. At
present the University is now aiming to establish dengue
vaccine production capability in Thailand.
The field of dengue vaccine development is entering

a new era. The application of molecular techniques to an
analysis of disease-casing organisms coupled with a better
understanding of the immune system are resulting in the
development of a range of molecular dengue vaccines.
The major goal of the article written by Prof. Usa This-
sayakorn demonstrates the results of the phase III efficacy
D
engue vaccine research and development in trials of the dengue vaccine produced by Sanofi Pasteur
Thailand was pioneered at the Center for Vaccine as conducted in both Asia and Latin America. The overall
Development of Mahidol University by the late efficacy against all four dengue viruses was reported to
Professor Natth Bhamarapravati in 1980. Thanks to his be around 60%. It could lower the severity of the disease
vision, Mahidol University has been recognised as one and revealed significant reduction in hospitalization.
of the World Leaders in the development of a vaccine for However, the vaccine is not recommended to be used in
dengue. For the past two decades the work by Professor children younger than nine years old. The idea at present
Sutee Yoksan has built on Professor Bhamarapravatis might be that the live attenuated dengue vaccines initiated
legacy and his successful interventions and breakthroughs. by Professor Natth might be an answer in the immunization
Attenuation attempts developed by scientists at Mahidol of children from 1-8 years of age.
University have been generally accepted to be the best

Book Review
Handbook of Targeted Cancer Therapy

Wolters Kluwer
Editors: Daniel D. Karp, MD

Professor of Medicine, Department of Investigational Cancer Therapeutics,
Medical Director, Clinic and Translational Research Center,
University of Texas MD Anderson Cancer Center Houston, Texas.
Gerald Falchook, MD, MS
Director, Drug Development Program Sarah Cannon Research Institute at
Health ONE Presbyterian/St. Lukes Medical Center Danver, Calorado.
ISBN: 978-1-4511-9326-8
Review by: Potjana Jitawatanarat, MD

Medical Oncology Department, Wattanosoth Hospital, Bangkok Hospital Group, Bangkok, Thailand.
O
ncologic treatment has seen drastic changes in recent years, from single modality to multimodalities treatment
including surgery, radiation and chemotherapy. Targeted therapy has been added to the oncologic treatment
arsenal and has become increasingly popular in the field of oncology. This handbook provides excellent
summaries of targeted therapy drugs, including clinical practice and ongoing developments in clinical trials. This
handbook covers the fundamental basics of targeted therapy in oncology as seen in the section on carcinogenesis, from
the perspective of targeted therapy, molecular targets and pathways, to the clinical implications of targeted organ therapy.
More than 140 targeted drugs are described among them drugs that are FDA approved in current clinical practice and
drugs in ongoing phase 1-3 clinical trials. In addition, the mechanism of action (MOA), dosing schedule and common side
effects are described. The handbook includes high quality illustrations with easy to understand diagrams outlining the
molecular target pathway. This is an essential handbook for academic and community oncologists, laboratory scientists,
pharmacists, oncology nurses, residents, fellows and others working in the oncology field. The handbook can be used as
an authoritative text in daily practice or as a quick reference guide. This handbook is an excellent enterprise. It is a work
of meticulous dedication, with full credit due to Professor Daniel D. Karp, Dr.Gerald Falchook and all the contributors
to this exceptional resource.

Co., Ltd., Thailands largest
www.bangkokmedjournal.com.
Fold along the dash and seal it (do not use clips) post back via post mail without fees
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Editor in Chief: Chirotchana Suchato, MD

Executive Consultation Editors

Staff - Production and Circulation

The Bangkok Medical Journal is published biannually (February and September)

The Bangkok Medical Journal Vol. 11; February 2016 A

INSTRUCTIONS for AUTHORS

The following types of material may be considered for * Title

B The Bangkok Medical Journal Vol. 11; February 2016

* Conclusion MANUSCRIPT SUBMISSION

The Bangkok Medical Journal Vol. 11; February 2016 C

General Submission and Peer Review

THE BANGKOK MEDICAL JOURNAL

D The Bangkok Medical Journal Vol. 11; February 2016

The Bangkok Medical Journal Vol. 11; February 2016 E

E The Bangkok Medical Journals Editor

6 Innovative Intracapsular Tonsillectomy: How we do it.

24 Effect of Participation in Type 2 Diabetes Mellitus (T2DM) Education Pathway on HbA1c

28 MRI Findings in Transient Global Amnesia

39 Liver Abscess caused by Klebsiella pneumoniae: A Case Report

42 EUS-Guided Rendezvous Pancreatic Duct Stenting in Symptomatic Chronic Pancreatitis Patient

F The Bangkok Medical Journal Vol. 11; February 2016

52 Outpatient Total Joint Arthroplasty-Can It Be Done Safely?: A Review

79 Demonstration of Ingested Fish Bone Embedding at Upper Esophagus by CT 3D Reconstruction

82 AA Amyloidosis in Systemic Lupus Erythematosus: Case Presentation Interhospital Renal Clinicopathological

85 Live-Attenuated Tetravalent Dengue Vaccine Development at Mahidol University

86 In Memoriam - Professor Natth Bhamarapravati (1928-2004)

87 Handbook of Targeted Cancer Therapy

The Bangkok Medical Journal Vol. 11; February 2016 G

Diagnosing Obstructive Sleep Apnea by Performing

Obstructive sleep apnea (OSA) is described as the repeated

The Bangkok Medical Journal Vol. 11; February 2016 1

Pre-procedure assessment Post-FOB and PEEP titration of mask CPAP

FOB and PEEP titration of mask CPAP

The FOB allowed direct visualization of the oropah-

2 The Bangkok Medical Journal Vol. 11; February 2016

The Bangkok Medical Journal Vol. 11; February 2016 3

Results is 2 months, and in Australia between 3 and 16 months.

4 The Bangkok Medical Journal Vol. 11; February 2016

The Bangkok Medical Journal Vol. 11; February 2016 5

Innovative Intracapsular Tonsillectomy: How we do it.

Keywords: innovation intracapsular tonsillectomy, CO2 laser intracapsular tonsil-

6 The Bangkok Medical Journal Vol. 11; February 2016

Recently, this new intracapsular tonsillectomy has Discussion

The Bangkok Medical Journal Vol. 11; February 2016 7

8 The Bangkok Medical Journal Vol. 11; February 2016

Figure 5 Figure 6 Figure 7

The Bangkok Medical Journal Vol. 11; February 2016 9

The new technique is developed to use the rotating

10 The Bangkok Medical Journal Vol. 11; February 2016

Evaluation of Liver and Kidney Toxicity in Rats Receiving

Keywords: proteoglycans, toxicity, liver, kidney, fish cartilage, burn wounds

The Bangkok Medical Journal Vol. 11; February 2016 11

12 The Bangkok Medical Journal Vol. 11; February 2016

Evaluation of renal function tests: The renal func- Results

Control (Cream base) *

The Bangkok Medical Journal Vol. 11; February 2016 13

The level of alanine transaminase enzyme: On day Discussion

14 The Bangkok Medical Journal Vol. 11; February 2016

Control (Cream base) ** **

Control (Cream base) **

Table 5: The level of creatinine on day 7, 14, 21 and 28 post-burn.

The Bangkok Medical Journal Vol. 11; February 2016 15

Control (Cream base)