Vol 1, Issue 1

i

Aims and Scope

El Mednifico Journal is an open access, quarterly, peer-reviewed journal from Pakistan that aims to publish scientifically sound research across all fields of biology and medicine. It is the first journal from Pakistan that publishes researches as soon as they are ready, without waiting to be assigned to an issue. The journal serves as a healthy platform for students and undergraduates, whose articles are considered on the basis of content and not on the basis of topic or scope. However, strict quality measures ensure a high standard.

The journal has certain unique characteristics:

• EMJ is one of the first journals from Pakistan that publishes articles in provisional versions as soon as they are ready, without waiting for an issue to come out. These articles are then proofread, copyedited and arranged into four issues per volume and one volume per year

• EMJ is one of the few journals where students and undergraduates form an integral part of the editorial team

• EMJ is one of the few journals that provides incentives to students and undergraduates

The rationale behind starting a journal offering incentives to students is three fold:

• To inculcate a sense of research in biomedical students by promoting healthy writing practices • To provide a platform where students can publish their research (after thorough peer review)

without the fear of getting rejected on the basis of topic or focus of the article • To ensure global outreach for articles published in the journal

EMJ is published once every 3 months by Mednifico Publishers. Editorial correspondence should be addressed to: The Editor-in-Chief, El Mednifico Journal, C2 Block R, North Nazimabad, Karachi, Sindh - 74700 - Pakistan. Tel: (92-334-2090696); Email: [email protected]; Website: http://mednifico.com Articles should be sent to: Submissions EMJ, C2 Block R, North Nazimabad, Karachi, Sindh - 74700 - Pakistan. Email: [email protected] Want to partner with EMJ? Send your proposal to: [email protected] We’re hiring! Send your CVs to: [email protected]

Volume 1, Issue 1 April - June, 2013

ii

Editorial BoardSenior Editor-in-Chief

Prof. Nazeer Khan

Executive Editors Syed Salman Ahmed,

Sajid Ali

Editor-in-Chief

Asfandyar SheikhManaging Editor

Syed Arsalan Ali

Dr. Mansoor Husain,

Dr. Muzaffar H Qazilbash, Dr. Tasneem Z Naqvi, Prof. Haruhiro Inoue,

Dr. Athanassios Kyrgidis, Dr. Asim A Shah,

Dr. Kothandam Sivakumar, Dr. Samina Abidi,

Dr. Rashid Mazhar,

Senior Editors Dr. Gautam Sikka,

Dr. Mosaddiq Iqbal, Prof. Javed Akram,

Prof. Abdul Bari Khan, Prof. Ashraf Ganatra, Dr. Raza Ur Rehman,

Dr. Waris Qidwai, Dr. Muhammad Ishaq Ghori,

Dr. Akber Agha,

Dr. Adnan Mustafa Zubairi,

Dr. Saqib Ansari, Dr. Mohsina Ibrahim,

Dr. Qamaruddin Nizami, Dr. Samra Bashir,

Dr. Nabeel Manzar, Dr. Asfandyar Khan Niazi, Muhammad Ashar Malik

Section Editors Ali Sajjad,

Hafiz Muhammad Aslam, Syed Askari Hasan,

Muhammad Uzair Rauf, Kainat Sheikh,

Syed Mumtaz Ali Naqvi

Editors Dr. Hussain Muhammad

Abdullah, Muhammad Danish Saleem,

Smith Giri, Iqra Ansari

Assistant Editors Uzair Ahmed Siddiqui,

Maheen Anwer, Anum Saleem, Imran Jawaid,

Hina Azhar Usmani, Izzah Vasim, Shayan Ali,

Shoaib Bhatti

Statistics Editors Mehwish Hussain,

Syed Ali Adnan

Marketing Editors Raza Mehmood Hussain,

Gulrayz Ahmed

Copyeditors Adnan Saleem, Maria Rahim

Layout Editor Shahzad Anwar

Proofreading Editors Bushra Iqbal

iv

Table of Contents FrontPage i Editorial Board ii Call for Papers iii Table of Contents iv

Editorial El Mednifico Journal: Objectively galvanizing research culture in students Asfandyar Sheikh, Syed Salman Ahmed, Sajid Ali

1

Original Articles

Effects of sleep behaviors on the academic performance of undergraduate medical and engineering students in Karachi Afshan Iqbal, Shafaq Tariq Minhas, Syeda Anam Azhar

2

Profiling of alopecia, its associated factors and reasons for seeking hair transplant Hannan Ayub, Subul Rashid, Hamza Ashraf, Muhammad Zohaib Zafar Khan

7

Short Report

Pattern and management of trauma: Pilot Survey at two tertiary care hospitals of Karachi Anam Hareem, Laraib Usman, Shahzad Anwar, Muhammad Danish Saleem, Shaikh Hamiz ul Fawwad

12

Review

Monoclonal antibodies: Revolutionary pharmaceuticals in modern therapeutics Saher Binte Haider, Ramsha Afaque, Sadia Ali Vohra, Nida Naim, Shahwar Shahid, Syed Umair Bin Akhtar, Ubaid Rais

15

Essays Clouds with silver lining: Defining conditions that serve as blessings in disguise Syed Muhammad Saad Anwer, Muhammad Haris Ansari

19

v

Multidimensional effects of glucagon-like peptide-1 Abdul Haseeb

20

Person in focus: Is your local barber shop as safe as you think? Muhammad Danish Saleem

21

Letters to Editor

Schmidt's Syndrome – Case report and review of literature Hira Ahmad, Sidra Mumtaz Shaikh, Zahabia Hakimi

22

Klippel-Trenaunay Syndrome or Proteus Syndrome? A case presenting a diagnostic dilemma Shahzad Saleem

24

Appendices

Instructions to Authors vi Best of Blogemia ix

Sheikh A, Ahmed SS, Ali S 1

http://www.mednifico.com/index.php/elmedj/article/view/4

Open Access Editorial El Mednifico Journal: Objectively galvanizing research culture in students Asfandyar Sheikh1, Syed Salman Ahmed1, Sajid Ali1

Editorial Research is, in principle, a refined aspect of human nature to be inquisitive. It is a continuum that lies between the confines of comprehension and curiosity. However, this “instinct” is often found to be lacking in majority of students from Pakistan, who consider research to be an insignificant formality and place it lower down in the list of priorities. This mentality sprouts from the fact that most students harbor the traditional point of view of research being a “game played by professionals.” This, coupled with the lack of research infrastructure and a paucity of available journals that offer incentives to students, implies that the brains of Pakistani students are never challenged enough, and majority of them are deprived of opportunities to learn and apply the scientific method. The situation in Pakistan is a direct contrast of that in other coun-tries such as Germany, where medical students have been reported to be involved in 28% of the publications of one institution [1].

The importance of students in the future of research in South Asia was highlighted by Aslam and colleagues [2]. Mushtaq et al. have reported a favorable trend in the number of publications originat-ing from Pakistani universities during the period 2007-2010 [3]. However, Pakistan still contributes to less than 0.04% of research publications (biomedical and non-biomedical) [4]. This is quite alarming, especially from a country having the likes of Ali Moeen Nawazish, Arfa Karim and Shadab Rasool Abro in its arsenal. The lack in interest can, therefore, not be wholly or partially attributed to scarcity of talent and/or ability. The problem lies elsewhere.

Under these circumstances, El Mednifico Journal seems to be no less than a blessing. The rationale behind starting a journal dedi-cated to students is three fold:

• To inculcate a sense of research in biomedical students by promoting healthy writing practices.

• To provide a platform where students can publish their re-search (after thorough peer review) without the fear of getting rejected on the basis of topic or focus of the article.

• To ensure global outreach for articles published in the journal.

1Dow Medical College, Dow University of Health Sciences, Baba-e-Urdu Road, Karachi, Pakistan Correspondence: Asfandyar Sheikh Email: [email protected]

The journal has certain unique characteristics:

• EMJ is one of the first journals from Pakistan that publishes articles as soon as they are ready, without waiting for an issue to come out.

• EMJ is one of the very few Open Journal Systems (OJS) based journals from Pakistan.

• EMJ is one of the few journals where students and undergrad-uates form an integral part of the editorial team.

• EMJ is one of the few journals that provide incentives to stu-dents and undergraduates. A section named “essays” has been especially added to the journal, and is reserved only for stu-dents.

The Governing Body has opted for the open access model which makes articles available to all without any fees. The authors retain the copyright under Creative Commons License. OJS has been adopted to provide backend platform. A competitive editorial team has been setup in order to ensure all the objectives of the journal are met without compromising quality.

Competing interests: The authors are editors at El Mednifico Journal. Received: 22 December 2012 Accepted: 22 December 2012 Published: 22 December 2012

References 1. Cursiefen C, Altunbas A: Contribution of medical student research to the

MedlineTM‐indexed publications of a German medical faculty. Medical education 1998, 32(4):439-440.

2. Aslam F, Shakir M, Qayyum MA: Why Medical Students Are Crucial to the Future of Research in South Asia. PLoS Med 2005, 2(11):e322.

3. Mushtaq A, Abid M, Qureshi MA: Assessment of research output at higher level of education in Pakistan. JPMA The Journal of the Pakistan Medical Association 2012, 62(6):628-632.

4. Mufti SA: Capacity-Building in Bio-Medical Research in Pakistan. In: Capacity Building for Science and Technology. edn. Edited by Khan HA, Qurashi MM, Hussain T, Hayee I, Siddiqui ZH. Islamabad: M/S Kamran Printers; 2003: 57-63.

2 Effects of sleep behaviors on the academic performance…

Vol 1, No 1

Open Access Original Article Effects of sleep behaviors on the academic performance of undergraduate medical and engineering students in Karachi Afshan Iqbal1, Shafaq Tariq Minhas1, Syeda Anam Azhar1

Introduction Sleep behavior is a term that describes the qualitative and quanti-tative aspects of sleep and their associated repercussions in indi-viduals. It is common knowledge that undergraduate programs, especially of Medicine and Engineering, demand long and tedious hours of and study and practical work by students. This often leads to students developing poor sleeping habits in attempts to give the academics their due time and effort. During exams and tests, in particular, many students pull all-nighters to undergo last minute revisions and often survive on very few hours of sleep per day, particularly on the night before the exam. For students in profes-sional colleges, passing exams with good grades becomes the foremost priority. However, such students are generally unaware of the potential benefits of proper sleeping habits during exams.

Among studies carried out worldwide on the association between sleep and academic performances, we would like to especially mention two studies that have been conducted on medical stu-dents [1, 2]. The first study, titled, ‘Daytime sleepiness and academ-ic performance in medical students’ sought to correlate sleepiness measured using the Epworth sleepiness scale with grades obtained in exams at the end of that school period [1]. The study demon-strated a negative correlation between academic performance and excessive daytime somnolence, but did not relate academic per-formance to other aspects of sleep behavior such as quality of sleep, and sleep timings [1]. The other study, titled ‘The sleep hab-its, personality and academic performance of medical students’ demonstrated a significant association between sleep timings and quality, and academic performance [2].

1Dow Medical College, Dow University of Health Sciences Correspondence: Afshan Iqbal Email: [email protected]

The significance of our study lies in the fact that only a single re-search paper elucidating the correlation between sleep with aca-demic performance in undergraduate students could be retrieved from a Pakistani medical journal [3]. Hence, it seems that there is a dearth of information regarding this issue, specifically in the con-text of Pakistani institutions.

The objective of this study was to analyze the interplay between sleep behavior and academic performance in undergraduate stu-dents of selected institutions in Karachi, in order to ascertain the specific sleeping habits that are associated with varying degrees of academic performance, and thus aid undergraduate students in planning their daily schedules in a manner that will accommodate a healthy sleeping routine, and will at the same time ensure highflying grades in their exams.

Methods A cross sectional survey was conducted on MBBS students at Dow Medical College and Mechanical Engineering students at NED Uni-versity of Engineering and Technology. The sample sizes for both institutions, calculated at a confidence level of 95%, and a confi-dence interval of 6% are as follows:

DMC: population enrolled in one batch = 308 (approx.); sample size = 144 per batch (x5), i.e. 720

NED: population enrolled in one batch = 187 (approx.); sample size = 110 per batch (x4), i.e. 440

Questionnaires were randomly distributed to students in their classes, and were collected after being filled. No specific list was used to select the respondents. Hence, the sampling remained purposive (convenient) by handing out questionnaires to every second student entering the lecture hall. A consent form was at-

Abstract Background: Undergraduate programs, especially of Medicine and Engineering, demand long and tedious hours of and study and practical work by students. This often leads to students developing poor sleeping habits in attempts to give the academics their due time and effort. Therefore, the objective of this study was to elucidate the different aspects of sleep behaviors and their effects on academic performance of medical and engineering undergraduate students from selected colleges in Karachi. Methods: This was a cross sectional survey conducted on medical students at Dow Medical College and Mechanical Engineering students at NED University of Science and Technology. Questionnaires with an attached consent form were randomly distributed among the candidates. Sleep behavior was assessed using the Basic Nordic Sleep Questionnaire, while academic performance was assessed by the subjects’ self-reported GPA/percentage of the last university exam, or by a personal assessment rated on a 7 point scale ranging from very poor to excellent. A personalized sleep report was emailed to each eligible participant. Results: A total of 1160 forms were distributed, of which 930 valid forms were received, giving a response rate of 80.2%. Data was analyzed using the SPSS v15.0 software. Students of both institutions reported similar and overall poor sleep patterns. Three significant aspects of sleep, i.e. quality of sleep, excessive sleepiness during the daytime and the duration of sleep at night were cross-tabulated with the academic performance of the subjects. Each of the above mentioned factors were statistically evaluated in relation to academic performance, and only the last two garnered a significant status (p<0.05). Conclusion: Our study failed to find any significant association between quality of sleep and academic performance. However, the latter’s association with excessive daytime sleepiness and duration of sleep at night was statistically significant. (El Med J 1:1; 2013) Keywords: Sleep, Academics, Medical Students, Engineering Students, Karachi

Iqbal A, Minhas ST, Azhar SA 3


tached to each questionnaire, requiring written consent from the participants. The form also presented an introduction to the study, assured participants of the confidentiality of the information they provided, and offered students the incentives of: (1) being entitled to a free entry in a lucky draw to win a Rs.1,000 voucher to pur-chase a book(s) of their choice from a bookstore, and (2) being sent a personalized report on their sleep behavior, and expert ad-vice on how to improve it in order to boost academic performance, for free via email. This served to motivate students to participate in the research, and ensured that those who chose not to participate were not skewed toward a particular category.

The personalized sleep reports were adapted from the ‘Sleep disor-ders screening survey’, and were approved by a Psychiatrist [4]. Expert advice for improving sleep was adapted from an article on the ‘Healthy Sleep’ Web Site, a production of WGBH Educational Foundation and the Harvard Medical School Division of Sleep Med-icine [5].

Sleep behavior was assessed for its qualitative and quantitative aspects at 2 independent time periods: during regular college days, and during exams/pre-exam preparatory leave. The Basic Nordic Sleep Questionnaire was used for this purpose [6]. A number of sleep evaluation scales and questionnaires have been developed, each evaluating particular aspects of sleep, such as sleepiness, sleep disorders, quality and timings of sleep, during a fixed period [7]. The Basic Nordic Sleep Questionnaire was specifically chosen because it is a comprehensive questionnaire that analyzes both quantitative and qualitative aspects of sleep behavior, and also has the added advantage of having a suitable number of questions (21), so students could willingly afford the time to fill in the ques-tionnaire. Academic performance was assessed through self-reported GPA/percentage of the last semester/annual exam under-taken, and the subjects’ personal assessment of their academic stature on a 7-point scale.

The names and roll numbers of the subjects were not taken to ensure confidentiality. The research was not confined to a particular gender, year or age group. Inclusion criterion was, therefore, any undergraduate student of the selected programs at the institutions in question. Students who did not appear in the last semes-ter/annual examination regardless of the reason were, however, excluded from the research. Forms, in which the respondents did not report their GPA and did not respond to the question on aca-demic stature based on personal assessment, were not considered for data analysis. Furthermore, forms in which responses to the sleep behavior section of the questionnaire were incomprehensible were also not considered. Data was entered on SPSS version 15, and analyzed under the supervision of a statistician.

The study has been registered at the Research Department of Dow University of Health Sciences, (registration number SR 71) and approved by Institutional Review Board. Official permission for reproducing the Basic Nordic Sleep Questionnaire for data collec-tion was acquired from the Wiley-Blackwell international publishers.

Results Table 1 presents the number of questionnaire forms that were distributed to each class, the number of valid filled forms that were received, and the response rates for each class.

Table 1: Sample sizes and response rates No. of

forms distributed

No. of valid forms

received

Response rate (%)

Mean GPA / percentage

DMC 1st Year 144 124 86.1 2.93 2nd Year 144 131 91.0 3.30 3rd Year 144 138 95.8 3.57 4th Year 144 105 72.9 3.18 5th Year 144 110 76.4 3.09 Total 720 608 84.4 3.23

NED 1st Year 110 97 88.2 Good* 2nd Year 110 87 79.1 76.55 3rd Year 110 82 74.5 77.00 4th Year 110 56 50.9 80.83 Total 440 322 73.2 77.60#

*1st year NED students had not appeared in any annual exam, so the mode response of their academic performance based on personal assessment has been given. 1st year DMC students, had however ap-peared in their first semester exams because DMC follows a ‘semester system’, with each year comprising of two semesters. #2nd, 3rd and 4th years

It should be noted that the questionnaires were distributed once to students of every class of DMC and NED, containing questions regarding sleep behavior during normal college days and during exams/pre exam preparatory leave. At the end, students were re-quired to answer a self-assessment of their academic performance and give their latest GPA.

The actual response rate was slightly higher, as 33 forms that had been improperly filled were disregarded from data analysis. Thus, 963 students participated in the study, of which the responses of 930 were considered valid for data analysis. Of all the (valid) re-spondents, 61.6% were females, 35.3% were males, and 3.1% did not state their gender.

Table 2 presents the mode responses of the questions in the ques-tionnaire. As can be seen from the table, the mode responses to most questions were the same in both institutions. Notable excep-tions are as follows. Most DMC students reported that during regu-lar college days, they felt excessively sleepy in the morning right after awakening and/or during daytime, never, or less than once per month. On the contrary, most NED students reported feeling excessively sleepy after awakening on 1-2 days per week. The same response was observed, daily or almost daily during daytime. Fur-thermore, while most DMC students reported taking sleep naps daily or almost daily, most NED students take a nap never or less than once per month.

The mean time respondents stay awake in bed before going to sleep was nearly the same in both institutions: a cumulative aver-age of 22.1 minutes during regular college days, and 5.5 minutes


Vol 1, No 1

Table 2: Responses DMC NED Both Institutions

Awake in bed before falling asleep 2A 21.77 ± 27.23 minutes* 22.71 ± 32.74 minutes* 22.09 ± 29.23 minutes* 2B 6.77 ± 18.66 minutes* 3.74 ± 2.25 minutes* 5.49 ± 15.27 minutes*

Awakened at night 3A Never or less than once per month (339)

Never or less than once per month (149)


3B Never or less than once per month (264)



Awakened too early in the morning without being able to fall asleep again

5A Never or less than once per month (386)






Quality of sleep 6A Well (384) Well (179) Well (563) 6B Never or less than once

per month (223) Never or less than once

per month (113) Never or less than

once per month (336) Excessively sleepy in the morning after awakening

8A Never or less than once per month (139)

Daily or almost daily (93)

1-2 days per week (203)




Excessively sleep during daytime 9A Never or less than once per month (156)

1-2 days per week (76) Never or less than once per month (226)




No. of hours of sleep per night 12A 6.54 ± 1.51 hours* 6.49 ± 1.82 hours* 6.52 ± 1.62 hours* 12B 5.86 ± 4.47 hours* 5.56 ± 2.08 hours* 5.76 ± 3.83 hours*

Snoring during sleep 16A Never or less than once per month (559)






Nocturnal sleep apnea 18A Never or less than once per month (584)






*Mean Value • A represents sleep behavior during regular college days • B represents sleep behavior during exams/ pre exam preparatory leave • Brackets indicate the no. of respondents who gave the particular response or the standard deviation of the response (where indicated)

during exams/pre-exam preparatory leave. The sleeping and awak-ening times at night also did not present an appreciable difference between the two institutions. It is, however, noteworthy that most students in both institutions sleep at or after midnight, and gener-ally wake up early in the morning.

The mean sleep nap duration was 1.83 hours during regular college days, and slightly less during exams/pre-exam preparatory leave (1.46). Most respondents did not report problems with their sleep. Of those that did, the problems were generally related to bad dreams, difficulty in falling asleep and interrupted sleep. The vast majority of students did not report using sleeping pills. 26 students reported using them during regular college days and 43 during exam/pre-exam preparatory leave indicating the increased preva-lence of sleep problems during that time.

Possible associations between academic performance and three aspects of sleep behavior during exams/ pre exam preparatory leave were analyzed:

1. Quality of sleep,

2. Excessive sleepiness during daytime, 3. Duration of sleep per night.

Students were required to report personal assessment on a 7-point scale ranging from very poor to excellent. A response of satisfacto-ry/average or better was considered to be academic performance equal to or above class average. 1st year NED students had not appeared in any annual exam, so their personal assessment was taken as an indicator of their academic performance. NED students of the other years are officially issued percentages by their institu-tion. For such students, the percentages were converted to GPAs using a standard conversion chart such as the one used for stu-dents of DMC. For DMC students, mean class GPAs, as enlisted in Table 1, were considered.

The results are displayed in Figure 1. The first bar displays the per-centage of students who slept well and scored equal to or above their class average (64.58%), and the second bar represents the percentage that did not sleep well and scored equal to or above their class average (64.05%). The 3rd bar displays the number of

Iqbal A, Minhas ST, Azhar SA 5


Figure 1: Sleep behavior and academic performance

students who, never or less than once per month, felt excessively sleepy, and scored equal to or above class average (67.77%). The following bar represents the no. of students who sometimes felt excessively sleepy during daytime, but still scored equal to or above class average (62.7%). Similarly, the 5th and 6th bars represent students who sleep more and less than the mean no. of hours at night, respectively and scored equal to or above class average (67.64 and 60.73, respectively).

These three aspects of sleep were then cross-tabulated with aca-demic performance. Chi square test was applied in order to eluci-date the association with the latter. The results failed to show any significant relation between quality of sleep and academic perfor-mance (p>0.05). However, interestingly, both daytime sleepiness and duration of sleep at night showed statistically significant asso-ciation with academic performance (p<0.05 for both).

Discussion Sleep is a naturally recurring state characterized by reduced or lacking consciousness, relatively suspended sensory activity, and inactivity of nearly all voluntary muscles. Sleep behavior is a term that describes the qualitative and quantitative aspects of sleep and their associated repercussions in individuals.

In this modern era where workload and stress are increasing day by day, it is quite common to find university students trying to juggle their academic studies within a 24 hour timeline. It is, therefore conventional for students to stay up late during normal days as well as during exam days to cover up their coursework. This in turn can have implications on their quality of sleep, daytime sleepiness and other aspects of sleep behavior. As the results show, most of the responses received were the same for students in both institu-tions, implying a striking similarity in their sleep behaviors. Most students from both institutions indicated that their quality of sleep was well, without being awakened at night never or less than once per month. This indicates that even though students are getting less hours of sleep, the quality of sleep is strong enough to help

get them through the day. As is well known, most medical and engineering students tend to have a busy schedule the entire day. However, they are able to rest peacefully at night. The quality of sleep far outweighs the quantity.

Furthermore, students from both institutions presented with rough-ly the same hours of sleep every night; having slept at midnight and awakened during weekdays at 6-7 AM, giving a 6-7 hour sleep. Research presents with an average of 7-9 hours of sleep sufficient to help the individual get through with the next day [8].

However, some sleep behaviors were found to be distinct among students of the 2 institutions. Firstly, DMC students reported a greater frequency of sleep naps. Because students from both insti-tutions reported nearly the same duration of sleep at night, this may be an indication that medical students are exposed to more tedious hours of study and workload, as they have to divide their college timings in lectures, laboratory work and rigorous clinical postings. Therefore, DMC students required afternoon naps more often to regain their energy so as to continue their studies and daily activities in the evening.

Secondly, there was a minority of students that reported problems with their sleep, such as bad dreams, difficulty in falling asleep and interrupted sleep. It is unclear whether the prevalence of these problems is the same as in the general student population in the country, since studies concerning this notion could not be re-trieved. Nevertheless, sleep problems in the minority of students can be attributed to anxiety associated with increasing workload and/or attaining and maintaining their required grades. This expla-nation may be further corroborated by the finding of increased use of sleeping pills during preparatory leave or exams during which stress levels escalate [9].

At DMC, it was found that 3rd year students reported the highest mean GPA compared to those of other batches. Similarly, it is also appreciated that in NED, 4th year students had a higher mean per-centage than those of 2nd and 3rd years. (Note: 1st year students had not appeared in an annual exam so a mean percentage could not be calculated).

Worldwide studies have been carried out on the association of sleep and academic performance, 2 of which were conducted on undergraduate medical students [1, 2]. The first research entitled “Daytime sleepiness and academic performance in medical stu-dents” correlated sleepiness measured using the Epworth sleepi-ness scale with grades obtained in exams at the end of the school period [1]. This study showed a negative correlation between aca-demic performance and excessive daytime somnolence, hence proving that the academic performance of those students did get affected by excessive daytime somnolence (somnolence is defined as the inability to maintain an adequate level of wakefulness, or as an excessive degree of daytime sleepiness) [1].

The second study, entitled “The sleep habits, personality and aca-demic performance of medical students” demonstrated a signifi-cant association between sleep timings and quality, and academic performance [2]. It illustrated that those students who rose early

56

58

60

62

64

66

68

70

Quality of

Sleep

Excessive

sleepiness

during

daytime

Duration of

sleep

during

night

Percentage of students

who score equal to or

above class average

while exhibiting the

particular sleep

behavior during regular

college days

Percentage of students

who score equal to or

above class average

while NOT exhibiting

the particular sleep

behavior during regular

college days


Vol 1, No 1

and went to bed early were able to achieve far better than those students who slept and rose quite late [2]. In addition, this study also found that the academic performance was not related to the long-term differences in the quality of sleep; a finding that also runs parallel with our findings [2].

Conclusion Although an analysis of the quality of sleep of students belonging to two different institutions revealed no significant association with their academic performance, we did manage to find the latter’s association with excessive daytime sleepiness and duration of night sleep. Hence, the popular belief that students follow a healthy sleeping pattern in order to achieve better grades could not be proven entirely. Nevertheless, the study still concludes that the students of the two institutions do have unhealthy sleeping pat-terns that may more significantly affect other aspects of their lives besides academic achievements.

Limitations The questionnaires required subjects to answer questions pertain-ing to their sleep behavior during regular college days, and during exams/pre-exam preparatory leave. Since the study was dependent on the respondents’ ability to recall, it may have been a target of recall bias. Subjects may have been unable to exactly recall the amount or quality of sleep they have and may have given an esti-mate that may range from slightly inaccurate to misleading. Fur-thermore, subjects may have been unwilling to provide accurate information on certain personal questions, such as the problems they have with their sleep, and the factors that influenced their GPAs/percentages, even if they were assured of the confidentiality of the information they provide. Moreover, in order to judge aca-demic performance, the subjects’ self-reported GPA had to be re-lied upon, as it was not feasible to send such a large number of forms to the Examination Department to verify. Moreover, self-reported performance was used for first year NED students, which

may have affected the results. Sample size may not have been a limitation because of a considerably large sample size (was taken (1160), corresponding to a confidence limit of 95%, and a confi-dence interval of 6. However, purposive sampling may limit the generalizability of our study results. Acknowledgements: We are grateful to Dr. Raza-ur-Rehman, Assistant Professor, Department of Psychiatry, Civil Hospital, Karachi, for supervising the study. Further, we are grateful to Dr. Imran Chaudhry, University of Manchester, U.K, for assisting us with the design of the study and for proofreading the project’s proposal. Jaweria Nawed, Mechanical Engineering student, NED, assisted us in data collection at NED. Competing interests: The authors declare that no competing interests exist. Received: 12 February 2013 Accepted: 26 March 2013 Published Online: 31 March 2013

References 1. Rodrigues RND, Viegas CA, Abreu e Silva AA, Tavares P: Daytime sleepiness

and academic performance in medical students. Arquivos de neuropsiquiatria 2002, 60(1):6-11.

2. Johns M, Dudley H, Masterton J: The sleep habits, personality and academic performance of medical students. Medical Education 1976, 10(3):158-162.

3. Khan UA, Pasha SN, Khokhar SK, Rizvi AA: Sleep habits and their consequences: a survey. Rawal Med J 2004, 29(1):3-7.

4. Sleep Disorders Screening Survey | Healthy Sleep [http://healthysleep.med.harvard.edu/healthy/getting/treatment/sleep-disorders-screening-survey]

5. Twelve Simple Tips to Improve Your Sleep | Healthy Sleep [http://healthysleep.med.harvard.edu/healthy/getting/overcoming/tips]

6. Partinen M, Gislason T: Basic Nordic Sleep Questionnaire (BNSQ): a quantitated measure of subjective sleep complaints. Journal of sleep research 2009, 4(s1):150-155.

7. Lomeli HA, Perez-Olmos I, Talero-Gutierrez C, Moreno CB, Gonzalez-Reyes R, Palacios L, de la Pena F, Munoz-Delgado J: Sleep evaluation scales and questionaries: a review. Actas Esp Psiquiatr 2008, 36(1):50-59.

8. How Much Sleep Do We Really Need? [http://www.sleepfoundation.org/article/how-sleep-works/how-much-sleep-do-we-really-need]

9. Sleep Disorders [http://www.healthieryou.com/sleep.html]

Ayub H, Rashid S, Ashraf H et al. 7


Open Access Original Article Profiling of alopecia, its associated factors and reasons for seeking hair transplant Hannan Ayub1, Subul Rashid1, Hamza Ashraf1, Muhammad Zohaib Zafar Khan1

Introduction Alopecia is the medical term for loss of hair on any part of the body [1]. However, the term generally refers to hair loss occurring on the scalp, which is a fairly common complaint in dermatological clinics [2]. It can affect both sexes at any age. Although it is generally more common in adult males, it tends to produce graver psycho-logical effects in women, due to the behavioral, social and cultural factors associated with it [3].

Under normal circumstances, hair growth involves three stages, namely anagen (growing phase), catagen (transitional phase) and telogen(resting phase) [4]. The pathophysiology of alopecia usually involves early entry of hair into the last phase, a phenomenon known as telogen effluvium [5]. The etiologic profile of alopecia is extensive, ranging from hormonal influences (androgenic alopecia) to psychiatric disorders such as trichotillomania (excessive pulling of hair). However, environmental factors may also play an im-portant role [6].

Anything that interrupts normal hair cycle can trigger diffuse hair loss. Finding the cause of the hair loss requires thorough patient history and complete physical examination. However, in cases where clinical evaluation fails to identify a definite cause, histologi-cal procedures (e.g. scalp biopsy) tend to assist in reaching a diag-nosis. Early identification of the cause is essential for appropriate and timely treatment. Treatment options may involve medical or surgical intervention. A fairly novel procedure, known as follicular unit transplantation (FUT), is rapidly gaining popularity among the masses [7]. Also known as hair transplant in layman terms, FUT involves moving individual hair follicles from the donor to the

1Jinnah Medical and Dental College, Karachi Correspondence: Muhammad Zohaib Zafar Khan Email: [email protected]

recipient site [7]. However, the costs and adverse effects (such as further thinning of hair) associated with FUT limit their wide scale applicability.

Triggers for alopecia may include a wide of variety of physiologic and emotional stresses, nutritional deficiencies and endocrine im-balance [8]. Physiological stresses include, but are not limited to fever, excessive hemorrhage and childbirth (telogen gravidarum) [9, 10]. The relationship between psychological factors and hair loss can be compared to a vicious cycle, whereby one may in turn lead to another. However, a true association between the two has yet to be established and remains largely controversial [10].

Nutritional deficiencies, such as those associated with chronic star-vation or malabsorption syndromes, have been well known as triggers for diffuse hair loss [11]. Deficiencies of iron and zinc are especially important, as these minerals play an important role in normal hair growth [12]. Similarly, drugs such as oral contraceptive pills and antidepressants are also linked with significant hair loss. The use of chemotherapeutic agents almost invariably leads to diffuse hair loss due to arrest of the anagen phase [13].

Endocrinologic abnormalities also tend to serve as triggers for alopecia. For example, both hypothyroidism and hyperthyroidism may cause diffuse hair loss [10]. Similarly, high serum testosterone levels may also lead to hair loss, a notion that carries special signifi-cance for patients with polycystic ovarian syndrome [14]. Hair loss is also an important feature of patients with diabetes mellitus [15]. Hormonal imbalance and poor circulation are major reasons for this effect [15].

Many studies on alopecia have been conducted throughout the world. For example, a study conducted on African American wom-en reported the incidence rate of extensive hair loss at 5.6%, with

Abstract Background: Alopecia is the medical term that refers to the loss of hair. It comes in a variety of patterns and has a number of causes. A host of factors has been found to be associated with its occurrence. For severe cases, hair transplantation may consequently be required. Our main objectives in this study were to perform profiling of alopecia, to determine the role of nutritional deficiency, stress and endocrine imbalance in alopecic population of Pakistan and to elucidate the reasons for seeking hair transplant. Methods: This was a cross sectional, interview-based survey carried out at five dermatological clinics and hair transplantation centers located in Clifton Area and dermatological clinics of Liaquat National, Jinnah Postgraduate Medical Center and Civil Hospital, Karachi from April – May 2012. Non-random convenience sampling was employed. Around 400 individuals of both sexes with Alopecia were approached, of which 330 consented (response rate = 82.5%). Domains included BMI, stress (using a questionnaire), endocrine abnormality and grade of alopecia (via Hamilton’s/Ludwig’s Scales & trichometric index). Results: Patients’ mean age was 39 ± 14 years. Grade 3 was the most common grade of alopecia, seen in 114 (34.5%) patients. The most repeated trichometric indices were 95% & 85%. Further interview revealed that many of the hair loss patients were overweight (37.6%), moderately prone to stress (79.4%) and had endocrine imbalance (30%). 21.5% patients wanted physical improvement through transplantation. Conclusion: Our study results indicate that stress may be a major player in triggering alopecia, and although we were unable to prove a role for nutritional deficiencies and endocrine dysfunctions, these factors have been reported to play an important role in previous studies. However, large studies involving a greater sample/geographical size are needed in order to further elucidate their effects on alopecia in this particular population. (El Med J 1:1; 2013) Keywords: Alopecia, Hair Loss, Stress, Endocrine, Hair Transplant

8 Profiling of alopecia, its associated factors and reasons…

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tinea capitis being the main risk factor [16]. Similarly, another study conducted on pediatric patients in Kuwait reported alopecia areata to affect 6.7% of the study subjects. However, data concerning alopecia in Pakistani populations is scarce. Furthermore, none of the previous studies aims to elaborate the link with different risk factors using a cross sectional approach. Keeping the above in mind, we designed this study with three main objectives, i.e. to perform profiling of alopecia, to determine the role of nutritional deficiency, stress and endocrine imbalance in alopecic population of Pakistan and to elucidate the reasons for seeking hair transplant.

Methods This was a cross sectional survey conducted at five private derma-tological clinics and hair transplantation centers located in Clifton Area from April – May, 2012. Due to paucity of available patients, we decided to extend our study to the dermatological clinics of Liaquat National Hospital (LNH), Jinnah Postgraduate Medical Cen-ter (JPMC) and Civil Hospital Karachi (CHK).

Study participants and protocol We tried to interview all patients whose chief complaint included hair loss. Hence, the sampling method remained non-random con-venient throughout the study. The names and presenting com-plaints were extracted from the main information counters in pri-vate dermatological clinics. In case of hospitals, the same infor-mation was acquired from the residents or attendings. The patients were then approached and their height/weight measured, followed by an interview-based evaluation of other variables. All of this was performed after seeking informed, written consent. For those who declined, no further questions were asked. The data was collected by group members, who had received special training sessions under the guidance of a professional dermatologist.

Inclusion and Exclusion Criteria The study included all the patients above the age of 18 who had experienced hair loss (ranging from minimal hair loss to alopecia totalis) in the past year. They were recruited from both the inpa-tient and outpatient departments of the hospitals. However, pa-tients whose chief presenting complaint did not include hair loss were excluded from the study. Similarly, patients who did not have documented hair loss history (as per patient records) were also excluded, as were those who declined to respond.

Ethical Review The Institutional Review Board of Jinnah Medical and Dental Col-lege approved the study. Confidentiality and anonymity of the data was maintained at all times, and names or any other variables that could risk identification were removed before analysis.

Study Questionnaire Variables included in the study were nutritional status (determined by Body Mass Index), stress, endocrine abnormality, and grading of alopecia. The questionnaire was divided into 5 sections. The first section of the questionnaire was concerned with the demographics of the patients, and also included space for noting down the pa-tient’s BMI. The second section contained a specialized ISMA stress questionnaire [17]. It contains a set of questions that judge the propensity of respondents to stress. A score of <4 indicates that the patient is least prone to stress, a score of 5-14 indicates that the

patient is modestly prone to stress, whereas a score >14 indicates that the patient is the most prone to stress. The third section in-cluded a checklist consisting of a list of endocrine disorders, an-swered using a yes/no approach. The fourth section included tools for analysis of hair loss. Hamilton-Norwood scale, which grades the severity of hair loss on a range of 1-7, was used for males [18]. A modified form of Ludwig’s scale was used for females (Ludwig’s scale originally has a scale from 1-3; however a modified form having a scale of 1-7 was used to ensure an even comparison) [18]. A trichometric index was also included. Trichometer is a new device for measuring hair quantity, hair loss and hair growth. Trichometric index (TI) = mm2 hair / cm2 of scalp multiplied by 100. Lower the TI, higher the severity and lesser is the eligibility for hair transplant. The last section inquired reasons for seeking or refusing hair trans-plant.

Analysis Data from the questionnaire was entered in SPSS (Statistical Pack-age for the Social Sciences) version 17 for analysis and the results were compared. P values were calculated to determine the signifi-cance of association between variables. A P value of less than 0.05 was considered to be significant.

Results The response rate was modest: 330 out of an original 400 consent-ed to the survey, giving a response rate of 82.5%. The mean age of the subjects was 39 ± 14 years, with a range of 62 years (16 – 78 years). The most frequent ages were 22 (5.5%), 24 (5%), 26 (4.5%) and 33 (4.5%) years. 198 (60%) patients were male while 132 (40%) patients were female.

Out of the total of 330 patients, 114 (34.5%) patients showed alo-pecia of Grade 3, of which 53.5% patients were male. 80 (24.2%) and 69 (20.9%) patients presented with Grade 2 and Grade 4 re-spectively. In Grade 4, 5, & 6, males were leading in numbers with a large margin (56 out of 69, 16 out of 20 and 11 out of 13 patients respectively).

Figure 1: Grading of hair loss using Hamilton’s/Ludwig’s Scale

In males, trichometric indices i.e. 85%, 80% and 95% were seen with 18.8%, 16.7% and 11.8% respectively. Similarly in females, 95% and 85% were the most common. Figures 1 and 2 provide this information in a graphical format.

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Figure 2: Distribution of Trichometric indices among males Figure 3: Distribution of Trichometric indices among females

50.9% of patients had a BMI within normal ranges, whereas 37.6% of patients (78 out of 198 males; 46 out of 132 female) were over-weight. It was seen that 79.4% (160 out of 198 male; 103 out of 132 females) of the patients were moderately prone to stress. 14.2% of the patients were the most prone to stress out of which 25 were males and 22 were females. Patients that are least prone to stress were only 6.1% of the total patients. Table 1 gives a summary.

Endocrine Imbalance was found in 30% (48 males; 51 females) of the subjects. Diabetes mellitus was found in 14.8% of the total, thyroid disorder in 12.1%, bone related disorders in 7.9%, adrenal problems in 2.7%, sexual dysfunction in 6.4% and pituitary compli-cations in 0.6% of the patients. 57.9% (124 males; 67 females) of the patients had one or more person in the family suffering from alopecia. 2.4% of the patients already had undergone hair trans-plantation. 148 (44.8%) expressed affirmation for hair transplant. Out of these, 21.5% wanted physical improvement, 9.7% said yes due to personal reasons, 7.3% due to social acceptance and 6.3% had job issues. The reasons for saying no to transplant given by the remaining 174 patients were as follows: don’t need (24.8% of the total), expensive (11.2%), and useless (10%) and dangerous (6.7%).

Using Kruskal-Wallis Test, we were only able to find a statistically significant association for stress (p=0.012). P values for BMI and endocrine dysfunction were not within the significant range.

Discussion In the words of the Larry David, "Anyone can be confident with a full head of hair, but a confident bald man - there's your diamond in the rough." Hair loss is considered to be a serious issue as it is indicative of many underlying problems. However, it is simply ne-glected in our society due to lack of proper education regarding hair loss and its management. Alopecia is a complex disease with many unknown aspects, and many studies have been conducted to unravel its mysteries.

In our study on 330 subjects, it was evident that more males rather than females suffered from alopecia, a finding that is consistent with previous studies, such as the one by Alzolibani et al [19]. Our survey revealed that most of the men and women suffer from Grade 3 alopecia according to the Hamillton’s/Ludwig’s scale; therefore most of the individuals had trichometric indices of 95% and 85%. Moreover, male percentage having Grade 4 alopecia with a trichometric index of 80% is much higher than the females. How-ever, a very low percentage of patients suffering from Grade 6, Grade 7 and Grade 8 were seen at the transplant clinics due to ineligibility to undergo a hair transplant. Here it should be noted that patients having a trichometric index below 70% are not eligi-ble for this procedure.

With the help of our interview based questionnaire we tried to

Table 1: Frequency distribution of Hamilton’s/Ludwig’s grading according to risk factors Body Mass Index Stress Score Endocrine Imbalance

<20 20-25 25-30 >30 <4 5-13 >14 Yes No Total Grade 1 2 23 5 1 1 26 4 4 27 31 Grade 2 8 42 28 2 10 63 7 21 59 80 Grade 3 12 54 43 5 6 86 22 42 72 114 Grade 4 4 38 27 0 2 58 9 20 49 69 Grade 5 3 9 7 1 1 17 2 6 14 20 Grade 6 0 2 11 0 0 12 1 4 9 13 Grade 7 0 0 3 0 0 1 2 2 1 3 Total 29 168 124 9 20 263 47 99 231 330

0

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40

60

100% 95

%

85%

80%

75%

40%

25%

N/A

Perc

enta

ge

Trichometric Index

100%

95%

85%

80%

75%

40%

25%

N/A

10 Profiling of alopecia, its associated factors and reasons…

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analyze various factors that contribute to alopecia. The most im-portant outcome of our study was the association of stress with alopecia. It was concluded that 263 subjects were more prone to stress, 47 were most prone to stress and only 20 were least prone. Previous studies have proven that episodes of alopecia have oc-curred after severely stressful life [20-23]. According to our study, 24-35 years and 42-52 years of age group were more prone to stress. These should not be ignored as these time periods may occupy special positions in an individual’s life.

However, we were unable to prove association of alopecia with endocrine dysfunctions. Only 99 of the included patients had en-docrine abnormalities, out of which 51 were females and 48 males. Many previously conducted studies have proven associations be-tween these two variables. Sehgal VN and Chu SY reported that hair loss accompanies several endocrine disorders [24, 25].

We were also unable to prove the association of alopecia with nutritional deficiencies. We believe the usage of BMI as a marker to be a culprit. Previous studies have however shown strong associa-tion between nutritional deficiencies and hair loss. For example, B12 deficiency has been known to lead to alopecia [26]. Similarly, alopecia has also been found to have a strong relation with defi-ciency of minerals such as zinc, iron, selenium and copper [27].

Many authors have published their works citing a variety of pater-nal and maternal hereditary factors to predispose to hair loss [28, 29]. Our study also hinted that patients with family history of alo-pecia are more prone to develop alopecia. Many of our patients had more than 2 people suffering from alopecia in their families. It is evident from our results that patients with a strong family history start to manifest symptoms of alopecia at an early age (22 years - 26 years).

With the rising incidence of alopecia, the alopecic population is keen to seek a cure for this problem. During our interviews at the dermatological clinics, we observed that a large percentage of alopecic population was still opting for conventional methods for this problem (such as use of different medicines), and hair trans-plants still remained an uncommon cure for many. According to our collected data, the most common age group seeking hair transplant was patients of 22-35 years of age. The most popular reasons were for physical improvement and for personal reasons. It is only natural for young age groups to seek transplant due to social and psychological factors.

Conclusion Our study results indicate that stress may be a major player in trig-gering alopecia, and although we were unable to prove a role for nutritional deficiencies and endocrine dysfunctions, these factors have been reported to play an important role in previous studies. However, large studies involving a greater sample/geographical size are needed in order to further elucidate their effects on alope-cia in this particular population.

Limitations As is the case with all researches, we acknowledge that there were certain limitations to our study, the foremost of them being lack of

data at the hair transplant clinics due which we had to extend our survey to the dermatological clinics of JPMC, LNH and CHK. Our study failed to differentiate between type I or type II diabetes melli-tus, hypo or hyperthyroidism and different sex disorders. Most of the variables were self-reported, and we were unable to confirm patient-reported pathological states of endocrine dysfunction due to lack of access to facilities. However, despite all the aforemen-tioned limitations, we were successful in harvesting sufficient data proving associations between our variables.

Competing interests: The authors declare that no competing interests exist. Received: 16 February 2013 Accepted: 31 March 2013 Published Online: 1 April 2013

References 1. What is Alopecia: What Causes Alopecia?

[http://www.medicalbug.com/what-is-alopecia-what-causes-alopecia/] 2. Alfonso M, Richter-Appelt H, Tosti A, Viera MS, Garcia M: The psychosocial

impact of hair loss among men: a multinational European study. Current medical research and opinion 2005, 21(11):1829-1836.

3. Bergfeld WF, Mulinari-Brenner F: Shedding: how to manage a common cause of hair loss. Cleve Clin J Med 2001, 68(3):256-261.

4. Paus R, Cotsarelis G: The biology of hair follicles. The New England journal of medicine 1999, 341(7):491-497.

5. Harrison S, Sinclair R: Telogen effluvium. Clinical and experimental dermatology 2002, 27(5):385-389.

6. McDonagh A, Tazi‐Ahnini R: Epidemiology and genetics of alopecia areata. Clinical and experimental dermatology 2002, 27(5):405-409.

7. Rousso DE, Presti PM: Follicular unit transplantation. Facial Plastic Surgery 2008, 24(4):381-388.

8. Harrison S, Bergfeld W: Diffuse hair loss: Its triggers and management. Cleveland Clinic journal of medicine 2009, 76(6):361-367.

9. Kligman AM: Pathologic dynamics of human hair loss. I. Telogen effuvium. Archives of dermatology 1961, 83:175-198.

10. Rook AD, Dawber R: Diffuse alopecia: endocrine, metabolic and chemical influences on the follicular cycle. In: Diseases of the Hair and Scalp. 2nd edn. Edited by Rook AD, Dawber R. Oxford, UK: Blackwell Science Publications; 1982: 115-145.

11. Headington JT: Telogen effluvium. New concepts and review. Archives of dermatology 1993, 129(3):356-363.

12. Rushton D: Nutritional factors and hair loss. Clinical and experimental dermatology 2002, 27(5):396-404.

13. Sperling LC: Hair and systemic disease. Dermatologic clinics 2001, 19(4):711-726, ix.

14. Camacho-Martinez FM: Hair loss in women. In: Seminars in cutaneous medicine and surgery: 2009: Elsevier; 2009: 19-32.

15. Hirsso P, Laakso M, Matilainen V, Hiltunen L, Rajala U, Jokelainen J, Keinanen-Kiukaanniemi S: Association of insulin resistance linked diseases and hair loss in elderly men. Finnish population-based study. Central european journal of public health 2006, 14(2):78-81.

16. Olsen EA, Callender V, McMichael A, Sperling L, Anstrom KJ, Shapiro J, Roberts J, Durden F, Whiting D, Bergfeld W: Central hair loss in African American women: Incidence and potential risk factors. Journal of the American Academy of Dermatology 2011, 64(2):245-252.

17. Stress Questionnaire – International Stress Management [http:// www.isma.org.uk/pdf/Downloads/Stress-questionnaire.pdf]

18. What’s the difference between Male and Female Pattern Baldness? [http://blog.baldness.com/2012/06/whats-the-difference-between-male-and-female-pattern-baldness/]

19. Alzolibani AA: Patient satisfaction and expectations of the quality of service of University affiliated dermatology clinics. Journal of Public Health and Epidemiology 2011, 3(2):61-67.

20. García-Hernández MJ, Ruiz-Doblado S, Rodriguez-Pichardo A, Camacho F: Alopecia areata, stress and psychiatric disorders: a review. The Journal of dermatology 1999, 26(10):625.

21. Manolache L, Benea V: Stress in patients with alopecia areata and vitiligo. Journal of the European Academy of Dermatology and Venereology 2007, 21(7):921-928.



22. Van der Steen P, Boezeman J, Duller P, Happle R: Can alopecia areata be triggered by emotional stress? An uncontrolled evaluation of 178 patients with extensive hair loss. Acta dermato-venereologica 1992, 72(4):279.

23. Hadshiew IM, Foitzik K, Arck PC, Paus R: Burden of hair loss: stress and the underestimated psychosocial impact of telogen effluvium and androgenetic alopecia. Journal of investigative dermatology 2004, 123(3):455-457.

24. Sehgal VN, Jain S: Alopecia areata: clinical perspective and an insight into pathogenesis. J Dermatol 2003, 30(4):271-289.

25. Chu SY, Chen YJ, Tseng WC, Lin MW, Chen TJ, Hwang CY, Chen CC, Lee DD, Chang YT, Wang WJ et al: Comorbidity profiles among patients with alopecia areata: the importance of onset age, a nationwide population-based study. J Am Acad Dermatol 2011, 65(5):949-956.

26. Piccardi N, Manissier P: Nutrition and nutritional supplementation: Impact on skin health and beauty. Dermato-endocrinology 2009, 1(5):271-274.

27. Finner AM: Nutrition and hair: deficiencies and supplements. Dermatologic clinics 2013, 31(1):167-172.

28. Lee WS, Oh Y, Ji JH, Park JK, Kim do W, Sim WY, Kim HO, Hwang SW, Yoon TY, Kye YC et al: Analysis of familial factors using the basic and specific (BASP) classification in Korean patients with androgenetic alopecia. J Am Acad Dermatol 2011, 65(1):40-47.

29. Bergfeld WF: Androgenetic alopecia: an autosomal dominant disorder. The American journal of medicine 1995, 98(1A):95S-98S.

12 Pattern and management of trauma…

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Open Access Short Report Pattern and management of trauma: Pilot Survey at two tertiary care hospitals of Karachi Anam Hareem1, Laraib Usman2, Shahzad Anwar1, Muhammad Danish Saleem1, Shaikh Hamiz ul Fawwad1

Background Trauma is one of the most commonly encountered medical emer-gencies and the second leading cause of death and disability in the age group between 15-44 years [1, 2]. In Karachi, violence contrib-utes significantly to trauma cases, but road traffic accidents (RTA) still contribute to most of the cases reported [2, 3].

Most of public sector and private tertiary care hospitals are well equipped to deal with all levels of trauma emergencies. Civil Hospi-tal Karachi (CHK), Jinnah Post Graduate Medical Centre (JPMC) and Abbasi Shaheed Hospital stand out as the three most visited public sector hospitals of the city. These hospitals lie in the midst of the city and receive trauma cases not just from within the city, but also from adjoining towns and localities [2]. They receive thousands of trauma patients annually ranging from daily routine trauma to RTA and bomb blasts [2]. Recently, however, a lot more cases of vio-lence related trauma are increasingly being reported [3].

In spite of the sheer patient influx, these tertiary care units are seldom subjected to a comparative analysis. There is limited data available on the distribution of the causes and virtually none on the management procedures [4-6]. There is no proper protocol for management designed in accordance with the local setup and situation. But knowing the pattern of trauma would help doctors, hospital management and staff to provide and lay down a protocol for better management of the patients in a cost effective way and help the government authorities in redistributing resources accord-ingly, a study elucidating the same carries immense importance [7].

1Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan 2Dow International Medical College, Dow University of Health Sciences, Karachi, Pakistan Correspondence: Anam Hareem Email: [email protected]

Hence the purpose of this study was to determine the pattern of trauma cases in patients reporting to the surgical emergency de-partment of CHK and JPMC.

Findings

Study Design, Setting and Sample This was a cross sectional analysis of total 200 patients, 100 each from surgical emergency departments of CHK and JPMC, present-ing in the month of May, 2012. Convenient sampling was employed to include all male and female patients above the ages of 12 years, presenting with trauma at the surgical emergency department, regardless of type, severity and time/day of arrival. Patients referred from other hospital/clinic after treatment/management had been started were not included. Informed consent was obtained from all the participants or their attendants before data collection.

Date Collection Tool A questionnaire was designed using the WHO guidelines. It con-sisted of four sections, each directed towards different aspects of the trauma and its initial management. First part of the question-naire covered demographics and details of the cause of trauma as per WHO guidelines. The different questions in this section were asked in the emergency department or ward, either from the pa-tient himself or anybody who brought him to the emergency. If the patient underwent emergency surgery or was admitted to the ward, he was followed up to record in case of any complication. The causes of trauma, as listed by WHO, were RTA, violent, falls, slips, suicide and others [1]. The second part of the questionnaire dealt directly with the type, site and management of trauma. It was noted by the data collectors after thorough inspection of the pa-tient. The most severe and major trauma in case of multiple was labeled as Trauma 1. The severity of the trauma was noted by an Abbreviated Injury Scale (AIS) [8]. All data recorded was recon-firmed with the doctor in charge of the patient.

Abstract Background: The aim of this study was to determine the pattern of trauma cases in patients reporting to the surgical emergency department of Civil Hospital Karachi (CHK) and Jinnah Post Graduate Medical Centre (JPMC) during the month of May 2012. Methods: This was a cross sectional analysis of a total of 200 patients, who presented with trauma and were 12 years or older. The first 100 patients were recruited from each hospital. Patients referred from other hospital/clinic after treatment/management were excluded. A questionnaire was designed using WHO guidelines. Data was collected by students and analyzed using SPSS v16.0 using simple descriptive statistics. Results: Of the 200 patients, 170(85%) were males. 92 and 97 patients were brought alive in JPMC and CHK respectively. Most common cause of trauma in both the hospitals was road traffic accident (RTA). Bikes (59.3%) were the most common cause of RTA with bikers (48.1%) most frequently injured. Only 24.5% bikers had worn helmets. Most patients suffered trauma while at work or travel and in the morning hours, usually between dawn and midday. The most common type of injury in JPMC was laceration (58%) and in CHK was blunt trauma (50%). Most common site was head/neck (35%) and leg (35%) in JPMC and CHK and the most common management was suturing (59%) and dressing (66%) respectively. Conclusion: RTA in bike riders without helmets was the most common cause of trauma in both hospitals. Lack of first-aid on site and time-delay are major contributors to poor outcomes. (El Med J 1:1; 2013) Keywords: Trauma, Karachi, Accidents, Violence, Emergency

Hareem A, Usman L, Anwar S et al. 13


Statistical Analysis Data collected was entered into EPI data software v3.1 and ana-lyzed by SPSS v16.0 to calculate frequencies and percentages for the variables. For continuous variables, standard deviation and central tendencies were calculated.

Results and Discussion Out of the 200 participants, 170 (85%) were male giving a male:female ratio of 5.66. The mean age of the study participants was 32.82 ± 16.55 years. Of the 100 patients each, 92 patients in JPMC and 97 in CHK were brought alive, while remainder had passed away en route to the hospital. None passed away in the emergency. Other relevant findings are listed in Table 1.

Table 1: Demographics* JPMC

N=100 CHK

N=100 Male 82 88 Female 18 12 Brought alive 92 97 First aid provided at site 13 22 Operated in emergency 1 14 Passed away in emergency 0 0 Admitted 13 23 *Percentages have not been quoted as all values have been calculated out of 100

History was mostly given by patients (50%) in JPMC and by attend-ants (67%) in CHK. Mean time delay was greater for JPMC (46.3 ± 99.9 minutes) than CHK (30.74 ± 65.1 minutes). Ambulance (50%) was commonly used to transport patient to JPMC and car (49%) was most frequently used in CHK.

Occupation was divided amongst students, laborers, farmers, self employed and unemployed with laborers/farmers highest in JPMC and students highest in CHK. Most common activity during trauma was travel and work. Most common location of trauma recorded was road, home and industrial. Most common time was in the morning usually dawn or midday. Distribution is shown in Table 2.

Table 2: Distribution of trauma by activity, site and intention* JPMC

N=100 CHK

N=100 Activity Travel 50 41

Work 23 31 Other 27 28

Site Road 72 53 Home 18 19

Industrial 6 19 Other 4 9

Intention Accidental 93 77 Intentional 5 19

Self-inflicted 2 4 *Percentages have not been quoted as all values have been calculated out of 100

Most common cause of trauma was road traffic accident (RTA) followed by fall/slip both in JPMC and CHK. (Refer to figure 1).

Figure 1: Causes of Trauma

The most common type of trauma in JPMC was laceration (58%) and in CHK was blunt (50%). Most common site was head/neck (35%) and leg (35%) in JPMC and CHK and most common man-agement was suturing (59%) and dressing (66%) respectively. 46 in JPMC and 41 IN CHK had a second site of trauma where leg and arm were most common sites, laceration, abrasion and fracture the common injuries and cleaning, suturing, dressing the common management. 9 patients in JPMC and 7 in CHK had a third trauma (Table 3).

Table 3: Details of Trauma 1 JPMC

N=100 CHK

N=100 Type* Blunt 8 50

Fracture 17 8 Abrasion 11 5

Contusion 2 5 Laceration 58 8

Penetrating 1 15 Incised 3 9

Site* Head and Neck 35 17 Face 8 3

Chest 5 10 Abdomen 1 16

Arm 19 16 Leg 25 35

External 7 3 Management± Cleaning 10(10.9%) 5(5.2%)

Cleaning and Dressing

5(5.4%) 66(68%)

Cleaning and Suturing

59 (64.1%) 4(4.1%)

Cast 1(1.1%) 8(8.3%) Laparotomy 16(17.4%) 13(13.4%)

Other Surgery 1(1.1%) 1(1%) *Percentages have not been quoted as all values have been calculated out of 100 ±Total has been calculated from alive patients only, which was 92 and 97 for JPMC and CHK respectively

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Bikes (59.3%) were the most common cause of RTA with bikers (48.1%) and pedestrians (27.8%) most frequently injured. Only 24.5% bikers had worn helmets. Firearms (48.4%) were the most common cause of violence related injury.

Our study pointed some very characteristic differences between the patterns of trauma accounted for at the two hospitals. CHK for instance had a greater percentage of patients who had suffered violence related intentional injuries. JPMC on the other hand re-ported a greater number of RTA. Patients reporting to CHK were mostly coming in cars, reaching faster and there were less causality en route. JPMC patients were reporting late, mostly coming in ambulances with greater en route casualty. This is majorly because, even with its densely populated and traffic infested location, CHK was closer and the obvious choice for patients with violence relat-ed injuries encountered in Lyari etc, who preferred a car over call-ing an ambulance. JPMC being more accessible from the main road falls as the obvious choice of ambulance drivers who cater to the numerous RTA observed in this part of the city.

Our results also showed that most of the trauma cases required very basic management that could have been provided in primary or secondary level trauma facilities or even on the site. This could negate the need to overcrowd the already overworked hospitals. If guidelines provided by WHO publication which gives a global overview of the system development and recommendation are met, there is a high probability that trauma victims will be treated in a very simple, basic and cost effective way [1]. Apart from the doctors, the emergency staff, paramedics and ambulance drivers should also be trained in a highly professional way. They should be well-versed in all the basic guidelines provided by WHO for the proper management of trauma victims.

Conclusion RTA in bike riders without helmets was the most common cause of trauma in both hospitals. Lack of first-aid on site and time-delay are major contributors to poor outcomes. Our study showed interest-ing differences between the patterns at the two hospitals, however further workup with detailed sample in ideal setting will give a better outcome.

Acknowledgements: The authors would like to acknowledge the help and guidance provided by Dr. Nahid Sultan and Dr. Zahid Ali Memon. Competing interests: The authors declare that no competing interests exist. Received: 6 January 2013 Accepted: 9 February 2013 Published Online: 9 February 2012

References 1. WHO. World Report On Violence and Health.

[http://www.who.int/violence_injury_prevention/violence/world_report/en/introduction.pdf]

2. Jamali AR: Trauma Care in Pakistan. J Pak Med Assoc 2008, 58(3):102-103. 3. Chotani HA, Razzak JA, Luby SP: Patterns of violence in Karachi, Pakistan.

Injury prevention: journal of the International Society for Child and Adolescent Injury Prevention 2002, 8(1):57-59.

4. Ali K, Arain GM, Masood AS, Aslam M: Pattern of injuries in trauma patients presenting in Accident and Emergency Department of Jinnah Hospital, Lahore. Ann King Edward Med Uni 2006, 12(2):267-269.

5. Sultana K, Anwer MA: Trend of Medicolegal cases and their Postmortem Examination at Accident and Emergency Department of Jinnah Postgraduate Medical Centre, Karachi. 1999, 4:143-145.

6. Ali U, Noor A, Shah MM, Alam W: Trauma management in a tertiary care hospital in Peshawar, Pakistan. Journal of Ayub Medical College, Abbottabad: JAMC 2008, 20(3):112-116.

7. Kahlon IA, Hanif A, Awais SM: Analysis of emergency care of trauma patients with references to the type of injuries, treatment and cost. Ann King Edward Med Uni 2010, 16(1):28-31.

8. TRAUMA.ORG: Abbreviated Injury Scale. [http://www.trauma.org/archive/scores/ais.html].

Haider SB, Afaque R, Vohra SA et al. 15


Open Access Review Monoclonal antibodies: Revolutionary pharmaceuticals in modern therapeutics Saher Binte Haider1, Ramsha Afaque1, Sadia Ali Vohra1, Nida Naim1, Shahwar Shahid1, Syed Umair Bin Akhtar1, Ubaid Rais1

Introduction The use of antibodies as therapeutic agents embodies them as a powerful tool in the treatment of several diseases [1]. Monoclonal antibodies (MoAbs) outline an important class of immunological drugs, the use of which has spread widely over the past decade [2]. Since the development of first MoAb by Kohler and Milstein, several advancements have been made in fields of molecular biology and biotechnology to improve the recombinant production of MoAbs on large scale [2]. The use of MoAbs has spread in the fields of oncology, immunology, hematology, cardiology, allograft rejection and infectious diseases [2, 3]. The most eminent use of these bio-logics has appeared in the field of oncology, for the treatment of various solid human tumors, where they serve to provide a more defined, targeted therapy in contrast to other cytotoxic chemother-apeutic agents and radiotherapy, which are less specific and invade normal cells along with neoplastic cells [2]. Since these drugs spe-cifically act by binding to immune system components, the number and risk of side effects with the use of MoAbs is thereby fewer than those with the conventional cytotoxic drugs. The common clinically encountered ones are immunosuppression, immunostimulation and hypersensitivity [3, 4].

To date, twenty two MoAbs are marketed in the US, while several are currently in clinical trials across the world [3, 5]. FDA has also approved radiolabeled antibodies for use in the diagnostic imaging of cancers as well as for in vivo imaging [1, 5]. Almost eight are currently being marketed in Pakistan, all of which are imported from abroad.

In this review, we focus on the mode of action followed by genera-tion and production of MoAbs. Furthermore, based on the opinions of some renowned oncologists in Pakistan, we highlight the current therapeutic applications of these agents across the country and the most frequent clinical side effects observed during therapy. Production In modern medicine, the revolutionary phase begun in 1975, with the advent of technologies to generate MoAbs for cancer chemo-

1Dow College of Pharmacy, Dow University of Health Sciences, Karachi, Pakistan Correspondence: Ubaid Rais Email: [email protected]

therapy. In the following lines, we present a step-by-step account of MoAbs production.

Immunization serves as the first step in MoAb production. The choice of host to be immunized can be determined by the source of the antigen, the myeloma line that is to be used for the fusion. When the target antigen is of human origin, both mouse and rat MoAbs have been successful [6]. Injection of an antigen X is used for the immunization of mouse to stimulate the production of antibodies against the target antigen X [7]. The number of times animal is immunized prior to the fusion will determine the class of antibody likely to be produced. For IgM MoAb, immunization should be done once or twice, but for IgG MoAb, since a secondary response is required three or more immunizations are recommend-ed [6].

Immunization is followed by cell fusion. The antibody forming cells are isolated from the mouse's spleen and then fused with the tu-mor cells grown in culture. The resulting cell is called a hybridoma [3]. A hybridoma is a biologically constructed hybrid between an antibody producing a mortal, lymphoid cell and a malignant, im-mortal myeloma cell [8].

The newly formed hybrids along with the original cell types are cultured in HAT (hypoxanthine/aminopterin/thymine) medium which only allows the hybridoma cells to grow [8].

When there is recognizable growth of hybridoma, a small aliquot of supernatant medium should be screened for secretion of the de-sired antibody by using various immunoassay procedures such as ELISA and dot blot assays [6].

To ensure that antibody produced is genuinely monoclonal, the selected cells are subcultured using special cloning procedures [8]. The newly formed MoAbs are then directed towards isotype de-termination and purification [6]. The final step is the storage. Puri-fied MoAbs can be stored in neutral isotonic buffer [6].

Mechanism of action EGF receptor (EGFR), or ErbB receptor, is a family of glycosylated transmembrane proteins which contains four receptors, the EGFR (ErbB1/EGFR/HER1), ErbB2 (HER2/neu), ErbB3 (HER3), and ErbB4 (HER4) [9, 10]. This receptor network undergoes signal transduction

Abstract Receptor tyrosine kinase inhibitors and monoclonal antibodies are popular EGF (Epidermal growth factor) receptor inhibitors, which hold evolving role in current therapeutic practice. Monoclonal antibodies, generated from a single clone of plasma cells, remain the focus of this review. Considering the fact that monoclonal antibodies based immunotherapy provides a highly efficacious and specific approach for the treatment of several diseases, we present an overview which focuses on methods and technologies used for generation of monoclonal antibodies, followed by their production on large scale. Following production methods, we highlight the basic mode of action of this inimitable class of drugs and their applications in therapeutic practice. We firmly believe that promotion of large scale production of antibody drugs, targeted at specific antigens can provide betterment in therapeutic practices across Pakistan. (El Med J 1:1; 2013) Keywords: Monoclonal Antibodies, Hybridomas, Immunotherapy, Chemotherapy, ErbB Receptor Antagonists

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Figure 1: Steps in the production of Monoclonal Antibodies

mechanism by forming heterodimers and causes multiple interac-tions among different cellular elements, which results in activation of the receptors [9, 10]. The intensity and duration of receptor signaling is tightly regulated by negative feedback mechanism, which is referred as the down regulation of EGFR. The deregulation of these signaling pathways can direct to malignant transformation [9, 11].

ErbB receptors are composed of a large extracellular binding do-main, a transmembrane domain and an intracellular juxtamem-brane domain to which protein tyrosine kinase is attached [9, 10]. Physiologically, a number of ligands can activate these receptors by forming homodimers and heterodimers but in neoplastic cells, several additional mechanisms can lead to their activation [9]. Interference of this receptor signaling by MoAbs serves as a poten-tial approach for targeting EGFR [9]. The cellular functions pro-duced by the anti-EGF MoAbs include cell cycle arrest, increased apoptosis, inhibition of angiogenesis and enhanced anti-tumor effects of chemotherapy and radiotherapy [9].

The major mechanisms by which MoAbs produce their biologic action are:

1. Recognition of specific tumor associated receptors that are only expressed by tumor cells and their inhibition results in blockade of tumor associated transduction pathways.

2. Suppression of tumor promoting molecules by administra-tion of MoAbs can interfere the binding of these molecules with to their receptors and increase their clearance.

3. Enhancing the functions of immune effector cells by specify-ing MoAbs for receptors that have enhanced or suppressed functions [12].

FDA Approved Monoclonal Antibodies Following are the FDA approved MoAbs with their year of approval [13].

Figure 2: FDA approved MoAbs for Cancer Therapy

Survey of practices across Pakistan To find out the applied use of monoclonal antibodies in Pakistan, we conducted a hospital survey where we interrogated some re-nowned oncologists at Liaquat National Hospital, Aga Khan Univer-sity Hospital and Memon Medical Institute Hospital. Regarding the use of monoclonal antibodies in their department, they were told that the drugs are being used in the treatment of lymphomas, carcinoma breast, carcinoma colon and chronic lymphocytic leu-kemia. When asked about general side effects that are observed clinically with the use of monoclonal antibodies, we were told that infusion related reactions are common especially with murine based MoAbs. Flushing, diarrhea, breathlessness and hypotension were also reported. All three oncologists agreed that the side ef-fects with the use of these agents are fewer in number, especially

Immunization

Isolation of Antibody forming cells

Cell fusion with tumor cells Hybridomas Screening of

Hybridomas

Clonal Expansion

Monoclonal Antibodies

Production of Monoclonal Antibodies

Haider SB, Afaque R, Vohra SA et al. 17


when treating lymphoma and that the production of MoAbs should be promoted across the country. The drugs are expensive; however individually, MoAbs based immunotherapy is cost-effective.

Monoclonal Antibodies Available In Pakistan

1. Rituximab (Mabthera) [2]: It is a chimeric monoclonal an-tibody targeting the CD20 antigen found on both normal B-cells and on most low grade and some higher grade B-cell lymphomas [15]. Rituximab is effective in variety of human lymphomas and chronic lymphocytic leukemia. It is effective as a sole agent in induction and maintenance therapy. It is primarily used, however, in combination with standard chemotherapies in the treatment of non-hodgkin’s B-cell lymphomas and chronic lymphocytic leu-kemia [15]. The drug has been shown to induce apoptosis, complement mediated lysis and antibody dependent cyto-toxicity [16].

2. Trastuzumab (Herceptin) [2]: It is a humanized monoclo-nal antibody that reacts with an epitope on the extracellu-lar domain of the human EGFR-2 (epidermal growth factor receptor-2). Trastuzumab is the first approved agent having activity against solid tumors [2]. It is effective as a sole agent in induction and maintenance therapy, but it is used primarily in conjunction with chemotherapy in the human epidermal growth factor receptor 2/neu- positive breast cancer [15]. Cardiomyopathy and pulmonary disorders are the most severe toxicities associated with trastuzumab [16].

3. Cetuximab (Erbitux) [2]: It is a chimeric monoclonal anti-body which shows its antitumor activity through specific targeting on EGFRs. It induces internalization and degrada-tion with down regulation of EGFR expression [2]. Cetuxi-mab is predominantly effective in combination with chem-otherapy and radiotherapy for the treatment of metastatic colorectal cancer as well as head and neck cancer [16]. It also enhances chemotherapy and radiotherapy of squa-mous cell cancers of head and neck [15, 16]. For the re-gression of metastatic colorectal cancer, cetuximab can be used in combination with irinotecan, folinic acid and 5-fluorouracil [2]. The drug can cause severe toxicities such as hypersensitivity, infusion related reactions and interstitial lung diseases including pulmonary heamorrhage [2].

4. Bevacizumab (Avastin) [2]: This humanized monoclonal antibody has been mainly used in human solid tumors be-cause it targets vascular endothelial growth factor (VEGF), which is the ligand for receptors (VEGFR-1 and VEGFR-2) on vascular endothelium [2, 15]. VEGF is the key regulator of tumor associated angiogenesis and is produced by the most types of malignant cells [2]. Bevacizumab effectively reduces blood supply to tumor nodules, thereby slowing and interrupting tumor growth [2]. Bevacizumab was ini-tially approved for the treatment of advanced colorectal cancer [15]. It is also used effectively in combinations for the treatment of advanced and metastatic non-small cell lung cancer, metastatic breast cancer and kidney cancer [15, 16]. It is also approved as second line treatment for pa-tients with recurrent glioblastoma after standard therapy

[16]. Most commonly observed side effects include hyper-tension, skin changes, abdominal pain and general weak-ness, due to widespread expression of VEGF [2].

5. Abciximab (Clotinab): Abciximab is a murine or human chimeric monoclonal antibody approved by FDA. It is indi-cated in patients with percutaneous coronary intervention, in patients with unstable angina who are unable to re-spond to conventional medical therapy and in high risk angioplasty [17, 18]. Side effects observed during therapy with abciximab include thrombocytopenia, sinus bradycar-dia, bleeding, anaphylaxis, stroke, confusion, hypotension, backache, vasculitis, hematoma, and vision problems [18].

6. Ranibizumab (Lucentis): Ranibizumab is a human anti-body fragment and it is an antagonist of vascular endothe-lial growth factor (VEGF-A) [18, 20]. It is indicated in pa-tients with age related macular degeneration and choroidal neovascular lesions [18, 19]. Adverse reactions with the use of ranibizumab mainly appear in eyes and include lacrima-tion, eye irritation, eye pain, conjunctival hyperemia, cata-ract, dry eye, visual disturbances, intraocular inflammation, intraocular pressure, vitreous floaters, vitreous detachment, intraocular inflammation, foreign body sensation in eyes, eye pruritis, ocular hyperemia, retinal disorder, maculopa-thy [18].

7. Basiliximab (Simulect): It is a chimeric murine monoclonal anti-interleukin-2 receptor (CD25) antibody. Basiliximab is used in combination with other immunosuppressant drugs in organ transplantation, prophylaxis of acute graft rejec-tion episodes, and to prevent graft rejection in acute rejec-tion in allogenic renal transplantation. Side effects ob-served with the use of basiliximab are hypertension, urinary tract infection, dizziness, headache, fatigue, nausea, fever, dyspnea, constipation, insomnia, abdominal pain, peripher-al edema, pain, dysuria, dyspepsia, weight gain, tremor, cough, rhinitis [18].

8. Daclizumab (Zenapax): Daclizumab is a humanized mon-oclonal antibody that prevents T-lymphocytes proliferation. It is an immunosuppressive agent that reduces acute rejec-tion in solid organ transplantation. It is specific for the subunit (Tac/CD25) of the interleukin IL–2 receptor on acti-vated T cells and achieves immunosuppression by competi-tive antagonism of IL-2-induced T cell proliferation [21]. Daclizumab is indicated in renal transplantation where it reduces the frequency of acute rejection in kidney-transplant recipients, in cardiac transplantation where it re-duces the frequency and severity of cardiac-allograft rejec-tion during the induction period without inducing global immunosuppression, in lung transplantation where it caus-es a significant decrease in the incidence of grade 2 or greater acute rejection after lung transplantation [22-24]. Its safety and partial efficacy is found in the treatment of pediatric onset multiple sclerosis [12]. Other indications in-clude some autoimmune diseases, ulcerative colitis, ocular inflammatory disorders and type-1 diabetes mellitus [25-28]. The severe adverse effects of Daclizumab include ana-phylactic reactions, lymph proliferative disorders while the symptomatic adverse reactions include headache, fatigue,

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tremor, hypersensitivity reactions, hypertension, GI disturb-ance, burning sensation of hands, and feet [29].

Acknowledgement: We thank Dr. Naila and Dr. Bisma; oncologists at Liaquat National Hospital, Dr. Nehal Masood; consultant oncologist and surgeon at Aga Khan University Hospital and Dr. Shakeel Amanullah, consultant oncologist at Memon Medical Institute Hospital for providing us information about monoclonal antibodies and helping us conduct out survey. We also thank Mr. Haider Raza for helping us conduct this survey. Competing interests: The authors declare that no competing interests exist. Received: 19 February 2013 Accepted: 31 March 2013 Published Online: 1 April 2013

References 1. Murali R, Greene MI: Structure Based Antibody-Like Peptidomimetics.

Pharmaceuticals 2012, 5(2):209-235. 2. Eisenbeis AM, Grau SJ: Monoclonal antibodies and Fc fragments for treating

solid tumors. Biologics : targets & therapy 2012, 6:13-20. 3. Chartrain M, Chu L: Development and production of commercial therapeutic

monoclonal antibodies in mammalian cell expression systems: an overview of the current upstream technologies. Current pharmaceutical biotechnology 2008, 9(6):447-467.

4. Descotes J: Immunotoxicity of monoclonal antibodies. mAbs 2009, 1(2):104-111.

5. Boswell CA, Brechbiel MW: Development of radioimmunotherapeutic and diagnostic antibodies: an inside-out view. Nuclear medicine and biology 2007, 34(7):757-778.

6. Ritter MA, Ladyman HM: Production, engineering and clinical application. In: Monoclonal antibodies. edn. Edited by Ritter MA, Ladyman HM. London, UK: Cambridge University Press; 1995.

7. Monoclonal Antibody Production [http://www.accessexcellence.org/RC/VL/GG/monoclonal.php]

8. Marx U, Embleton M, Fischer R, Gruber F, Hansson U, Heuer J, Deleeuw W, Logtenberg T, Merz W, Portetelle D: Monoclonal Antibody Production-The Report and Recommendations of ECVAM Workshop 23. Alternatives to Laboratory Animals [= ATLA] 1997, 25(2).

9. Mendelsohn J, Baselga J: Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer. Journal of clinical oncology 2003, 21(14):2787-2799.

10. Citri A, Yarden Y: EGF–ERBB signalling: towards the systems level. Nature reviews Molecular cell biology 2006, 7(7):505-516.

11. Sorkin A, Goh LK: Endocytosis and intracellular trafficking of ErbBs. Experimental cell research 2009, 315(4):683-696.

12. Bellati F, Napoletano C, Gasparri ML, Visconti V, Zizzari IG, Ruscito I, Caccetta J, Rughetti A, Benedetti-Panici P, Nuti M: Monoclonal antibodies in gynecological cancer: a critical point of view. Clinical & developmental immunology 2011, 2011:890758.

13. FDA Approved Monoclonal Antibodies (mAbs) for Cancer Therapy [http://lifesciencedigest.com/2011/03/05/fda-approved-mabs-for-cancer-therapy/]

14. Available Brands of Rituximab [http://druginfosys.com/Drug.aspx?query=10%20mg/ml&form=Inj&drugCode=1655&drugName=Rituximab&type=8&Ing==1]

15. Oldham RK, Dillman RO: Monoclonal antibodies in cancer therapy: 25 years of progress. Journal of clinical oncology 2008, 26(11):1774-1777.

16. Cartron G, Watier H, Golay J, Solal-Celigny P: From the bench to the bedside: ways to improve rituximab efficacy. Blood 2004, 104(9):2635-2642.

17. Abciximab Approval Information - Licensing Action [http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/ucm093338.htm]

18. Introduction of Abciximab [http://druginfosys.com/Drug.aspx?drugCode=776&DrugName=Abciximab &type=1]

19. Mitchell P, Korobelnik J-F, Lanzetta P, Holz FG, Prünte C, Schmidt-Erfurth U, Tano Y, Wolf S: Ranibizumab (Lucentis) in neovascular age-related macular degeneration: evidence from clinical trials. British Journal of Ophthalmology 2010, 94(1):2-13.

20. Ranibizumab ophthalmic - Uses, Side Effects, Dosage, Interactions - Drug Directory | Comparison Shopping for Health Insurance – Vimo [http://www.vimo.com/pharma/drug-details/Ranibizumab-ophthalmic/d05835/83436]

21. Carswell CI, Plosker GL, Wagstaff AJ: Daclizumab: A Review of its Use in the Management of Organ Transplantation. BioDrugs 2001, 15(11):745-773.

22. Vincenti F, Kirkman R, Light S, Bumgardner G, Pescovitz M, Halloran P, Neylan J, Wilkinson A, Ekberg H, Gaston R et al: Interleukin-2-receptor blockade with daclizumab to prevent acute rejection in renal transplantation. Daclizumab Triple Therapy Study Group. The New England journal of medicine 1998, 338(3):161-165.

23. Beniaminovitz A, Itescu S, Lietz K, Donovan M, Burke EM, Groff BD, Edwards N, Mancini DM: Prevention of rejection in cardiac transplantation by blockade of the interleukin-2 receptor with a monoclonal antibody. New England Journal of Medicine 2000, 342(9):613-619.

24. Garrity Jr ER, Villanueva J, Bhorade SM, Husain AN, Vigneswaran WT: Low rate of acute lung allograft rejection after the use of daclizumab, an interleukin 2 receptor antibody. Transplantation 2001, 71(6):773-777.

25. Nussenblatt RB, Fortin E, Schiffman R, Rizzo L, Smith J, Van Veldhuisen P, Sran P, Yaffe A, Goldman CK, Waldmann TA et al: Treatment of noninfectious intermediate and posterior uveitis with the humanized anti-Tac mAb: A phase I/II clinical trial. Proceedings of the National Academy of Sciences 1999, 96(13):7462-7466.

26. Van Assche G, Dalle I, Noman M, Aerden I, Swijsen C, Asnong K, Maes B, Ceuppens J, Geboes K, Rutgeerts P: A pilot study on the use of the humanized anti–interleukin-2 receptor antibody daclizumab in active ulcerative colitis. The American journal of gastroenterology 2003, 98(2):369-376.

27. Papaliodis GN, Chu D, Foster CS: Treatment of ocular inflammatory disorders with daclizumab. Ophthalmology 2003, 110(4):786-789.

28. Hulme MA, Wasserfall CH, Atkinson MA, Brusko TM: Central Role for Interleukin-2 in Type 1 Diabetes. Diabetes 2012, 61(1):14-22.

29. Side Effects of Daclizumab [http://druginfosys.com/Drug.aspx?drugCode=1783&drugName=Daclizumab&type=7]

Anwer SMS, Ansari MH 19


Open Access Essay

Clouds with silver lining: Defining conditions that serve as blessings in disguise Syed Muhammad Saad Anwer1, Muhammad Haris Ansari1

Essay Diseases are often looked upon as manifestations of undesirable conditions within us that take physical form in order for them to be dealt with and eliminated. They are considered a reflection of the never-ending conflict between our endogenous state and exoge-nous existence. However, among these lie a group of conditions that, although offensive on their own accord, nevertheless serve to eradicate, or at least play a definitive role in curtailing the disability caused by some of the arguably more debilitating ailments. These conditions have been referred to as “blessings in disguise” in this manuscript.

For example, people with sickle cell disease, G6PD deficiency and thalassemia have been known to be resistant to malaria. Although the mechanism remains largely elusive, it has been proposed that low oxygen content in such cells is inadequate for malarial replica-tion. Similarly, GB Virus C has been reported to decrease disease progression in HIV patients [1]. Another example of such an asso-ciation is that of gout. Recent reports suggest that high concentra-tions of uric acid serve as efficient immunomodulators by instigat-ing a fulminant T-cell immune response which protects against pathogens and also helps in tumor rejection [2]. Hyperuricemia has also been proposed to provide a selective advantage by acting as an antioxidant in the nervous system (after sciatic nerve injury), liver (after hemorrhagic shock), lungs (in respiratory distress) and arterial walls (in significant atherosclerosis) [3]. In addition to this, hyperuricemia may also have a role in blood pressure maintenance [2].

Recent evidence suggests that preeclampsia may prove to be bene-ficial in the long run as it reduces the risk for breast cancer [4].

1Dow Medical College, Dow University of Health Sciences, Baba-e-Urdu Road, Karachi, Pakistan Correspondence: Syed Muhammad Saad Anwer Email: [email protected]

Similarly, fever in children, although worrying for parents, has been considered by experts to be good for the child’s health, as it is an assuring sign of a robust immune system. Allergies, another indica-tor of a hyperactive immune system, have also been found to be associated with a reduced risk of cancer [5].

The above mentioned examples, when taken collectively, suggest that the “adverse” conditions that we see today may just be a product of natural selection; diseases may not be mere nuisances, but one of nature’s ways of evolution. This is particularly relevant as far as rare diseases are concerned. This notion implies that large-scale experiments are conducted in order to further our under-standing from an entirely new perspective.

Competing interests: The authors declare that they have no competing interests. Received: 31 December 2012 Accepted: 31 December 2012 Published: 31 December 2012

References 1. Tillmann HL, Heiken H, Knapik-Botor A, Heringlake S, Ockenga J, Wilber JC,

Goergen B, Detmer J, McMorrow M, Stoll M: Infection with GB virus C and reduced mortality among HIV-infected patients. New England Journal of Medicine 2001, 345(10):715-724.

2. Pillinger M, Rosenthal P, Abeles A: Hyperuricemia and gout: new insights into pathogenesis and treatment. Bulletin of the NYU Hospital for joint diseases 2007, 65(3):215.

3. Agudelo CA, Wise CM: Gout: diagnosis, pathogenesis, and clinical manifestations. Current opinion in rheumatology 2001, 13(3):234-239.

4. Vatten L, Romundstad P, Trichopoulos D, Skjærven R: Pre-eclampsia in pregnancy and subsequent risk for breast cancer. British journal of cancer 2002, 87(9):971-973.

5. Turner MC, Chen Y, Krewski D, Ghadirian P: An overview of the association between allergy and cancer. International journal of cancer 2006, 118(12):3124-3132.

Abstract Diseases are often looked upon as manifestations of undesirable conditions within us that take physical form in order for them to be dealt with and eliminated. They are considered a reflection of the never-ending conflict between our endogenous state and exogenous existence. However, among these lie a group of conditions that, although offensive on their own accord, nevertheless serve to eradicate, or at least play a definitive role in curtailing the disability caused by some of the arguably more debilitating ailments. These conditions have been referred to as "blessings in disguise" in this manuscript. (El Med J 1:1; 2013) Keywords: Blessings, Disguise, Rare Conditions, Malaria, Hyperuricemia, GB Virus C

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Open Access Essay

Multidimensional effects of glucagon-like peptide-1 Abdul Haseeb1

Essay Incretins, which include glucagon-like peptide-1 (GLP-1) and glu-cose-dependent insulinotropic polypeptide (GIP), are a group of gastrointestinal hormones generally known to cause release of insulin from beta cells of the islets of Langerhans after an oral glu-cose challenge, before blood glucose levels become elevated. However, incretin release is controlled by a pleiotropic gene, which implies that it controls multiple phenotypic traits [1].

Apart from augmenting the pancreatic response, incretins are con-sidered to be related to other traits through complicated mecha-nisms. They have been found to preserve neuronal cells, promote wound healing, improve hepatic inflammation, ameliorate hepa-tosteatosis and insulin resistance and are actively involved in bone health. GLP-1 receptor has an extensive network, ranging from pancreas, heart, vascular smooth muscles, monocytes and macro-phages, endothelial cells, lungs gastrointestinal tract, kidney to peripheral as well as central nervous system, which helps explain the multi-dimensional actions of this hormone [2].

GLP-1 and its analogs enjoy a cardiovascular-friendly profile and have direct and indirect effects on the heart and vascular smooth muscle. For example, exenatide, a synthetic GLP-1 analog, delays gastric emptying, thus indirectly decreasing the rate at which glu-cose appears in blood stream. It has a restrained yet extended effect to reduce appetite and therefore promotes weight loss by acting on the satiety centers of brain. It has also been found to reduced liver fat [3]. Since obesity is an important modifiable risk factor of cardiovascular diseases, the aforementioned actions may have a favorable effect in such patients. Similarly, GLP-1 has also been found to have direct cardiovascular effects, which range from the control of blood pressure and attenuation of atherosclerosis to cardioprotection in patients with heart failure and coronary artery disease [4]. Another synthetic GLP-1 analog, Liraglutide, has been

1Dow Medical College, Dow University of Health Sciences, Baba-e-Urdu Road, Karachi, Pakistan Correspondence: Abdul Haseeb Email: [email protected]

shown to possess anti-apoptotic effects thus promoting regenera-tion of beta islet cells [5]. Furthermore, it also lowers triglyceride levels, diminishes appetite and maintains a lean body weight [6]. The pleiotropic profile of GLP-1 is further established by the fact that the above mentioned effects are abrogated in knock out ex-periments for GLP-1R gene [7].

In short, incretins may have future therapeutic benefits that are in addition to their hypoglycemic effects. However, further research in both pre-clinical as well as clinical settings is required in order to completely elucidate the delicate mechanisms of their functioning.

Competing interests: The author declares that he has no competing interests. Received: 3 January 2013 Accepted: 28 January 2013 Published: 29 January 2013

References 1. Stearns FW: One hundred years of pleiotropy: a retrospective. Genetics 2010,

186(3):767-773. 2. Gupta V: Pleiotropic effects of incretins. Indian Journal of Endocrinology and

Metabolism 2012, 16(Suppl1):S47. 3. Ding X, Saxena NK, Lin S, Gupta N, Anania FA: Exendin‐4, a glucagon‐like

protein‐1 (GLP‐1) receptor agonist, reverses hepatic steatosis in ob/ob mice. Hepatology 2005, 43(1):173-181.

4. Fields AV, Patterson B, Karnik AA, Shannon RP: Glucagon‐like Peptide‐1 and Myocardial Protection: More than Glycemic Control. Clinical cardiology 2009, 32(5):236-243.

5. Brubaker P, Drucker D: Minireview: glucagon-like peptides regulate cell proliferation and apoptosis in the pancreas, gut, and central nervous system. Endocrinology 2004, 145(6):2653-2659.

6. Nauck M, Frid A, Hermansen K, Shah NS, Tankova T, Mitha IH, Zdravkovic M, Düring M, Matthews DR: Efficacy and Safety Comparison of Liraglutide, Glimepiride, and Placebo, All in Combination With Metformin, in Type 2 Diabetes The LEAD (Liraglutide Effect and Action in Diabetes)-2 study. Diabetes care 2009, 32(1):84-90.

7. Gros R, You X, Baggio LL, Kabir MG, Mungrue IN, Parker TG, Huang Q, Drucker DJ, Husain M: Cardiac function in mice lacking the glucagon-like peptide-1 receptor. Endocrinology 2003, 144(6):2242-2252.

Abstract Incretins, which include GLP-1 and GIP, are a group of gastrointestinal hormones generally known to cause release of insulin from beta cells of the islets of Langerhans after an oral glucose challenge, before blood glucose levels become elevated. However, incretin release is controlled by a pleiotropic gene, which implies that it controls multiple phenotypic traits. (El Med J 1:1; 2013) Keywords: GLP-1, incretins, diabetes, pleiotropism

Saleem MD 21


Open Access Essay

Person in focus: Is your local barber shop as safe as you think? Muhammad Danish Saleem1

Essay Shoaiba is a young, healthy male who works around 12 hours daily at a local barber shop in one of the busiest localities of Karachi. He works on a fixed salary of fifteen thousand rupees and has been working in the same shop for the past four years.

If one would meet Shoaib, they would instantaneously be drawn to his good etiquettes and fine skills. I found him to be very jovial and friendly. Maybe that’s why he is so popular amongst his clients. But there is a dark side to Shoaib that none of his clients know. He is amongst the 4.9 percent population of Pakistan who are Hepatitis C positive [1].

Hepatitis C is a fast growing problem in Pakistan with more than 10 million people affected [2]. Waheed et al. in their review pointed out a very high prevalence of positive HCV serotype in injecting drug abusers and the multi-transfused, and increasing rates in the general population [2]. Complications of this chronic hepatitis can lead to liver cirrhosis and carcinoma and treatment, if at all, is very expensive. Prevention both by awareness and reducing transmis-sion seem the most important thing that we can do at his stage.

Shoaib is amongst the thousands of male immigrants who have poured in Karachi in search of bread and butter. He shares a cot-tage with two more inhabitants all of whom, like him, are tempo-rary visitors in this city. All three are barbers by profession and all have tested positive for Hepatitis C.

Though aware of his positive status, Shoaib was unmoved by the deadly implications this disease could hold for him. The diagnosis, he recalls, had been by a lucky chance when he was screened dur-ing an interview for a job at a military base. It has been six months since he has tested positive and the treatment still continues in a local government center. He had limited knowledge about Hepati-tis C and its transmissibility. His ignorance is not his fault as Wa-heed in his review also stressed upon the low level of public

1Dow Medical College, Dow University of Health Sciences, Baba-e-Urdu Road, Karachi, Pakistan Correspondence: Muhammad Danish Saleem Email: [email protected]

awareness about Hepatitis C [2].

What is important to note is that the institute where he was diag-nosed and where he is being currently treated also failed to teach him about the implications of his disease and how he could have further avoided its transmission to his roommates. He is still work-ing the regular hours and catering to his numerous clients. He is still engaging in regular sexual activity without any protection. He has still not been vaccinated for either Hepatitis A or B. Most im-portantly, he finds no harm in missing two or three doses of his treatment regimen.

Barbers of third world countries like Pakistan have often been im-plicated in the transmission of infectious agents like Hepatitis C through the repeated use of razors and scissors for different cus-tomers without sterilizing them first [2]. It would seem now that they may actually be carriers as well. How many other Shoaibs are sprawling across this huge city of Karachi? Unaware and untreated, what threat do they hold? One can only guess.

Author’s Declaration: The author declares that proper informed consent was taken before conducting the interview. Competing interests: The author declares that he has no competing interests. Received: 6 February 2013 Accepted: 6 February 2013 Published: 6 February 2013

References 1. Qureshi H, Bile K, Jooma R, Alam S, Afridi H: Prevalence of hepatitis B and C

viral infections in Pakistan: findings of a national survey appealing for effective prevention and control measures. Eastern Mediterranean health journal = La revue de sante de la Mediterranee orientale = al-Majallah al-sihhiyah li-sharq al-mutawassit 2010, 16:S15-23.

2. Waheed Y, Shafi T, Safi SZ, Qadri I: Hepatitis C virus in Pakistan: A systematic review of prevalence, genotypes and risk factors. World journal of gastroenterology: WJG 2009, 15(45):5647.

aThe name has been changed to protect the identity of the person.

Abstract Shoaib is a young, healthy male who works around 12 hours daily at a local barber shop in one of the busiest localities of Karachi. But there is a dark side to Shoaib that none of his clients know. He is amongst the 4.9 percent population of Pakistan who are Hepatitis C positive. Barbers of third world countries like Pakistan have often been implicated in the transmission of infectious agents like Hepatitis C through the repeated use of razors and scissors for different customers without sterilizing them first. (El Med J 1:1; 2013) Keywords: Hepatitis C, Barber

22 Schmidt's Syndrome – Case report…

Vol 1, No 1

Open Access Letter to Editor Schmidt's Syndrome – Case report and review of literature Hira Ahmad1, Sidra Mumtaz Shaikh1, Zahabia Hakimi1

Introduction Autoimmune polyglandular syndrome (APS) is a broad spectrum of various autoimmune endocrinopathies and may show similarities with other endocrine or non-endocrine autoimmune diseases. It comprises of four groups, which have been conveniently numbered from 1 through 4. APS-1 is a relatively uncommon that is due to a defect in the AIRE gene [1]. APS-2 and APS-3 are more common occurring with or without adrenal failure respectively [1]. APS-4 includes all the combinations not included in the other three.

APS-2, also known as Schmidt’s syndrome, is characterized by dia-betes mellitus type 1, hypothyroidism and Addison’s disease. Hy-pogonadism, alopecia, myasthenia gravis or vitiligo may also occur.

Case report A 50 year old male, known patient of type 1 diabetes mellitus, presented with a history of persistent headache for 1 year, not relieved by rest or medicines, associated with vomiting, but not with fever or fits. 4 months back, he developed vertigo on standing, couldn’t maintain his posture and kept falling on the side when trying to walk. The vertigo seemed to disappear on sitting and lying. It was also associated with buzzing sensation in both ears. The patient also complained of urinary incontinence.

Physical examination revealed mild alopecia, palmer erythema (figure 1) and hyperpigmentation on the dorsal surface of the feet (figure 2). A postural drop of 35/20 mm Hg systolic/diastolic blood pressure was also observed. Neurologic examination revealed brisk reflexes in all four limbs. Cerebellar examination revealed ataxic gait, past pointing and dysdiadochokinesis on the left side. Rom-berg’s Test was negative.

1Dow University of HealthSciences, Karachi, Pakistan. Correspondence: Hira Ahmad Email: [email protected]

Investigations revealed fasting blood sugar of 221mg/dl and post-prandial blood sugar of 365mg/dl. Total triglyceride level was 240mg/dl, LDL was 165mg/dl. Serum T4 was 3.51ug/dl and TSH was 49.41mIU/ml. Random cortisol was 0.011ug/dl, and cosyntropin suggested primary adrenal insufficiency. MRI of brain revealed a contrast enhancing lesion in left cerebellum on axial (figure 3) and coronal (figure 4) sections. Hence a diagnosis of APS-2 was given, and the patient was referred to the neurosurgery department for further workup.

Discussion The etiology of APS-2 has been linked to multiple genes. It is more common in women in the third or fourth decade of life, and associ-ated with HLA DR3/DR4 haplotypes [1, 2]. The prevalence rate of APS-2 has been estimated at approximately 14-20 people per mil-lion [3]. The most common triad of symptoms includes Addison’s disease, Hashimoto’s thyroiditis and type 1 diabetes mellitus.

Only a single case report of APS-2 with cerebellar ataxia could be retrieved after literature search [4]. However, that case was due to atrophy of the cerebellum and the anterior pituitary gland. There-fore, this is the only case of APS-2 presenting with a cerebellar

Abstract Autoimmune polyglandular syndrome (APS) is a broad spectrum of various autoimmune endocrinopathies and may show similarities with other endocrine or non-endocrine autoimmune diseases. APS-2, also known as Schmidt’s syndrome, is characterized by diabetes mellitus type 1, hypothyroidism and Addison’s Disease. Here we present a case of Schmidt’s syndrome presenting with a left cerebellar mass. (El Med J 1:1; 2013) Keywords: Autoimmune Polyglandular Syndrome Type 2, Schmidt’s Syndrome, Cerebellar Mass

Figure 1: Palmer Erythema

Figure 2: Hyperpigmentation

Figure 3: Axial MRI showing contrast enhancement of the

left cerebellar lesion

Figure 4: Coronal MRI

Ahmad H, Shaikh SM, Hakimi Z 23


mass. Hence, the theory that neurological deficits in APS-2 are due to targeting of cerebellar pathways may, in principle, hold sub-stance [4].

Conclusion In this letter, we have described the first case of APS-2 presenting with a cerebellar lesion. The significance of reporting this case is substantiated by the fact that it is divergent from the commonly reported epidemiological characteristics of APS-2 (i.e. females in thirties/forties).

Author’s Declaration: The author declares that proper informed consent was obtained from the patient. Competing interests: The author declares that no competing interests exist. Received: 18 March 2013 Accepted: 25 March 2013 Published Online: 2 April 2013

References 1. Betterle C, Zanchetta R: Update on autoimmune polyendocrine syndromes

(APS). Acta bio-medica : Atenei Parmensis 2003, 74(1):9-33. 2. Dittmar M, Kahaly GJ: Polyglandular autoimmune syndromes:

immunogenetics and long-term follow-up. The Journal of clinical endocrinology and metabolism 2003, 88(7):2983-2992.

3. Gupta AN, Nagri SK: Schmidt's syndrome - Case report. The Australasian medical journal 2012, 5(6):292-295.

4. Manto M, Jissendi P: Brain imaging in cerebellar ataxia associated with autoimmune polyglandular syndrome type 2. Journal of neuroimaging : official journal of the American Society of Neuroimaging 2012, 22(3):308-311.

24 Klippel-Trenaunay Syndrome or Proteus Syndrome…

Vol 1, No 1

Open Access Letter to Editor Klippel-Trenaunay Syndrome or Proteus Syndrome? A case presenting a diagnostic dilemma Shahzad Saleem1

Introduction Klippel-Trenaunay syndrome (KTS), also known as angioosteohy-pertrophy syndrome, is a rare congenital condition characterized by a triad of port-wine stain, vascular anomalies and asymmetric soft-tissue hypertrophy of the affected limb [1]. The etiology of KTS still remains elusive, although many theories have been put forward. For example, Seville was of the view that deep venous abnormali-ties are the cause for this condition [2]. On the other hand, Biznak and Baskerville believed in pre-natal insults (intrauterine damage or mesodermal defects) as the cause [3, 4]. Although it is primarily considered as a sporadic disorder, genetic factors have also been implicated [5, 6]. Proteus syndrome (PS) is a congenital disorder that causes overgrowth of different body parts, accompanied by vascular malformations and several types of tumors [7]. Its etiology remained unknown until recently, when Lindhurst et al. discovered a somatic activating mutation in AKT1 to be responsible [8].

These two syndromes have various overlapping features. A review of the available literature reveals at least 3 different case reports where the authors were presented with a diagnostic dilemma con-cerning these two conditions [9-11].

Case report An 18 year old male, born off non-consanguineous parents, pre-sented with a history of pain, tortuous veins (figure 1) and dispro-portionate hypertrophy in both legs (figure 2).

He had a port-wine stain on the back since birth, along with scolio-sis to the left and an abnormal gait. He also complained of a mass in the left limb below the knee joint (figure 3). The mass was firm and non-tender. A radiographical evaluation of the mass revealed a soft tissue shadow without any evidence of calcification.

1Dow Medical College, Dow University of HealthSciences, Karachi, Pakistan. Correspondence: Shahzad Saleem Email: [email protected]

The patient did not give a history of any other significant health conditions and exhibited normal cognitive levels. There was also no family history of such lesions. A detailed physical examination re-vealed unilateral macrodactyly (2nd finger of left hand), bilateral overlapping fourth and fifth toe (figure 4) and bilateral non-pitting edema of the legs. All routine investigations were within normal limits.

Discussion KTS was first described by two French doctors, Klippel and Trenaunay in 1900. Later, another doctor named Weber, described similar cases with certain distinctive features (eg. arteriovenous fistulas). According to a study conducted at Mayo Clinic, port wine staining is the most common feature of this syndrome. These le-sions are red purple in color, and are caused by underlying capillary hemangiomas [12]. If thrombocytopenia is also present, then this sequence is known as Kasabach–Merritt syndrome. Other features of KTS include varicose veins, caused by defective valves, and soft tissue hypertrophy, caused by increased growth. Usually, the lower limb is involved, and its hypertrophy often leads to vertebral scolio-sis, gait abnormalities and limited mobility.

Proteus syndrome is named after the Greek god Proteus due to its widely varying presentation. Macrodactyly is an important feature of this condition [13]. Due to its variable nature, it is often confused with other syndromes such as KTS. The diagnosis of PS may be established using the criteria mentioned by Biesecker et al [14]. These include mandatory general criteria, such as sporadic oc-curence, mosaic distribution of lesions and progressive course, and specific criteria, such as connective tissue nevus [14].

Similar cases have been reported in the past. For example, Sansom et al. described a case that was provisionally diagnosed as KTS. The diagnosis was later revised to PS [11]. Puri et al. reported a similar case that presented with hypertrophy of the face and tongue, syn-dactyly and port wine stains [9]. Further workup revealed lym-

Abstract Klippel-Trenaunay syndrome is a rare congenital condition characterized by a triad of port-wine stain, vascular anomalies and asymmetric soft-tissue hypertrophy of the affected limb. Proteus syndrome is a congenital disorder that causes overgrowth of different body parts, accompanied by vascular malformations and several types of tumors. Here we present a case with features representing both these conditions, hence leading to a diagnostic dilemma. (El Med J 1:1; 2013) Keywords: Klippel-Trenaunay Syndrome, Proteus Syndrome, Dilemma, Rare Congenital Disorders

Figure 1: Tortuous veins in left leg

Figure 2: Disproportionate hypertrophy

Figure 3: Mass in the left leg

Figure 4: Overlapping toes

Saleem S 25


phangioma circumscriptum [9]. Gupta reported similar symptomat-ic profile with chylous ascites [10].

Table 1 (adapted from Puri et al [9]) provides a breakdown of the similarities and differences between KTS and Proteus syndrome.

Table 1: Comparison of features of PS and KTS (adapted from Puri et al [9])

PS KTS Hypertrophy of the limbs ++ ++

Port wine stains + ++ Varicosities + ++

Macrodactyly ++ + + May occur ++ Characteristic of this condition

Hence, our diagnosis was inclined towards KTS. Macrodactyly and limb hypertrophy were the only feature that suggested the oppo-site.

Conclusion The case presented in this letter has overlapping characteristics of both KTS and PS. A diagnostic dilemma concerning these two con-ditions has occurred only rarely, and we were able to retrieve only 3 such case reports.

Author’s Declaration: The author declares that proper informed consent was obtained from the patient. Competing interests: The author declares that no competing interests exist. Received: 3 March 2013 Accepted: 25 March 2013 Published Online: 1 April 2013

References 1. You C, Rees J, Gillis D, Steeves J: Klippel-Trenaunay syndrome: a review.

Canadian journal of surgery Journal canadien de chirurgie 1983, 26(5):399. 2. Servelle M: Klippel and Trenaunay's syndrome. 768 operated cases. Annals of

surgery 1985, 201(3):365. 3. Bliznak J, Staple TW: Radiology of angiodysplasias of the limb. Radiology

1974, 110(1):35-44. 4. Baskerville PA, Ackroyd JS: The etiology of the Klippel-Trenaunay syndrome.

Annals of surgery 1985, 202(5):624. 5. Ceballos‐Quintal JM, Pinto‐Escalante D, Castillo‐Zapata I: A new case of

Klippel‐Trenaunay‐Weber (KTW) syndrome: Evidence of autosomal dominant inheritance. American journal of medical genetics 1996, 63(3):426-427.

6. Kihiczak GG, Meine JG, Schwartz RA, Janniger CK: Klippel–Trenaunay syndrome: a multisystem disorder possibly resulting from a pathogenic gene for vascular and tissue overgrowth. International journal of dermatology 2006, 45(8):883-890.

7. FAQs | Proteus Syndrome Foundation [http://www.proteus-syndrome.org/proteus-syndrome/faqs/]

8. Lindhurst MJ, Sapp JC, Teer JK, Johnston JJ, Finn EM, Peters K, Turner J, Cannons JL, Bick D, Blakemore L et al: A mosaic activating mutation in AKT1 associated with the Proteus syndrome. The New England journal of medicine 2011, 365(7):611-619.

9. Puri KJPS, Malhotra SK, Akanksha J: Klippel Trenaunay and Proteus Syndrome overlap--a diagnostic dilemma. Egyptian Dermatology Online Journal 2009, 5(2):10.

10. Gupta N, Kabra M, Ramesh K, Garg G, Kaur D, Gupta A, Bal CS: A female with hemihypertrophy and chylous ascites - Klippel-Trenaunay syndrome or Proteus syndrome: a diagnostic dilemma. Clinical Dysmorphology 2006, 15(4):229-231.

11. Sansom JE, Jardine P, Lunt PW, Schutt WH, Kennedy CT: A case illustrating Proteus and Klippel-Trenaunay syndrome overlap. Journal of the Royal Society of Medicine 1993, 86(8):478-479.

12. Jacob AG, Driscoll DJ, Shaughnessy WJ, Stanson AW, Clay RP, Gloviczki P: Klippel-Trenaunay syndrome: spectrum and management. Mayo Clinic proceedings Mayo Clinic 1998, 73(1):28-36.

13. Barmakian JT, Posner MA, Silver L, Lehman W, Vine DT: Proteus syndrome. The Journal of hand surgery 1992, 17(1):32-34.

14. Biesecker LG, Happle R, Mulliken JB, Weksberg R, Graham JM, Jr., Viljoen DL, Cohen MM, Jr.: Proteus syndrome: diagnostic criteria, differential diagnosis, and patient evaluation. Am J Med Genet 1999, 84(5):389-395.

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Best of Blogemia

Time “Heels” Everything Hira Hussain Khan

http://blogemia.com/time-heels-everything/

The materialistic world has pushed us to such limits that we do not restrain from harming ourselves. Appearing extravagant is one of the undeniable natural instincts girls own and many are proud of executing it. Majority of women live under the im-pression that a higher status can be repre-sented only when you are heels bound. Focusing more on the apparels, accessories and gadgets, women strut around like divas and prefer walking high, down the hallway carpets. However, this demeanor may ulti-mately prove to be devastating, if what holds the balance and weight of the body turns out to be big-sized heels, especially for those professional women who carry them around for a major chunk of their time on a daily basis.

The natural tendency of body to align itself is markedly disturbed which results in crea-

tion of unwelcomed pressure points. The pedestal feeling may temporarily look ap-pealing on stilettos but the aftermath can be severe. Pros: the towering demeanor, cons: skeleton compromise. Striving for the stylish get up can ultimately cost the ease of the back and feet. Women wearing heels are at greater chances of developing sore feet because of the pain. The tears and bruises on skin can wreak intensifying pain further upon rubbing the feet against inner shoe surface. The thickened skin emerges due to the confined toes in the limited space of tapering footwear. Frequent use can exacerbate the pain and growth of the feet can be invariably compromised with progressing age as feet become wider. The main factor is the concentration and aggre-gation of entire body’s pressure on the feet. The vertebra that runs down the back is the site to deal with the impact of moderate to high sized heels. Compression of spinal nerves is met causing numbness and tin-gling sensation that can be felt if vertebra is thrown out of its natural alignment due to excessive use of heels.

Heels promote unnatural postural position. Excessive heels usage limits the stretching of Achilles’ tendon which is responsible for the tendon stiffness. This very tendon also assists in downward pointing of foot. Neu-romas, hammertoes and bunions, are among many other complications arising due to walking in heels. Unwillingly, if the balance is lost and stumbling over heels occurs, the injurious impact may result in fracture. Many of the ankle fractures have also been documented as being a direct result of unsafe use of heels. Stress frac-tures are defined as many tiny cracks in feet bones, which can be anticipated too. In-flamed muscles of legs taking the strain cause knee wear and tear associated with osteoarthritis.

The drawbacks are witnessed with pro-gressing age and time, so development of a safe strategy is recommended from the very beginning. The overall disadvantage of carrying your legs in heels is the reduction in activity and efficacy of the women com-paratively with those walking in flat foot-wear. Undoubtedly, heels may contribute to enhancing self-esteem but switching to comfortable footwear has its own charm and satisfaction. If ladies are addicted to heels, then it is advisable to wear short

sizes over long ones. Measure your foot size before purchasing heels because over-crowded feet may result in many of the aforementioned problems. Feet and back pain can be reversed by massages. In short, the bottom line is: “your high life should not jeopardize your balance, standing ability and mobility”.

Euthanasia: To Kill or not to Kill? Salman Ahmed

http://blogemia.com/euthanasia-to-kill-or-not-to-kill/

Abdul Jabbar*, a 81 year old male suffering from end stage chronic liver disease associ-ated with left sided hemiplegia for the last 17 years waits anxiously for being dis-charged from the hospital, as the only sur-viving member of his known family who had been financing his medical bills died in a Bomb blast in Karachi last week. Now he feels dejected and disconsolate and sees no reason whatsoever for being alive. Although he was fortunate enough to survive a facto-ry fire incident which left him paralyzed 17 years back, but due to the ever increasing cost of medical expenses and absolute dependency on others for assistance in day to day activities, Abdul Jabbar wants an end to this dilemma by placing a final full stop to all his sufferings. He deliberately asks the hospital management for euthanasia as there are no remedies available to relieve him of his agonies and afflictions.

He is the one of the thousands of terminally ill patients in Pakistan whose fate is de-pendent on the prevalent laws against Euthanasia, or “mercy killing”, as they are considered Haram/strictly forbidden under the Islamic Law. One of the House Officers I met at that hospital reacted sarcastically and critically when he was asked about his opinions regarding euthanasia, and whether or not this should be legalized by our legis-lation. He accepted the fact that suicide is forbidden by Islamic laws, but pointed out: “so is alcohol consumption, singing, music, corruption, adultery, bank interest etc. So how come they are openly being practiced and promoted by the society while on the other hand euthanasia is considered a ma-jor sin? How do you justify this fact?” I was

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left speechless, even though deep inside I also reject the concept of euthanasia but at that moment I just couldn’t respond to his query and wasn’t able to entertain him with an appropriate answer.

Euthanasia has been a controversial topic of debate for years in major western coun-tries, as this always attracts hostile attitude of people considering this a “major sin”. However in Netherlands, Belgium, Switzer-land, Luxemburg, and the US states of Ore-gon and Washington some form of physi-cian assisted killings are legalized by the constitution but still considered a taboo by majority of the local population. The pro-mercy killing social group justify their incli-nation towards euthanasia for terminally ill individuals by stating that it is better to depart from this world peacefully than to miserably rot and restlessly suffer waiting for the ultimate eventual end.

This concept of mercy killing strictly contra-dicts with that of teachings of the major religions of the world as this clearly oppose the concept of basic human instincts of survival. However, the fact of Abdul Jab-bar’s sufferings do bother me emotionally, as doctors term his condition pitiful and pathetic. Logically, the only possible way to relieve him of his miseries is to perform a physician assisted killing, but is our society mentally and psychologically ready to ac-cept the phenomenon of mercy killing to be legal and justified in the light of Islamic Laws? If not then who will write the script of Abdul Jabbar’s remaining pathetic end-ing? I can’t find a better quote to conclude this controversial topic:

Jack Kevorkian in his book Prescription Medicine: The Goodness of Planned Death states “In quixotically trying to conquer death doctors all too frequently do no good for their patients’ “ease” but at the same time they do harm instead by prolonging and even magnifying patients’ dis-ease.”

* The name has been changed to protect the patient’s privacy.

Post-Traumatic Stress Disorder: No Less than an Epidemic Mustajab Ahmed

http://blogemia.com/post-traumatic-stress-disorder-no-less-than-an-epidemic/

Since the very beginning of its species, mankind has been prone to trauma. From being attacked by wild animals through battles to the current era of car accidents, plane crashes, street crimes and terrorist attacks, terrifying events have always af-fected the masses and they are increasing with each passing day. The injuries to the body may heal, but the psychological trau-ma lasts much longer. Post-traumatic stress disorder (PTSD) is a type of anxiety disorder that is triggered by a terrifying event that involved the threat of injury or death. The cause of PTSD is not fully known yet. Fac-tors involved could be genetic, psychologi-cal, social or physical. In addition, the rea-son why traumatic events cause PTSD in some people but not in others is not yet known either. One of the risk factors for getting PTSD after a recent traumatic event could be a history of trauma. The symptoms of PTSD typically exhibit for more than a month. Though, they may not appear until years after the event in a small number of cases. These symptoms are generally classi-fied into three types: intrusive memories (re-experience), avoidance and numbing, and increased anxiety or emotional arousal (hyperarousal).

Symptoms of intrusive memories may in-clude:

• Flashbacks of the traumatic event for minutes or even days at a time

• Upsetting dreams about the traumatic event

Symptoms of avoidance and emotional numbing may include:

• Trying to avoid thinking or talking about the traumatic event

• Feeling emotionally numb

• Avoiding activities once enjoyed • Hopelessness about the future • Memory problems • Trouble concentrating • Difficulty maintaining close relationships

Symptoms of anxiety and increased emo-tional arousal may include:

• Irritability or anger • Overwhelming guilt or shame • Self-destructive behavior, such as drink-

ing too much • Trouble sleeping • Being easily startled or frightened • Hearing or seeing things that aren’t there

PTSD can affect anyone at any age. Howev-er, it is especially common among those who have served in wars. It is sometimes known as combat stress. But many other traumatic events also can lead to PTSD, including road accidents, street crimes, fire, assault, plane crash, torture, kidnapping, life-threatening medical diagnosis, bomb blasts and other extreme or life-threatening events.

People with PTSD are mainly treated with psychotherapy, medications, or both. Psy-chotherapy includes exposure therapy which uses imagery, writing or visiting the place where the event happened in order to re-expose the patients to the event in a safe way; cognitive restructuring which helps people make sense of the bad events ena-bling them to look at the event in a realistic way; and stress inoculation training which tends to reduce the symptoms of PTSD by teaching them how to reduce anxiety. Med-ications mainly include antidepressants, benzodiazepines and antipsychotics.

People with PTSD need emotional support, patience and encouragement. They need to be carefully listened to and measures should be taken to prevent them from harming themselves. Although it is not easy for people who go through traumatic events to adjust for some period, but they usually get better with time when taken care of along with continued therapy.

We require avid bloggers and medical writers to lead our sister blog, Blogemia. We are looking for section heads, editors and contributors. Those hired will be responsible for submitting at least five blogs (>500 words) per month. Individuals working in any of the aforementioned capacities will receive a share of the advertisement revenue. To apply, send your CVs along with samples at: [email protected]

We accept Original Articles, Review Articles, Case Reports, Opinions and Debates, Essays, Letters to the Editor. There are no paper submission charges. Submit your articles via the online system or send as an email to: [email protected]

We require editors, programmers, layout designers and proofreaders for our editorial staff. We also require avid medical bloggers for our sister website, http://blogemia.com. We are also looking for journal representatives from different medical schools. To apply, send your CV to: [email protected]

El Mednifico Journal, Address: C2 Block R, North Nazimabad, Karachi – 74700 – Pakistan. Email: [email protected]. Phone: (92-334)2090696.

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Vol 1, Issue 1