Digital Commons Network^™

Synaptotagmin-2 Controls Regulated Exocytosis But Not Other Secretory Responses Of Mast Cells*, Qun-Fang Wan, Alejandro Vila, Zhen-Yu Zhou, Ruth Heidelberger

Faculty, Staff and Student Publications

To better understand synaptic signaling at the mammalian rod bipolar cell terminal and pave the way for applying genetic approaches to the study of visual information processing in the mammalian retina, synaptic vesicle dynamics and intraterminal calcium were monitored in terminals of acutely isolated mouse rod bipolar cells and the number of ribbon-style active zones quantified. We identified a releasable pool, corresponding to a maximum of 7 s. The presence of a smaller, rapidly releasing pool and a small, fast component of refilling was also suggested. Following calcium channel closure, membrane surface area was restored to baseline with a time …

Obesity And Cardiac Metabolism In Women, Heinrich Taegtmeyer, Mohamed F Algahim

Faculty, Staff and Student Publications

No abstract provided.

Hypotension At Presentation Is An Indicator Of Poor Prognosis In Acute Intracerebral Haemorrhage, Mohammad Wasay, Bhojo A Khealani, Saad Shafqat, Ayesha Kamal, Nadir Ali Syed

Section of Neurology

OBJECTIVE: To identify frequency of hypotension in a large cohort of patients with intracerebral haemorrhage and its prognostic significance.

METHODS: We retrospectively reviewed medical records of 920 patients with spontaneous intracerebral haemorrhage (ICH). Patients were divided in three groups based on Diastolic blood pressure (DBP); hypotensive group (DBP < 70 mmHg), normotensive group (DBP; 71-90 mmHg) and hypertensive group (DBP > 90 mmHg).

RESULTS: Of the total patients with ICH, 7% (64) presented with hypotension, 13% (120) were normotensive and 80% (736) were hypertensive. In the hypotensive group, 37% (24) patients died as compared to 25%(30) in normotensive group and 25% (182) in hypertensive group (p = 0.03). Hypotension at presentation, thalamic and …

Helicobacter Pylori Gastritis And Risk Of Ischaemic Stroke, Mohammad Wasay, Wasim Jafri, Bhojo Khealani, Iqbal Azam, Akber Hussaini

Section of Neurology

OBJECTIVE: To identify the association between H. Pylori gastritis and stroke.

METHOD: Patients with biopsy proven H. Pylori gastritis and non H. Pylori gastritis were enrolled. Patients were followed for a period of two years.

RESULTS: A total of 326 patients were included in the study. 162 patients were with H. Pylori gastritis. There was no significance difference in age, sex and duration of symptoms in the two groups. Three patients in H. Pylori group had stroke or TIA as compared to one in non H. Pylori group. Patients with H. Pylori gastritis were more likely to die or have …

Brain Death: Concepts And Knowledge Amongst Health Professionals In Province Of Sindh, Pakistan, Mughis Sheerani, Mian Zainul Sajadeen Urfy, Bhojo A Khealani, Junaid Patel, Qamarunnisa, Suresh Rath

Section of Neurology

OBJECTIVE: Last few decades have seen improved resuscitative measures and use of life saving machines like ventilators. Due to these dramatic interventions, end of life decisions, including brain death and organ transplantation, have become more complex and a major problem in our clinical practice. This study was done to find the opinion and awareness of physicians regarding issues surrounding brain death in this region.

METHODS: A total of 259 questionnaires were analyzed that encompassed physicians at different level of training and students in the final year of their training, from five major tertiary care centres, located at Karachi and Hyderabad …

Diagnostic Yield Of Transthoracic Echocardiography For Stroke Patients In A Developing Country, Muhib Alam Khan, Bhojo A Khealani, Bilal Hameed, Ayeesha Kamal, Mohammad Wasay, Nadir Ali Syed

Section of Neurology

OBJECTIVE: To assess the utility and cost effectiveness of transthoracic echocardiography (TTE) as part of stroke workup in a developing country.

METHODS: All patients over the age of 14 years with acute stroke were prospectively enrolled in Aga Khan University stroke databank from August 1999 to May 2001 (22 month period). All patients were evaluated by a consultant neurologist and underwent standard stroke work up such as neuroimaging, TTE, carotid doppler sonography and blood tests e.g. serum glucose, lipid profile, blood urea nitrogen and serum creatinine. For the purpose of this study, patients with ischemic stroke were identified and their …

Stroke In Pakistan, Bhojo A Khealani, Bilal Hameed, Uzma U Mapari

Section of Neurology

Stroke is the most common cause of disability and a leading cause of mortality world wide. Though the incidence is falling in West but probably is rising in Asia. The burden of stroke risk factors in Pakistan is enormous e.g. by 2020 Pakistan will be 4th most populous country in terms of diabetic patients. Similarly every 3rd person above age of 45 years has hypertension. Ironically a great majority of these patients are unaware of their diagnosis. This is further complicated by the fact that most of diagnosed patients have uncontrolled hypertension, as a result of poor compliance on patients …

Post Stroke Seizures: Descriptive Study From A Tertiary Care Centre In Pakistan, Bhojo A Khealani, Sajjad Ali, Shahid M Baig

Section of Neurology

OBJECTIVE: To determine the frequency, mode of onset and outcome of post stroke seizures in a local setting.

METHODS: The retrospective (Aug 1999 to July 2001) and prospective (August 2001 to July 2002) data of patients aged 14 years and above, with post stroke seizures was collected from a tertiary care centre in a metropolitan city. The demographic, clinical, radiological, laboratory, neurophysiologic and outcome data was recorded and analyzed.

RESULTS: During the three year period 1548 patients with stroke were admitted to the hospital. Four hundred thirty one (28%) had intracerebral haemorrhage (ICH) and 1117 (72%) had ischaemic stroke. One …

A Non-Randomized Study Of Safety And Efficacy Of Heparin For Dvt Prophylaxis In Intracerebral Haemorrhage, Mohammad Wasay, Saqibuddin Khan, Khawaja S. Zaki, Bhojo A. Khealani, Ayeesha Kamal, Iqbal Azam, Ismail A. Khatri

Department of Medicine

Objective: To evaluate the safety and efficacy of subcutaneous heparin for deep venous thrombosis (DVT) prophylaxis in patients with intracerebral haemorrhage (ICH) during acute phase in comparison to elastic stockings.

Methods: The diagnosis of ICH was based on imaging (CT or MRI) and DVT was based on Doppler ultrasound.

Results: A total of 458 patients were identified over a period of 5 years (1997-2001). Median age was 59 years (range:12-99 years). Two hundred (44%) patients received heparin (heparin group) in addition to elastic stockings and 258 (56%) patients were only given elastic stockings (stockings group). These two groups were not …

Time Trends In The Incidence Of Cancer Cervix In Karachi South, 1995-2002, Yasmin Bhurgri, Shahid Pervez, Naila Kayani, Muneeza Afif, Imran Tahir, Kauser Nazir, Ahmed Usman, Naveen Faridi, Hadi Bhurgri, Jawaid Malik, Imtiaz Bashir, Asif Bhurgri, Rashida Ahmed, Sheema H Hasan, Mohammad Khurshid, S. M. H. Zaidi

Department of Pathology and Laboratory Medicine

Introduction:The objective of the study was to determine the trends of cancer cervix in Karachi South during an eight (1995-2002) year period. Methododology: Cancer cervix cases recorded at Karachi Cancer Registry during 1st January 1995 to 31st December 2002 were analyzed. Trends were studied by analyzing the age standardized incidence rates (ASR)s in 2 time periods, 1995-97 and 1998-2002.

Results:

Cancer cervix ranked sixth in the 1995-97 period the age standardized incidence rate (ASR) world and crude incidence rate (CIR) per 100,000 were 6.81 and 3.22. It reached the fifth ranking in the 1998-2002 period with an ASR and …

Perinatal Arterial Ischaemic Stroke: An Update With Literature Review, S. H. Ibrahim, Zafar Abdul Mueed

Department of Paediatrics and Child Health

Perinatal arterial ischaemic strokes are a major cause of morbidity in the neonatal period and leads to significant neurological morbidity. It is however under recognized as an entity and usually missed till the baby is 3-4 months of age when they first present with hemiplegia. Perinatal arterial ischaemic strokes are not reported from our country and this may be due to the fact that neurodiagnostic modalities were not available until the last few years. Even now this is not available in the smaller cities of our country. In this review we will discuss the common issues related to etiology and …

The Effect Of Intensity Of Aerobic Training On Insulin Sensitivity, Carmine Richard Grieco Iii

Human Movement Studies & Special Education Theses & Dissertations

Epidemiological studies have demonstrated that the prevalence of type 2 diabetes is increasing. It is estimated that I 0. 7% of adults over the age of 20 years and 23.1 % of adults over the age of 60 years have diabetes (NIH, 2007). Individuals with type 2 diabetes are 2-4 times more likely to die from heart disease than those without diabetes and twice as likely to die of all-cause mortality (CDC, 2005). Additionally Mokdad et al. (2000) report that the prevalence of diabetes increased 33% between 1990 and 1998. Furthermore it has been estimated that nearly 26% of the …

Development Of A Technique To Diagnose Subtalar Joint Instability, Ajaya Dhakal

Mechanical & Aerospace Engineering Theses & Dissertations

Most patients escape diagnosis of subtalar joint instability for years before treatment. Therefore, a clinically relevant technique to diagnose subtalar joint instability will improve its management. Towards this goal, a six degree of freedom positioning and loading device was developed to apply physiologic loads to the hindfoot. Because the ideal loading configuration to detect subtalar joint instability is unknown, the device was designed to apply rotational and translational forces simultaneously. Specifically, plantarflexion/dorsiflexion, inversion/eversion, and internal/external rotation can be applied individually or as coupled motions along with an anterior/posterior drawer. Kinematic data were collected from calcaneus, talus and tibia using a …

In Vivo Murine Melanoma Tumor Responses To Nanosecond Pulsed Electric Field Treatment, Xinhua Chen

Theses and Dissertations in Biomedical Sciences

High intensity nanosecond pulsed electric fields (nsPEF) were applied to melanoma tumors to observe functional and structural biological changes and to investigate the possible molecular mechanisms responsible. An animal model was set up by injecting B16F10 mouse melanoma cells into SKH-1 mice. A treatment (Tx) of 100 pulses: 300 nanosecond duration; 40 kV/cm field strength; at 0.5 Hz rate were delivered to melanoma tumors in 120 mice. The nsPEF Txcaused tumor self-destruction with sharply decreased cell volumes and shrunken nuclei. The apoptotic biochemical tests confirmed nsPEF Tx induced apoptosis in a time-dependent manner. Examination of gross vessel and micro-vessel density …

Nanosecond Pulsed Electric Fields Induce A Mitochondria-Independent Apoptosis In B16f10 Melanoma Cells In Vitro, Wentia Elissa Ford

Theses and Dissertations in Biomedical Sciences

Nanosecond pulsed electric fields (nsPEFs) are ultra-short pulses that induce direct electric field and biological effects that initiate apoptosis. Here the application of ten 300ns pulses ranging in electric fields from 12kV/cm-60kV/cm was administered to determine the effects on B16F10 melanoma cells evaluated by in vitro studies. Initial application of nsPEFs demonstrated apoptosis induction in an electric field- and pulse number-dependent manner measured by caspase activation that correlated with decrease in cell viability 24hr post pulse. In addition caspase activity was shown to be independent of calcium mobilization though ions may play a part in other aspects of apoptosis. The …

Study To Prospectively Evaluate Reamed Intramedually Nails In Patients With Tibial Fractures (S.P.R.I.N.T.): Study Rationale And Design, Franklin D. Shuler Md, Phd

Orthopaedics

Background: Surgeons agree on the benefits of operative treatment of tibial fractures – the most common of long bone fractures – with an intramedullary rod or nail. Rates of re-operation remain high – between 23% and 60% in prior trials – and the two alternative nailing approaches, reamed or non-reamed, each have a compelling biological rationale and strong proponents, resulting in ongoing controversy regarding which is better.

Methods/Design: The objective of this trial was to assess the impact of reamed versus non-reamed intramedullary nailing on rates of re-operation in patients with open and closed fractures of the tibial shaft. The …

Blood Utilization In Children Managed Non-Operatively For Blunt Solid Organ Injury., Scott J. Keckler, Kuojen Tsao, Susan W. Sharp, G W. Holcomb Iii, Daniel J. Ostlie, Shawn D. St Peter

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Blood product utilization is an important issue in health care, given the frequent shortages in hospitals and the societal burden required to maintain the supply. Therefore, we retrospectively audited our blunt spleen/liver trauma experience to determine the percentage of cross-matched blood that was transfused to see whether more stringent typing criteria should be applied.

METHODS: A retrospective analysis of a recent 7-year experience with nonoperative management in patients with blunt spleen or liver injury was performed. Demographics, packed red blood cells prepared by cross-match, and transfusions were measured. Unmatched, O-type blood given in the trauma bay was excluded. Patients …

Role Played By Serum, A Biological Cue, In The Adherence Of Enterococcus Faecalis To Extracellular Matrix Proteins, Collagen, Fibrinogen, And Fibronectin, Sreedhar R Nallapareddy, Barbara E Murray

Faculty, Staff and Student Publications

BACKGROUND: Most previous studies have found that Enterococcus faecalis isolates do not show significant adherence to fibronectin and fibrinogen.

METHODS: The influence of various conditions on E. faecalis adherence to extracellular matrix (ECM) proteins was evaluated using a radiolabeled-cell adherence assay.

RESULTS: Among the conditions studied, growth in 40% horse serum (a biological cue with potential clinical relevance) elicited adherence of all 46 E. faecalis strains tested to fibronectin and fibrinogen but not to elastin; adherence levels were independent of strain source, and adherence was eliminated by treating cells with trypsin. As previously reported, serum also elicited adherence to collagen. …

Management Of Pediatric Acute Appendicitis In The Computed Tomographic Era., Kuojen Tsao, Shawn D. St Peter, Patricia A. Valusek, Troy L. Spilde, Scott J. Keckler, Abhilash Nair, Daniel J. Ostlie, G W. Holcomb Iii

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND/PURPOSE: The treatment options for complicated appendicitis in children continue to evolve. Optimal management of complicated appendicitis relies on an accurate preoperative diagnosis. We examined the accuracy of our preoperative diagnosis including computed tomography (CT) and the influence on the management of children with perforated and nonperforated appendicitis.

METHODS: Following IRB approval, a 6-year review of all patients that underwent an appendectomy for suspected appendicitis was performed. Treatments included immediate operations and initial nonoperative management (antibiotic therapy +/- percutaneous drainage of abscess). Appendicitis was confirmed by histological examination.

RESULTS: One thousand seventy-eight patients underwent appendectomy for suspected appendicitis. Preoperative CT …

Estrogen Replacement Therapy Induces Functional Asymmetry On An Odor Memory/Discrimination Test, Richard L. Doty, Mehreen Kisat, Isabelle Tourbier

Section of Otolaryngology, Head & Neck Surgery

The secondary afferents of the olfactory system largely project to the ipsilateral cortex without synapsing in the thalamus, making unilateral olfactory testing a useful probe of ipsilateral hemispheric activity. In light of evidence that lateralized performance on some perceptual tasks may be influenced by estrogen, we assessed left:right nostril differences in two measures of olfactory function in 14 post-menopausal women receiving estrogen replacement therapy (ERT) and 48 post-menopausal women receiving no such therapy. Relative to women not taking ERT, those receiving ERT exhibited better performance in the left nostril and poorer performance in the right nostril on an odor memory/discrimination …

Emergence Of Carbapenem Resistant Gram Negative And Vancomycin Resistant Gram Positive Organisms In Bacteremic Isolates Of Febrile Neutropenic Patients: A Descriptive Study., Seema Irfan, Faiza Idrees, Vikram Mehraj, Faizah Habib, Salman Adil, Rumina Hasan

Department of Pathology and Laboratory Medicine

Background:This study was conducted to evaluate drug resistance amongst bacteremic isolates of febrile neutropenic Patients with particular emphasis on emergence of carbapenem resistant Gram negative bacteria and vancomycin resistant Enterococcus species.

Methods:

A descriptive study was performed by reviewing the blood culture reports from febrile neutropenic Patients during the two study periods i.e., 1999-00 and 2001-06. Blood cultures were performed using BACTEC 9240 automated system. Isolates were identified and antibiotic sensitivities were done using standard microbiological procedures.

Results:

Seven twenty six febrile neutropenic Patients were admitted during the study period. A total of 5840 blood cultures were received, off …

Fluorescence Tomography Characterization For Sub-Surface Imaging With Protoporphyrin Ix, Dax Kepshire, Scott C. Davis, Hamid Dehghani, Keith D. Paulsen, Brian W. Pogue

Dartmouth Scholarship

Optical imaging of fluorescent objects embedded in a tissue simulating medium was characterized using non-contact based approaches to fluorescence remittance imaging (FRI) and sub-surface fluorescence diffuse optical tomography (FDOT). Using Protoporphyrin IX as a fluorescent agent, experiments were performed on tissue phantoms comprised of typical in-vivo tumor to normal tissue contrast ratios, ranging from 3.5:1 up to 10:1. It was found that tomographic imaging was able to recover interior inclusions with high contrast relative to the background; however, simple planar fluorescence imaging provided a superior contrast to noise ratio. Overall, FRI performed optimally when the object was located on or …

Clinical Features And Management Of Autoimmune Hepatitis, Edward L. Krawitt

Dartmouth Scholarship

Autoimmune hepatitis (AIH) is a chronic hepatitis of unknown etiology which can progress to cirrhosis. Its clinical manifestations are highly variable and sometimes follow a fluctuating course. Diagnosis is based on characteristic histologic, clinical, biochemical and serological findings. Anti-inflammatory/immunosuppressive treatment frequently induces remission but long-term maintenance therapy is often required. Liver transplantation is generally successful in patients with decompensated cirrhosis unresponsive to or intolerant of medical therapy.

Waiting For Liver Transplantation In Canada: Waitlist History 2000--2004 And Sensitivity Analysis For The Future., David Stanford, Elizabeth Renouf, Vivian Mcalister

Data and Test Instruments

This study comprises a historical review of liver transplants performed in Canada during 2000--2004, and sensitivity analyses to assess the impact of possible changes in the operation of the waitlists. In the first part, overall statistics are reported, and the notable impact that blood type plays in affecting waiting time is discussed. Waiting times and numbers of transplants are also reported by gender, age, and geographic region (waitlist), and statistical analyses of the patient placement and cadaveric donations processes are performed. These analyses establish that the service times of an appropriate queuing model are closely approximated by an exponential distribution. …

Spinal Cord Stimulation For Control Of Pain, Stephen Falowski Md

JHN Journal

Spinal cord stimulation (SCS) is an adjustable, non-destructive procedure which delivers therapeutic doses of electrical current to the spinal cord for the management of neuropathic pain. The most common indications include post-laminectomy (“failed back surgery”) syndrome, complex regional pain syndrome (CRPS), ischemic limb pain, and angina. Other reported applications include visceral/abdominal pain, cervical neuritis pain, spinal cord injury pain, post-herpetic neuralgia, and neurogenic thoracic outlet syndrome.

Nerve Growth Factor Regulation Of Cyclin D1 In Pc12 Cells Through A P21ras Extracellular Signal-Regulated Kinase Pathway Requires Cooperative Interactions Between Sp1 And Nuclear Factor-Kappab., Francesco Marampon, Mathew C Casimiro, Maofu Fu, Michael J Powell, Vladimir M Popov, Jaime Lindsay, Bianca M Zani, Carmela Ciccarelli, Genichi Watanabe, Richard J Lee, Richard G Pestell

Department of Cancer Biology Faculty Papers

The PC12 pheochromocytoma cell line responds to nerve growth factor (NGF) by exiting from the cell cycle and differentiating to induce extending neurites. Cyclin D1 is an important regulator of G1/S phase cell cycle progression, and it is known to play a role in myocyte differentiation in cultured cells. Herein, NGF induced cyclin D1 promoter, mRNA, and protein expression via the p21(RAS) pathway. Antisense- or small interfering RNA to cyclin D1 abolished NGF-mediated neurite outgrowth, demonstrating the essential role of cyclin D1 in NGF-mediated differentiation. Expression vectors encoding mutants of the Ras/mitogen-activated protein kinase pathway, and chemical inhibitors, demonstrated NGF …

Drug Overdose: A Wake Up Call! Experience At A Tertiary Care Centre In Karachi, Pakistan, Muhammad Junaid Patel, Muhammad Shahid, Mehmood Riaz, Waqaruddin Kashif, Syed Imran Ayaz, Muhammad Shoaib Khan, A. Jawwad Samdani, Ayesha L Sorathia, Muhammad Furqan

Department of Emergency Medicine

OBJECTIVE: To study the characteristics of patients admitted with drug overdose caused either by accidental overdose of the prescribed medications or as an act of deliberate self harm (DSH) at a tertiary care hospital in Karachi, Pakistan.METHODS: A retrospective case series review was conducted at the Aga Khan University Hospital from January 2002 to October 2006. Three hundred and twenty four adult patients admitted with drug overdose were included in the study.RESULTS: Our sample group revealed mean age of 36.2 +/- 17.0 years, more females (59%), housewives (34%), and students (20%). Fifty six percent of patients committing DSH were married …

Syncope: Experience At A Tertiary Care Hospital In Karachi, Pakistan., Muhammad Junaid Patel, Nadeem Ullah Khan, Abdul Jawwad Samdani, Muhammad Furqan, Aamir Hameed, Muhammad Sohaib, Syed Imran Ayaz, Muhammad Omer Jamil

Department of Emergency Medicine

Introduction:Our aim was to determine the characteristics of Patients presenting with syncope at a tertiary care hospital in Karachi, Pakistan.
Methods: A review of medical records was conducted retrospectively at the Department of Medicine, Aga Khan University Hospital, Karachi. Patients aged 16 and above, admitted from January 2000 to December 2005 with the diagnosis of syncope made by the attending physician were included.
Results:A total of 269 Patients were included (75% males, mean age: 57.4 years). Neurogenic (vasovagal) syncope was the most common cause (47%), followed by cardiogenic syncope (18%) and orthostatic syncope (9%). A total of 24% …

Primary Cerebral Angitis Of The Central Nervous System: Case Report, S. Das, J. O. Jowi, K. Hameed, F. S. Rana

Pathology, East Africa

We report a case of a 28 year old female who presented with variedly progressive stroke like illness and raised intracranial pressure. Brain MRI scans revealed pericallosal and periventricular hyperintensities with oedema. Various medications like intravenous immunoglobulin, antibiotics, acyclovir, methyl prednisolone and management for raised intracranial pressure were instituted. She rapidly deteroriated and died on tenth hospital day. Only at autopsy was the diagnosis of primary angitis of central nervous system established.

Does Choice Of Therapy Save Costs And Improve Outcomes In Hyperthyroid Patients, Lubna M Zuberi, Safia Awan, Najmul Islam, J. Akhter, Abdul Jabbar

Section of Internal Medicine

OBJECTIVE: To compare cost of treating hyperthyroidism with antithyroid medications (ATD) versus radioactive iodine (RAI). As secondary outcome we also analyzed data in terms of remission rates.

METHODS: This was a retrospective comparative analysis of hyperthyroid patients treated with ATD or RAI from January 2000 to December 2005. Cost of ATD, TSH. FT4, doctors visits; thyroid technetium scan and RAI treatment were calculated for the duration of treatment and for one year of follow-up after remission.

RESULTS: A total of 143 patients were included, with an average duration of follow-up of 32 months. Mean age was 41 +/- 15.5 years …