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Pre-eclampsia and eclampsia are leading causes of maternal and perinatal morbidity and mortality worldwide. The exact prevalence, however, is unknown. The majority of pre-eclampsia related deaths in LMIC occur in the community and therefore, interventions must be focused at this level. There are a number of unique challenges facing LMIC but the principles of care for women with pre-eclampsia remain the same as in well resourced settings. Three primary delays lead to an increased incidence of maternal mortality from pre-eclampsia- delays in triage, transport and treatment. There are a number of other challenges facing LMIC and the health care worker shortage is particularly significant. Task shifting is a potential strategy to address this challenge. Community health care workers, specifically lady health care workers, are an integral part of the health care force in many LMIC and can be employed to provide timely care to women with pre-eclampsia. Prevention strategies should be applied to every pregnant woman since we cannot predict who will develop pre-eclampsia given the limitation in resources. Aspirin and calcium are the only two recommended therapies at this time. Measuring blood pressure and proteinuria is challenging in LMIC due to financial cost and lack of training. A detection tool that is affordable and can be easily applied is needed. Magnesium sulfate is the drug of choice for the prevention and treatment of eclampsia but it is underutilized due to barriers on multiple levels., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objective: To assess whether students find concept mapping a useful learning methodology to conceptualize and organize topics studied in CNS module of Pharmacology; and to evaluate whether addition of concept mapping assignment could help to improve examination scores., Study Design: An analytical study., Place and Duration of Study: College of Dentistry, Jinnah Medical and Dental College, Karachi, Pakistan, from March to May 2009., Methodology: A class of 50 BDS students was recruited for the study. Two randomly selected groups of 12 students each, prepared concept maps in topics from CNS pharmacology which were displayed and discussed during tutorial sessions. The other two groups (n = 25) following the traditional teaching methodology, served as controls. Scores from best choice questions and short essay questions were compared between the investigational and control groups using the student's t-test with significance at p < 0.05. Feedback obtained after completion of the study was evaluated as percent response., Results: One-best-choice test of the control group showed a mean grade of 57.1 ± 16.7 vs. test group mean of 58.8 ± 13. For the short essay questions, control group obtained a mean of 52.3 ± 18.8 vs. test group mean grade of 53.8 ± 22.5. Both results were not significantly different (p > 0.05). However, feedback about concept mapping showed that the technique helped the students to conceptualize difficult topics in CNS pharmacology (86.36%). Concept mapping was particularly beneficial in preparing for exams as it provided a quick overview of the entire subject (68.68%)., Conclusion: Students found concept mapping as a useful pedagogical tool which could potentially be used to acquire meaningful learning in Pharmacology as a supplement to traditional teaching techniques. It was not found beneficial in improving examination grades probably because standard examinations and concept mapping measure different cognitive domains.

Hypertension, proteinuria and biochemical changes caused by pre-eclampsia may persist for several weeks and even months postpartum. Hypertension and pre-eclampsia may even develop for the first time postpartum. Care in the six weeks postpartum should include management of hypertension and screening for secondary causes of hypertension including renal disease if abnormalities persist beyond six weeks. Optimal postpartum monitoring for patients with preeclampsia has not been determined, and care needs to be individualized. The postpartum period also provides a window of opportunity for planning for the next pregnancy in addition to discussing long term implications of pre-eclampsia. Increased risk for the development of premature cardiovascular disease is the most significant long term implication of pre-eclampsia. Pre-eclampsia and cardiovascular disease share a common disease pathophysiology. Women who develop pre-eclampsia have pre-existing metabolic abnormalities or may develop them later in life. Women with early onset pre-eclampsia are at the highest risk of ischemic heart disease. Women with a history of pre-eclampsia should adopt a heart healthy lifestyle and should be screened and treated for traditional cardiovascular risk factors according to locally accepted guidelines., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Packed red blood cell (PRC) transfusion with iron chelation is the mainstay of treatment for β-thalassemia major. This prospective interventional trial serves as a follow up to our similar earlier study that evaluated the efficacy and safety of hydroxyurea (HU) in minimizing PRC transfusions in patients with β-thalassemia major., Methods: One hundred fifty-two patients with β-thalassemia major received HU at a mean dose of 16 mg/kg/d. The results were analyzed at the end of 24 months. Transfusion requirement during the 6 months preceding the study was considered as the control., Results: One hundred forty-six of 152 patients were evaluated after 24 months of follow up; 6 patients were either lost to follow-up or withdrew consent. Grade 1 myelosuppression was observed in 4 patients and diarrhea in 2 patients. Sixty children (41%) did not require any transfusion after using HU; 57 patients (39%) showed partial response with greater than 50% reduction in PRC transfusion; and 29 patients (20%) were nonresponders with less than 50% reduction in PRC transfusion. The mean volume of PRC transfused was reduced for all patients., Conclusions: HU was found to be safe in patients with β-thalassemia major, and resulted in the reduction of transfusion requirement and in an increase in the interval between transfusions.

Considering the significance of progesterone receptor (PR) modulators, the present study is explored to envisage the biophoric signals for binding to selective PR subtype-A using ligand-based quantitative structure activity relationship (QSAR) and pharmacophore space modeling studies on nonsteroidal substituted quinoline and cyclocymopol monomethyl ether derivatives. Consensus QSAR models (Training set (Tr): n(Tr)=100, R(2) (pred)=0.702; test set (Ts): n(Ts)=30, R(2) (pred)=0.705, R(2) (m)=0.635; validation set (Vs): n(Vs)=40, R(2) (pred)=0.715, R(2) (m)=0.680) suggest that molecular topology, atomic polarizability and electronegativity, atomic mass and van der Waals volume of the ligands have influence on the presence of functional atoms (F, Cl, N and O) and consequently contribute significant relations on ligand binding affinity. Receptor independent space modeling study (Tr: n(Tr)=26, Q(2)=0.927; Ts: n(Ts)=60, R(2) (pred)=0.613, R(2) (m)=0.545; Vs: n(Vs)=84, R(2) (pred)=0.611, R(2) (m)=0.507) indicates the importance of aromatic ring, hydrogen bond donor, molecular hydrophobicity and steric influence for receptor binding. The structure-function characterization is adjudged with the receptor-based docking study, explaining the significance of the mapped molecular attributes for ligand-receptor interaction in the catalytic cleft of PR-A.

Dental traumatic injuries are widespread in the population and are a frequent pathology among children and teenagers. Dentists and especially pediatric dentists are commonly confronted with managing dental crown root fractures on a regular basis. Fiber-reinforced composite (FRC) have been used as an alternative to conventional space maintainers in pediatric dentistry. We present here a case of a 11-year-old boy with oblique crown root fracture, treated by placing extracted natural crown with FRC as space maintainer., (© 2011 John Wiley & Sons A/S.)

Background: The purpose of this study was to identify the prognostic factors affecting the outcome in patients with mucoepidermoid carcinoma (MEC) of the parotid gland., Methods: A total of 113 patients with MEC who were treated between 1993 and 2002 were analyzed., Results: At median follow-up of 49 months (range, 1-143 months), disease-free survival (DFS) at 5 and 10 years was 84.6 and 84.6%, 80.7% and 67.3%, and 52.5% and 35.0% for low-grade, intermediate-grade, and high-grade tumors, respectively. Five-year and 10-year overall survival was 96.8% for low-grade tumors; 94.1% and 82.4%, respectively, for intermediate-grade tumors; and 73.3% for high-grade tumors. High-grade tumors and lymph node cancer-positive neck tumors strongly predicted poor locoregional control and DFS, while close or positive cut margins showed a trend toward poorer outcomes., Conclusion: Histologic grade is the most important factor affecting outcome in parotid MEC. Adjuvant radiotherapy is recommended for high-grade tumors and should be tailored according to the expected risk of recurrence for low-grade and intermediate-grade tumors., (Copyright © 2010 Wiley Periodicals, Inc.)

Manganese ion (Mn(2+)) is a calcium (Ca(2+)) analog that can enter neurons and other excitable cells through voltage gated Ca(2+) channels. Mn(2+) is also a paramagnetic that shortens the spin-lattice relaxation time constant (T(1)) of tissues where it has accumulated, resulting in positive contrast enhancement. Mn(2+) was first investigated as a magnetic resonance imaging (MRI) contrast agent approximately 20 years ago to assess the toxicity of the metal in rats. In the late 1990s, Alan Koretsky and colleagues pioneered the use of manganese enhanced MRI (MEMRI) towards studying brain activity, tract tracing and enhancing anatomical detail. This review will describe the methodologies and applications of MEMRI in the following areas: monitoring brain activity in animal models, in vivo neuronal tract tracing and using MEMRI to assess in vivo axonal transport rates.

Background: The gram-negative bacterium Francisella tularensis survives in arthropods, fresh water amoeba, and mammals with both intracellular and extracellular phases and could reasonably be expected to express distinct phenotypes in these environments. The presence of a capsule on this bacterium has been controversial with some groups finding such a structure while other groups report that no capsule could be identified. Previously we reported in vitro culture conditions for this bacterium which, in contrast to typical methods, yielded a bacterial phenotype that mimics that of the bacterium's mammalian, extracellular phase., Methods/findings: SDS-PAGE and carbohydrate analysis of differentially-cultivated F. tularensis LVS revealed that bacteria displaying the host-adapted phenotype produce both longer polymers of LPS O-antigen (OAg) and additional HMW carbohydrates/glycoproteins that are reduced/absent in non-host-adapted bacteria. Analysis of wildtype and OAg-mutant bacteria indicated that the induced changes in surface carbohydrates involved both OAg and non-OAg species. To assess the impact of these HMW carbohydrates on the access of outer membrane constituents to antibody we used differentially-cultivated bacteria in vitro to immunoprecipitate antibodies directed against outer membrane moieties. We observed that the surface-carbohydrates induced during host-adaptation shield many outer membrane antigens from binding by antibody. Similar assays with normal mouse serum indicate that the induced HMW carbohydrates also impede complement deposition. Using an in vitro macrophage infection assay, we find that the bacterial HMW carbohydrate impedes TLR2-dependent, pro-inflammatory cytokine production by macrophages. Lastly we show that upon host-adaptation, the human-virulent strain, F. tularensis SchuS4 also induces capsule production with the effect of reducing macrophage-activation and accelerating tularemia pathogenesis in mice., Conclusion: F. tularensis undergoes host-adaptation which includes production of multiple capsular materials. These capsules impede recognition of bacterial outer membrane constituents by antibody, complement, and Toll-Like Receptor 2. These changes in the host-pathogen interface have profound implications for pathogenesis and vaccine development.

Libman-Sacks endocarditis is a well-known and rather common cardiac manifestation of systemic lupus erythematosus. Transesophageal and transthoracic echocardiography are the definitive imaging methods used to evaluate cardiac valvular involvement in this disease. Valvular masses (vegetations) and valvular thickening are 2 common morphologic echocardiographic patterns. Libman-Sacks lesions are typically characterized by single-valve involvement and their small size of 1 to 4 mm.Herein, we present the unusual case of a 22-year-old woman with newly diagnosed systemic lupus erythematosus who had large, sterile vegetations of Libman-Sacks endocarditis that involved the mitral and aortic valves. This compromised coronary blood flow and resulted in ventricular fibrillation cardiac arrest. The vegetations were surgically excised, and the patient's cardiac function recovered. We discuss the treatment of the patient and that of Libman-Sacks endocarditis.

Stem and progenitor cells are emerging as a potential source for cell-based therapies, in which large homogenous populations of differentiated cells are frequently deemed necessary for efficacy. Methods focused on biochemical cues have not yet yielded the numbers of endothelial cells thought necessary for cardiovascular applications. Interest in alternate methods has prompted the study of physical cues on stem and progenitor cell differentiation. In this study, fluid-based shear stress, at levels comparable to those experienced by endothelial cells in large vessels, was applied during the first few days of mouse embryonic stem cell differentiation. After 2 days of applied shear stress, there were increases in cell proliferation and in protein expression of endothelial markers (FLK1, VECAD, and PECAM). Further, treatment increased the number of FLK1+ cells from 1% to 40%, which were then capable of forming vessel-like structures in vitro. Thus, shear stress may be used to direct differentiation of embryonic stem cells toward an endothelial-like phenotype, helping to address the cell sourcing issue in cardiovascular regenerative medicine and tissue engineering.

Background: Anencephaly is a fatal congenital abnormality characterised by absence of cerebral hemisphere and cranial vault. Overall incidence of anencephaly is 3.8-6.0/1,000 births. This study was conducted to determine the prevalence, diagnosis and management of anencephaly in District Swat., Methods: This prospective study was carried out over a period of one year from January 2007 to December 2007 at Saidu Teaching Hospital/Saidu Medical College Swat. Pregnant women having foetuses with neural tube defects (NTDs) admitted in Labour Room/Obstetric Ward of the Saidu Teaching Hospital Swat were selected as subjects. Those women who delivered normal babies were taken as control subjects. A proper history was taken from each subject and all the relevant information were recorded on a proforma., Results: A total of 5,560 subjects were included in this study. Out of them, 69 were having NTDs, 63 had anencephaly, 4 had spina bifida, and 2 foetuses were having multiple neural tube defects. Prevalence of anencephaly was 11.33/1000 births and that of spina bifida was 0.72/1000 births. Eighty percent (80%) anencephaly and 50% spina bifida were diagnosed by ultrasonography. Most of the cases (52, 75.36%) were delivered through normal vaginal delivery after induction. Twelve (17.40%) had spontaneous vaginal delivery, 4 (5.80%) had caesarean section, and hysterectomy was done in 1 (1.45%)., Conclusion: Anencephaly is common congenital anomaly in Swat. Complications can be prevented by implementing screening program for early diagnosis, treatment, and management. Prevalence can be decreased by folic acid supplementation periconceptionally.

The majority of pregnant women experience nausea and vomiting during pregnancy. However, nausea and vomiting in pregnancy is not always nausea and vomiting of pregnancy (NVP). The differential diagnosis of nausea and vomiting in pregnancy can be extensive and the underlying cause can sometimes be difficult to diagnose. However, the timing or onset of the symptoms is important in differentiating NVP from other causes. A thorough history and physical examination, with appropriate investigations, should be carried out in symptomatic women.

Restoration of the vascular supply to ischemic tissues is of high clinical relevance, and proangiogenic therapies aim to reduce morbidity and mortality rates associated with the onset of cardiovascular disease. Stem cell therapy has been proposed as a potentially useful proangiogenic therapy. Mesenchymal stem cells (MSCs) have been shown to be proangiogenic and produce a number of cytokines involved in vessel development and maturation. Preclinical studies have reported increased angiogenesis after MSC delivery to the heart, and similar outcomes have been reported in recent clinical trials. Stem-cell-mediated neovascularization has been augmented by genetic modification with overexpression of angiogenic cytokines, including vascular endothelial growth factor (VEGF) and platelet-derived growth factor, showing promising results. In this study we aimed to enhance the proangiogenic capability of MSCs. MSCs were genetically modified to overexpress a versatile molecule, Ephrin-B2, involved in tissue morphogenesis and vascular development to enhance inherent neovascularization potential. Using nucleofection, Ephrin-B2 was transiently overexpressed on the cell surface of MSCs to recapitulate embryonic signaling and promote neovascularization. Ephrin-B2-expressing MSCs adopted an early endothelial phenotype under endothelial cell culture conditions increasing expression of von Willebrand factor and VEGF-Receptor 2. The cells had an increased ability to form vessel-like structures, produce VEGF, and incorporate into newly formed endothelial cell structures. These data indicate that MSCs expressing Ephrin-B2 represent a novel proangiogenic cell source to promote neovascularization in ischemic tissues.

Background: Gram-negative Enterobacteriaceae with resistance to carbapenem conferred by New Delhi metallo-beta-lactamase 1 (NDM-1) are potentially a major global health problem. We investigated the prevalence of NDM-1, in multidrug-resistant Enterobacteriaceae in India, Pakistan, and the UK., Methods: Enterobacteriaceae isolates were studied from two major centres in India--Chennai (south India), Haryana (north India)--and those referred to the UK's national reference laboratory. Antibiotic susceptibilities were assessed, and the presence of the carbapenem resistance gene bla(NDM-1) was established by PCR. Isolates were typed by pulsed-field gel electrophoresis of XbaI-restricted genomic DNA. Plasmids were analysed by S1 nuclease digestion and PCR typing. Case data for UK patients were reviewed for evidence of travel and recent admission to hospitals in India or Pakistan., Findings: We identified 44 isolates with NDM-1 in Chennai, 26 in Haryana, 37 in the UK, and 73 in other sites in India and Pakistan. NDM-1 was mostly found among Escherichia coli (36) and Klebsiella pneumoniae (111), which were highly resistant to all antibiotics except to tigecycline and colistin. K pneumoniae isolates from Haryana were clonal but NDM-1 producers from the UK and Chennai were clonally diverse. Most isolates carried the NDM-1 gene on plasmids: those from UK and Chennai were readily transferable whereas those from Haryana were not conjugative. Many of the UK NDM-1 positive patients had travelled to India or Pakistan within the past year, or had links with these countries., Interpretation: The potential of NDM-1 to be a worldwide public health problem is great, and co-ordinated international surveillance is needed., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

Wheat production in Pakistan is seriously constrained due to rust diseases and stripe rust (yellow) caused by Puccinia striiformis f. sp. tritici, which could limit yields. Thus development and cultivation of genetically diverse and resistant varieties is the most sustainable solution to overcome these diseases. The first objective of the present study was to evaluate 100 Pakistan wheat cultivars that have been grown over the past 60 years. These cultivars were inoculated at the seedling stage with two virulent stripe rust isolates from the United States and two from Pakistan. None of the wheat cultivars were resistant to all tested stripe rust isolates, and 16% of cultivars were susceptible to the four isolates at the seedling stage. The data indicated that none of the Pakistan wheat cultivars contained either Yr5 or Yr15 genes that were considered to be effective against most P. striiformis f. sp. tritici isolates from around the world. Several Pakistan wheat cultivars may have gene Yr10, which is effective against isolate PST-127 but ineffective against PST-116. It is also possible that these cultivars may have other previously unidentified genes or gene combinations. The second objective was to evaluate the 100 Pakistan wheat cultivars for stripe rust resistance during natural epidemics in Pakistan and Washington State, USA. It was found that a higher frequency of resistance was present under field conditions compared with greenhouse conditions. Thirty genotypes (30% of germplasms) were found to have a potentially high temperature adult plant (HTAP) resistance. The third objective was to determine the genetic diversity in Pakistan wheat germplasms using molecular markers. This study was based on DNA fingerprinting using resistance gene analog polymorphism (RGAP) marker analysis. The highest polymorphism detected with RGAP primer pairs was 40%, 50% and 57% with a mean polymorphism of 36%. A total of 22 RGAP markers were obtained in this study. RGAP, simple sequence repeat (SSR) and sequence tagged site (STS) markers were used to determine the presence and absence of some important stripe rust resistance genes, such as Yr5, Yr8, Yr9, Yr15 and Yr18. Of the 60 cultivars analyzed, 17% of cultivars showed a RGAP marker band for Yr9 and 12% of cultivars exhibited the Yr18 marker band. No marker band was detected for Yr5, Yr8 and Yr15, indicating a likely absence of these genes in the tested Pakistan wheat cultivars. Cluster analysis based on molecular and stripe rust reaction data is useful in identifying considerable genetic diversity among Pakistan wheat cultivars. The resistant germplasms identified with 22 RGAP markers and from the resistance evaluations should be useful in developing new wheat cultivars with stripe rust resistance.

Melanomas are malignant neoplasms of melanocytes developing predominantly in the skin, but occasionally arising from eyes, mucous membranes, and the central nervous system (CNS). The CNS can be affected by a spectrum of melanocytic lesions ranging from diffuse neurocutaneous melanosis, to a focal and benign neoplasm (melanocytoma), and to an overtly malignant tumor (melanoma). Primary melanocytic lesions involving the CNS are typically concentrated in the perimedullary and high cervical region. Primary CNS melanoma cannot be reliably distinguished from metastatic melanoma on neuroimaging and histopathological characteristics alone: its diagnosis is established only after exclusion of secondary metastatic disease from a cutaneous, mucosal or retinal primary. We present two patients with primary CNS melanoma and discuss relevant issues, available treatment options, and expected outcomes. Awareness of disease spectrum and clinico-biological differences may be used to guide therapeutic decision-making for a patient with a proven or suspected primary CNS melanoma.

An outdoor soil burial test was carried out to evaluate the degradation of commercially available LDPE carrier bags in natural soil for up to 2 years. Biodegradability of low density polyethylene films in soil was monitored using both optical and scanning electron microscopy (SEM). After 7-9 months of soil exposure, microbial colonization was evident on the film surface. Exposed LDPE samples exhibit progressive changes towards degradation after 17-22 months. SEM images reveal signs of degradation such as exfoliation and formation of cracks on film leading to disintegration. The possible degradation mode and consequences on the use and disposal of LDPE films is discussed., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Background: The vaginal contraceptive ring is a hormonal contraceptive that releases etonogestrel and ethinyl estradiol. Cerebral venous sinus thrombosis (CVST) is a rare but serious complication of hormonal contraceptive use., Case: We present a case of CVST in a 33-year-old nulligravid woman who was using a vaginal contraceptive ring. At the time of presentation, she had been using the ring for 18 months, having previously used oral contraceptives for 13 years. She had no additional risk factors for thrombosis apart from cigarette smoking. Despite vigorous management, the patient died from the effects of the CVST., Conclusion: The serious adverse effects of the vaginal contraceptive ring are not well known, although deep vein thrombosis, pulmonary embolism, and aortic thrombosis in association with use of the ring have been reported to Health Canada. Continuing post-market surveillance of thrombotic risk in users of the vaginal contraceptive ring is critical.

Lymphomatoid granulomatosis is an Epstein-Barr virus-associated multisystem disease that combines granulomatous inflammatory process with lymphoproliferative potential. It predominantly affects lungs, skin, and brain and is characterized by multifocal, transmural, angiocentric, and angiodestructive pleomorphic lymphoid infiltrate in a perivascular distribution. Lymphomatoid granulomatosis is generally considered to be a neoplastic B-cell proliferation that has traditionally been associated with poor prognosis, evolving as a progressive multisystem disease transforming into B-cell lymphoma, with a median survival of 14 to 16 months only. Its lymphomatous nature explains prompt response to steroids and systemic chemotherapy, although appropriate optimal management still remains to be defined. The authors report on a young boy who presented with features of raised intracranial tension and sudden onset seizures. Neuroimaging showed 2 space-occupying lesions, larger in the left frontoparietal region with heterogeneous enhancement, moderate perifocal edema, compression, and mass effect. He underwent surgical decompression of the dominant lesion with prompt relief of symptoms. The diagnosis of lymphomatoid granulomatosis was confirmed on light microscopy and immunohistochemistry. An extensive systemic work-up ruled out other site(s) of involvement. He was successfully treated with aggressive systemic chemotherapy and moderate dose of whole-brain radiotherapy. Awareness of disease spectrum in the central nervous system may permit early diagnosis and thus allow institution of timely appropriate therapy.

Objective: To determine the frequency of anxiety and depression among medical students of Wah Medical College and their associations with sociodemographic and educational characteristics if any., Study Design: Cross-sectional survey., Place and Duration of Study: Wah Medical College, from September 2007 to March 2008., Methodology: A sample of 279 students was included in the study after excluding first year medical students because they were admitted for less than 6 months. A self administered Encounter Form was administered. Sociodemographic and educational characteristics included age, gender, birth order, number of siblings, monthly income, monthly expenditure on education, academic performance in professional examination, past medical and past psychiatric history, substance abuse and family history of psychiatric illness. Beck depression inventory and beck anxiety inventory were used to assess the level of depression and anxiety. The chi-square test was applied at 5% level of significance to determine associated factors for anxiety and depression respectively., Results: The mean age of students was 21.4+/-1.41 years with female preponderance i.e. 202 (72.4%). Anxiety was present in 133 (47.7%) students and depression in 98 (35.1%) students. Both were found concomitantly in 68 (24.37%) students. Age (p=0.013), gender (p=0.016), examination criteria dissatisfaction (p=0.002) and overburden with test schedule (p=0.002) were significantly associated with depression. Anxiety was significantly associated with gender (p=0.007), birth order (p=0.049), year of study (p=0.001), examination criteria dissatisfaction (p=0.010) and overburden with test schedule (p=0.006)., Conclusion: One third of students were found to have anxiety and depression which was associated with the sociodemographic and educational factors as stated above.

Targeting protein kinases with small molecules outside the highly conserved ATP pocket to stabilize inactive kinase conformations is becoming a more desirable approach in kinase inhibitor research, since these molecules have advanced pharmacological properties compared to compounds exclusively targeting the ATP pocket. Traditional screening approaches for kinase inhibitors are often based on enzyme activity, but they may miss inhibitors that stabilize inactive kinase conformations by enriching the active state of the kinase. Here we present the development of a kinase binding assay employing a pyrazolourea type III inhibitor and enzyme fragment complementation (EFC) technology that is suitable to screen stabilizers of enzymatically inactive kinases. To validate this assay system, we report the binding characteristics of a series of kinase inhibitors to inactive p38alpha and JNK2. Additionally, we present protein X-ray crystallography studies to examine the binding modes of potent quinoline-based DFG-out binders in p38alpha.

Cisplatin mediated nephrotoxicity is remarkably documented by reactive oxygen species. Carnosine is a naturally occurring dipeptide and has a scavenging property. The aim of present study was to assess the lipid peroxidation and antioxidant enzymes in association with oxidative stress in cisplatin -treated and 10 subsequent doses of carnosine-pretreated rats. 24 male Albino Wistar rats, were randomly divided into four groups (n=6). Group I remains untreated; Group II received Cisplatin (3 mg / kg) for 5 alternate days; Group III received Carnosine (10 mg / kg) for consecutive 10 days; Group IV received Carnosine (10 mg / kg) before administration of Cisplatin (3 mg / kg). The effects of carnosine on cisplatin-induced nephrotoxicity were evaluated by plasma creatinine, urea, malondialdehyde, nitrate; kidney tissue malondialdehyde, 4-HNE, superoxide dismutase and catalase activities. Cisplatin-induced oxidative stress was indicated by increased level of tissue MDA, 4-HNE and decreased level of tissue GSH, SOD and Catalase. Marked elevation of kidney weight and reduced body weight and pathological changes in kidney tissues were also observed in Cisplatin-treated rats. Carnosine reduced these pathological changes and counteracted the deleterious effects of cisplatin. The results divulge the beneficial effect of Carnosine pretreatment with cisplatin in experimental rat model.

Objective: To determine frequency of HIV in children with disseminated tuberculosis and tuberculous meningitis in a low HIV prevalence area, and to study clinical profile of those found HIV positive., Study Design: Cross-sectional, descriptive study., Place and Duration of Study: Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, India from February 2005 to January 2008., Methodology: The study was conducted on 215 children under 14 years of age with either disseminated tuberculosis or tuberculous meningitis. HIV infection was diagnosed in accordance with WHO strategy II. In children younger than 18 months, the strategy (to cut down costs) was to screen first by HIV antibody testing and subject only positive cases to virological tests. Parents of HIV positive children were also tested for HIV and counselled. The clinical profile of HIV positive patients was noted., Results: The frequency of HIV was 5.12%, while that in cases of disseminated tuberculosis was much higher (22%). No case with isolated tuberculous meningitis was HIV positive. The majority (45.45%) of patients with HIV were between 1-5 years of age. The mode of infection in 7 (63.63%) cases was parent to child transmission. Loss of weight, prolonged fever, pallor, hepato-splenomegaly and oral candidiasis were the commonest clinical manifestations among HIV positive patients., Conclusion: Clinically directed selective HIV screening in cases of disseminated tuberculosis can pickup undiagnosed cases of the same in areas with low prevalence of HIV infection.

Bone marrow-derived mesenchymal stem cells (MSCs) have received much attention as a potential treatment for myocardial infarction because of their potential to integrate into the host myocardium and repair the injured heart. The mode of action of stem cell-mediated cardiac repair is still somewhat unclear, including the potential role of MSCs in neovascularization. The objective of this study was to determine the in vitro effect of MSCs on angiogenesis-related endothelial cell (EC) behavior, including migration, monolayer permeability, and vessel formation and stabilization. In a noncontact coculture system, we found that MSCs increase EC proliferation and migration, promoting early events of angiogenesis, while also decreasing EC monolayer permeability. Further, in a time- and dose-dependent manner, MSCs in direct coculture with ECs on Matrigel can increase the persistence of preexisting vessels by greater than threefold, with complex vessels remaining stable for more than 10 days. The results demonstrate that MSCs play an active role in the cellular processes involved in the formation, stabilization, and maturation of newly formed vessels. Further, these outcomes are not governed solely by either paracrine or direct contact effects and are both time and dose dependent.

Objective: To determine the prevalence of metabolic syndrome (MS) in renal transplant recipients (RTR) using the modified Asian National Cholesterol Education Programme-Adult Treatment Panel III (NCEP-ATP III) criteria., Methods: A cross-sectional study was conducted on 200 RTRs between January 2008-August 2008. All were more than six months post transplant and above 18 years of age. Subjects with pre-transplant diabetes or New Onset Diabetes Mellitus after renal transplantation, with overt infections, dyslipidaemia or on lipid lowering medication and taking immunosuppressive drugs of the target organ inhibitor group as rapamycin, were excluded. The prevalence of MS was determined using the (NCEP-ATP III) criteria modified for Asians which includes waist circumference, triglycerides, HDL cholesterol, blood pressure and fasting blood glucose., Results: Of the 200 recipients studied, 87 (43.5%) had MS. There were 58 (39.4%) males and 29 (54.7%) females which shows female predominance. The mean age of the MS group was more then that of the non MS group (p < 0.0001). Hypertension and New Onset Diabetes Mellitus were prevalent more in MS group (p < 0.001 and p < 0.0001 respectively). Mean serum creatinine was higher in MS group but there was no significant difference. The prevalence of MS was 4.5% in the first twelve months, with a rise in this figure to 41.3% between one to five years after transplantation., Conclusion: There is a high prevalence of MS in Renal Transplant Recipients specifically after one year of transplantation.

Context: Accelerated partial-breast irradiation (APBI) using various approaches is being increasingly employed for selected women with early breast cancer (EBC)., Aims: To conduct a case-control study comparing disease control, cosmesis, and complications in patients with EBC undergoing APBI using multicatheter interstitial brachytherapy vs those receiving conventional whole breast radiotherapy (WBRT)., Settings and Design: Women with EBC fulfilling the American Brachytherapy Society (ABS) criteria were selected as 'cases' if treated with APBI or as 'controls' if offered WBRT during the period from May 2000 to December 2004., Materials and Methods: APBI patients were treated with high-dose-rate brachytherapy (HDR) to a dose of 34 Gy/10#/6-8 days. WBRT was delivered to the whole breast to a dose of 45 Gy/25# followed by tumor bed boost, either with electrons (15 Gy/6#) or interstitial brachytherapy (HDR 10 Gy/1#)., Results: At the median follow-up of 43.05 months in APBI and 51.08 months in WBRT there was no difference in overall survival (OS), disease-free survival (DFS), late arm edema, and symptomatic fat necrosis between the two groups. However, APBI resulted in increase in mild breast fibrosis at the tumor bed. Telangiectasias were observed in three patients of the APBI group. The cosmetic outcome was significantly better in the APBI group as compared to the WBRT group (P = 0.003)., Conclusions: This study revealed equivalent locoregional and distant disease control in the two groups. APBI offered better overall cosmetic outcome, though at the cost of a slight increase in mild breast fibrosis and telangiectasias.

Mesenchymal stem cells (MSCs) are a component of many cardiovascular cell-based regenerative medicine therapies. There is little understanding, however, of the response of MSCs to mechanical cues present in cardiovascular tissues. The objectives of these studies were to identify a model system to study the effect of well-defined applied cyclic strain on MSCs and to use this system to determine the effect of cyclic equibiaxial strain on the cellular and cytoskeletal organization of MSCs. When exposed to 10%, 1 Hz cyclic equibiaxial strain for 48 h, MSCs remained viable, retained characteristic gene and protein markers, and rearranged to form multicellular structures defined as clusters and knobs. This novel observation of cluster (overlapping cells surrounded by radial cellular projections) and knob (more dome-like structure containing significantly more cells than a cluster) formation did not involve changes in cytoskeletal proteins and resulted from cellular rearrangements initiated within 8 h of applied strain. Observed cellular responses were found to be dependent on substrate coating, but not on cell density for the 8-fold ranges tested. This system can thus be used to study the mechanoresponse over hours to days of MSCs exposed to applied cyclic strain in the context of cell-cell and cell-matrix interactions.

Objectives: This retrospective analytical study was carried out to observe the frequency of Hepatitis B and Hepatitis C among the pregnant women of Swat., Methods: The study was carried out from January 2008 to December 2008. It was a retrospective study based on review of records of pregnant women admitted to Labour Room of Obstetrics/Gynaecology Unit, Saidu Teaching Hospital, Swat. Patients were screened for Hepatitis B and C by Immuno Chromatographic Technique (ICT) device. The findings were recorded on proforma and analysed. Those found positive on screening test were confirmed by ELISA., Results: Total number of patients screened was 5607. The frequency of Hepatitis B and C (Combined) was 223 (3.98%), out of which 77 (1.37%) were HBsAg positive, 141 (2.52%) were anti HCV positive and 5 (0.09%) were both HBsAg and anti HCV positive. The frequency of Hepatitis B amongst age groups 14-19, 20-29, 30-39 and 40-49 years were 2/77, 33/77, 40/77, and 2/77) respectively. The frequency of Hepatitis C amongst age groups 14-19, 20-29, 30-39 and 40-49 years was 4/141, 59/141, 67/141 and 11/141 respectively. The frequency of Hepatitis B and C in multigravida was 41/77, 67/141, in grand multigravida it was 20/77, 43/141 and in primigravida it was 16/77, 31/141 respectively. The frequency of Hepatitis B and Hepatitis C amongst urban and rural population was 32 (39.02%) and 50 (60.98%); and 40 (27.40%) and 106 (72.60%) respectively. The frequency of Hepatitis B and C (Combined) in urban, rural population were 72 (31.58 %) and 156 (68.15%) respectively., Conclusion: HBsAg and HCV was common infections in pregnant women of Swat. Therefore, every pregnant woman undergoing delivery and/or any other surgical procedure must be screened for Hepatitis B and Hepatitis C.

Background and Purpose: To compare the efficacy of computed tomographic angiography (CTA) to that of digital subtraction angiography (DSA) in the detection of secondary causes of intracerebral hemorrhage (ICH)., Methods: Between January 2001 and February 2007 there were 286 patients that had both CTA and DSA for intracranial hemorrhage of all types. Those with primarily subarachnoid hemorrhage or recent trauma were excluded. Fifty-five patients formed the study cohort. Three reviewers independently analyzed the CTAs in a blinded protocol and classified them based on presence or absence of a secondary etiology. Results were compared with the reference standard DSA and kappa values determined for interobserver variability., Results: The overall sensitivity, specificity, positive predictive value, negative predictive value and accuracy of CTA were 89%, 92%, 91%, 91% and 91%, respectively. Kappa value for interobserver agreement ranged from 0.78 to 0.89. Two of four dural arteriovenous fistulas (dAVF) were missed on CTA by all three reviewers., Conclusion: CTA is nearly as effective as DSA at determining the cause of secondary intracerebral hemorrhage, but with a lower sensitivity for dAVFs. This supports the use of CTA as the first screening test in patients presenting with spontaneous ICH.

Objective: To determine the frequency distribution of various types of dissociative disorders, along with existing co-morbid depression and its level of severity in patients with dissociative disorder., Study Design: Observational, cross-sectional study., Place and Duration of Study: The Institute of Psychiatry, Rawalpindi General Hospital from October 2004 to March 2005., Methodology: Fifty consecutive patients were included in the study through non-probable purposive sampling technique. Encounter form included socio-demographic profile and brief psychiatric history. ICD 10 diagnostic criteria for research were administered for determining the presentation of dissociative disorder. Present state examination was applied to make diagnosis of depressive disorder in the studied patients. Descriptive statistics for frequency analysis of sociodemographic variables, type of presentation of dissociative disorder and the frequency of depressive disorder in patients of dissociative disorder., Results: The mean age was 23.6+/-8.67 years with female preponderance (n=40, 80% patients). Most of them were single, unemployed and belonged to urban population. Main stress was primary support group issue. Mixed category of dissociative disorder was highest (n=18, 38%) followed by unspecified and motor symptoms (n=13, 26%) in each group. Depression was present in 42 (84%) patients. Moderate depression was most frequent (n=19, 38%)., Conclusion: Mixed dissociative symptoms were found in 38%, while 26% had motor and unspecified category of dissociative symptoms respectively. Depressive disorder was present in 42 (84%) cases of dissociative disorder with 38% having moderate depression.

Background: The psychological aspects of burn injury have been researched in different parts of world producing different outcomes. Therefore objective of this research is to determine the frequency of Anxiety and Depression in burn patients. To assess the socio-demographic distribution of patients developing Anxiety and Depression and to determine the effects of burn related factors on development of Anxiety and Depression., Methods: A Case series was conducted at the Department of Burn, Pakistan Ordinance Factory Hospital, Wah Cantt. for a duration of 12 months commencing from June 2007 and concluded in May 2008. The study population comprised of hospitalized patients with 1% to 50%, selected through non probable sampling technique who were assessed for Anxiety and Depression on fifteen day after burn injury. Testing protocol comprised of questionnaire having socio-demographic variables and burn related variables. Beck Depression Inventory and Beck Anxiety Inventory was applied to evaluate Anxiety and Depression in Burn patients. Descriptive statistics like mean with Standard Deviation was calculated for age. Frequencies along with percentages were calculated for socio-demographic variables. The frequencies and proportions were also calculated for presence and extent of severity of depression and anxiety in burn patients., Results: Fifty patients were included in the study, thirty patients (60%) were male and 20 (40%) were females. The mean age of participants was 33.64 +/- 19 years. Majority of participants, 38 (76%) had sustained burn injury up to 25%. Flame was found to be most common agent of burn injuries affecting 19 (38%) patients. Depression was seen amongst 29 (58%) patients. Thirteen (26 %) patients had mild, 7 (14%) had moderate and 9 (18%) had severe Depressive symptoms. Anxiety was seen among 41 (82%) patients, thirteen (26%) patients had mild, 11 (22%) had moderate and 17 (34%) had severe Anxiety symptoms., Conclusion: Anxiety was present in 41 (82%) and Depression was present in 29 (58%) patients following burn injury. This study highlights the importance of the simultaneous evaluation and management of Anxiety and Depression in burn injured patients.

Objective: To determine the efficacy of single dose of magnesium sulphate versus the standard Pritchard regime in the management of pre-eclampsia., Study Design: Quasi-experimental study., Place and Duration of Study: Jinnah Postgraduate Medical Centre, Karachi, from January 2004 to January 2006., Methodology: All women with severe pre-eclampsia and impending eclampsia were included in the study. Patients with pregnancy induced hypertension and mild to moderate pre-eclampsia were excluded. From the 100 women included in the study, after matching for age, parity and gestational age, 50 were given only bolus dose of magnesium sulphate and 50 were given the standard regime. They were observed for one week for the number of convulsions. Fisher's exact test and Chi-square test were used to analyze results., Results: There was no significant difference in the two groups in term of occurrence of seizures, one patient developed fit with Pritchard regimen. The rate of caesarean section was lower in group A, 12% versus 30% in group B (p=0.05). There was no significant difference in perinatal outcome in either group (82% live births in group A versus 72% amongst group B (p=0.2). Few side effects like vomiting, dizziness and irritation at the site of injection were observed when standard treatment was used. Single dose treatment was also found to be cost-effective costing Pak Rs. 45 (US $ 0.56) as compared to Pak Rs. 195 (US $ 2.4) in control group. No maternal death was observed in either group., Conclusion: Having the equal effectiveness, ease of monitoring and cost-effectiveness, single loading dose of magnesium sulphate is preferable over the standard regime in the management of pre-eclampsia as a prophylactic measure for prevention of seizure.

Missense mutations in the PTPN11 gene, which encodes the protein tyrosine phosphatase SHP-2, cause clinically similar but distinctive disorders, LEOPARD (LS) and Noonan (NS) syndromes. The LS is an autosomal dominant disorder with pleomorphic developmental abnormalities including lentigines, cardiac defects, short stature and deafness. Biochemical analyses indicated that LS alleles engender loss-of-function (LOF) effects, while NS mutations result in gain-of-function (GOF). These biochemical findings lead to an enigma that how PTPN11 mutations with opposite effects on function result in disorders that are so similar. To study the developmental effects of the commonest LS PTPN11 alleles (Y279C and T468M), we generated LS transgenic fruitflies using corkscrew (csw), the Drosophila orthologue of PTPN11. Ubiquitous expression of the LS csw mutant alleles resulted in ectopic wing veins and, for the Y279C allele, rough eyes with increased R7 photoreceptor numbers. These were GOF phenotypes mediated by increased RAS/MAPK signaling and requiring the LS mutant's residual phosphatase activity. Our findings provide the first evidence that LS mutant alleles have GOF developmental effects despite reduced phosphatase activity, providing a rationale for how PTPN11 mutations with GOF and LOF produce similar but distinctive syndromes.

We present a case involving a 76-year-old man with a massive right-sided vascular neck mass that had been present since birth. The mass had been stable throughout the patient's life, but recently a portion of it had become hard. Physical examination revealed a firm, palpable focus within the vascular lesion in the right side of the neck. Computed tomography revealed the presence of numerous hyperdense foci, many more than 2 cm in size, which were confirmed by fine-needle aspiration to be phleboliths. The patient was followed for 6 months to ensure that the vascular mass and phleboliths remained stable.

Objective: The objective of the study was to determine completeness of 24-hour urine collection in pregnancy., Study Design: This was a retrospective laboratory/chart review of 24-hour urine collections at British Columbia Women's Hospital. Completeness was assessed by 24-hour urinary creatinine excretion (UcreatV): expected according to maternal weight for single collections and between-measurement difference for serial collections., Results: For 198 randomly selected pregnant women with a hypertensive disorder (63% preeclampsia), 24-hour urine collections were frequently inaccurate (13-54%) on the basis of UcreatV of 97-220 micromol/kg per day (11.0-25.0 mg/kg per day) or 133-177 micromol/kg per day (15.1-20.1 mg/kg per day) of prepregnancy weight (respectively). Lean body weight resulted in more inaccurate collections (24-68%). The current weight was frequently unavailable (28%) and thus not used. For 161 women (81% proteinuric) with serial 24-hour urine levels, a median [interquartile range] of 11 [5-31] days apart, between-measurement difference in UcreatV was 14.4% [6.0-24.9]; 40 women (24.8%) had values 25% or greater, exceeding analytic and biologic variation., Conclusion: Twenty-four hour urine collection is frequently inaccurate and not a precise measure of proteinuria or creatinine clearance.

A new heterogeneous precipitate of an organic-inorganic composite cation-exchanger poly-o-toluidine Zr(IV) phosphate was utilized for the preparation of a Hg(II) ion-sensitive membrane electrode for the determination of Hg(II) ions in real aqueous as well as in real samples. The electrode showed good potentiometric response characteristics, and displayed a linear log[Hg(2+)] versus EMF response over a wide concentration range of 1 x 10(-1) - 1 x 10(-6) M with a Nernstian slope of 30 mV per decade change in concentration with a detection limit of 1 x 10(-6). The membrane electrode showed a very fast response time of 5 s and could be operated well in the pH range 2 - 8. The selectivity coefficients were determined by the mixed-solution method, and revealed that the electrode was selective in the presence of interfering cations; however most of these did not show significant interference in the concentration range of 1 x 10(-1) - 1 x 10(-4) M. The lifetime of the membrane electrode was observed to be 120 days. The analytical utility of this electrode was established by employing it as an indicator electrode in the potentiometric titrations of Hg(2+) ions from a synthetic mixture as well as drain water.

Objective: To review the spot protein:creatinine ratio and albumin:creatinine ratio as diagnostic tests for significant proteinuria in hypertensive pregnant women., Design: Systematic review., Data Sources: Medline and Embase, the Cochrane Library, reference lists, and experts. Review methods Literature search (1980-2007) for articles of the spot protein:creatinine ratio or albumin:creatinine ratio in hypertensive pregnancy, with 24 hour proteinuria as the comparator., Results: 13 studies concerned the spot protein:creatinine ratio (1214 women with primarily gestational hypertension). Nine studies reported sensitivity and specificity for eight cut-off points, median 24 mg/mmol (range 17-57 mg/mmol; 0.15-0.50 mg/mg). Laboratory assays were not well described. Diagnostic test characteristics were recalculated for a cut-off point of 30 mg/mmol. No significant heterogeneity in cut-off points was found between studies over a range of proteinuria. Pooled values gave a sensitivity of 83.6% (95% confidence interval 77.5% to 89.7%), specificity of 76.3% (72.6% to 80.0%), positive likelihood ratio of 3.53 (2.83 to 4.49), and negative likelihood ratio of 0.21 (0.13 to 0.31) (nine studies, 1003 women). Two studies of the spot albumin:creatinine ratio (225 women) found optimal cut-off points of 2 mg/mmol for proteinuria of 0.3 g/day or more and 27 mg/mmol for albuminuria., Conclusion: The spot protein:creatinine ratio is a reasonable "rule-out" test for detecting proteinuria of 0.3 g/day or more in hypertensive pregnancy. Information on use of the albumin:creatinine ratio in these women is insufficient.

The aqueous extract of the aerial roots the Indian Banyan, Ficus benghalensis L. (Family: Moraceae) was evaluated for its effect on both specific and non-specific immunity. This extract exhibited a significant increase in percentage phagocytosis by human neutrophils in the in vitro tests. It exhibited promising immunostimulant activity at doses of 50, 100, 200 and 400 mg/kg body weight in SRBC induced hypersensitivity reaction and hemagglutination reaction in rats. The aqueous extract was found to stimulate the cell mediated and antibody mediated immune responses.

Background: The side effects of various treatments for prostate cancer have a measurable impact on the general as well as disease-related quality of life, which is of pivotal concern as an outcome measure., Aim: Translation and pilot testing of the European Organization for Research and Treatment of Cancer (EORTC) prostate cancer-specific module (PR-25) into Hindi and Marathi., Materials and Methods: The translation procedure described by the EORTC was adopted; this comprised two forward translations of the original English questionnaire into Hindi and Marathi each with formation of first intermediary questionnaires and two back translations of the first intermediary questionnaires into English. The first intermediary questionnaires were adapted as the second intermediary questionnaires and pilot tested in ten prostate cancer patients as no modifications were suggested by the back translators., Results: Each patient, after completing the questionnaire, was interviewed by the local project coordinator who questioned them about each item in the second intermediary questionnaire. The patients were asked whether there was any difficulty in answering, confusion while answering, or difficulty in understanding the questions; whether the questions were upsetting; and if the patients themselves would have framed the question in a different way. Based on the suggestions or interpretations of this pilot testing, the necessary changes were incorporated and the final Hindi and Marathi questionnaires were formed., Conclusion: Both the translations were submitted to the EORTC for review and have been subsequently approved for clinical studies.

Diabetic nephropathy is the leading cause of death that affects more than 40% of diabetic patients. Its metabolic derangements are frequently accompanied with electrolyte imbalances. This study was aimed to evaluate the electrolyte homeostasis during the progression of diabetic nephropathy in various stages of developing nephropathy. Patients admitted in diabetic wards of various hospitals of Karachi were selected and divided into 4 groups with 50 individuals each. Group I (healthy normotensive, non-diabetics with normal renal functions as control). Group II (diabetic patients with normal blood pressure and renal functions). Group III (diabetic hypertensive patients without renal disease). Group IV (diabetic nephropathy patients with nephropathy). Their fasting blood samples were drawn and analyzed for the estimations of intra erythrocyte and serum electrolytes and NA(+)-K(+)-ATPase activity. Group II patients showed a significant increase in intra erythrocyte sodium, serum potassium and calcium levels where as intra erythrocyte potassium, NA(+)-K(+)-ATPase, serum sodium and magnesium were significantly decreased as compared to control. Group III showed a significant rise in intra erythrocyte sodium levels but intra erythrocyte potassium, NA(+)-K(+)-ATPase, serum sodium, calcium and magnesium were significantly lowered as compared to control. Group IV revealed a significant increase in intra erythrocyte sodium and significant decrease in intra erythrocyte potassium, NA(+)-K(+)-ATPase, serum sodium, calcium and magnesium levels as compared to control. The results suggest the progressive trends in electrolyte abnormalities in diabetes mellitus leading to end stage renal disease along with the abnormality of their chief transport mechanism. It points towards the potentiality of electrolytes disturbances as indicators for the progression of diabetic nephropathy and also beneficial in prognosis and treatment of the disease.

A postmenopausal lady with an in situ pacemaker developed a lump in the left breast and was diagnosed to have breast cancer. The patient underwent breast conservative surgery and was planned for post operative radiotherapy. The location of the tumor relative to the pacemaker provided a unique challenge in planning radiotherapy and the patient had an uneventful post radiotherapy course. A literature review revealed that modern generation pacemakers are very sensitive to radiation compared to their older counterparts. The present article makes suggestions towards reducing dose in radiotherapy planning in pacemaker patients.

Background: Packed red blood cell (PRC) transfusion with iron chelation is the mainstay of treatment for patients with beta-thalassemia major. Hemoglobin F augmentation is another approach to treat this hemoglobinopathy. This study evaluates the efficacy and safety of hydroxyurea (HU) in minimizing PRC transfusions in patients with beta-thalassemia major., Method: Twenty-three patients with beta-thalassemia major received HU at a mean dose of 16 mg/kg/d. The results were analyzed at the end of 24 months. Transfusion requirement during the 6 months preceding the study was considered as the control., Result: Twenty patients were evaluable after 24 months. The mean volume of PRC transfused was reduced from 2126.45 mL to 1489.59 mL (P<0.001). The interval between transfusions was increased by 68.7%. Grade I myelosuppression was observed in 4 patients and diarrhea in 2 patients., Conclusions: HU was found to be safe in patients with beta-thalassemia major, and resulted in reduction in the transfusion requirements and in increase of the intervals between transfusions.

Background: Residents play an important role in teaching of medical undergraduate students. Despite their importance in teaching undergraduates they are not involved in any formal training in teaching and leadership skills. We aimed to compare the teaching skills of residents with faculty in facilitating small group Problem Based Learning (PBL) sessions., Methods: This quasi experimental descriptive comparative research involved 5 postgraduate year 4 residents and five senior faculty members. The study was conducted with all phase III (Final year) students rotating in Gastroenterology. The residents and faculty members received brief training of one month in facilitation and core principles of adult education. Different aspects of teaching skills of residents and faculty were evaluated by students on a questionnaire (graded on Likert Scale from 1 to 10) assessing i) Knowledge Base-content Learning (KBL), ii) PBL, iii) Student Centered Learning (SCL) and iv) Group Skills (GS)., Results: There were 33 PBL teaching sessions in which 120 evaluation forms were filled; out of these 53% forms were filled for residents and 47% for faculty group. The faculty showed a statistically greater rating in "KBL" (faculty 8.37 Vs resident 7.94; p-value 0.02), "GS" (faculty 8.06 vs. residents 7.68; p-value 0.04). Differences in faculty and resident scores in "the PBL" and "SCL" were not significant. The overall score of faculty facilitators, however, was statistically significant for resident facilitators. (p = .05)., Conclusion: 1) Residents are an effective supplement to faculty members for PBL; 2) Additional facilitators for PBL sessions can be identified in an institution by involvement of residents in teacher training workshops.

Aim: To review the causes of death in patients admitted via the emergency department (ED) who died within 7 days of admission and to identify any ways in which ED care could have been better. The study also aims to compare the diagnosis made in the ED and the mortality diagnosis., Methods: A retrospective study; subjects were all patients who attended the ED over 4 months and died within 7 days of admission. The paramedics' notes, ED case cards, inpatient medical notes and details of postmortem findings were examined to identify the time and date of arrival in the ED, presenting complaint, provisional diagnosis made by the ED, treatment plan devised by the ED, diagnosis made in wards, and the cause of death as issued on death certificates or from postmortem findings. Summary sheets of cases where the care provided by the emergency department could have been improved were reviewed, errors were identified and deaths were classified as preventable or unpreventable., Results: Database revealed 3521 admissions via the ED over 4 months, of which 95 cases (2.69%) died within 7 days of admission. 78 patients (82.1% of cases) were appropriately diagnosed and managed whereas 17 (17.87% of cases) were identified with deficiencies in either the diagnosis or the management provided in the ED. We reviewed the quality of care provided in the ED for these cases and rated deaths according to our preventability criteria: 5 (5.26%) deaths were unpreventable despite the deficiency in care provided in the ED; 3 (3.15%) deaths were definitely preventable; 3 (3.15%) were probably preventable; and 6 (6.31%) were possibly preventable deaths., Conclusion: The ED is playing a good role in the management of critically ill patients, with appropriate diagnosis and management in 82% of cases. Training of junior doctors is required to prevent occurrence of errors and thus preventable deaths, but all deaths are not preventable. New guidelines for sepsis management and management of undifferentiated clinical presentations are being introduced and we intend to audit the implications of new guidelines.

Objective: To determine the effect of partogram on the frequency of prolonged labour, augmented labour, operative deliveries and whether appropriate interventions based on the partogram will reduce maternal and perinatal complications., Method: A case controlled, prospective and interventional study on 1000 women in labour was carried out in the obstetric unit of Jinnah Post graduate medical center, Karachi, from 1st July to 30th December, 2002. Five hundred women were studied before and after the introduction of partogram. Duration of labour, mode of delivery, number of cases augmented and neonatal outcome were noted, Results: Labour was shorter than 12 hours in 80.8% primigravida, 18.4% had labour shorter than 24 hours and only 0.8% had labour longer than 24 hours. After introduction of partogram 91.6% delivered within 12 hours and rest (8.4%) delivered within 24 hours. Normal vaginal delivery was had in 88%, 5.6% had operative vaginal delivery and 6.4% had caesarean section. Introduction of partogram showed significant impact on duration of labour (p < 0.001) as well as on mode of delivery (p < 0.01). In multigravidae 94.4% delivered within 12 hours and rest 5.6% delivered within 24 hours when partogram was used while 88.4% delivered within 12 hours and the rest 11.6%) within 24 hours before the use of partogram. Partogram showed significant reduction in duration of labour (p < 0.01). Results also showed significant reduction in number of augmented labour (p < 0.001) and vaginal examinations (p < 0.001)., Conclusion: By using partogram, frequency of prolonged and augmented labour, postpartum haemorrhage, ruptured uterus, puerperal sepsis and perinatal morbidity and mortality was reduced.

Brain metastases are a significant cause of morbidity and mortality in patients with breast cancer. HER-2 positivity is an increasingly recognized risk factor for the development of brain metastases. Although considerable progress has been made in the treatment of this complication, supportive measures like steroids, anti-seizure medication and whole-brain radiation remain the cornerstones of management in the majority of patients. The current review discusses the above and other issues like surgical excision, stereotactic radiotherapy, adjuvant radiation, radiosensitization and chemotherapy. A brief discussion of the recent evidence for the use of 'HER-1/ HER-2'-targeted therapy is also present.

Beta-lactamase is a well established reporter for monitoring cellular events while chemiluminescence is the preferred read-out mode in high throughput screens. Here, we report the first chemiluminescent assay for beta-lactamase using beta-galactosidase based enzyme fragment complementation technology. The enzyme fragment complementation technology employs a large protein fragment called the enzyme acceptor and a small peptidic fragment called an enzyme donor. These fragments are inactive separately but recombine rapidly in solution to yield active beta-galactosidase detected by chemiluminescence or fluorescence. A cyclic enzyme donor comprising a substituted cephalosporin moiety is used as the lactamase substrate. The cyclic substrate does not complement with enzyme acceptor to yield active beta-galactosidase, but upon cleavage with lactamase yields the linear enzyme donor which complements readily with enzyme acceptor. This methodology has been exploited in a simple, sensitive, homogeneous cell based reporter gene assay to monitor G-protein coupled receptor activation in a microtitre plate with a chemiluminescent read out.

Objective: To determine the effectiveness of 50 microg misoprostol for midtrimester termination of pregnancies., Design: Experimental, cross-sectional study., Place and Duration of Study: Department of Gynaecology and Obstetrics, Unit II, Jinnah Postgraduate Medical Centre, Karachi, a tertiary care centre, from 1st Jan 2003 to 30th June 2005., Patients and Methods: The study subjects were 54 pregnant women admitted during the 2nd trimester (14-26 weeks) of gestation, willing or requiring termination of pregnancy. Those patients were included in the study who were admitted with closed cervical os, either had intrauterine death, fetal anomaly, medical disorder (hypertension or diabetes) or history of previous ceasrean section. Cases of placenta previa, acute asthma, glaucoma, cardiac diseases and allergy to prostaglandins were excluded. Each patient received 50 microg misoprostol intravaginally. Maximum 4 doses were given at 4 hours interval and state of cervical os was assessed by vaginal examination before insertion of next dose or at the onset of uterine contractions. After 4 doses of misoprostol, patients were kept under observation and watched for uterine contractions to start or for expulsion of products. Syntocinon infusion was started to augment labour where products of conception failed to expel out inspite of open os. Outcome measures include success rate of termination within 12, 24, 36 and 48 hours, mean induction - abortion time interval and maternal side effects., Results: The success rate of termination within 12, 24, 36 and 48 hours were 27.7%, 83.3%, 94.4% and 96.3% respectively. Mean induction to abortion time interval, in case of abortion within 48 hours, was found to be 18.9 +/- 11.58 (range 4 - 48 hours). Dead fetuses were aborted earlier than alive fetuses. The mean induction abortion time interval was 17.01 +/- 8.7 hours in dead and 23.4+/-15.9 hours in alive fetuses (t -value:1.9, p: 0.05). Two patients failed to deliver within 48 hours of induction. Two patients suffered from febrile illness., Conclusion: Vaginal administration of 50 microg misoprostol every 4 hourly is an effective and safe agent for ripening of cervix and convenient way of inducing abortion during 2nd trimester of pregnancy in a women either with alive or dead fetus. It is associated with a low frequency of side effect.