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Previous studies along the banks of the tidal Meghna River of the Ganges-Brahmaputra-Meghna Delta demonstrated the active sequestration of dissolved arsenic (As) on newly formed iron oxide minerals (Fe(III)-oxides) within riverbank sands. The sand with high solid-phase As (>500 mg/kg) was located within the intertidal zone where robust mixing occurs with oxygen-rich river water. Here we present new evidence that upwelling groundwater through a buried silt layer generates the dissolved products of reductive dissolution of Fe(III)-oxides, including As, while mobilization of DOC by upwelling groundwater prevents their reconstitution in the intertidal zone by lowering the redox state. A three end-member conservative mixing model demonstrated mixing between riverbank groundwater above the silt layer, upwelling groundwater through the silt layer, and river water. An electrochemical mass balance model confirmed that Fe(III)-oxides were the primary electron acceptor driving the oxidation of DOC sourced from sediment organic carbon in the silt. Thus, the presence of an intercalating silt layer in the riverbanks of tidal rivers can represent a biogeochemical hotspot of As release while preventing its retention in the hyporheic zone.

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Earthquakes present severe hazards for people and economies and can be primary drivers of landscape change yet their impact to river-channel networks remains poorly known. Here we show evidence for an abrupt earthquake-triggered avulsion of the Ganges River at ~2.5 ka leading to relocation of the mainstem channel belt in the Bengal delta. This is recorded in freshly discovered sedimentary archives of an immense relict channel and a paleo-earthquake of sufficient magnitude to cause major liquefaction and generate large, decimeter-scale sand dikes >180 km from the nearest seismogenic source region. Precise luminescence ages of channel sand, channel fill, and breached and partially liquefied floodplain deposits support coeval timing of the avulsion and earthquake. Evidence for reorganization of the river-channel network in the world's largest delta broadens the risk posed by seismic events in the region and their recognition as geomorphic agents in this and other tectonically active lowlands. The recurrence of comparable earthquake-triggered ground liquefaction and a channel avulsion would be catastrophic for any of the heavily populated, large river basins and deltas along the Himalayan arc (e.g., Indus, Ganges, Brahmaputra, Ayeyarwady). The compounding effects of climate change and human impacts heighten and extend the vulnerability of many lowlands worldwide to such cascading hazards.

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This study aims at the application of two chemometric techniques to visible spectra of acetic acid solutions of Co (II) and Co (III) for simultaneous determination thereof. Spectral data of 145 samples in the range of 400-700 nm were used to build the models. Partial least squares regression models were developed for which latent variables were determined using internal cross-validation with a leave-one-out strategy and 3 and 2 latent variables were selected for Co(II) and Co(III) based on root mean square error of cross-validation. For these models, root mean square errors of prediction were 1.16 and 0.536 mM and coefficients of determination were 0.975 and 0.892 for Co (II) and Co (III). As an alternate method, artificial neural networks consisting of three layers, with 10 neurons in hidden layer, were trained to model spectra and concentrations of cobalt species. Levenberg-Marquardt algorithm with feed-forward back-propagation learning resulted root mean square errors of prediction of 0.316 and 0.346 mM for Co (II) and Co (III) respectively and coefficients of determination were 0.996 and 0.988.

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ABSTRACT: Pulmonary hamartoma is the most common benign tumor of the lung and often discovered incidentally on imaging. We report the case of a 49-year-old woman recently diagnosed with left breast cancer with suspicious left axillary lymph nodes. 18 F-FDG PET/CT showed well-circumscribed, lobulated, low-attenuation soft tissue mass in the right lower lobe lung with mild to no significant metabolic activity. CT-guided biopsy showed the lesion composed of fat, cartilage, and smooth muscle, admixed with fibroconnective tissue. The findings are consistent with pulmonary hamartoma. The presence of fat in a well-circumscribed solitary pulmonary nodule along with low metabolic activity helps in the characterization of the lesion, which can alter patient management.

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The principal nature-based solution for offsetting relative sea-level rise in the Ganges-Brahmaputra delta is the unabated delivery, dispersal, and deposition of the rivers' ~1 billion-tonne annual sediment load. Recent hydrological transport modeling suggests that strengthening monsoon precipitation in the 21st century could increase this sediment delivery 34-60%; yet other studies demonstrate that sediment could decline 15-80% if planned dams and river diversions are fully implemented. We validate these modeled ranges by developing a comprehensive field-based sediment budget that quantifies the supply of Ganges-Brahmaputra river sediment under varying Holocene climate conditions. Our data reveal natural responses in sediment supply comparable to previously modeled results and suggest that increased sediment delivery may be capable of offsetting accelerated sea-level rise. This prospect for a naturally sustained Ganges-Brahmaputra delta presents possibilities beyond the dystopian future often posed for this system, but the implementation of currently proposed dams and diversions would preclude such opportunities.

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Primary vaginal cancer is a rare malignancy with a lack of international guidelines and supporting clinical trial evidence to guide decision making. Historical results have shown poor outcomes with chemotherapy for stage IVB vaginal squamous cell carcinoma (SCC). The evolving role of checkpoint inhibitors in rare gynaecological cancers prompted us to investigate the role of pembrolizumab in this setting. The efficacy of pembrolizumab in vaginal SCC has never been investigated in any clinical trial. There is established data to support the use of concurrent chemoradiotherapy in gynaecological cancers, however, the data for concurrent use of immunotherapy and radiotherapy is still lacking but is the subject of several clinical trials. We herein present the first reported case of chemotherapy refractory vaginal SCC with complete response to pembrolizumab and concurrent pelvic radiotherapy. We also present wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) as a rare but new immune related adverse event.

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Gastric cancers are the third leading cause of cancer mortality in the world. Helicobacter pylori causes over 60 % of all stomach cancers. Colonization of the gastric mucosa by H. pylori results in increased DNA damage. Repair of DNA damage may also be reduced by H. pylori infection. Reduced DNA repair in combination with increased DNA damage can cause carcinogenic mutations. During progression to gastric cancer, gastric epithelium goes through stages of increasing pathology. Determining the levels of DNA repair enzymes during progression to gastric cancer could illuminate treatment approaches. Our aim is to determine the level of gastric expression of DNA repair proteins ERCC1 (a nucleotide excision repair enzyme) and PMS2 (a mismatch repair enzyme) in the presence of H. pylori infection at successive stages of gastric pathology and in gastric cancers. We analyzed gastric tissues of 300 individuals, including 30 without dyspepsia, 200 with dyspepsia and 70 with gastric cancers. The presence of H. pylori, gastric pathology and expression of DNA repair proteins ERCC1 and PMS2 were evaluated. Infection by H. pylori carrying the common cagA gene reduced median nuclear expression of ERCC1 and PMS2 to less than 20 % and 15 % of normal, respectively, in all pathologic stages preceding cancer. ERCC1 and PMS2 nuclear expression was 0-5 % of normal in gastric cancers. H. pylori can cause deficiency of ERCC1 and PMS2 protein expression. These deficiencies are associated with gastric pathology and cancer. This reduction in DNA repair likely causes carcinogenic mutations. Substantially reduced ERCC1 and PMS2 expression appears to be an early step in progression to H. pylori-induced gastric cancer.

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BACKGROUND: Chronic allograft nephropathy (CAN) is a common cause of delayed allograft failure throughout the world. Its prevalence and risk factors vary depending on a number of factors. There is little information on the prevalence and risk factors for early CAN in live related renal transplant patients. OBJECTIVES: We aimed to determine the prevalence and the risk factors of early CAN in our setup. PATIENTS AND METHODS: The study was conducted at Sindh Institute of Urology & Transplantation (SIUT), Karachi, from 2002 to 2005 on patients who had live related kidney transplantation and underwent at least one allograft biopsy within 18 months of transplantation. The biopsies were performed and prepared in accordance with established indications and guidelines. The Banff 97 classification and its updates were used to diagnose and categorize the biopsy pathology. Patients were divided into two groups depending on the presence or absence of CAN on biopsies. Following parameters were compared among the groups: age, sex, human leukocyte antigen (HLA) match, immunosuppression used, acute rejection (AR) episodes, urinary tract infections (UTIs), viral infections, cyclosporine levels, early and late graft function monitored by serum creatinine. RESULTS: A total of 164 patients fulfilled the study inclusion criteria. The mean age of recipients and donors was relatively young. The majority of the donors were siblings. The overall prevalence of CAN was 25.6% (42/164), between 3 and 18 months post transplantation. The median time to the appearance of CAN was 9 months post-transplant. The prevalence of CAN increased as post-transplant duration increased. In 39 (92.8%) subjects, CAN was detected on the second or subsequent graft biopsy. Only 3 (7.2%) patients showed CAN on the first graft biopsy. The majority of cases belonged to moderate degree or grade II CAN. The mean serum creatinine values were higher in the CAN group at the time of discharge and all times post-transplantation. CONCLUSIONS: In conclusion, the results show that serum creatinine at the time of discharge is a useful predictor of later development of chronic changes in the allograft. Further studies are needed to identify the risk factors for the early development of chronic changes in living related renal transplant program.

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BACKGROUND: Epithelioid trophoblastic tumor (ETT) is a rare gestational trophoblastic neoplasm of intermediate trophoblasts. It was first described by Shih and Kurman [Am J Surg Pathol 1998;22:1393-1403] who outlined its clinicopathologic characteristics in 14 cases, establishing it as a distinct entity of gestational trophoblastic tumors. It represents 1.39% of all gestational trophoblastic diseases. Most cases are reported in reproductive-age women following a prior gestation with a time interval between 2 weeks and 30 years. ETT is extremely rare in postmenopausal women. It is commonly misdiagnosed as a squamous cell carcinoma (SCC), poorly differentiated carcinoma or another gestational trophoblastic tumor. Limited data is available regarding its cytological features on Pap smears. CASES: We report 2 cases of uterine ETT occurring in postmenopausal women. In both cases, an initial diagnosis of an SCC and a poorly differentiated carcinoma was rendered. We highlight the features of ETT helpful in differentiating it from other mimickers with emphasis on rarely reported cytological features of this neoplasm. CONCLUSION: ETT is a rare tumor with characteristic cytological features, but is commonly confused with SCC. A high index of suspicion is needed to make the correct diagnosis or to raise the consideration of ETT, especially in cases with an increased ß-human chorionic gonadotropin.

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Paraganglioma of the urinary bladder is extremely rare. In this report of a young man, hypertensive crisis and ventricular arrhythmia was provoked during cystoscopic evaluation of a bladder mass. A diagnosis of pheochromocytoma was considered following detection of high serum and urinary catecholamine levels. A preoperative meta-iodobenzylguanidine scan was, however, negative. The bladder mass was surgically removed following initiation of antihypertensive therapy. Pathological confirmation of extraadrenal pheochromocytoma was established. During a serial follow-up, serum and urine catecholamine levels were persistently elevated. This was explained by abnormalities on fluorodeoxyglucose positron emission tomography scan, which were considered to represent a metastatic malignant neuroendocrine tumour. The patient is on palliative chemotherapy for malignant paraganglioma. This case highlights variable presentation of pheochromocytoma, importance of having a high index of clinical suspicion for early recognition and prompt management and serious adverse consequence of a delayed diagnosis.

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OBJECTIVE: To assess the clinical course, complications and predictors of mortality in reducing the consequent morbidity and mortality in patients with tuberculous meningitis. METHODS: A prospective study was carried out at Civil Hospital Karachi from January 2009 to January 2011. Fifty-two confirmed cases of tuberculous meningitis were included. The entire clinical course with complications and predictors of mortality were assessed. Data was analyzed using SPSS version 17.0. RESULTS: The mean age of the patients was 36.29 +/- 16.7 years with an equal gender distribution. The presenting complaints were fever 51 (98.1%), neck-stiffness 44 (84.61%), and altered level of consciousness 40 (76.9%), headache 31 (59.6%), vomiting 19 (36.5%) and focal weakness 10 (19.2%). Among CNS signs, 47 (90.4%) patients had signs of meningeal irritation, 14 (26.9%) had cranial nerve palsies with abducent nerve being the most commonly involved cranial nerve (25%). Mean GCS was 11.4 +/- 2.9 and most of the patients presented with medical research council Stage 2 of tuberculous meningitis (which is minimally altered level of consciousness with minor focal neurological signs). Overall mortality was 21.1%. Univariate analysis revealed old age; advanced stage of tuberculous meningitis, serum sodium < 125 mmol/l, TLC > 9000/microL development of hydrocephalus and use of mechanical ventilation as major predictors of mortality. CONCLUSION: Tuberculous meningitis is a frequently reported problem in our part of the world. Hydrocephalus along with other sequelae are common complications. All patients should be assessed for the presence of risk factors affecting mortality of the disease.

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BACKGROUND/AIMS: Malnutrition is a significant problem in cirrhosis of the liver worldwide. Inadequate data is available on the nutritional status of Pakistani patients. This study aimed to determine the frequency and severity of malnutrition in patients having cirrhosis of the liver and to compare the degree of malnutrition with the severity of liver disease. MATERIALS AND METHODS: Two hundred ninety-eight patients with liver cirrhosis were included in the study. Nutritional status was assessed using the Royal Free Hospital Global Assessment scheme for cirrhotics. The patients were categorized into well-nourished, and mild to moderately and severely malnourished. Various degrees of malnutrition were compared with severity of disease according to Child-Pugh staging. RESULTS: In the 298 patients with liver cirrhosis, hepatitis C (54,36%) and B (35,90%) were the commonest aetiologies, followed by autoimmune hepatitis (3,35%), primary billiary cirrhosis (2,34%), Wilson's disease (1,34%), haemochromatosis (1,0%), cryptogenic cirrhosis (1,0%), and alcohol being the rare cause (0,67%). 14,42% patients were well-nourished, (54,02%) were mildto moderately malnourished and (31,54%) were severely malnourished. Malnutrition is more frequent in virus-related cirrhosis, and the degree of malnutrition increases with increasing clinical severity as assessed by Child- Pugh stages with statistically significant p-value of 0.001. CONCLUSION: Moderate to severe malnutrition among diverse aetiologies of cirrhosis is quite common in Pakistan. The degree of malnutrition increases with increasing clinical severity of cirrhosis of liver.

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OBJECTIVE: To determine the risk factors of urinary tract infection in renal transplant recipients and its effect on graft function among transplanted patients visiting the outpatients department of Sindh Institute of Urology and Transplantation. METHODS: This cohort study was conducted at Transplantation department, Sindh Institute of Urology and Transplantation Karachi. The period of the study enrollment extended from April 2008 to September 2008 included were two hundred adult live related renal transplant recipients who were enrolled during the initial post transplant period and followed up for one year. Analysis was done by using SPSS ver 10.0. The level of significance was taken as 0.05. Student's t test and chi square test were used to compare the variables in both groups. RESULTS: The mean age of the patients was 30 +/- 10 years. Sixty six (33%) renal transplant recipients had at least one episode of urinary tract infection which occurred in 51 (77%) patients during the first two months after renal transplant and 8 (12%) patients had recurrence of infection. Gram negative bacilli were the principally isolated agents. E. coli was found in 34 (51%) patients and Pseudomonas in 12 (18%). Renal stone disease, structural abnormalities, delays in Foleys removal, and post operation hospital stay were statistically significant risk factors for urinary tract infection in the patients. Twenty three recipients of the study developed early graft dysfunction due to urinary tract infection. No graft was lost in either groups. CONCLUSION: Structural abnormalities, renal stone disease, delay in removal of Foley's catheter and increased post transplant hospital stay are risk factors leading to UTI in renal transplant recipients.

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OBJECTIVE: To compare the acceptable colonoscopy completion rates in three successive audits, identifying the reasons for failure of completion and rectifying them to improve the performance at our endoscopy unit. METHODS: Study was conducted at Endoscopy unit of Medical Unit One Civil Hospital Karachi. The first audit was conducted retrospectively on the colonoscopy results, done from November 2004 to November 2005. As the information was incomplete, a performa was designed for the next prospective audit from December 2005 to November 2006. The shortcomings found in the results of this audit were improved in the third audit done prospectively from December 2006 to November 2007. RESULTS: In the first audit 164 patients (111 male) underwent colonoscopy. The mean age was 40 +/- 10.08 years. The overall caecal intubation rate was 55%, but adjusted caecal intubation was not calculated because of inadequate documentation. In the second audit, 119 patients (66 male) underwent colonoscopy. The mean age was 45 +/- 10.17 years. After implementing changes the overall crude caecal intubation rate was 54.8% and the adjusted caecal intubation rate was 75% with exclusion of strictures and poor preparation. In the third audit, 122 patients (58 males) underwent colonoscopy. The mean age was 38 +/- 11.07 years. With further improvement in methodology the overall crude caecal intubation rate was (80.3%) and the adjusted caecal intubation rate was (98%). CONCLUSION: These audits allowed us to evaluate our endoscopy services and to detect the short comings and deviation from standard techniques and hence improving the performance in the subsequent year for the benefit of patients.

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OBJECTIVE: To compare liver histology in HCV RNA positive patients with normal and elevated Alanine Aminotransferase Level (AST). METHODS: This Cohort (prospective) study was conducted at Civil Hospital Karachi from Jan 2007 to July 2007. Forty patients with positive HCV RNA were included. Their liver function tests were followed for three months. Those having normal ALT on three occasions were taken as controls and those having elevated ALT were taken as cases. Liver biopsy was performed, Specimens were reviewed by single pathologist. Scheuer's scoring for grading of inflammation and staging of fibrosis of chronic hepatitis was used. RESULTS: Out of Forty patients having positive HCV RNA, 14 (35%) were male and 26 (65%) were female. Mean ALT in control group was 27.3 +/- 6.1 u/l, mean ALT in cases was 91.7 +/- 39.95 u/l. Mean age in controls was 34.2 +/- 10.75 years and in cases was 33.6 +/- 9.40 years. On histopathology, the mean grade of inflammation in controls was 1.40 +/- 0.681 while in cases was 1.20 +/- 0.834, which was not statistically significantly different in the two groups (p = 0.411). Similarly mean staging of fibrosis in controls was 1.20 +/- 0.768 and in cases was 1.35 +/- 1.348 which was also not statistically different in the two groups (p = 0.668). Stage 3 and 4 fibrosis was seen only in raised ALT group and not in the controls. CONCLUSION: Patients with persistently normal ALT and elevated ALT, although had similar grading of inflammation but the fibrosis score was more in elevated ALT group. None of the patients with normal ALT had normal histology, so decision for antiviral treatment should be individualized in this group also.

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OBJECTIVE: To assess the clinical presentation and management of patients with epilepsy presenting with periocular post burn scarring. DESIGN: Prospective and descriptive study. PLACE AND DURATION OF STUDY: Department of Ophthalmology, Jinnah Postgraduate Medical Centre, Karachi from September 1999 to September 2002. SUBJECTS AND METHODS: This study included 23 patients who had epilepsy and presented with periocular post-burn scarring to the eye department for management. All patients had contractures of their lids with variable amounts of corneal scarring and damaged to the eye ball. The surgical procedure performed consisted of release of contracture, horizontal lid shortening and application of free skin graft. RESULTS: There were 18 (78.26%) female and 5 (21.73%) male patients. The age range was from 18 to 45 years with a mean of 28 years. In 17 (73.91%) patients, lid contracture was released to cover their eyeballs. In 6 (26.08%) patients the eyeball was lost due to late presentation. CONCLUSION: There should be a high index of suspicion in facial burns for ophthalmic damage and early referral to an ophthalmologist should be made to prevent complications. Early release of contracture with application of full or partial thickness skin grafts is advisable.

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The purpose of this study was to determine whether human galanin, a pleiotropic 30-amino acid neuropeptide, expresses amphipathic properties in vitro and, if so, whether these properties modulate its vasoactive effects in the intact peripheral microcirculation. We found that human galanin aggregates in an aqueous solution and forms micelles with a critical micellar concentration (CMC) of 0.4 microM. In addition, the peptide interacted with model membrane as indicated by long and significant increase of the surface pressure of the biomimetic monolayer membrane in vitro. Interactions of human galanin with sterically stabilized phospholipid micelles (SMM) were not associated with a significant change in peptide conformation. Using intravital microscopy, we found that suffusion of human galanin alone elicited significant concentration-dependent vasoconstriction in the intact hamster cheek pouch. This response was amplified when human galanin in SSM was suffused onto the cheek pouch. The effects of human galanin alone and in SSM were mediated by galanin receptors because galantide, a galanin receptor antagonist, abrogated galanin-induced vasoconstriction. Collectively, these data show that human galanin expresses amphipathic properties in the presence of phospholipids which in turn amplifies its vasoactive effects in the intact peripheral microcirculation.

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