Lewisite and many other similar arsenicals are warfare vesicants developed and weaponized for use in World Wars I and II. These chemicals, when exposed to the skin and other epithelial tissues, cause ...rapid severe inflammation and systemic damage. Here, we show that topically applied arsenicals in a murine model produce significant acute kidney injury (AKI), as determined by an increase in the AKI biomarkers NGAL and KIM‐1. An increase in reactive oxygen species and ER stress proteins, such as ATF4 and CHOP, correlated with the induction of these AKI biomarkers. Also, TUNEL staining of CHOP‐positive renal tubular cells suggests CHOP mediates apoptosis in these cells. A systemic inflammatory response characterized by a significant elevation in inflammatory mediators, such as IL‐6, IFN‐α, and COX‐2, in the kidney could be the underlying cause of AKI. The mechanism of arsenical‐mediated inflammation involves activation of AMPK/Nrf2 signaling pathways, which regulate heme oxygenase‐1 (HO‐1). Indeed, HO‐1 induction with cobalt protoporphyrin (CoPP) treatment in arsenical‐treated HEK293 cells afforded cytoprotection by attenuating CHOP‐associated apoptosis and cytokine mRNA levels. These results demonstrate that topical exposure to arsenicals causes AKI and that HO‐1 activation may serve a protective role in this setting.
We show that topically applied arsenicals in a murine model produce significant acute kidney injury (AKI) that was correlated with an increase in reactive oxygen species (ROS) and ER stress proteins and a systemic inflammatory response. The arsenical‐mediated inflammation involves activation of AMPK/Nrf2 signaling pathways, which regulate heme oxygenase‐1 (HO‐1). We show that HO‐1 can be a potential therapeutic target for antidote development against vesicant‐induced systemic damage.
Pathology-based cancer data is a high quality reflection of the patterns of cancer in the population it represents, provided the demographic details of the patients are carefully recorded. Relative ...frequency data is neither a replacement for population-based data nor a suggested alternative; it simply enhances the quality of population data and in very large data sets reflects the cancer patterns observed in the representative populations. Aware of the standard shortfalls of pathology-based data, the department of pathology, The Aga Khan University Hospital (AKUH) standardized its data, representing 53.4% of the cancer data of Karachi Division (Pakistan) and also reflecting the cancer pattern of other provinces of Pakistan. This data was compared with 4 different population and institutional-based data sets. The findings substantiate the observation that despite the problems of interpretation of data from pathology laboratories, they are an invaluable source of information on cancer patterns in much of the world where incidence data are unavailable . If developing countries, unable to organize National Population- Based Registry should as an alternate develop National Pathology-based Registers a well targeted and monitored, a Cancer Control Program would be possible. A good quality, large-scale pathology data with demographic details of the patient recorded can also be extended to give coverage to the population.
Chronic inflammation caused by ulcerative colitis (UC) causes a pro-neoplastic drive in the inflamed colon, leading to a markedly greater risk of invasive malignancy compared to the general ...population. Despite surveillance protocols, 50% of cases proceed to cancer before neoplasia is detected. The Enhanced Neoplasia Detection and Cancer Prevention in Chronic Colitis (ENDCaP-C) trial is an observational multi-centre test accuracy study to ascertain the role of molecular markers in improving the detection of dysplasia. We aimed to validate previously identified biomarkers of neoplasia in a retrospective cohort and create predictive models for later validation in a prospective cohort.
A retrospective analysis using bisulphite pyrosequencing of an 11 marker panel (SFRP1, SFRP2, SRP4, SRP5, WIF1, TUBB6, SOX7, APC1A, APC2, MINT1, RUNX3) in samples from 35 patients with cancer, 78 with dysplasia and 343 without neoplasia undergoing surveillance for UC associated neoplasia across 6 medical centres. Predictive models for UC associated cancer/dysplasia were created in the setting of neoplastic and non-neoplastic mucosa.
For neoplastic mucosa a five marker panel (SFRP2, SFRP4, WIF1, APC1A, APC2) was accurate in detecting pre-cancerous and invasive neoplasia (AUC = 0.83; 95% CI: 0.79, 0.88), and dysplasia (AUC = 0.88; (0.84, 0.91). For non-neoplastic mucosa a four marker panel (APC1A, SFRP4, SFRP5, SOX7) had modest accuracy (AUC = 0.68; 95% CI: 0.62,0.73) in predicting associated bowel neoplasia through the methylation signature of distant non-neoplastic colonic mucosa.
This multiplex methylation marker panel is accurate in the detection of ulcerative colitis associated dysplasia and neoplasia and is currently being validated in a prospective clinical trial.
The ENDCAP-C study was funded by the National Institute for Health Research Efficacy and Mechanism Evaluation (EME) Programme (11/100/29).
An unusual case of congenital benign hibernoma, in the submandibular region, in a 2.5 years old girl, is reported, who presented with a progressively increasing neck swelling. A CAT scan of neck ...revealed a superficial and deep low density mass. Surgical excision revealed a benign hibernoma. A 3-year follow-up shows no recurrence.
To overcome the diagnostic dilemma in proliferative conditions of the liver which sometimes pose a problem to the working pathologist especially when the material is inadequate, a special staining ...technique (AgNOR) has been applied.By using this technique, nucleolar organizer regions were counted which determine the proliferative status of the cells.This prospective study included 65 cases of randomly selected liver core and fine needle aspiration biopsies.AgNOR staining was performed on formalin-fixed, paraffin-embedded tissue sections NOR dots were counted in 100 randomly selected hepatocytes at ×100 oil immersion objective, and the mean count per cell was calculated for each case.Statistical analysis was done by using the Mann Whitney U test.AgNOR count results were later compared with the histologic diagnosis.The study revealed a gradual increase in mean AgNOR counts from normal liver through cirrhosis to hepatocellular carcinoma.The difference in NOR counts was significant in these three groups.The hepatocellular carcinomas were graded according to the Edmondson-Steiner histological grading system.The Grade I hepatocellular carcinomas show AgNOR counts ranging between 5-6/cell, a score which is much higher than in the normal liver, where it ranges between 1.2–2.0/cell.This technique can be used to assess the lesions where the distinction between normal liver andGrade I hepatocellular carcinoma is difficult with the use of routine methods.AgNOR counts in normal liver and chronic hepatitis cases were insignificant, but there was an appreciable difference between cases of chronic hepatitis, cirrhosis and hepatocellular carcinoma.In view of the results of this study, the AgNOR staining method is found to be a useful diagnostic tool to differentiate between normal liver, cirrhosis and hepatocellular carcinoma and also to precisely discriminate between cases of normal liver and Grade I hepatocellular carcinoma.
The objective of the study was to provide an overview of the demographics of cancer of the oral cavity and pharynx in Karachi South (1995-2001), and identify potential risk factors. Cases recorded ...for Karachi South, at Karachi Cancer Registry during 1(st) January 1995 to 31(st) December 2002 were analysed. For maximum completion of data cancer cases, recorded from 1(st) January 1995 to 31(st) December 2001 were included for final analysis. The age standardized incidence rates per 100000 population (ASIRs) for cancer of the oral cavity (excluding salivary gland) in Karachi South were 17.1 and 16.5 in males and females whereas the ASIRs for cancer of the pharynx (excluding nasopharynx) were 7.1 and 2.4 in males and females, respectively. The oral pharyngeal ratios were 2.4 and 6.9 for males and females and gender ratios (M F) were 1.04 for the oral cavity and 3.0 for the pharynx. The mean ages were 51 years (95% CI 49.6; 52.2) and 56.1 years (95% CI 54.4; 57.8) respectively. Cancer of the oral cavity ranked 2(nd) in Karachi in both genders. Cancer of the pharynx ranked 7(th) in males and 14(th) in females. Approximately 97% of the oral cavity and pharyngeal cancers were histologically confirmed. The majority of the oral (47.1%) and pharyngeal (51.9%) cancer cases presented as grade II lesions, and were discovered at advanced stages. Of the cancers reported during 1995-2001, 60.4% of the oral and 78.1% of the pharyngeal lesions had spread to a distant site at the time of diagnosis. Squamous cell carcinoma comprised 96.5% and 91.8% of the totals. The incidences of these cancers are comparable to the highest risk regions of the world. As distinct from other geographical areas oral cancer is as common in females as in males, which may reflect the pattern of exposure to known risk factors such as betal quid, arecanut and tobacco and the absence of alcohol as a risk factor in both genders. Apergillus contamination of arecanut could also be a risk factor but no confirmation studies or quantification is available. Despite the common risk factors, incidence of pharyngeal cancer is three times higher in men as compared with women. The keys to reducing the incidence and mortality due to oral and pharyngeal cancers are prevention and control, emphasizing cessation of tobacco use and cancer screening. However a targeted cancer and tobacco control program does not presently exist in Pakistan.
Gynecomastia is the most common cause of breast enlargement in males.
Trichophyton rubrum is a common dermatophyte, is responsible for a variety of infections, and may rarely manifest as a ...dermatophytic pseudomycetoma. We report the case of a 52-year-old man who presented with progressive bilateral breast enlargement. This is the first reported case of bilateral breast pseudomycetoma due to
T. rubrum. Long-term antifungal therapy with itraconazole was successful.
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