Correlation between intestinal stem cell niche changes and small bowel crypt failure in patients with treatment-naïve celiac disease.

OBJECTIVES: We hypothesized that crypt failure in the small bowel results in villous flattening in patients with celiac disease (CeD). We investigated whether alterations in the stem cell niche (ISC) are responsible for this phenomenon. MATERIALS AND METHODS: We included 92 duodenal (D2/3) biopsies from treatment-naive patients of CeD and 37 controls. All underwent screening for serum anti-tissue transglutaminase and endoscopic upper small bowel biopsy. Immunohistochemical markers were used to investigate ISC niche alterations, including LGR5 for crypt basal cells (CBC), Bmi1 for position 4+ cells, ß-Defensin for Paneth cells, R-spondin1 as WNT activator, transcription factor-4 as WNT transcription factor, BMP receptor1A as WNT inhibitor, fibronectin-1 as periepithelial stromal cell marker, H2AX as apoptosis marker, and Ki67 as proliferation marker. We also analyzed IgA anti-tTG2 antibody deposits by using dual-color immunofluorescence staining. RESULTS: We found that in biopsies from patients with treatment-naive CeD with modified Marsh grade 3a-3c changes, the epithelial H2AX apoptotic index was upregulated than in controls. LGR5+ crypt basal cells were upregulated in all modified Marsh grades compared to controls. However, the Ki67 proliferation index, expressions of WNT-activator RSPO1, and position-4 cell marker Bmi1 did not significantly alter in patients' biopsies as compared to controls ( P = 0.001). We also observed depletion of pericrypt stromal fibronectin-1 in patients with CeD compared to controls. In addition, we identified IgA anti-TG2 antibody deposits in pericrypt stroma. CONCLUSIONS: Our data suggests that ISC niche failure is a plausible hypothesis for villous flattening in patients with CeD, resulting from pericrypt IgA anti-TG2 antibody complex-mediated stromal depletion.

Bioactive fractions from Allium humile alleviate the risk of high fat diet induced atherosclerosis in albino Wistar rats by inhibiting protein kinase C.

Atherosclerosis is a global concern that worsens with age, and plants that are effective medicinal herbs can give a viable alternative. PKC is a key factor in cardiovascular and other disorders; targeting it can reduce the risk of these diseases. We evaluated Allium humile for PKC inhibition and therapeutic efficacy against atherosclerosis. Soxhlet extraction was done to obtain extracts (hexane, ethyl acetate, methanol, ethanol and aqueous) and then tested for DPPH radical scavenging and PKC inhibitory activity. The methanolic extract was more active than the other extracts, so it was subjected to column chromatography, and seventeen fractions were obtained. Only 11, 12, and 15 showed good activity against PKC. Wistar rats were divided into six groups and each group received high fat diet for 30 days. Then the three potent fractions (10 mg/kg) were administered for 15 days along with high fat diet. Fraction II had the highest effectiveness (P < 0.0001) in decreasing lipid levels, lipid peroxidation, reducing IL-6 and TNF-α expression, and raising nitric oxide. This also demonstrated a decrease in PKC activity, as well as a decrease in the formation of the lipoidal layer in the aorta wall and rupture of the intima and media as validated by histological analysis. The two compounds, phytol acetate and cyanidin 3-(6″-o-malonyllaminaribioside) were characterised in fraction II by NMR and HRMS and cyanidin 3-(6″-o-malonyllaminaribioside) inhibited PKC more efficiently. Thus, Allium humile has strong anti-atherogenic activity as well as the ability to inhibit PKC both in vitro and in vivo.

Etiopathological and Clinical Study of Acute Generalized Exanthematous Pustulosis: Experience from a Tertiary Care Hospital in North India.

BACKGROUND: Acute generalized exanthematous pustulosis (AGEP) is a type of severe cutaneous adverse reaction that is characterized by the rapid development of nonfollicular, sterile pustules on an erythematous base. OBJECTIVES: The aim of our study was to enroll all cases of AGEP reporting to our department over a period of one year and to find out the clinical and etiological profile of the patients. MATERIALS AND METHODS: All the patients reporting to our department with clinical features suggestive of AGEP were enrolled for the study. Careful history and examination were done to rule out other causes of pustular eruptions, which can resemble AGEP. AGEP validation score of the EuroSCAR study group was used to establish the diagnosis. RESULTS: A total of 16 patients were enrolled during the study period of one year. The majority of the patients were females with a mean age of 28.41 ± 12.2 years. Twelve (75%) of the patients had a history of drug intake while 4 (25%) had developed AGEP following an insect bite. Penicillins were the causative factor in five patients followed by cephalosporins in three patients, nonsteroidal anti-inflammatory drugs (NSAIDs) in 2 patients, and terbinafine in 1 patient. Tetanus toxoid was responsible for the development of AGEP in one patient. The insect bites were all spider bites. CONCLUSION: AGEP is a rare type of severe cutaneous adverse drug reaction.We encountered 16 patients of AGEP over a period of one year. An important cause of AGEP was spider bite in our study group.

Fabry's Disease: Case Series and Review of Literature.

Fabry's disease is an X-linked lysosomal storage disorder caused by a deficiency of alpha-galactosidase A enzyme with the progressive accumulation of globotriaosylceramide in vascular endothelial cells leading to cardiovascular, renal, gastrointestinal, neuropathic, lenticular, and dermatological manifestations. It is a rare cause of end-stage renal disease. It classically affects males whereas 10-15% of female heterozygote carriers are affected depending on localization. Both the FD and its association with ESRD is rare. With this background, this case series of five patient's along with the review of literature is presented here.

Thalidomide-Related Eosinophilic Pneumonia: A case report and brief literature review.

Thalidomide has regained value in the multimodality treatment of leprosy, multiple myeloma, prostate, ovarian and renal cancer. Complications related to arterial and venous complications are well described. However, pulmonary complications remain relatively uncommon. The most common pulmonary side-effect reported is non-specific dyspnea. We report a patient with multiple myeloma, who developed an eosinophilic pneumonia, shortly after starting thalidomide. She had complete resolution of her symptoms and pulmonary infiltrates on discontinuation of the drug and treatment with corticosteroids. Physicians should be cognizant of this potential complication in patients receiving thalidomide who present with dyspnea and pulmonary infiltrates.

Lung cancer screening: is it time for a change in policy?

Two recent studies of computed tomography (CT) as a screening test for lung cancer have heightened debate about this topic. Although the International Early Lung Cancer Action Program investigators (N Engl J Med 2006; 355:1763-1771) concluded that annual CT screening can detect lung cancer that is curable, Bach et al (JAMA 2007; 297:953-961) concluded that it may not meaningfully reduce the risk of advanced lung cancer or death from lung cancer. We feel that questions remain about the degree of reduction in lung cancer-specific mortality, the potential morbidity caused by screening, the appropriate group to screen, and the cost-effectiveness of screening. These questions warrant further study prior to accepting CT screening as the standard of care. Hopefully, much of this knowledge will be gained when the results of ongoing controlled studies are available.

Esophageal atresia with or without tracheoesophageal fistula: success and failure in 94 cases.

BACKGROUND: The management of newborns with esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) has evolved considerably over the years. Currently an overall survival of 85% to 90% has been reported from developed countries. In developing countries, several factors contribute to higher mortality rates. We describe our experience with 94 consecutive cases of EA with or without TEF. PATIENTS AND METHODS: We retrospectively studied 94 patients with EA with or without TEF treated at our hospital over a period of 15 years. Medical records were reviewed for age at diagnosis, sex, birth weight, associated anomalies, aspiration pneumonia, method of diagnosis, treatment, postoperative complications and outcome. RESULTS: Ninety-four newborns (55 males and 39 females) with EA/TEF were treated at our hospital. Their mean birth weight was 2.2 kg (700 g to 3800 g). Age at diagnosis ranged from birth to 7 days. At the time of admission 37 (39.4%) had aspiration pneumonia. Associated anomalies were seen in 46 (49%) patients. Thirteen patients had major associated anomalies that contributed to mortality. Postoperative complications were similar to those from developed countries but overall operative mortality (30.8%) was high. CONCLUSIONS: The overall mortality was high but excluding major congenital malformations, sepsis was the most frequent cause of death. Factors contributing to mortality included prematurity, delay in diagnosis with an increased incidence of aspiration pneumonia and a shortage of qualified nurses. To improve overall outcome, factors contributing to sepsis should be evaluated and efforts should be made to overcome them.