Long-Term Use of Proton Pump Inhibitors Disrupts Intestinal Tight Junction Barrier and Exaggerates Experimental Colitis.

BACKGROUND: Proton pump inhibitors [PPIs] are widely used to treat a number of gastro-oesophageal disorders. PPI-induced elevation in intragastric pH may alter gastrointestinal physiology. The tight junctions [TJs] residing at the apical intercellular contacts act as a paracellular barrier. TJ barrier dysfunction is an important pathogenic factor in inflammatory bowel disease [IBD]. Recent studies suggest that PPIs may promote disease flares in IBD patients. The role of PPIs in intestinal permeability is not clear. AIM: The aim of the present study was to study the effect of PPIs on the intestinal TJ barrier function. METHODS: Human intestinal epithelial cell culture and organoid models and mouse IBD models of dextran sodium sulphate [DSS] and spontaneous enterocolitis in IL-10-/- mice were used to study the role of PPIs in intestinal permeability. RESULTS: PPIs increased TJ barrier permeability via an increase in a principal TJ regulator, myosin light chain kinase [MLCK] activity and expression, in a p38 MAPK-dependent manner. The PPI-induced increase in extracellular pH caused MLCK activation via p38 MAPK. Long-term PPI administration in mice exaggerated the increase in intestinal TJ permeability and disease severity in two independent models of DSS colitis and IL-10-/- enterocolitis. The TJ barrier disruption by PPIs was prevented in MLCK-/- mice. Human database studies revealed increased hospitalizations associated with PPI use in IBD patients. CONCLUSIONS: Our results suggest that long-term use of PPIs increases intestinal TJ permeability and exaggerates experimental colitis via an increase in MLCK expression and activity.

RISK FACTORS LEADING TO DEVELOPMENTAL COMPLICATIONS AFTER OPEN REDUCTION IN DEVELOPMENTAL DYSPLASIA OF HIP.

BACKGROUND: The developmental dysplasia of the hip (DDH) is regarded as one of the commonest congenital deformities. Its incidence has been estimated to be one in 60 live births according to some estimates. Different forms of treatment modalities have been suggested and their success depends on the age of the patient. The study was done with the objectives to observe the post-operative complications of open reduction in patients with DDH and to determine the possible risk factors associated with these complications. METHODS: A total of 60 patients were enrolled with DDH in this descriptive cross-sectional study from August 2013 to November 2015. After obtaining an informed consent, the patients underwent open reduction and in some cases, subsequent osteotomy. The patients were followed-up at three months intervals for at least 9 months to look for development of complications, if any. RESULTS: The mean age of the patients was 31.32 ± 2.52 months. Majority 45 (75%) of the study population was female. The most common complication observed was osteonecrosis (5 patients; 8.33%) followed by residual dysplasia and re-dislocation in 3 (5%) patients each. Infection was identified as a complication in 2 (3.33%) patients. When stratified with complications of open reduction, female sex and bilateral hip involvement were found to have a significant association with the development of complications. CONCLUSION: Female sex and bilateral hip involvement confer a greater risk of developing a complication following open reduction for DDH.

Clinical presentation of non-HIV Kaposi Sarcoma.

Kaposi Sarcoma (KS) is a rare entity. In the north west of Pakistan and Afghanistan, we mostly come across non-HIV related Kaposi sarcoma as Human Immunodeficiency Virus (HIV). Infections are rare in this part of the world. Here, we present a case of a non-auto Immunodeficiency Disease (AIDS) related KS. A 45-year-old male, Afghan patient presented to our oncology outpatient's unit with multiple subcutaneous nodules. The sites of involvement were the periorbital region, retro-auricular region, forearms, legs, chest and back. Oral mucosa was spared at the nodules. The patient had no visceromegaly at the time of presentation. A biopsy specimen from the retro-auricular region revealed a KS with dermal lymphatic involvement. His serum was negative for the common types of viral infections including Human Immunodeficiency Virus (HIV) on routine serology. His total B-lymphocytes (CD 19+), total T-lymphocyte (CD3+), total CD4+ lymphocyte (CD3+, CD4+) and total CD8+ (CD3+, CD8+) counts were all normal or borderline high. The patient was under treatment with 3 weekly chemotherapeutic regimens of Adriamycin, Bleomycin, Vincristine (ABV) keeping in view socioeconomical constrains, logistical difficulties in getting proper medical care and side effects of other options like radiotherapy for extended surface areas.