Nonalcoholic Fatty Liver Disease: A Clinical Review

Nonalcoholic fatty liver disease may be the most common liver disease in the United States, with a high prevalence in the obese, type 2 diabetic population, and it is probably underestimated as a cause for cirrhosis. Clinicopathologically, it represents a wide spectrum of histologic abnormalities and clinical outcomes, ranging from benign hepatic steatosis to cirrhosis. Pathophysiologically, insulin resistance is thought to be pivotal in the development of steatosis, after which a second oxidative stressor produces lipid peroxidation and nonalcoholic steatohepatitis (NASH). Liver biopsy is the gold standard for diagnosis and prognosis. The need for an effective treatment is both clear and urgent, yet in the absence of proven therapies, treatment is directed toward weight loss and comorbidity management. For patients with NAFLD at risk of disease progression, there is a lack of large, randomized, placebo-controlled trials of adequate treatment duration, with baseline stratification according to histologic severity.     

Zydis selegiline reduces off time in Parkinson's disease patients with motor fluctuations: a 3-month, randomized, placebo-controlled study.

Zydis selegiline dissolves on contact with saliva and undergoes pregastric absorption. This minimizes first-pass metabolism and provides high plasma concentrations of selegiline. In this study, the efficacy and safety of Zydis selegiline was assessed in Parkinson's disease (PD) patients who were experiencing motor fluctuations with levodopa. Patients were randomly assigned to either drug or placebo in a 2:1 ratio in this double-blind, multicenter trial. Significant reductions in daily off time occurred at 4 to 6 weeks with the 1.25 mg dose (9.9%, P = 0.003) and 10 to 12 weeks with the 2.5 mg dose (13.2%, P < 0.001). The total number of off hours was reduced by 2.2 hours at Week 12 from baseline (compared with 0.6 hours in the placebo group). The average number of dyskinesia-free on hours for the Zydis selegiline patients increased by 1.8 hours at Week 12. There was no change in mean percentage of "Asleep" time throughout the study. No apparent differences were detected in the occurrence of drug-related adverse events between the Zydis selegiline group and placebo-treated groups. Adverse events were consistent with known effects of levodopa therapy. Zydis selegiline safely reduces daily off time when used as adjunctive therapy with levodopa in patients with PD.     

Clinical profile and frequency of delta f508 mutation in Indian children with cystic fibrosis

OBJECTIVE: To document clinical profile of cystic fibrosis (CF) in Indian children and the prevalence of delta F508 mutation in these patients. DESIGN: Observational study. Setting:Pediatric chest clinic in an urban tertiary care center in north India. PERIOD OF STUDY: July 1995 to June 2002. METHODS: Clinical features of 120 children diagnosed as CF by quantitative pilocarpine iontophoresis were recorded. A polymerase chain reaction based test for identification of delta F 508 mutation was performed on all children. RESULTS: Out of 3500 new cases registered in Pediatric Chest Clinic during this period 120, (3.5%) children were diagnosed as CF. Origin of parents of patients traced from almost all the States of north India. Family history suggestive of CF was present in 41 (34%) and consanguinity in 19 (61%) patients. Common clinical manifestations at the time of presentation included recurrent or persistent pneumonia in 118 (98%), failure to thrive in 108 (90%), malabsorption in 96 (80%), history of meconium ileus in 10 (8%), and rectal prolapse was present in 16 (13%). History of salt craving, salty taste on kissing and skin rashes was present in 5 patients each. 49(41%) patients were severely malnourished. Nasal polyposis was present in 5 (4%) patients. Examination of chest revealed evidence of hyperinflation in 100 (83%), kyphosis 20 (17%), crepitations 110 (92%), wheezing 40 (25%) and bronchial breathing in 20 (17%) patients. Average clinical CF scores were 51 (95%; CI 20-80). 48 (40%) patients had a CF score of LT40. Pseudomonas spp was cultured from respiratory secretions of 51 (42%), Staphylococcus spp in 18 (15%), Klebsiella spp in 8 (7%) and Hemophilus influenzae in 2 (2%) patients. Delta F508 mutation was positive in 45 chromosomes out of 240 tested. Patients originated from Pakistan had more frequency of delta F508 mutations. CONCLUSIONS: Cystic fibrosis does occur in Indian children; clinical features are classical. Diagnosis is often delayed and the disease is advanced in most patients at the time of diagnosis. Frequency of Delta F508 mutation is 19% i.e., less than that seen in Caucasian population. There is need to create awareness about occurrence of CF in Indian children.     

Nasopharyngeal carriage of Haemophilus influenzae

OBJECTIVE: Nasopharyngeal colonization of Haemophilus influenzae (H. influenzae) in young children may be important in developing countries. METHOD: In this study, we screened school going children for carriage of H. influenzae. A total of 44 H. influenzae isolates out of a collection of 162 were characterized for biotypes, capsular serotypes and antibiotic resistance. RESULTS: A significant proportion of H. influenzae (25/44) isolates were serotype b. High antibiotic resistance was observed against commonly administered antibiotics like ampicillin (79%), chloramphenicol (20%), trimethoprim sulfamethoxazole (84%) and erythromycin (95%). Comparison of antibiotic resistance profile of nasopharyngeal isolates was observed to be correlated with those of H. influenzae from disease. CONCLUSION: Multidrug resistant nasopharyngeal H. influenzae in young healthy children may act as reservoir. Monitoring of antibiotic resistance among nasopharyngeal H. influenzae as a surrogate for invasive H. influenzae seems an attractive option.