Multi-dimensional clinical phenotyping of a national cohort of adult cystic fibrosis patients

BackgroundCystic Fibrosis (CF) is a multi-systemic disorder resulting from genetic variation in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene which can result in bronchiectasis, chronic sinusitis, pancreatic malabsorption, cholestatic liver disease and distal intestinal obstructive syndrome. This study generates multi-dimensional clinical phenotypes that capture the complexity and spectrum of the disease manifestations seen in adult CF patients using statistically robust techniques.MethodsPre-transplant clinical data from adult (age ≥18 years) CF patients (n = 992) seen in six regionally distinct US CF centers between 1/1/2014 and 6/30/2015 were included. Demographic, spirometry, nutritional, microbiological and therapy data were used to generate clusters using the Random Forests statistical-learning and Partitioning around Medoids (PAM) clustering algorithms. Five commonly measured demographic, physiological and nutritional parameters were needed to create the final phenotypes that are highly similar to a regionally matched group of patients from the CF Foundation Patient RegistryResultsThis approach identified high-risk phenotypes with expected characteristics including high rates of pancreatic insufficiency, diabetes and Pseudomonas aeruginosa colonization. It also identified unexpected populations including a) a male-dominated, well-nourished group with good lung function with a high prevalence of severe genotypes (i.e. 60% subjects had two minimal function CFTR variations), b) and an older, “survivor” phenotype that had high rates of chronic P. aeruginosa infection.ConclusionsThis study identified recognizable phenotypes that capture the clinical complexity in a statistically robust manner and which may aide in the identification of specific genetic and environmental factors responsible for these disease manifestation patterns.     

EFFICACY OF SUCRALFATE IN PREVENTING GASTROINTESTINAL SIDE EFFECTS OF NSAIDs

To find out the efficacy of sucralfate in preventing gastrointestinal side effects of non-steroidal anti-inflammatory drugs (NSAIDs) a prospective, randomised single blind study was conducted from 1989 to 1992. Patients with osteoarthritis, rheumatoid arthritis and other long standing painful conditions, who were expected to receive NSAIDs for over three months, were recruited into the study. All medicines were discontinued for a period of 10–15 days prior to initial endoscopic assessment. NSAID therapy was started and the patients were randomised to receive either placebo (group A) or sucralfate (group B) in addition. Patient were reassessed clinically every week and an endoscopic examination was repeated after 6–8 weeks of follow-up. A total of 176 patients were studied in group A (n=91) and group B (n=85). At the end of 8 weeks gastrointestinal symptoms were present in 30.6% and 26.4% patients of group A and B respectively. Endoscopic assessment showed superficial lesions in 36.5% and 18.7% while endoscopic ulcer in 2.4% and 1.1% patients of groups A and B respectively. Thus in patients receiving chronic NSAID therapy, simultaneous administration of sucralfate reduces the incidence of superficial gastric lesions but has no significant effect on symptoms or ulcer formation.KEY WORDS: Gastropathy, Sucralfate, Nonsteroidal anti-inflammatory drugs     

Typhoid fever in a 7 month old infant

The clinical profile of typhoid fever in an infant is variable and non-specific. A rare case of typhoid fever in a 7 month old infant is reported. The child presented with only a day's history of fever and loose motions which resulted in severe dehydration, acute tubular necrosis and death. The diagnosis of typhoid fever was made only on post-mortem study. The problem in diagnosing typhoid fever in a young infant is highlighted with a brief literature review on the subject.     

THE ROLE OF RAPID SLIDE CULTURE IN THE DIAGNOSIS AND MANAGEMENT OF PULMONARY TUBERCULOSIS

Rapid slide culture method using human blood medium was utilized for the primary culture of Mycobacterium tuberculosis and the results obtained were compared with results of smear examination of sputum specimens from fresh cases of pulmonary tuberculosis. Smear and rapid slide culture results of a total of 320 patients were analyzed. Slide culture was positive in 104 cases whereas smears were positive in 90 cases. Early culture confirmation in 7 days coupled with positivity better than smear examination, makes rapid slide culture a better method for diagnosis.KEY WORDS: Mycobacterium tuberculosis, Rapid slide culture, Bacteriological techniques, Colony count microbial     

Neural tissue transplant in the lateral hypothalamic lesioned rats: functional recovery pattern

Transplantation has come of age as an important investigative tool for studying normal growth and development of the brain tissue. The present study reports the effect of lateral hypothalamic (LHA) lesion and foetal hypothalamic tissue transplantation on the feeding behaviour. In a group of rats, LHA was lesioned bilaterally by passing direct current. Subsequently, in a separate group of rats, foetal hypothalamic tissue was transplanted at the lesioned site. Following LHA lesion, all the rats died of aphagia and adipsia within 7 days, whereas, the rats in whom foetal hypothalamus was transplanted, started taking food and water in small quantities from the first day of transplantation itself. Later, they were able to attain their preoperative values. This recovery of the feeding behaviour following foetal tissue transplantation may be due to the formation of synaptic connections or due to the release of neurotrophic factors.     

Seasonal affective symptoms in adults with residual attention-deficit hyperactivity disorder.

There is evidence from clinical, epidemiological, and neuroimaging studies that attention-deficit hyperactivity disorder (ADHD) and seasonal affective disorder (SAD) may have several features in common. To assess seasonal affective symptoms in adults with ADHD, 115 individuals attending an adult ADHD clinic in Toronto, Ontario, Canada were asked to complete the Seasonal Pattern Assessment Questionnaire (SPAQ). From this clinic population of 115, a total of 56 completed SPAQs were returned. Assuming that all individuals failing to complete the SPAQ were nonseasonal and depending on which case-finding criteria were used, the rate of SAD in the overall clinic sample was estimated at either 10.4% (Terman criteria) or 19.1% (criteria of Kasper et al.). These prevalence rates are significantly greater than the rates reported in large population surveys at similar latitudes. There was an apparent relationship between female gender, impulsive-subtype ADHD, and seasonality. Future studies to examine whether core symptoms of ADHD fluctuate across the seasons and to assess the efficacy of light therapy in "seasonal" ADHD patients would be of great theoretical and clinical interest.     

Influence of UV-irradiation on enzymes in mouse ocular lens: in vitro studies

PURPOSE: In vitro study of the enzymes involved in aerobic, anaerobic and hexose monophosphate shunt in ultraviolet radiation exposed mice lenses. METHOD: Of the selected enzymes, lactic dehydrogenase (LDH) was representative of anaerobic glucose oxidation, succinic dehydrogenase (SDH) of the aerobic oxidation, and Glucose-6-phosphate dehydrogenase (G-6-PDH) of the Hexose Monophosphate (HMP) shunt. Other enzymes studied were ATPase and glutathione reductase (GR). RESULTS: Experiments with mice lenses in vitro showed that transparent lens became opaque following UV-irradiation at 360 nm. Opacification of the lens was accompanied by a change in enzyme activities for energy metabolism. CONCLUSION: These changes were progressive in a manner analogous to sequential morphological changes, which would be crucial in maintaining lens transparency.