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.     

T-cell signature cytokines distinguish pulmonary sarcoidosis from pulmonary tuberculosis

Sarcoidosis is a systemic inflammatory disorder characterized by tissue infiltration due to mononuclear phagocytes and lymphocytes and associated noncaseating granuloma formation. Pulmonary sarcoidosis (PS) shares a number of clinical, radiological, and histopathological characteristics with that of pulmonary tuberculosis (PTB). Due to this, clinicians face issues in differentiating between PS and PTB in a substantial number of cases. There is a lack of any specific biomarker that can diagnose PS distinctively from PTB. We compared T-cell-based signature cytokines in patients with PS and PTB. In this study, we proposed a serum biomarker panel consisting of cytokines from cells: T helper (Th) 1 [interferon-gamma (IFN-γ); tumor necrosis factor-alpha (TNF-α)], Th9 [interleukin (IL)-9], Th17 [IL-17], and T regulatory (Treg) [IL-10; transforming growth factor-beta (TGF-β)]. We performed the principal component analysis that demonstrated that our serum cytokine panel has a significant predictive ability to differentiate PS from PTB. Our results could aid clinicians to improve the diagnostic workflow for patients with PS in TB endemic settings where the diagnosis between PS and PTB is often ambiguous.     

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.     

Dengue haemorrhagic fever in children in the 1996 Delhi epidemic.

An epidemic of dengue haemorrhagic fever (DHF) occurred in Delhi in 1996. A total of 240 children between the age of 4 months to 13 years of either sex, admitted in one hospital, were evaluated. Two hundred and sixteen (90%) children were from Delhi. A clinical diagnosis of dengue fever (DF) was made in 25 (10%), dengue fever with unusual bleeding (DFB) in 22 (9%), DHF in 80 (33%) and dengue shock syndrome (DSS) in 113 (47%) of the children strictly according to the WHO classification. The age peaked at 8 years. There was no association between various grades of severity of illness and age-groups though girls suffered from more severe illness. No association between severity of malnutrition and severity of illness was observed. Tourniquet test was positive in 40% with DF, 18% with DFB, 62% with DHF and 64% with DSS. In DSS haematemesis was present in 55 (49%), epistaxis in 39 (35%), melaena in 27 (24%) and ecchymosis in 34 (30%) patients. Children diagnosed as DFB had haematemesis and epistaxis in 12 (55%) and 10 (45%) respectively. Intravenous fluid requirement was clearly less in DFB patients than in DHF/DSS patients. Unusual clinical features in the form of jaundice were present in 7 (6%), hepatic encephalopathy in 6 (5%) and dengue encephalopathy in 6 (5%) patients. Dengue 2 virus was isolated from 10 of the 50 patients for whom viral culture was done on C6/36 clone of Aedes albopictus cell line. Eighteen patients suffering from DSS died giving an overall case fatality of 7.5%. The mortality rate in DHF/DSS was 9.3%. It is further suggested that DFB is a distinct entity. Most patients could be classified by the WHO classification if a retrospective packed cell volume was used to assess haemoconcentration. We suggest that development of area-specific criteria for diagnosis and management is desirable.     

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.     

Plant foods, antioxidants, and prostate cancer risk: findings from case-control studies in Canada

Epidemiological data on most cancer sites suggest that consumption of plant foods, which contain high levels of antioxidants, might slow or prevent the appearance of cancer. We used data from three case-control studies to test this hypothesis. The total study population consisted of 617 incident cases of prostate cancer and 636 population controls from Ontario, Quebec, and British Columbia. Dietary information was collected by an in-person interview with a detailed quantitative dietary history. Unconditional logistic regression analyses were performed to estimate odds ratios (ORs) and 95% confidence intervals (CIs). A decreasing, statistically significant association was found with increasing intakes of green vegetables (OR = 0.54, 95% CI = 0.40-0.71 for 4th quartile), tomatoes (OR = 0.64, 95% CI = 0.45-0.91), beans/lentils/nuts (OR = 0.69, 95% CI = 0.53-0.91), and cruciferous vegetables (OR = 0.69, 95% CI = 0.52-0.91 for 3rd quartile). Higher intakes of fruit were associated with higher ORs (OR = 1.51, 95% CI = 1.14-2.01 for 4th quartile), an effect that was seen for total fruit and citrus fruit, as well as for all other noncitrus fruits. Among the grains, refined-grain bread intake was associated with a decrease in risk (OR = 0.65 for 4th quartile), whereas whole-grain breakfast cereals were associated with a higher risk for prostate cancer. Of all the antioxidant nutrients studied, the ORs were higher with higher intakes of cryptoxanthin (OR = 1.44, 95% CI = 1.09-1.89 for 4th quartile). Exposure to certain dietary components of plant origin, which are potentially modifiable, indicates the theoretical scope for reducing the risk from prostate cancer. Future experimental studies or trials are warranted for further understanding.     

Antifertility effect of aqueous extract of seeds of Cassia fistula in female rats

Oral administration of aqueous extract of seeds of Cassia fistula to mated female rats from day 1-5 of pregnancy at the doses of 100 and 200 mg/kg body weight resulted in 57.14% and 71.43% prevention of pregnancy, respectively, whereas 100% pregnancy inhibition was noted at 500 mg/kg bw. In the uterine bioassay test carried out in immature bilaterally ovariectomized female rats, aqueous extract of seeds of Cassia fistula (100 mg/kg bw) increased the uterine wet weight (p<0.05) and luminal epithelial cell height (p<0.001) but did not induce premature opening of the vagina. This suggests a mild estrogenic activity of the extract. However, when the extract was administered conjointly with estradiol valerate (EDV, 0.1 mg/kg bw), it significantly (p<0.001) prevented the estrogen-induced uterotrophic effect, thus showing an antiestrogenic nature of the extract in the presence of a strong estrogen.