Family history of cancer and the risk of squamous cell carcinoma of oesophagus: a case-control study in Kashmir, India.

BACKGROUND: Only a few studies have examined the association between family history of cancer (FHC) and the risk of oesophageal squamous cell carcinoma (ESCC) in high incidence areas of ESCC. We conducted a case-control study to evaluate the relationship between FHC and ESCC risk in Kashmir, India, with analysis of detailed epidemiological data and information on multiple gene polymorphisms. METHODS: We collected detailed information on FHC and a number of socio-demographic and lifestyle factors, and also obtained blood samples for genetic analysis from 703 histopathologically confirmed ESCC cases and 1664 individually matched controls. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: Participants who had FHC showed a strong association with ESCC risk, and the risk was stronger when first-degree relatives (FDRs) had FHC (OR=6.8; 95% CI=4.6-9.9). Having a sibling with a cancer showed the strongest association (OR=10.8; 95% CI=6.0-19.3), but having a child with a cancer was not associated with ESCC risk. A history of any cancer in the spouse was also associated with ESCC risk (OR=4.1; 95% CI=1.6-10.2). Those with two or more relatives with FHC were at a higher risk of ESCC. After restricting FHC to familial ESCC only, the above associations were strengthened, except when spouses were affected with ESCC (OR=2.5; 95% CI=0.7-8.9). When we examined the associations between several single-nucleotide polymorphisms and ESCC in those with and without FHC, the associations of variant genotypes in cytochrome P450 (CYP) 2C19 and CYP2D6 and the wild genotype of CYP2E1 with ESCC were much stronger in those with FHC. The FHC had an additive interaction with several risk factors of ESCC in this population. CONCLUSION: Our results showed that FHC was strongly associated with ESCC risk in Kashmir. It seems both genetic factors and shared environment are involved in this association.

Poor oral hygiene and risk of esophageal squamous cell carcinoma in Kashmir.

BACKGROUND: Several studies have suggested an association between poor oral health and esophageal squamous cell carcinoma (ESCC). We conducted a case-control study in Kashmir, a region with relatively high incidence of ESCC in north India, to investigate the association between oral hygiene and ESCC risk. METHODS: We recruited 703 histologically confirmed ESCC cases, and 1664 controls individually matched to the cases for age, sex, and district of residence. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We found an inverse association between teeth cleaning and ESCC risk. As compared with never cleaning teeth, the OR (95% CI) was 0.41 (0.28-0.62) for cleaning less than daily and 0.44 (0.25-0.77) for cleaning at least once a day (P for trend=0.026) in models adjusted for multiple potential confounders, including several indicators of socioeconomic status. This association persisted after we limited our analyses to never tobacco users. The inverse association between cleaning teeth and ESCC was stronger with using brushes than with using sticks/fingers. We also found an association between the number of decayed, filled, and missing teeth and ESCC risk, but the trend of the associations was not statistically significant. Avoiding solid food and cold beverages because of teeth and oral problems were also associated with ESCC risk. CONCLUSION: We found an association between poor oral hygiene indicators and ESCC risk, supporting the previous studies that showed the same associations.

Approaches to Muslim Biomedical Ethics: A Classification and Critique.

This paper provides a perspective on where contemporary Muslim responses to biomedical-ethical issues stand to date. There are several ways in which Muslim responses to biomedical ethics can and have been studied in academia. The responses are commonly divided along denominational lines or under the schools of jurisprudence. All such efforts classify the responses along the lines of communities of interpretation rather than the methods of interpretation. This research is interested in the latter. Thus, our criterion for classification is the underlying methodology behind the responses. The proposed classification divides Muslim biomedical-ethical reasoning into three methodological categories: 1) textual, 2) contextual, and 3) para-textual.

Hookah smoking, nass chewing, and oesophageal squamous cell carcinoma in Kashmir, India.

BACKGROUND: Although cigarette smoking is an established risk factor for oesophageal squamous cell carcinoma (ESCC), there is little information about the association between other smoking and smokeless tobacco products, including hookah and nass, and ESCC risk. We conducted a case-control study in Kashmir Valley, India, where hookah smoking, nass chewing, and ESCC are common, to investigate the association of hookah smoking, nass use, and several other habits with ESCC. METHODS: We recruited 702 histologically confirmed ESCC cases and 1663 hospital-based controls, individually matched to the cases for age, sex, and district of residence from September 2008 to January 2012. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: Ever-hookah smoking (OR=1.85; 95% CI, 1.41-2.44) and nass chewing (OR=2.88; 95% CI, 2.06-4.04) were associated with ESCC risk. These associations were consistent across different measures of use, including intensity, duration, and cumulative amount of use, and after excluding ever users of the other product and cigarette smokers. Our results also suggest an increased risk of ESCC associated with ever-gutka chewing and -bidi smoking. However, the latter associations were based on small number of participants. CONCLUSION: This study shows that hookah and nass use are associated with ESCC risk. As prevalence of hookah use seems to be increasing among young people worldwide, these results may have relevance not only for the regions in which hookah use has been a traditional habit, but also for other regions, including western countries.

A new accurate method for predicting lithium clearance and daily dosage requirements in adult psychiatric patients.

OBJECTIVE: The present study aimed to derive new equations for estimating lithium clearance and daily dosage requirements needed to achieve an intended lithium serum level for adult psychiatric inpatients and outpatients. METHODS: Data were retrospectively collected from 60 adult psychiatric patients (34 males and 26 females, aged between 18-80 years) in both inpatient and outpatient settings. All variables that might affect lithium clearance and/or lithium serum concentration were included and analyzed by stepwise multiple linear regression to produce equations describing lithium clearance and daily dosage requirements for these patients. The validation of the developed equations was performed by application to another 60 psychiatric subjects in both the inpatient and outpatient settings. The bias and accuracy of the new methods were also compared to those set forth by the empirical method and the a priori methods developed by Zetin, Pepin, Jermain and Terao and colleagues. RESULTS: The following prediction equations for lithium clearance (CL(Li)) were obtained: CL(Li) (inpatients) = 0.932 + 0.185CL(Cr) and CL(Li) (outpatients) = 1.021 + 0.141CL(Cr). The equations derived for daily dosage requirements were: daily dose (inpatients, mg) = 350.15 + 289.92 (desired lithium level, mmol/L) + 0.84 (weight, kg) - 1.76 (age, years) + 34.43 [tricyclic antidepressant (TCA), yes = 1, no = 0] + 62.1(CL(Cr), L/h) + 13.1 [blood urea nitrogen (BUN), mmol/L] + 40.9 (sex, male = 1, female = 0) and daily dose (outpatients, mg) = 784.92 + 530.22 (desired lithium level, mmol/L) + 8.61 (weight, kg) - 12.09 (age, years) - 11.14 (TCA, yes = 1, no = 0) - 7.63 (CL(Cr), L/h) - 42.62 (BUN, mmol/L) - 23.43 (sex, male = 1, female = 0). In the present method, the prediction error for clearance was 10.31% and 6.62% for inpatients and outpatients, respectively, and the prediction error for daily dosage requirements was 3.96% and 2.95% for inpatients and outpatients, respectively. CONCLUSIONS: Compared to previously reported methods, the present method proved to be accurate and can be safely used for the prediction of lithium clearance and daily dosage requirements in psychiatric inpatients and outpatients.

Associations of vitamin D status and vitamin D-related polymorphisms with sex hormones in older men.

OBJECTIVE: Evidence regarding relationships of serum 25-hydroxyvitamin D (25(OH)D) with sex hormones and gonadotropin concentrations remains inconsistent. Polymorphisms in vitamin D-related genes may underly these relationships. Our aim was to examine the relationship of vitamin D status and polymorphisms in vitamin D-related genes with sex hormone and gonadotropin levels. DESIGN AND MEASUREMENTS: We analysed data from the Longitudinal Aging Study Amsterdam, an ongoing population-based cohort study of older Dutch individuals (65-89 years). We included data of men with measurements of serum 25-hydroxyvitamin D (25(OH)D) (n=643) and determination of vitamin D-related gene polymorphisms (n=459). 25(OH)D concentrations were classified into four categories: <25, 25-50, 50-75 and >75nmol/L. Outcome measures were total testosterone, calculated bioavailable and free fraction testosterone, SHBG, estradiol, LH and FSH concentrations. Hypogonadism was defined as a total testosterone level <8.0nmol/L. RESULTS: Serum 25(OH)D was positively associated with total and bioavailable testosterone levels. After adjustments for confounders, men with serum 25(OH)D less than 25 (n=56), 25-50 (n=199) and 50-75nmol/L (n=240) had lower total testosterone levels compared to men with serum 25(OH)D higher than 75nmol/L (n=148) (ß (95% confidence interval): -2.1 (-3.7 to -0.4nmol/L), -0.8 (-1.9 to 0.4nmol/L) and -1.4 (-2.4 to -0.3nmol/L), respectively). For bioavailable testosterone the association was significant only for men with serum 25(OH)D less than 25nmol/L (-0.8 (-1.4 to -0.1nmol/L)) compared to men with serum 25(OH)D >75nmol/L. Serum 25(OH)D was not related to SHBG, estradiol or gonadotropin levels. Hypogonadism (n=29) was not associated with lower serum 25(OH)D. No significant differences were found in hormone levels between the different genotypes of the vitamin D-related gene polymorphisms. Also, the polymorphisms did not modify the relationships of serum 25(OH)D with sex hormones or gonadotropins. CONCLUSION: Vitamin D status is positively associated with testosterone levels. No association was found between vitamin D-related gene polymorphisms and hormone levels.

Liquid chromatographic assay of abouthiouzine in plasma and its application to pharmacokinetic studies.

Abouthiouzine is a newly synthesized antithyroid agent with a proposed less adverse effects profile than other currently used drugs. A simple and rapid reversed phase high performance liquid chromatography assay was developed to determine the concentration of abouthiouzine in human plasma. The procedure involved extraction of the drug and propranolol (internal standard) from the plasma using ethylacetate. The extract was evaporated under nitrogen and the residue was constituted with the mobile phase and injected onto micro-Bondapack phenyl column (10 microm, 3.9 mm x 150 mm). The mobile phase consisted of 10 mM potassium dihydrogen phosphate buffer, acetonitrile, and methanol in the ratio of 60:25:15 (v/v/v, pH=3.0), which was delivered at a rate of 1.5 ml/min. Abouthiouzine and the internal standard were monitored using UV detection at 240 nm; the run time was less than 5 min. The detection limit of abouthiouzine is 0.5 microg/ml. The within- and between-day coefficients of variation were less than 7%. Our method has been successfully used to measure abouthiouzine plasma concentrations in a rabbit model following an intravenous administration of the drug.

[A report of 9 cases of neurosarcoidosis]. / Neurosarcoïdose. Etude de neuf cas.

INTRODUCTION: Neurological involvement in sarcoidosis is rare and highly variable. To date, no consensus was reached about the diagnosis approach. We report a case series of 9 patients with neuosarcoidosis, with favorable outcome under therapy. MATERIALS AND METHODS: We examined a case series of 9 patients with neurosarcoidosis. Clinical, radiological, therapeutic features and outcome were studied. RESULTS: Six of the nine patients were females. Patients' age ranged from 31 to 70 years. Initial neurological symptoms lead to the diagnosis of systemic sarcoidosis in all patients. Central nervous system involvement was found in 77 percent with cranial nerve involvement in 55 percent. Twenty-three percent of patients presented with peripheral neuropathy and 33 percent with meningitis. The diagnosis was definite in 2 patients, probable in one and possible in six others. All patients were given steroid therapy. Total remission was obtained in three and partial remission in three. Three patients remained stable and one died. CONCLUSION: Histological signs are not constant in neurosarcoidosis. The lack of these signs should lead the physician to search for latent extraneurological symptoms which are suggestive of the diagnosis. Nervous biopsy can thus be avoided.

[Cavernous sarcoid granuloma of the skull base: a case report]. / Granulome sarcoïdien de la loge sphéno-caverneuse.

A case of cavernous sarcoid granuloma, revealed by a slit sphenoidal syndrome is reported. Brain MRI showed a cavernous pseudo-tumoral lesion. The diagnosis of sarcoidosis was confirmed by the epithelioid and giant-cell granuloma without caseous necrosis found at hepatic biopsy. Outcome was favorable with corticosteroid therapy alone.

Associations of serum 25-hydroxyvitamin D concentrations with quality of life and self-rated health in an older population.

CONTEXT: Vitamin D deficiency has been associated with impaired physical functioning, depression, and several chronic diseases and might thereby affect quality of life and self-rated health. OBJECTIVE: The aim of this study was to assess relationships of serum 25-hydroxyvitamin D [25(OH)D] with quality of life and self-rated health and to examine whether physical performance, depressive symptoms, and number of chronic diseases mediate these relationships. DESIGN: We analyzed data from the Longitudinal Aging Study Amsterdam, an ongoing population-based cohort study of older Dutch individuals. MAIN OUTCOME MEASURES: Serum 25(OH)D was classified into the following categories: less than 25, 25-50, and 50 nmol/L or greater. We assessed quality of life (QOL) using the Short Form-12 Health Survey (SF-12; n = 862) and self-rated health (SRH) with a single question, dichotomized into good vs poor SRH (n = 1248). RESULTS: Individuals with serum 25(OH)D less than 25 nmol/L scored lower on the physical component score of the SF-12 and had a lower odds on good SRH score compared with individuals with serum 25(OH)D greater than 50 nmol/L (ß (95% confidence interval) -3.9 (-6.5 to -1.3) for SF-12, and odds ratio [95% confidence interval) 0.50 (0.33-0.76) for SRH]. Physical performance, depressive symptoms, and the number of chronic diseases were associated with vitamin D status, QOL, and SRH. Adding all these potential mediators to regression models attenuated associations of 25(OH)D less than 25 nmol/L with QOL with 78% and SRH with 32%. CONCLUSION: Lower 25(OH)D status is related to lower scores on QOL and SRH. A large part of the association with QOL can statistically be explained by physical performance, depressive symptoms, and the number of chronic diseases.

Disposition of abouthiouzine: a novel antihyperthyroid drug.

Abouthiouzine is a novel antithyroid agent with a profile of fewer reported adverse effects than other currently used drugs. The purpose of this current work was to explore, for the first time, the disposition of abouthiouzine following intravenous and oral administration using an animal model; also, to study its plasma protein binding properties. Abouthiouzine (2 mg/kg intravenously) was administered to healthy male Vole rabbits and Beagle dogs. A dose of 20 mg/kg of the drug was also given orally to another group of Beagle dogs. Abouthiouzine plasma concentrations were measured using an HPLC method, and its pharmacokinetic parameters were determined by non-compartmental analysis. Abouthiouzine plasma protein binding was determined using an ultrafiltration technique. The drug was quickly eliminated from the rabbit and dog systemic circulations with terminal half-lives (T(1/2 lambda)) of 0.7 h and 1.9 h, respectively. The calculated T(1/2 lambda) following the oral administration in dogs was 1.8 h. Total abouthiouzine clearance (CL) in rabbits was 7.84+/-0.87 ml/min/kg, and 4.03+/-0.83 ml/min/kg in dogs. The apparent volume of distribution at steady state (V(ss)) in rabbits and dogs was 360.09+/-63.41 ml/kg and 481.10+/-62.64 ml/kg, respectively. The absolute oral bioavailability in dogs was approximately 16%, which may indicate poor absorption characteristics of the pure drug and/or an extensive first past effect. Protein binding studies have demonstrated that abouthiouzine has moderate-to-high binding properties ( approximately 63%-86%). Further studies are needed to evaluate the route of elimination of abouthiouzine in these animal models including any metabolite formation and the role of enterohepatic recycling in this process.