A genome-wide association study of alcohol-dependence symptom counts in extended pedigrees identifies C15orf53.

Several studies have identified genes associated with alcohol-use disorders (AUDs), but the variation in each of these genes explains only a small portion of the genetic vulnerability. The goal of the present study was to perform a genome-wide association study (GWAS) in extended families from the Collaborative Study on the Genetics of Alcoholism to identify novel genes affecting risk for alcohol dependence (AD). To maximize the power of the extended family design, we used a quantitative endophenotype, measured in all individuals: number of alcohol-dependence symptoms endorsed (symptom count (SC)). Secondary analyses were performed to determine if the single nucleotide polymorphisms (SNPs) associated with SC were also associated with the dichotomous phenotype, DSM-IV AD. This family-based GWAS identified SNPs in C15orf53 that are strongly associated with DSM-IV alcohol-dependence symptom counts (P=4.5 × 10(-8), inflation-corrected P=9.4 × 10(-7)). Results with DSM-IV AD in the regions of interest support our findings with SC, although the associations were less significant. Attempted replications of the most promising association results were conducted in two independent samples: nonoverlapping subjects from the Study of Addiction: Genes and Environment (SAGE) and the Australian Twin Family Study of AUDs (OZALC). Nominal association of C15orf53 with SC was observed in SAGE. The variant that showed strongest association with SC, rs12912251 and its highly correlated variants (D'=1, r(2) 0.95), have previously been associated with risk for bipolar disorder.

Dietary profile of urban adult population in South India in the context of chronic disease epidemiology (CURES-68).

OBJECTIVE: Few dietary surveys have been done with reference to chronic diseases, such as diabetes, in India, which is considered to be the diabetes capital of the world. We report on the dietary intake of urban adults living in Chennai, South India. DESIGN: A population-based cross-sectional study. SETTING: A representative population of urban Chennai in southern India. SUBJECTS: The study population comprised 2042 individuals aged≥20 years selected from the Chennai Urban Rural Epidemiological Study (CURES). Dietary intake was measured using a validated and previously published interviewer-administered semi-quantitative meal-based FFQ. RESULTS: The mean daily energy intake was 10,393 (sd 2347) kJ (male: 10953 (sd 2364) kJ v. female: 9832 (sd 233) kJ). Carbohydrates were the major source of energy (64%), followed by fat (24%) and protein (12%). Refined cereals contributed to the bulk of the energy (45.8%), followed by visible fats and oils (12.4%) and pulses and legumes (7.8%). However, energy supply from sugar and sweetened beverages was within the recommended levels. Intake of micronutrient-rich foods, such as fruit and vegetable consumption (265 g/d), and fish and seafoods (20 g/d), was far below the FAO/WHO recommendation. Dairy and meat products intake was within the national recommended intake. CONCLUSIONS: The diet of this urban South Indian population consists mainly of refined cereals with low intake of fish, fruit and vegetables, and all of these could possibly contribute to the risk of non-communicable diseases such as diabetes in this population.

Clinical efficacy of a new variant of a foam-based NWPT system.

OBJECTIVE: To evaluate the clinical efficacy of a new variant of a foam-based negative wound pressure wound therapy (NPWT) system. METHOD: A newly available polyurethane foam-based NPWT system (RENASYS-F, Smith & Nephew) was used to treat 18 patients in a prospective, multi-centre study. The patients had a variety of wound types including pressure ulcers, diabetic foot ulcers, traumatic and surgical wounds. RESULTS: The mean patient age was 48.3 years (range 25-72). Mean treatment duration was 14.6 days (range 5-29). At the end of therapy, 83% (15) wounds had progressed sufficiently, leading to a change in treatment from NPWT. Median reductions in wound area, depth and volume of 31.3%, 45.5% and 74.2% respectively were observed over the course of therapy. This equated to a weekly reduction in area, depth and volume of 12.9%, 20.0% and 32.1% respectively. Exudate level (p = 0.013) and wound malodour (p = 0.03) were significantly reduced between the onset and the end of NPWT. The percentage cover of 'beefy' red granulation tissue in the wound bed was significantly increased (p < 0.001) and non-viable tissue significantly reduced (p = 0.008) between the onset and the end of NPWT. CONCLUSION: These data demonstrate that an alternative foam-based NPWT system (RENASYS-F) is able to address the common treatment goals associated with application of NPWT including reduction in wound dimensions, reduction in exudate levels and an improvement in wound bed quality.

Necrotizing fasciitis: a 10-year retrospective study of cases in a single university hospital in Oman.

OBJECTIVE: (1) To study the clinical profile of all cases of necrotizing fasciitis (NF) diagnosed in a university hospital in Oman. (2) To evolve a strategy for early diagnosis. PATIENTS AND METHODS: The inpatient records of the Sultan Qaboos University hospital from 1990-99 were searched for the words "fasciitis", "necrosis" or "gangrene" and cases of NF (defined as a soft tissue infection characterized by widespread necrosis of the subcutaneous tissues confirmed at surgery or pathology or both) were selected and analyzed. Cases with necrosis due to other obvious causes were excluded. RESULTS: Of the seven cases of NF (hospital incidence-8.4/10(5)), there were three post-operative, three spontaneous and one post-traumatic. Sites involved: upper limb (1), lower limb (2), abdomen (2), gluteal (1), and breasts (1). The median age was 50 years (range 21-85) and the male:female ratio was 4:3. All patients had local pain out of proportion to the signs and six had fever. Hypotension, liver or kidney dysfunction or coagulopathy were seen in four and a drop in haemoglobin was seen in six. In none was NF even considered by the referring or admitting physician, diagnosis being delayed by 2-10 days. In four cases a diagnostic incision under local anesthesia revealed the correct diagnosis. At surgery, extensive fascial and fat necrosis were seen in all, but only two had myonecrosis. The commonest isolate was beta-hemolytic group D streptococcus (4/7). Blood and tissue were positive for beta-hemolytic group A streptococci in one fatal case. Mean hospital stay was 54.5 days (11-134), mean surgical procedures were 2.3 per case, two required ICU admission with one death. CONCLUSION: NF is a rare but serious bacterial disease that is often incorrectly diagnosed. Unexplained severe local pain, deep tenderness without impressive local signs, fall in haemoglobin, organ system dysfunction and constitutional upsets were regular features. A high index of suspicion and immediate direct inspection of the fascia facilitates an early diagnosis.

Effect of Lugol's iodine on the vascularity of thyroid gland in hyperthyroidism.

Vascularity of the thyroid gland was measured in twenty thyrotoxic patients (including Graves and multinodular goitres) and eight normal subjects by a new objective parameter--'Thyroid Vascularity Index' (TVI). The TVI was calculated by comparing the areas under the normalized thyroid and carotid artery curves up to the time of peak of the arterial curve caused by the first passage of a radioactive bolus. Compared to normal thyroid, all the toxic goitres had increased TVI (p less than 0.001); it being maximum in Graves disease (p less than 0.05). TVI in Graves disease was not affected by carbimazole therapy but decreased dramatically in eight out of ten patients (p less than 0.01) two weeks after Lugol's iodine was added. There was a sustained fall in TVI in all the ten patients (p less than 0.001) with chronic iodine therapy up to six weeks without any hormonal escape. TVI in multinodular goitres showed no significance change with carbimazole or iodine therapy.

Laparoscopic vaginoplasty: using a sliding peritoneal flap for correction of complete vaginal agenesis.

In this technique of peritoneal neo-vaginoplasty, the recto-vesical space is dissected through the vulva under synchronous laparoscopic monitoring. Then the cranial limit of the pelvic peritoneum is incised circumferentially by laparoscopic approach and the two circular edges sutured sequentially. The isolated pelvic peritoneal sleeve is opened inferiorly and sutured to introital mucosal flaps.

Papillary carcinoma of a thyroglossal duct remnant with Hashimoto's thyroiditis.

A rare case of papillary carcinoma of the thyroglossal duct remnant with Hashimoto's thyroiditis of the nonneoplastic ectopic thyroid tissue and the thyroid gland is described. The need for fine-needle aspiration cytologic examination in the management is stressed. The prognosis is excellent when the tumor is limited to the ectopic thyroid tissue and managed by a combination of the Sistrunk procedure and subtotal thyroidectomy followed by long-term thyroid suppression.

Insight to neoplastic thyroid lesions by fine needle aspiration cytology.

BACKGROUND: Fine needle aspiration cytology (FNAC) is a valuable adjunct to pre-operative screening in the diagnosis of thyroid nodules, and in most cases, it can distinguish between benign and malignant lesions. AIM: To study the cytology of neoplastic thyroid lesions to minimize surgical intervention and for confirmation of the diagnosis by histopathological study. MATERIALS AND METHODS: 100 cases of thyroid FNAC smears were analyzed and cyto-histopathological correlation was done in 47 cases. Galen and Gambino's method was used to calculate the sensitivity and positive predictive value. RESULTS: Of the 100 cases, 90 were diagnosed as neoplastic lesions by FNAC and ten cases as non-neoplastic lesions, which turned out to be neoplasms on histopathological study. Among 100 cases, 47 were biopsied and subjected to histopathological study. The sensitivity of FNAC was 75.60%, and positive predictive value was 83.78% for malignant lesions. CONCLUSIONS: FNAC is a rapid, efficient, cost-effective, relatively painless procedure with a high diagnostic accuracy. It has high rate of sensitivity and positive predictive value in diagnosing thyroid neoplastic lesions. Hence, it is a valuable tool in the diagnosis and management of patients.

Bone marrow examination in pancytopenia.

Pancytopenia is defined by reduction of all the three formed elements of blood below the normal reference. It may be a manifestation of a wide variety of disorders, which primarily or secondarily affect the bone marrow. Haematological investigation forms the bedrock in the management of patients with pancytopenia and therefore needs detailed study. The total number of cases studied were 100 over a period of two years in the department of pathology, JSS Hospital, Mysore. Megaloblastic anaemia (33%) was the commonest cause of pancytopenia. Other causes were nutritional anaemia (16%), aplastic anaemia (14%), hypersplenism (10%), sepsis (9%) and leukaemia (5%). Less common causes were alcoholic liver disease, haemolytic anaemia, HIV, dengue, systemic lupus erythematosus, viral hepatitis, disseminated TB and multiple myeloma. Most of the patients were in the age group of 11-30 years with a male:female ratio of 1.6:1.Generalised weakness and fatigue (88%) were the commonest presenting complaints. Haemoglobin level varied from 1-10 g/dl with majorIty (70%) of them in the range of 5.1-10 g/dI. TLC was in the range of 500-4000 cells/cmm. Most (34%) of them had 3100-4000 cells/cmm. Platelet count was in the range of 4000-1,40,000 cells/cmm. Reticulocyte count varied from 0.1%-15% with majority (82%) of them ranging from 0.1%-2%. The bone marrow cellularity was hypocellular in 14%, hypercellular in 75%, and normocellular in 11% of the patients. Pancytopenia is a relatively common entity with inadequate attention in Indian subcontinent. A comprehensive clinical and haematological study of patients with pancytopenia will usually help in the identification of the underlying cause. However in view of wide array of aetiologies, pancytopenia continues to be a diagnostic challenge for haematologists.

Neurocognitive deficits in male alcoholics: an ERP/sLORETA analysis of the N2 component in an equal probability Go/NoGo task.

In alcoholism research, studies concerning time-locked electrophysiological aspects of response inhibition have concentrated mainly on the P3 component of the event-related potential (ERP). The objective of the present study was to investigate the N2 component of the ERP to elucidate possible brain dysfunction related to the motor response and its inhibition using a Go/NoGo task in alcoholics. The sample consisted of 78 abstinent alcoholic males and 58 healthy male controls. The N2 peak was compared across group and task conditions. Alcoholics showed significantly reduced N2 peak amplitudes compared to normal controls for Go as well as NoGo task conditions. Control subjects showed significantly larger NoGo than Go N2 amplitudes at frontal regions, whereas alcoholics did not show any differences between task conditions at frontal regions. Standardized low resolution electromagnetic tomography analysis (sLORETA) indicated that alcoholics had significantly lower current density at the source than control subjects for the NoGo condition at bilateral anterior prefrontal regions, whereas the differences between groups during the Go trials were not statistically significant. Furthermore, NoGo current density across both groups revealed significantly more activation in bilateral anterior cingulate cortical (ACC) areas, with the maximum activation in the right cingulate regions. However, the magnitude of this difference was much less in alcoholics compared to control subjects. These findings suggest that alcoholics may have deficits in effortful processing during the motor response and its inhibition, suggestive of possible frontal lobe dysfunction.

Family-based genome-wide association study of frontal θ oscillations identifies potassium channel gene KCNJ6.

Event-related oscillations (EROs) represent highly heritable neuroelectric correlates of cognitive processes that manifest deficits in alcoholics and in offspring at high risk to develop alcoholism. Theta ERO to targets in the visual oddball task has been shown to be an endophenotype for alcoholism. A family-based genome-wide association study was performed for the frontal theta ERO phenotype using 634 583 autosomal single nucleotide polymorphisms (SNPs) genotyped in 1560 family members from 117 families densely affected by alcohol use disorders, recruited in the Collaborative Study on the Genetics of Alcoholism. Genome-wide significant association was found with several SNPs on chromosome 21 in KCNJ6 (a potassium inward rectifier channel; KIR3.2/GIRK2), with the most significant SNP at P = 4.7 × 10(-10)). The same SNPs were also associated with EROs from central and parietal electrodes, but with less significance, suggesting that the association is frontally focused. One imputed synonymous SNP in exon four, highly correlated with our top three SNPs, was significantly associated with the frontal theta ERO phenotype. These results suggest KCNJ6 or its product GIRK2 account for some of the variations in frontal theta band oscillations. GIRK2 receptor activation contributes to slow inhibitory postsynaptic potentials that modulate neuronal excitability, and therefore influence neuronal networks.

CT-guided fine needle aspiration cytology diagnosis of extra-adrenal pheochromocytoma.

Pheochromocytoma is a rare tumor, accounting for <0.1% of the hypertensive population. Extra-adrenal pheochromocytomas (EAPs) are rarer still, accounting for 10% of all pheochromocytomas. Pheochromocytomas are functional catecholamine-secreting tumors of the paraganglionic chromaffin cells found in the adrenal medulla and the extra-adrenal paraganglia cells. EAPs are readily detected by computed tomography (CT) as soft tissue masses closely associated with the entire length of the abdominal aorta. Here, we present a rare case of EAP in a 45-year-old male hypertensive patient diagnosed by CT-guided fine needle aspiration cytology. The smears showed loosely cohesive tumor cells with prominent anisokaryosis and abundant eosinophilic, granular cytoplasm. The diagnosis was later confirmed by histopathology. The present case also highlights the fact that fine needle aspiration of pheochromocytoma is not necessarily contraindicated.