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OBJECTIVES: This study:Healthy Active and in Control (HA1C), examined the feasibility and acceptability of yoga as a complementary therapy for adults with Type-2 Diabetes (T2DM). DESIGN: A 2-arm randomized clinical trial comparing Iyengar yoga with a supervised walking program. SETTING: Hospital based gym-type facility and conference rooms. INTERVENTIONS: Participants were randomized to a 12-week program of either; (1) a twice weekly Iyengar yoga, or (2) a twice-weekly program of standard exercise (SE). MAIN OUTCOME MEASURES: Primary outcomes assessed feasibility and acceptability, including enrollment rates, attendance, study completion, and participant satisfaction. Secondary outcomes included HbA1c, physical activity, and measures of diabetes-related emotional distress, self-care and quality of life (QOL). Assessments were conducted at baseline, end of treatment, 6-months and 9-months post-enrollment. RESULTS: Of 175 adults screened for eligibility, 48 (30 women, 18 men) were eligible and enrolled. The most common reasons for ineligibility were orthopedic restrictions, HbA1c levels <6.5 and BMI > 42. Session attendance was high (82% of sessions attended), as was follow-up completion rates (92%). Program satisfaction rated on a 5-point scale, was high among both Yoga (M = 4.63, SD = 0.57) and SE (M = 4.77, SD = 0.52) participants. Overall 44 adverse events (26 Yoga, 18 SE) were reported. Of these, six were deemed "possibly related" (e.g., neck strain, back pain), and 1 "probably related" (ankle pain after treadmill) to the study. Yoga produced significant reductions in HbA1c. Median HbA1c at 6 months was 1.25 units lower for Yoga compared to SE (95% CI: -2.54 -0.04). Greater improvements in diabetes self-care, quality of life, and emotional distress were seen among Yoga participants than among SE participants. Increases in mindfulness were seen in Yoga but not in SE. CONCLUSIONS: The yoga intervention was highly feasible and acceptable, and produced improvements in blood glucose and psychosocial measures of diabetes management.

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Membrane lipid rafts (i.e., cholesterol/sphingolipids domains) exhibit functional roles in both healthy and pathological states of the nervous system. However, due to their highly dynamic nature, it remains a challenge to characterize the fundamental aspects of lipid rafts that are important for specific neuronal processes. An experimental approach is presented here that allows for the interfacing of living neurons with an experimentally accessible model membrane where lipid order in cellular rafts can be reproducibly mimicked. It is demonstrated that coexisting lipid microdomains in model membranes can regulate axonal guidance and establish stable presynaptic contacts when interfaced with neurons in vitro. Experimental evidence is provided where specific functional groups and lateral organizations are favored by neurons in establishing synaptic connections. The model membrane platform presented in this work provides an accessible and direct means to investigate how lipid rafts regulate synapse formation. This experimental platform can similarly be extended to explore a variety of other cellular events where lipid lateral organization is believed to be important.

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The purpose of this study is to determine the relevance of the hygiene hypothesis; that is to determine if worm infestation has a protective role against the development of allergic rhinitis. A prospective case controlled study was conducted. Specific IgG levels to Toxocara were studied in 85 patients confirmed to have allergic rhinitis and were compared to levels in another 85 controls, with no form of allergy. The IgG assay was done using ELISA technique. There was a higher incidence of positive specific IgG to Toxocara in the controls as compared to allergic patients. The values were statistically significant [Chi square test (p=0.002)]. This negative association between worm infestation and allergic rhinitis suggests that a previous worm infestation could protect against the development of allergic rhinitis.

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The purpose of this study is to determine the relevance of the hygiene hypothesis; that is to determine if worm infestation has a protective role against the development of allergic rhinitis. A prospective case controlled study was conducted. Specific IgG levels to Toxocara were studied in 85 patients confirmed to have allergic rhinitis and were compared to levels in another 85 controls, with no form of allergy. The IgG assay was done using ELISA technique. There was a higher incidence of positive specific IgG to Toxocara in the controls as compared to allergic patients. The values were statistically significant [Chi square test (p=0.002)]. This negative association between worm infestation and allergic rhinitis suggests that a previous worm infestation could protect against the development of allergic rhinitis.

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OBJECTIVES: Human prion diseases are heterogeneous but invariably fatal neurodegenerative disorders with no known effective therapy. PRION-1, the largest clinical trial in prion disease to date, showed no effect of the potential therapeutic quinacrine on survival. Although there are several limitations to the usefulness of survival as an outcome measure, there have been no comprehensive studies of alternatives. METHODS: To address this we did comparative analyses of neurocognitive, psychiatric, global, clinician-rated, and functional scales, focusing on validity, variability, and impact on statistical power over 77 person-years follow-up in 101 symptomatic patients in PRION-1. RESULTS: Quinacrine had no demonstrable benefit on any of the 8 scales (p > 0.4). All scales had substantial numbers of patients with the worst possible score at enrollment (Glasgow Coma Scale score being least affected) and were impacted by missing data due to disease progression. These effects were more significant for cognitive/psychiatric scales than global, clinician-rated, or functional scales. The Barthel and Clinical Dementia Rating scales were the most valid and powerful in simulated clinical trials of an effective therapeutic. A combination of selected subcomponents from these 2 scales gave somewhat increased power, compared to use of survival, to detect clinically relevant effects in future clinical trials of feasible size. CONCLUSIONS: Our findings have implications for the choice of primary outcome measure in prion disease clinical trials. Prion disease presents the unusual opportunity to follow patients with a neurodegenerative disease through their entire clinical course, and this provides insights relevant to designing outcome measures in related conditions.

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Primary localised amyloidosis involving the retroperitoneum is a rare disease. We report a 71-year-old diabetic man who presented with generalised fatigue, malaise and elevated serum creatinine. Investigations confirmed obstructive uropathy secondary to a retroperitoneal mass behind the urinary bladder, causing extrinsic compression of both the ureters, resulting in bilateral hydroureteronephrosis. Following initial bilateral percutaneous nephrostomies to stabilise renal function, a computed tomography-guided biopsy of the pelvic lesion which was done, was suggestive of amyloidosis. We present this case due to the rarity of localised retroperitoneal amyloidosis as a cause of obstructive uropathy.

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BACKGROUND: Reports from India on the prevalence and determinants of female sexual dysfunction (FSD) are scant. AIMS: To determine the prevalence and risk factors for FSD. SETTINGS AND DESIGN: A cross-sectional survey in a medical outpatient clinic of a tertiary care hospital. MATERIALS AND METHODS: We administered a Tamil version of the Female Sexual Function Index (FSFI) to 149 married women. We evaluated putative risk factors for FSD. We elicited participant's attributions for their sexual difficulties. STATISTICAL ANALYSIS: We estimated the prevalence of possible FSD and sexual difficulties from published FSFI total and domain cut-off scores. We used logistic regression to identify risk factors for possible FSD. RESULTS: FSFI total scores suggested FSD in two-thirds of the 149 women (73.2%; 95% confidence intervals [CI] 65.5% to 79.6%). FSFI domain scores suggested difficulties with desire in 77.2%; arousal in 91.3%; lubrication in 96.6%; orgasm in 86.6%, satisfaction in 81.2%, and pain in 64.4%. Age above 40 years (odds ratios [OR] 11.7; 95% CI 3.4 to 40.1) and fewer years of education (OR 1.2; 95% CI 1.0 to 1.3) were identified by logistic regression as contributory. Women attributed FSD to physical illness in participant or partner, relationship problems, and cultural taboos but none had sought professional help. CONCLUSIONS: Sexual problems suggestive of dysfunction, as suggested by FSFI total and domain scores, are highly prevalent in the clinic setting, particularly among women above 40 and those less educated, but confirmation using locally validated cut-off scores of the FSFI is needed.

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In Graves' disease (GD) immunized T cells reactive to TSH-receptor epitopes contribute to pathogenesis through B cell help, and cytotoxicity. We evaluated T cell responses to synthetic TSH-receptor epitopes in hyperthyroid patients with GD prior to therapy, at 6-8 weeks after radioactive iodine (RAI) administration, or 6-8 months later when euthyroid, and in control subjects. All T cell responses were relatively low as generally found in human autoimmune diseases. Responses in hyperthyroid GD patients were significantly greater than among controls, were augmented 6-8 weeks after RAI treatment, were still present after patients became euthyroid, and did not differ between DR3+ and non-DR3+ patients. Patient's T cells reacted to multiple different epitopes, and reactivity differed depending on the course of the disease and treatment.While certain epitopes most commonly cause T cell reactivity, we did not find evidence for a single or few "dominant" epitopes.

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The liver is a major metabolic and endocrine organ of critical importance in the regulation of growth and metabolism. Its function is determined by a complex interaction of nutritionally regulated counter-regulatory hormones. The extent to which hepatic endocrine sensitivity can be programed in utero and whether the resultant adaptations persist into adulthood is unknown and was therefore the subject of this study. Young adult male sheep born to mothers that were fed either a control diet (i.e.100% of total live weight-maintenance requirements) throughout gestation or 50% of that intake (i.e. nutrient restricted (NR)) from 0 to 95 days gestation and thereafter 100% of requirements (taking into account increasing fetal mass) were entered into the study. All mothers gave birth normally at term, the singleton offspring were weaned at 16 weeks, and then reared at pasture until 3 years of age when their livers were sampled. NR offspring were of similar birth and body weights at 3 years of age when they had disproportionately smaller livers than controls. The abundance of mRNA for GH, prolactin, and IGF-II receptors, plus hepatocyte growth factor and suppressor of cytokine signaling-3 were all lower in livers of NR offspring. In contrast, the abundance of the mitochondrial protein voltage-dependent anion channel and the pro-apoptotic factor Bax were up regulated relative to controls. In conclusion, maternal nutrient restriction in early gestation results in adult offspring with smaller livers. This may be mediated by alterations in both hepatic mitogenic and apoptotic factors.

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INTRODUCTION: The urinary bladder is commonly involved in pelvic malignancy. The incidence of apparent extension into adjacent organs in locally advanced colorectal malignancy is 5-12%. It is not known with other pelvic malignancy. No guidelines are available for its management. Often a dilemma exists between cystectomy and a bladder-sparing procedure. We studied the validity of bladder-sparing surgery (BSS) in locally advanced nonurological pelvic malignancy. METHODS: Hospital records of patients who underwent BSS along with other surgeries (abdomino-perineal resection, anterior resection, anterior exenteration, debulking surgery and total pelvic exenteration) from January 1992 to May 2003 were reviewed. RESULTS: BSS was done in 15 patients. 10 had locally advanced colorectal malignancy, 3 with soft tissue masses of the lateral pelvic wall, 1 had ovarian malignancy and the other had residual mass following radiotherapy and chemotherapy of cancer cervix. In those with locally advanced colorectal malignancy, symptoms suggestive of lower urinary tract involvement were present in 8 (80%). Urine examination and ultrasonography was not helpful in suggesting bladder involvement, unlike CT scan of abdomen and pelvis. Preoperative cystoscopy showed endoscopic evidence of bladder involvement in 7 (87.5%). Bladder was involved supratrigonally in 7. Partial cystectomy was done in 9 patients. The left ureter was involved in 6 patients, and they required ureteric reimplantation. Palliative transurethral resection was done in 1 patient with tumor infiltration at the bladder neck and prostate. 50% patients had bothersome lower urinary tract symptoms at 1 year. One patient died in the immediate postoperative period due to a nonurological cause. Overall 3-year survival rate was 40%. CONCLUSION: Unlike primary bladder cancers these lesions are not multifocal and hence en block conservative bladder-sparing surgery can be offered. Preoperative CT scan or MRI can predict lower urinary tract involvement and help in decision-making by both surgeon and patient. The ultimate decision for bladder sparing is based on intraoperative findings. Sparing the bladder might provide better quality of life by avoiding urinary diversion without altering survival.

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The prenatal diet can program an individual's cardiovascular system towards later higher resting blood pressure and kidney dysfunction, but the extent to which these programmed responses are directly determined by the timing of maternal nutritional manipulation is unknown. In the present study we examined whether maternal nutrient restriction targeted over the period of maximal placental growth, i.e. days 28-80 of gestation, resulted in altered blood pressure or kidney development in the juvenile offspring. This was undertaken in 6-month-old sheep born to mothers fed control (100-150 % of the recommended metabolisable energy (ME) intake for that stage of gestation) or nutrient-restricted (NR; 50 % ME; n 6) diets between days 28 and 80 of gestation. Controls were additionally grouped according to normal (>3, n 7) or low body condition score (LBCS; <2, n 6), thereby enabling us to examine the effect of maternal body composition on later cardiovascular function. From day 80 to term (approximately 147 d) all sheep were fed to 100 % ME. Offspring were weaned at 12 weeks and pasture-reared until 6 months of age when cardiovascular function was determined. Both LBCS and NR sheep tended to have lower resting systolic (control, 85 (se 2); LBCS, 77 (se 3); NR, 77 (se 3) mmHg) and diastolic blood pressure relative to controls. Total nephron count was markedly lower in both LBCS and NR relative to controls (LBCS, 59 (se 6); NR, 56 (se 12) %). Our data suggest that maternal body composition around conception is as important as the level of nutrient intake during early pregnancy in programming later cardiovascular health.

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We studied HIV prevalence in couples in Chennai, India. In 56% both partners were infected. Among discordant couples, 35 men and seven women were infected. Heterosexual intercourse is the primary risk factor. Concordance was related to sex with commercial sex workers for men and to genital ulcer disease for women. Median CD4 count was 97 cells/mm(3) among concordant men, 222 cells/mm(3) among discordant men. Condom use increased, and frequency of sexual intercourse decreased, among all couples after HIV diagnosis.

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Epidemiological and animal studies strongly indicate that the environment experienced in utero determines, in part, an individual's likelihood of developing cardiovascular disease in later life. This risk has been further linked to impaired kidney function, as a result of compromised development during fetal life. The present study therefore examined the influence of maternal nutrient restriction (NR), targeted at specific periods of kidney development during early to mid gestation, on the mRNA abundance of receptors for glucocorticoid (GCR), growth hormone (GHR) and insulin-like growth factors-I (IGF-IR) and -II (IGF-IIR), and the IGF-I and -II ligands. This was undertaken in both singleton and twin fetuses. At conception ewes were randomly allocated to either an adequately fed control group or one of four nutrient-restricted groups that were fed half the control amount from 0 to 30, 31 to 65, 66 to 110 or 0 to 110 days gestation. At 110 days gestation all ewes were humanely euthanased and fetal kidneys and surrounding adipose tissue sampled. There was no effect of NR or fetal number on kidney weight, shape or nephron number, but the surrounding fat mass was increased in singleton fetuses exposed to NR for 110 days. An increase in kidney mRNA abundance with NR only occurred in singleton fetuses where IGF-IR mRNA was enhanced with NR from 66-110 days gestation. In twin fetuses, NR had no effect on mRNA abundance. However, for all genes examined mRNA expression was lower in the kidneys of twin compared with singleton fetuses following NR, and the magnitude of the effect was dependent on the timing of NR. In conclusion, the abundance of mRNA for receptors which regulate fetal kidney development are lower in twin animals compared with singletons following periods of nutrient deficiency. This may impact on later kidney development and function.

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BACKGROUND: A severe degree of ureteral obstruction is viewed as a predictor of poor outcome in shockwave lithotripsy (SWL). Impacted stones are often considered a contraindication to in-situ SWL. PATIENTS AND METHODS: Impaction in our study was defined as failure to visualize the ureter distal to the calculus with proximal hold-up of contrast for as long as 3 hours on an intravenous urogram (IVU). We evaluated 30 patients with impacted ureteral calculi, who were compared with a second unimpacted group matched for stone size and stone location. The calculi were reorganized into < or =10-mm and >10-mm groups. The results were compared in terms of clearance rates, number of shockwaves, number of sessions, and number of days between the start of SWL and clearance. RESULTS: Between January 1998 and December 2001, 30 impacted stones were treated with lithotripsy. Complete clearance rates in the impacted as well as the non-impacted group were 76.7%. There was no statistical difference in the number of shockwaves, sessions, or time to clearance. The results were poorer in lower-ureteral than upper-ureteral calculi, but this difference did not reach statistical significance. However, the differences between the < or =10-mm and >10-mm stones were statistically significant. CONCLUSION: Impaction on an IVU does not affect the results of lithotripsy.

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The prenatal nutritional environment influences the subsequent risk of hypertension in adulthood. Animal studies have used, generally, the rat as a model species to illustrate the association between maternal nutrient intake and blood pressure in the resulting adult offspring. No study to date has shown programming of adult cardiovascular function in the sheep through maternal dietary intervention. We therefore fed pregnant sheep to either 100% recommended intake from day 0 of gestation to term [ approximately 147 days gestational age (dGA); controls n = 8] or to 50% recommended intake from day 0 to 95 dGA and thereafter to 100% intake (NR; n = 9). Sheep lambed naturally, offspring were weaned at 16 wk, and the male offspring were reared on pasture until 3 yr of age. At this time, cardiovascular catheters were inserted under halothane anesthesia and sheep were allowed 2-4 days recovery. Basal cardiovascular status and pressor responses to infusion of norepinephrine, angiotensin II, and captopril were then assessed alongside basal plasma concentrations of glucose, cortisol, and leptin. NR sheep were of similar birth weight to controls but at 3 yr of age had higher blood pressure before, but not after, feeding. Peripheral sensitivity to vasoconstrictor infusion was similar between dietary groups, although a reflex bradycardia was not apparent in NR sheep during norepinephrine infusion. Circulating leptin correlated well with fat mass and increased more after vasoconstrictor infusion in NR sheep. In conclusion, early NR has been shown to program aspects of cardiovascular control and adipocyte function in adult sheep.

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Radiotherapy has been recognized as a valuable modality of treatment in the management of head and neck cancers. It can have a direct bactericidal effect on the normal flora of the oropharynx. The objective of this study is to determine the changes in the oropharyngeal flora after external beam radiation. This prospective non randomized control study was performed to aid in identification of organisms involved in sepsis, as well as aid in choosing appropriate antibiotics for surgical procedures in irradiated patient. Forty patients with various head and neck malignancy and thirty control patients were selected. Oropharyngeal swabs were taken prior to radiotherapy, at the end and one month after radiotherapy. A single swab was taken from the control group. A full bacteriological analysis was performed. There was a statistically significant decrease in Alpha Hemolytic Streptococci and Neisseria species post radiotherapy. B Proteus and Candida Albicans showed a statistical significant increase in patients with head and neck cancer post radiotherapy. These changes remained even one month after radiotherapy.

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Samaderin B, or (1R,2S,5R,5aR,7aS,11S,11aS,11bR,14S)-1,7,7a,11,11a,11b-hexahydro-1,11-dihydroxy-8,11a,14-trimethyl-2H-5a,2,5-(methanoxymetheno)naphth[1,2-d]oxepine-4,6,10(5H)-trione, C(19)H(22)O(7), and samaderin C, or (1R,2S,5R,5aR,7aS,10S,11S,11aS,11bR,14S)-7,7a,10,11,11a,11b-hexahydro-1,10,11-trihydroxy-8,11a,14-trimethyl-2H-5a,2,5-(methanoxymetheno)naphth[1,2-d]oxepine-4,6(1H,5H)-dione, C(19)H(24)O(7), were isolated from the seed kernels of Samadera indica and were shown to exhibit antifeedant activity against Spodoptera litura third-instar larvae. The replacement of the carbonyl group in samaderin B by a hydroxy group in samaderin C causes conformational changes at the substitution site, but the overall conformation is not affected; however, the compounds pack differently in the crystal lattice.

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Maternal nutrient restriction at specific stages of gestation has differential effects on fetal development such that the offspring are programmed to be at increased risk of adult disease. We investigated the effect of gestational age and maternal nutrition on the maternal plasma concentration of leptin and cortisol together with effects on fetal adipose tissue deposition plus leptin, IGF-I, IGF-II ligand, and receptor mRNA abundance near to term. Singleton bearing ewes were either nutrient restricted (NR; consuming 3.2-3.8 MJ/d of metabolizable energy) or fed to appetite (consuming 8.7-9.9 MJ/d) over the period of maximal placental growth, i.e. between 28 and 80 d gestation. After 80 d gestation, ewes were either fed to calculated requirements, consuming 6.7-7.5 MJ/d, or were fed to appetite and consumed 8.0-10.9 MJ/d. Pregnancy resulted in a rise in plasma leptin concentration by 28 d gestation, which continued up to 80 d gestation when fed to appetite but not with nutrient restriction. Plasma cortisol was also lower in NR ewes up to 80 d gestation, a difference no longer apparent when food intake was increased. At term, irrespective of maternal nutrition in late gestation, fetuses sampled from ewes NR in early gestation possessed more adipose tissue, whereas when ewes were fed to appetite throughout gestation, fetal adipose tissue deposition and leptin mRNA abundance were both reduced. These changes may result in the offspring of NR mothers being at increased risk of obesity in later life.

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Epidemiological and experimental studies have demonstrated that maternal undernutrition during pregnancy is associated with abnormal placental growth. In sheep, maternal nutrient restriction over the period of rapid placental growth (30-80 days) restricts placentome growth. Then following adequate nutrition up to term (147 days), placental mass is greater in association with a higher total abundance of the predominant placental glucose transporter-1. The resulting lambs are larger at birth, have heavier kidneys with an increased expression of the glucocorticoid-responsive type 1 angiotensin II receptor. Near to term, these fetuses possess more adipose tissue, the endocrine sensitivity of which is markedly enhanced. For example, the abundance of mRNA for 11beta-hydroxysteroid dehydrogenase type 1, which catalyses the conversion of cortisone to bio-active cortisol is increased. This is associated with a higher abundance of both leptin and glucocorticoid receptor mRNA. At 6 months of age, the juvenile offspring of nutrient restricted ewes have lower resting blood pressure that was positively correlated with plasma cortisol concentration, suggesting their blood pressure could be more strongly driven by circulating cortisol. These offspring also exhibited a greater pressor response to vasoconstrictor challenges, but showed no difference in vasodilatory response. At this age, the kidney weight was similar between groups, but the abundance of cytochrome c in kidney mitochondria was enhanced in lambs born to nutrient restricted ewes that could indicate increased mitochondrial activity. Reduced maternal nutrition during the period of rapid placental growth may therefore contribute to hypertension in later life through physiological and vascular adaptations during fetal life.

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