An association study between 5-HTTLPR polymorphism, COMT polymorphism, and Tourette's syndrome

Several lines of evidence suggest that a genetic component underlies Tourette's syndrome (TS). We investigated both the role of the insertion/deletion polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) and that of the Val-158-Met substitution in the catechol-O-methyl-transferase (COMT) gene in conferring susceptibility to TS. Fifty-two TS patients were recruited and compared with a control group of 63 healthy subjects. Neither a genotypic nor an allelic association was found; subdividing TS patients according to clinical variables, such as a co-diagnosis of obsessive–compulsive disorder (OCD) and a positive family history for obsessive compulsive disorder or tics, also failed to reveal a significant association. The lack of significance for 5-HTTLPR and COMT polymorphisms in conferring liability to TS does not exclude a role of different functional polymorphisms in genes coding for serotonergic or dopaminergic structures in the etiology of TS. In fact, TS is a complex disorder and these genes most likely have only a minor genetic effect in its etiology.     

Phase III study of fluorouracil, leucovorin, and levamisole in high-risk stage II and III colon cancer: final report of Intergroup 0089.

PURPOSE: In 1990, fluorouracil (FU) plus levamisole for 1 year became standard adjuvant treatment for patients with high-risk stages II and III colon cancer. Intergroup (INT) 0089 assessed the relative contributions of leucovorin and levamisole in such patients. PATIENTS AND METHODS: From 1988 to 1992, 3,794 patients were randomly assigned. Experimental treatment consisted of one of three chemotherapy regimens: the low-dose leucovorin plus FU (Mayo Clinic; LDLV) regimen, the high-dose leucovorin plus FU (Roswell Park; HDLV) regimen, and the low-dose leucovorin plus levamisole plus FU (LDLV plus LEV) regimen, each administered for 30 to 32 weeks. The control arm was levamisole plus FU (LEV) for 1 year. RESULTS: After a median follow-up of 10 years, of 3,561 eligible patients, 1,691 (47%) have died and 1,330 (37%) have experienced disease recurrence; 137 (10%) of those experiencing recurrence are still alive. A total of 481 patients (13%) died without evidence of recurrence, and 1,723 (48%) are alive and disease free. Although there were toxicity differences among the four arms, none was statistically superior in disease-free or overall survival. CONCLUSION: The 6- to 8-month regimens of LDLV and HDLV without levamisole used in this trial, rather than the previous standard regimen of 12 months of LEV, have become widely used. INT-0089 has long-term follow-up of the largest clinical trial of patients with high-risk colon cancer, documenting not only the durability of the treatment effects, but also the natural history of patients with high-risk colon cancer, and analyses of treatment based on age, race, and comorbid conditions such as obesity, diabetes, and second primary cancers.     

The Role of Individual and Neighborhood Factors: HIV Acquisition Risk Among High-Risk Populations in San Francisco

We examined socioeconomic status and social and sexual network factors and their relationship to HIV acquisition risk among HIV-negative Black MSM (BMSM), White MSM (WMSM) and transfemales (male to female transgenders). Geographic analysis examined residential patterns and neighborhood patterns of HIV prevalence in San Francisco. Factors associated with engaging in more episodes of potentially HIV serodiscordant unprotected receptive anal intercourse were analyzed. Transfemales and BMSM were more likely to live in areas of higher HIV prevalence and lower income compared to WMSM. BMSM and transfemales had lower socioeconomic scores (SES) scores compared to WMSM. BMSM were more likely to report serodiscordant partnerships and higher numbers of potentially serodiscordant unprotected sex acts. Decreasing individual SES did not predict serodiscordant partnerships in any group. Increasing neighborhood HIV prevalence predicted an increase in the number of potentially serodiscordant unprotected sex acts among transfemales and BMSM but only significantly so for transfemales. Prevention interventions must consider neighborhood HIV prevalence, and HIV prevalence in social/sexual networks, in addition to considering individual level behavior change or poverty reduction.     

From recipe to research: introducing undergraduate students to the nature of science using a hybrid practical course centred on drug discovery for neglected diseases

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Trends in the incidence of basal cell carcinoma by histopathological subtype

Background As a result of the high prevalence, basal cell carcinoma (BCC) causes a significant and expensive health care problem. Objective In this study, we evaluate the proportional increase in BCC by histological subtype over the last two decades. Methods We retrospectively reviewed all primary histological confirmed BCCs diagnosed in the Maastricht University Medical Centre in The Netherlands in the years 1991, 1999 and 2007. Results An annual increase of the number of BCCs of 7% for both genders was shown. The age‐standardized incidence rates for BCC increased between 1991 and 2007 from 54.2 to 162.1 per 100 000 men and from 61.7 to 189.8 per 100 000 women. The proportion of superficial BCC increased significantly from 17.6% to 30.7%. Conclusion The incidence of BCC is continuing to increase this century. The observed shift to the superficial histological subtype, which can be treated non‐surgically, might reduce the workload in the busy dermatologists practice.     

PATHWAYS FROM SCHOOL SUSPENSION TO ADOLESCENT NONVIOLENT ANTISOCIAL BEHAVIOR IN STUDENTS IN VICTORIA,AUSTRALIA AND WASHINGTON STATE,UNITED STATES

School suspension is associated with school dropout, crime, delinquency, and alcohol and other drug use for the suspended student. Important research questions are how academic and related factors are relevant to the school suspension process and the generality of the process in different sites. State‐representative samples of Grade 7 students (N = 1,945) in Washington State, United States and Victoria, Australia were followed from 2002 to 2004. In both states, Grade 7 school suspension was associated with higher rates of nonviolent antisocial behavior and suspension 24 months later, before Grade 8 factors were entered into the model. Relevant factors were Grade 8 low school grades and association with antisocial peers, as well as Grade 8 antisocial behavior in Washington State only. The implications of these findings for the ways in which suspension is used in schools are outlined.     

Locoregional therapy and systemic cetuximab to treat colorectal liver metastases

AIM: To investigate efficacy and safety of second-line treatment with irinotecan-loaded drug-eluting beads (DEBIRI) and cetuximab (DEBIRITUX) of unresectable colorectal liver metastases.METHODS: Patients with the following characteristics were included in the study: unresectable hepatic metastases from colorectal carcinoma (CRC-LM), progression after first line chemotherapy (any type of chemotherapeutic drug and combination was allowed), second line treatment (mandatory), which included for each patient (unregarding the KRas status) two cycles of DEBIRI (using 100-300 μm beads loaded with irinotecan at a total dose 200 mg) followed by 12 cycles of cetuximab that was administered weekly at a first dose of 400 mg/m² and then 250 mg/m²; good performance status (0-2) and liver functionality (alanine aminotransferase and gamma-glutamyl transferase not exceeding three times the upper limit of normal, total bilirubin not exceeding 2.5 mg/mL). Data were collected retrospectively and included: tumor response (evaluated monthly for 6 mo then every 3 mo), overall response rate (ORR), KRas status, type and intensity of adverse events (G according to the Common Terminology Criteria for Adverse Events v3.0, CTCAE), overall survival (OS) and progression free survival (PFS).RESULTS: Forty consecutive cases of CRC hepatic metastases were included in the study. Median duration of DEBIRITUX was 4.4 mo (range, 4.0-6.5). Sixteen patients (40%) received the planned 2 cycles of DEBIRI and an average of 10 cetuximab cycles. ORR of the whole sample was 50%, in particular 4 patients were complete responders (10%) and 16 (40%) partial responders. The most observed side effects (G2) were: post-embolization syndrome (30%), diarrhea (25%), skin rushes (38%) and asthenia (35%). The retrospective evaluation of KRas status (24 wild type, 16 mutated) showed that the group of patients with wild type KRas had ORR significantly higher than mutant KRas. Median follow-up was 29 mo (8-48 range); median PFS was 9.8 mo and OS was 20.4 mo. Future randomized trials are required in this setting to establish a role for DEBIRITUX compared with systemic chemotherapy.CONCLUSION: DEBIRITUX seems to be efficacious after first line chemotherapy for the treatment of unresectable CRC-LM.     

Nitric oxide is involved in the insulin release in rats byl-arginine

The insulinogenic effect ofl-arginine has been demonstrated bothin vivo andin vitro, but the mechanism by which this amino acid stimulates the pancreatic B-cells to release insulin is not entirely clear. Recently it was shown thatl-arginine-derived nitric oxide may mediatel-arginine-induced insulin release, and data were also provided to suggest that nitric oxide (NO) has no part in this process. To further investigate whether NO is involved in the release of insulin induced byl-arginine, we infused different doses ofl- andd-arginine in rats. L-Arginine (25 and 100 mg/kg/minute) elicited dose-dependent increases of the plasma insulin levels by up to 18.65±2.13 and 48.6±6.6 U/L, respectively, and increased the plasma glucose levels by up to 1.18±0.13 and 1.43±0.1 mmol/L, respectively. D-Arginine (25 and 100 mg/kg/minute) also elicited dose-dependent increases of the plasma insulin levels by up to 9.08±1.23 and 23.33±2.33 U/L, and increased the plasma glucose levels by up to 0.32±0.09 and 0.46±0.08 mmol/L. Thus, the increases in plasma insulin and glucose levels were significantly smaller during infusion ofd-arginine. We conclude that the plasma insulin response to i.v. infusion ofl-arginine is at least partly mediated by augmented NO synthesis by the pancreatic islets, althoughl-arginine-derived NO is not an obligatory stimulus for insulin release.     

Effectiveness of diclofenac versus paracetamol in knee osteoarthritis: a randomised controlled trial in primary care

Background

The effectiveness of diclofenac versus paracetamol in primary care patients with pain caused by knee osteoarthritis is unclear.

Aim

To assess the effectiveness of diclofenac compared with paracetamol over a period of 2, 4, and 12 weeks in patients with knee osteoarthritis.

Design and setting

Randomised controlled trial in general practice.

Method

There were 104 patients included in the study, they were aged ≥45 years consulting their GP with knee pain caused by knee osteoarthritis. Patients were randomly allocated to diclofenac (n = 52) or paracetamol (n = 52) for at least 2 weeks. Primary outcomes were daily knee pain severity, and knee pain and function measured with the Knee Injury and Osteoarthritis Outcome Score (KOOS).

Results

Over a period of 2- and 4-weeks follow-up, no significant difference in daily knee pain was found between the patient groups: estimated differences of 0.5 (95% CI = −0.2 to 1.3) and −0.2 (95% CI = −1.0 to 0.7), respectively. Over the 12-weeks follow-up, no significant differences were found between both groups for KOOS pain: estimated difference of −2.8 (95% CI = −10.7 to 5.1) and KOOS function of −2.7 (−10.6 to 5.0).

Conclusion

Over a period of 2- and 4-weeks follow-up no significant difference in daily measured knee pain severity was found between primary care patients with knee osteoarthritis taking paracetamol or diclofenac. Also, over a period of 12-weeks follow-up no significant differences were found regarding KOOS pain and KOOS function between both groups. Patients more frequently reported minor adverse events after taking diclofenac (64%) than paracetamol (46%).