A functional polymorphism of the mu-opioid receptor gene (OPRM1) influences cue-induced craving for alcohol in male heavy drinkers

BACKGROUND: The mu-opioid receptor gene (OPRM1) codes for the mu-opioid receptor, which binds beta-endorphin. The A118G polymorphism in this gene affects beta-endorphin binding such that the Asp40 variant (G allele) binds beta-endorphin 3 times more tightly than the more common Asn40 variant (A allele). This study investigated the influence of the A118G polymorphism on cue reactivity after exposure to an alcoholic beverage in male heavy drinkers. METHODS: Participants were either homozygous for the A allele (n=84) or carrying at least 1 copy of the G allele (n=24). All participants took part in a cue-reactivity paradigm where they were exposed to water and beer in 3-minute trials. The dependent variables of main interest were subjective craving for alcohol, subjective arousal, and saliva production. RESULTS: G allele carriers reported significantly more craving for alcohol than the A allele participants (as indicated by the within-subject difference in craving after beer vs after water exposure). No differences were found for subjective arousal and saliva. Both groups did not differ in family history of alcoholism. Participants with the G allele reported a significantly higher lifetime prevalence of drug use than participants homozygous for the A allele. CONCLUSIONS: A stronger urge to drink alcohol after exposure to an alcoholic beverage might contribute to a heightened risk for developing alcohol-related problems in individuals with a copy of the G allele. The G allele might also predispose to drug use in general.     

Results of a prospective phase 2 study combining imatinib mesylate and cytarabine for the treatment of Philadelphia-positive patients with chronic myelogenous leukemia in chronic phase

In chronic myelogenous leukemia (CML) imatinib mesylate has been shown to selectively inhibit the tyrosine kinase domain of the oncogenic bcr-abl fusion protein. Using this agent alone high rates of cytogenetic responses were recorded. However, several mechanisms of resistance have been described. In vitro studies examining the effects of imatinib mesylate plus cytarabine have shown synergistic antiproliferative effects of this combination. Thus, the CML French Group decided to perform a phase 2 trial testing a combination of imatinib mesylate and low-dose cytarabine in 30 previously untreated patients in chronic phase. Treatment was administered on 28-day cycles. Patients were treated continuously with imatinib mesylate orally at a dose of 400 mg daily. Cytarabine was given on days 15 to 28 of each cycle at an initial dose of 20 mg/m2/d via subcutaneous injection. Adverse events were frequently observed with grade 3 or 4 hematologic toxicities and nonhematologic toxicities in 53% (n = 16) and 23% (n = 7) of patients, respectively. The cumulative incidence of complete cytogenetic response (CCR) at 12 months was 83% and at 6 months 100% of the patients achieved complete hematologic response (CHR). We concluded that the combination was safe and promising given the rates of response.     

Ultrasound detection of free intraperitoneal fluid associated with hepatic and splenic injuries

BACKGROUND: The objective of this study was to compare the sensitivity and specificity of 5 abdominal views for detecting free intraperitoneal fluid in trauma patients later diagnosed with hepatic or splenic injuries. METHODS: This retrospective study conducted over a 17-month period enrolled patients with trauma. A Focused Abdominal Sonogram for Trauma (FAST) examination was done using 5 abdominal views. Exploratory laparotomy or computed tomography (CT) confirmed the presence of intraperitoneal fluid and associated injuries. The sensitivity and specificity were determined. RESULTS: Of the 245 study patients, 29 had injuries to the liver or spleen or both. The 5-view FAST examination's sensitivity for detecting free intraperitoneal fluid associated with hepatic, splenic, or combined injuries was 77%, 90%, and 100%, respectively. The sensitivity of the single Morison's pouch view in detecting free intraperitoneal fluid associated with hepatic, splenic, or combined injuries was 38%, 20%, and 67%, respectively. CONCLUSION: For identifying free intraperitoneal fluid associated with hepatic or splenic injuries, no single view of the FAST examination could match the sensitivity provided by the 5-view technique.     

Involvement of Renin-Angiotensin System in Pressure-Flow Relationship: Role of Angiotensin-converting Enzyme Gene Polymorphism

Background: The renin-angiotensin system is involved in blood pressure regulation. The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene is known to be associated with variation of plasma and cellular ACE concentrations. Furthermore, changes in arterial function have been suggested to be associated to the DD genotype. The aim of the study was to investigate the arterial vascular response to a physiologic stimulus (i.e., flow) according to the I/D ACE gene polymorphism.

Methods: Sixty patients scheduled for coronary artery bypass grafting (n = 24) or valve surgery (n = 36) under normothermic cardiopulmonary bypass were genotyped in a blind manner by polymerase chain reaction. Mean arterial pressure was measured at pump flows ranging from 1 to 3 l [middle dot] min-1 [middle dot] m-2 by 0.25 l [middle dot] min-1 [middle dot] m-2 step each 15 s, to obtain a pressure-flow relation. Independent factors associated with the variation of the slope of the pressure-flow relation curve were assessed by multivariate analysis.

Results: We found a D allelic frequency of 0.54. Patients were separated in two groups (DD, n = 16;ID/II, n = 44). There were no significant difference with regard to preoperative and intraoperative data between the two groups. DD patients had their pressure-flow relation curves shifted upward (with higher pressures as flow increased), indicating a lesser decrease in vascular resistance. Furthermore, DD genotype was the only independent predictor of the slope of the curves (21.5 +/- 4.2 vs. 18.1 +/- 5 mmHg/[l [middle dot] min-1 [middle dot] m-2] for DD and ID/II, respectively;P = 0.02; values are mean +/-SD).     

Family-based case-control study of MAOA and MAOB polymorphisms in Parkinson disease.

Monoamine oxidase (MAO) is an enzyme regulating metabolism of neurotransmitters such as dopamine. Two distinct forms of enzyme, encoded by genes MAOA and MAOB located on the X chromosome, have been considered as possible factors in the pathogenesis of Parkinson disease (PD). Previous association studies of PD and MAO genes reported inconsistent results. In this study, we used a large family-based data set to test associations between MAO genes and a risk of PD. The data set includes 298 female discordant sibpairs and 348 male discordant sibpairs. For this study, all subjects analyzed were white and families with known parkin mutations were removed. We analyzed 15 single nucleotide polymorphisms (SNPs) and a dinucleotide repeat marker in the MAO genes. Association was found with the intron 13 SNP of MAOB in the female subset (P = 0.02). No significant association was found in the male subset. Our results add to the evidence of involvement of MAOB in PD and suggest that the effect may be stronger in women.     

Rehabilitation Regimens Following Surgical Repair of Extensor Tendon Injuries of the Hand—A Systematic Review of Controlled Trials

There is no consensus on the most effective rehabilitation regimen following extensor tendon repair of the hand. This systematic review evaluates the outcomes of the various regimens. The Cochrane, MEDLINE, EMBASE, CINAHL, AMED, PEDro, OTseeker databases were searched for any prospective randomised clinical trials comparing rehabilitation regimens for acute extensor tendon injuries in adults. Five papers met the inclusion criteria. The regimens were static immobilisation, dynamic splinting and early active motion (EAM). There was no standard format of reporting. The sample size ranged from 27 to 100 patients. The duration of follow-up ranged from 8 to 24 weeks. Overall, patients’ total active motion improved with time. Early mobilisation regimens (active and passive) achieve quicker recovery of motion than static immobilisation but the long-term outcome appears similar. Given the comparable outcomes between dynamic splinting and EAM, we therefore favour EAM which is simpler and more convenient.

Electronic supplementary material

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