Opioid receptor gene (OPRM1, OPRK1, and OPRD1) variants and response to naltrexone treatment for alcohol dependence: results from the VA Cooperative Study

BACKGROUND: Pharmacotherapy of alcohol dependence (AD) is at an early stage of development; currently available medications have limited efficacy. It would be clinically valuable to identify, before initiation of a course of treatment, those patients who, based on genetic markers, are most likely to respond to a specific pharmacotherapy. A previous report suggested that a functional variant at the genetic locus encoding the mu opioid receptor (Asn40Asp) is such a marker, in short-term (3-month) treatment with the opioid-blocking drug naltrexone (NTX). METHODS: We studied polymorphic variants at each of the 3 opioid receptor genes--OPRM1, OPRD1, and OPRK1, which encode the mu, delta, and kappa opioid receptors, respectively--including the OPRM1 Asn40Asp variant--as predictors of response to NTX or placebo in 215 alcohol-dependent male subjects who participated in Veterans Affairs Cooperative Study 425, "Naltrexone in the Treatment of Alcohol Dependence." RESULTS: At the 3-month time point, treatment condition, age, and the pretreatment number of drinks per drinking day were all significant (p<0.05) predictors of the rate of relapse and time to relapse. Although NTX had no significant effect on relapse to heavy drinking in the overall sample in CSP 425, it significantly reduced relapse in the subgroup that provided DNA for analysis (i.e., the present study sample). There were no significant interactions between any individual single nucleotide polymorphisms studied and NTX treatment response. CONCLUSIONS: These results do not support association of the OPRM1 Asn40Asp polymorphism with NTX treatment response for AD.     

Risk factors for adverse outcomes of bacterial meningitis

Objective : To identify risk factors for adverse outcomes from bacterial meningitis.
Methodology : From a cohort of 166 children with bacterial meningitis who were studied prospectively, 130/158 (82%) survivors underwent neurological, neuropsychological, audiological and behaviour assessments 5–9 years following their illness.
Results : Major adverse outcomes included 8/166 (4.8%) deaths and severe neurological, intellectual or audiological sequelae in 11/130 (8.5%) children followed. Another 24 (18.5%) had cognitive, auditory or behaviour disorders. Bivariate analysis found age ≤12 months, tertiary referral, symptoms >24 h before diagnosis, seizures, focal neurological signs, deteriorating conscious state in hospital, Streptococcus pneumoniae infection and serum sodium concentration < 130 mmol/L were associated with adverse outcomes. Multivariate analysis showed age ≤12 months, symptoms >24 h, seizures after 72 h in hospital and focal neurological signs as independent risk factors. These were present in 18/19 (95%) children with major sequelae, but absent in 9/24 (37.5%) children with minor disabilities.
Conclusions : As minor disabilities following meningitis cannot be predicted, all survivors require assessment during their early school years.     

Making heel pricks less painful

A mechanical lancet, the Autolet, was compared with a manual heel prick in 36 newborn infants undergoing routine blood sampling for the Guthrie test and hypothyroid screening. Each method was equally effective in obtaining satisfactory blood samples but the Autolet was considerably less painful.     

Prevalence and distinct correlates of anxiety, substance, and combined comorbidity in a multi-site public sector sample with bipolar disorder

BACKGROUND: Recent data indicate high prevalence of both anxiety and substance comorbidity in bipolar disorder. However, few studies have utilized public sector samples, and only one has attempted to separate contributions of each type of comorbidity. METHODS: 328 inpatient veterans with bipolar disorder across 11 sites were assessed using selected Structured Clinical Interview for DSM-IV modules and self-reports. RESULTS: Comorbidity was common (current: 57.3%; lifetime: 78.4%), with multiple current comorbidities in 29.8%. Substance comorbidity rate was comparable to rates typically reported in non-veteran inpatient samples (33.8% current, 72.3% lifetime). Selected anxiety comorbidity rates exceeded those in other inpatient samples and appeared more chronic than episodic/recurrent (38.3% current, 43.3% lifetime). 49% of PTSD was due to non-combat stressors. Major correlates of current substance comorbidity alone were younger age, worse marital status, and higher current employability. Correlates of current anxiety comorbidity alone were early age of onset, greater number of prior-year depressive episodes, higher rates of disability pension receipt, and lower self-reported mental and physical function. Combined comorbidity resembled anxiety comorbidity. LIMITATIONS: This is a cross-sectional analysis of acutely hospitalized veterans. CONCLUSIONS: Distinct patterns of substance and anxiety comorbidity are striking, and may be subserved by distinct neurobiologic mechanisms. The prevalence, chronicity and functional impact of anxiety disorders indicate the need for improved recognition and treatment of this other dual diagnosis group is warranted. Clinical and research interventions should recognize these divergent comorbidity patterns and provide individualized treatment built "from the patient out."     

Total endoprosthesis of knee joint for the severe deformity of the femoral and tibial condyles

The method of knee joint endoprosthesis for its pronounced deformity was proposed. As a transplant there was applied the ceramic hydroxiapatite, manufactured according to special technology. The implant was fixed on the transplant adjusted.