Electrical stimulation of the anterior limbs of the internal capsules in patients with severe obsessive-compulsive disorder: anecdotal reports

Anterior capsular stimulation induces some improvement in severe treatment-resistant OCD patients. At this stage, not all stimulation-induced effects can be explained. The effects are a valuable source for further neurophysiologic and neuroanatomic research. It was reassuring that when the group of Drs Rasmussen, Greenberg, and Friehs in Providence and the group of Drs Rezai, Montgomery, and Malone in Cleveland started to operate on OCD patients using exactly the same technique, similar effects were seen in the patients. The authors still want to stress that anterior capsular stimulation remains investigational and needs optimization, especially to try to solve the problem of the short battery life of the stimulators.     

Long-term follow-up after repair of Ebstein's anomaly.

OBJECTIVE: We studied the long-term results of vertical plication repair of Ebstein's anomaly according to Carpentier. METHODS: Between 1988 and 2007, 28 patients (mean age 28.8+/-15.7 years, range 4-58 years) underwent vertical plication repair of Ebstein's anomaly. At operation the anomaly was classified according to Carpentier. In three patients (11%) a cavopulmonary shunt was added at the repair on the indication of impaired right ventricular function. RESULTS: There was no operative mortality. Early mortality was 3.6% (one patient). Actuarial survival and actuarial freedom from reoperation at 19 years were 96% (95% CI; 96-97%) and 72% (95% CI; 53-92%), respectively. Six patients required reoperation, with a successful re-repair in three patients. Mean duration of follow-up was 10.7+/-6.5 years. One year postoperatively, tricuspid incompetence had decreased significantly (p<0.001), as had New York Heart Association (NYHA) functional class (p<0.001). In addition, exercise tolerance had increased (70+/-19% to 92+/-9% of predicted values, p<0.05). Both tricuspid function and NYHA functional class remained essentially unchanged at the end of follow-up, indicating durable haemodynamic and functional results. CONCLUSION: This study demonstrates favourable long-term results following vertical plication repair of Ebstein's anomaly with low mortality, acceptable morbidity and good haemodynamic and functional results.     

Toll-Like Receptor-4 Coordinates the Innate Immune Response of the Kidney to Renal Ischemia/Reperfusion Injury

Toll-like receptors (TLRs) can detect endogenous danger molecules released upon tissue injury resulting in the induction of a proinflammatory response. One of the TLR family members, TLR4, is constitutively expressed at RNA level on renal epithelium and this expression is enhanced upon renal ischemia/reperfusion (I/R) injury. The functional relevance of this organ-specific upregulation remains however unknown. We therefore investigated the specific role of TLR4 and the relative contribution of its two downstream signaling cascades, the MyD88-dependent and TRIF-dependent cascades in renal damage by using TLR4−/−, MyD88−/− and TRIF-mutant mice that were subjected to renal ischemia/reperfusion injury. Our results show that TLR4 initiates an exaggerated proinflammatory response upon I/R injury, as reflected by lower levels of chemokines and infiltrating granulocytes, less renal damage and a more preserved renal function in TLR4−/− mice as compared to wild type mice. In vitro studies demonstrate that renal tubular epithelial cells can coordinate an immune response to ischemic injury in a TLR4-dependent manner. In vivo we found that epithelial- and leukocyte-associated functional TLR4 contribute in a similar proportion to renal dysfunction and injury as assessed by bone marrow chimeric mice. Surprisingly, no significant differences were found in renal function and inflammation in MyD88−/− and TRIF-mutant mice compared with their wild types, suggesting that selective targeting of TLR4 directly may be more effective for the development of therapeutic tools to prevent I/R injury than targeting the intracellular pathways used by TLR4. In conclusion, we identified TLR4 as a cellular sentinel for acute renal damage that subsequently controls the induction of an innate immune response.     

Ignoring theory and misinterpreting evidence: the false belief in fear appeals

Use of fear appeals assumes that when people are emotionally confronted with the negative effects of their behaviour they will change that behaviour. That reasoning is simple and intuitive, but only true under specific, rare circumstances. Risk perception theories predict that if people will experience a threat, they want to counter that threat. However, how they do so is determined by their coping efficacy level: if efficacy is high, they may change their behaviour in the suggested direction; if efficacy is low, they react defensively. Research on fear appeals should be methodologically sound, comparing a threatening to a non-threatening intervention under high and low efficacy levels, random assignment and measuring behaviour as outcome. We critically review extant empirical evidence and conclude that it does not support positive effects of fear appeals. Nonetheless, their use persists and is even promoted by health psychology researchers, causing scientific insights to be ignored or misinterpreted.     

Concerted action of androgens and mechanical strain shifts bone metabolism from high turnover into an osteoanabolic mode

Adhesion of bone cells to the extracellular matrix is a crucial requirement for osteoblastic development and function. Adhesion receptors connect the extracellular matrix with the cyto-skeleton and convey matrix deformation into the cell. We tested the hypothesis that sex hormones modulate mechanoperception of human osteoblastic cells (HOB) by affecting expression of adhesion molecules like fibronectin and the fibronectin receptor. Only dihydrotestosterone (DHT), but not 17beta-estradiol, stimulated fibronectin (137%) and fibronectin receptor (252%) protein expression. The effects of deformation strain on HOB metabolism were investigated in a FlexerCell strain unit. Cyclically applied strain (2.5% elongation) increased DNA synthesis (125%) and interleukin-6 (IL-6) production (170%) without significantly affecting alkaline phosphatase (AP) activity, type I collagen (PICP), or osteoprotegerin (OPG) secretion. 10 nM DHT pretreatment abolished the mitogenic response of HOB to strain and increased AP activity (119%), PICP (163%), and OPG production (204%). In conclusion, mechanical strain stimulates bone remodeling by increasing HOB mitosis and IL-6 production. DHT enhances the osteoanabolic impact of deformation strain by increasing bone formation via increased AP activity and PICP production. At the same time, bone resorption is inhibited by decreased IL-6 and increased OPG secretion into the bone microenvironment.     

Selective serotonin re-uptake inhibiting antidepressants and the risk of overanticoagulation during acenocoumarol maintenance treatment

AIM

The aim of this study was to investigate the effects of co-medication with selective serotonin re-uptake inhibitors (SSRIs) on overanticoagulation during acenocoumarol maintenance treatment.

METHODS

All subjects from The Rotterdam Study who received acenocoumarol maintenance treatment between April 1 1991 and September 9 2009 were followed for the event of an international normalized ratio (INR) ≥6, until death, end of treatment or end of the study period. With the Andersen-Gill extension of the Cox proportional hazards model, risks for repeated events of overanticoagulation in relation to concomitant SSRI use were calculated.

RESULTS

The risk for overanticoagulation during acenocoumarol maintenance treatment was increased in combination with fluvoxamine (HR 2.63, 95% CI 1.49, 4.66) and venlafaxine (HR 2.19, 95% CI 1.21, 3.99). There was no increase in risk for the other SSRIs, but numbers of exposed cases were low for all SSRIs except paroxetine.

CONCLUSION

Fluvoxamine and venlafaxine were associated with a more than double risk of INR values ≥6 in acenocoumarol treated subjects.     

Long-Term Health-Related Quality of Life in Major Pediatric Trauma: A Pilot Study

Abstract Background:   Major trauma is the leading cause of mortality and morbidity in children of developed countries. Little research has been done about the health-related quality of life (HRQL) in these children. The aim of the current research is to describe the HRQL of children in the long term after major trauma and to compare it with healthy peers. Methods:   A prospective cohort study of severely injured children (ISS ≥ 16, age < 16 years) who survived the trauma and were admitted to the emergency department of a Dutch level 1 trauma center in 1999 and 2000 (n = 40) was conducted. Between 6 and 8 years after trauma (mean 7.3, SD 0.7 years), outcome was assessed by the Pediatric Quality of Life Inventory (PedsQL 4.0), the EuroQol 5D (EQ-5D), and the EuroQol Visual Analogue Scale (EQ-VAS). Results:   The mean age at the time of the accident was 8.9 years (SD 4.6 years), the mean ISS was 24.9 (SD 11.1), and 25 (63%) cases were male; 28 out of 40 patients were followed up. The mean score on the PedsQL was 81.2 and this did not differ significantly from the norm value. On the EQ-5D, more health problems were reported than in a healthy reference population. The mean EQ-VAS score was 79.4 and was significantly lower than in healthy peers. The lowest scores on the PedsQL and the EQ-VAS were seen in teenagers and in respondents with spinal cord and/or severe cerebral injury. Conclusion:   The results on HRQL in children in the long term after major trauma are inconclusive. Special attention should be given to teenagers with spinal cord or severe cerebral injury who reported the lowest HRQL.     

Autograft or allograft aortic valve replacement in young adult patients with congenital aortic valve disease.

AIMS: We analysed the outcome of young adults with congenital aortic valve disease who underwent allograft or autograft aortic valve or root replacement in our institution and evaluated whether there is a preference for either valve substitute. METHODS AND RESULTS: Between 1987 and 2007, 169 consecutive patients with congenital aortic valve disease aged 16-55, participating in our ongoing prospective follow-up study, underwent 63 autograft and 106 allograft aortic valve replacements (AVRs). Mean age was 35 years (SD 10.8), 71% were males. Aetiology was 71% bicuspid valve, 14% other congenital, and 15% BV endocarditis. Twenty-two percent underwent previous cardiac surgery; 11% had an ascending aorta aneurysm. Two patients died in hospital. During follow-up six more patients died and 45 patients required valve-related re-operations. Thirteen-year survival was 97% for autograft and 93% for allograft recipients, 13 year freedom from valve-related re-operation was 63% for autograft and 69% for allograft patients. CONCLUSION: In patients with congenital aortic valve disease, autograft and allograft AVR show comparable satisfactory early and long-term results, with the increasing re-operation risk in the second decade after operation remaining a major concern.