US as a primary diagnostic tool in relation to negative appendectomy: six years experience

PURPOSE: To evaluate the effect of ultrasonography (US) on the rate of appendectomy after false-positive diagnosis of acute appendicitis (negative appendectomy). MATERIALS AND METHODS: Data were analyzed in 736 pediatric patients (mean age, 13.2 years) who had undergone appendectomy between 1995 and 2000. Histologic data were compared in patients who underwent US with those who did not undergo imaging prior to surgery. US was performed by a radiologist or a pediatric surgeon or both. RESULTS: A total of 643 (87.4%) of the 736 pediatric patients underwent preoperative US, and 93 (12.6%) of the 736 did not undergo preoperative US. Of the 736 patients, 97 (13.2%) underwent negative appendectomy. Thirty-four (36.6%) of the 93 patients who underwent appendectomy with no preoperative US and 63 (9.8%) of the 643 patients who underwent preoperative US underwent negative appendectomy. There was a significant association between US and positive appendectomy (P <.001). CONCLUSION: US in pediatric patients suspected of having appendicitis can significantly lower the negative appendectomy rate.     

Evaluation of bone reduction in osteo-odontokeratoprosthesis (OOKP) by three-dimensional computed tomography

PURPOSE: To study the stability and preservation of the osteodental lamina in osteo-odontokeratoprosthesis (OOKP) according to Strampelli with spiral computed tomography (CT). METHODS: Computed tomography of the orbit was performed in nine patients after successful OOKP surgery. Indications for surgery included ocular pemphigoid (three patients), Lyell's syndrome (two patients), graft versus host disease (one patient), and severe chemical burns (three patients). In four eyes, the osteodental lamina was covered with a buccal mucosa graft; in five eyes, a "transpalpebral" approach with the placement of the optical cylinder through the patient's own lid skin was used. The mean time from surgery to examination was 4 years. The age of the patients ranged from 32 to 75 years (mean, 52). Spiral CT in the transaxial plane was performed, followed by three-dimensional (3D) surface reconstruction of the OOKP. The dimensions of the osteodental lamina were measured and compared with measurements taken at the time of surgery. RESULTS: A minor reduction of the lamina, mainly in the anterior and inferior part, could be found in all the patients without loss of stability and integrity of the lamina cylinder complex in seven patients. One patient showed complete resorption of the inferior half of the osteodental lamina, and another patient demonstrated "moth-eaten" dissolution of dentine and bone tissue. No correlation between the degree of reduction in the dimensions and patient age, diagnosis, or length of follow-up could be found. CONCLUSION: Osteo-odontokeratoprosthesis shows good results in patients with corneal blindness not amenable to keratoplasty. Nevertheless, the surgeon must be aware of eventual signs of dissolution of the osteodental lamina, making close follow-up mandatory. Because ultrasound biomicroscopy cannot be used in these cases, spiral CT with 3D reconstruction seems to be a good diagnostic alternative.     

Optimization of 2-phenylaminoimidazo[4,5-h]isoquinolin-9-ones: orally active inhibitors of lck kinase

The tyrosine kinase p56lck (lck) is essential for T cell activation; thus, inhibitors of lck have potential utility as autoimmune agents. Our initial disclosure of a new class of lck inhibitors based on the phenylaminoimidazoisoquinolin-9-one showed reasonable cellular activity but did not work in vivo upon oral administration. Our current work highlights the further use of rational drug design and molecular modeling to produce a series of lck inhibitors that demonstrate cellular activity below 100 nM and are as efficacious as cyclosporin A in an in vivo mouse model of anti-CD3-induced IL-2 production.     

A genome-wide scan in families with maturity-onset diabetes of the young: evidence for further genetic heterogeneity

Maturity-onset diabetes of the young (MODY) is a heterogeneous single gene disorder characterized by non-insulin-dependent diabetes, an early onset and autosomal dominant inheritance. Mutations in six genes have been shown to cause MODY. Approximately 15-20% of families fitting MODY criteria do not have mutations in any of the known genes. These families provide a rich resource for the identification of new MODY genes. This will potentially enable further dissection of clinical heterogeneity and bring new insights into mechanisms of beta-cell dysfunction. To facilitate the identification of novel MODY loci, we combined the results from three genome-wide scans on a total of 23 families fitting MODY criteria. We used both a strict parametric model of inheritance with heterogeneity and a model-free analysis. We did not identify any single novel locus but provided putative evidence for linkage to chromosomes 6 (nonparametric linkage [NPL]score 2.12 at 71 cM) and 10 (NPL score 1.88 at 169-175 cM), and to chromosomes 3 (heterogeneity LOD [HLOD] score 1.27 at 124 cM) and 5 (HLOD score 1.22 at 175 cM) in 14 more strictly defined families. Our results provide evidence for further heterogeneity in MODY.     

Regulation of protease-activated receptor 1 (PAR1) on platelets and responsiveness to thrombin receptor activating peptide (TRAP) during systemic inflammation in humans

Thrombin is a coagulation protease that activates platelets, endothelial cells, leukocytes and mesenchymal cells. Thrombin signaling is mediated at least in part by protease-activated receptors (PARs). As little is known about the in vivo regulation of PAR1, this study aimed to characterize the effects of systemic thrombin formation during human endotoxemia on the regulation of PAR1 and the associated responsiveness of human platelets to thrombin receptor activating peptide (TRAP). Endotoxin (2 ng/kg) was infused into 40 healthy men to study the regulation of PAR1 in systemic human inflammation. The SPAN12 antibody was used to determine the in vivo regulation of PAR1. To measure whether modulation of the PAR1 receptor may be associated with altered platelet reactivity, whole blood was stimulated with TRAP ex vivo. Thrombin generation was determined by prothrombin (F(1+2)) fragment. F(1+2) levels increased almost 9-fold from 0.5+/-0.1 nmol/L to 4.5+/-1.9 nmol/L at 4 h (p<0.001). PAR1 decreased by approximately 8% (p<0.001) within 2 h after endotoxin infusion and stayed at those levels until 6 h. Concomitantly, TRAP induced P-selectin expression maximally decreased by 18% (p<0.001) at 6 h. In conclusion, PAR1 expression is down-regulated on platelets during systemic thrombin formation induced by inflammation in humans which results in decreased responsiveness to subsequent stimulation of the PAR1 receptor.     

Non-uniform effectiveness of structured patient�Cclinician communication in community mental healthcare: an international comparison

Background

The effectiveness of psychosocial interventions in community mental healthcare has been shown to depend on the setting in which they are implemented. Recently structured patient?Cclinician communication was found to be effective in a multi-centre trial in six European countries, the DIALOG trial. In the overall study, differences between centres were controlled for, not studied. Here, we test whether the effectiveness of structured patient?Cclinician communication varies between services in different countries, and explore setting characteristics associated with outcome.

Methods

The study is part of the DIALOG trial, which included 507 patients with schizophrenia or related disorder, treated by 134 keyworkers. The keyworkers were allocated to intervention or treatment as usual.

Results

Positive effects were found on quality of life (effect size 0.20: 95% CI 0.01?C0.39) and treatment satisfaction (0.27: 0.06?C0.47) in all centres, but reductions in unmet needs for care were only seen in two centres (?0.83 and ?0.60), and in positive, negative and general symptoms in one (?0.87, ?0.78, ?0.87). The intervention was most effective in settings with patient populations with many unmet needs for care and high symptom levels.

Conclusions

Psychosocial interventions in community mental healthcare may not be assumed to have uniform effectiveness across settings. Differences in patient population served and mental healthcare provided, should be studied for their influence on the effectiveness of the intervention. Structured patient?Cclinician communication has a uniform effect on quality of life and treatment satisfaction, but on unmet needs for care and symptom levels its effect differs between mental healthcare settings.     

Comparison of carbon fibre and aluminium materials in the construction of ultralight wheelchairs

Abstract

Carbon fibre-reinforced polymers have been used in the sporting goods industry for decades, and wheelchairs have incorporated the material since the late 1980s. There is no independently collected data available on carbon fibre-reinforced polymer wheelchairs’ performance on the ANSI/RESNA testing standards, however. This study evaluated three full carbon fibre wheelchair specimens to determine their performance versus similar wheelchairs. Testing determined that while the frames survived more testing cycles than any other wheelchair, the casters and rear tires failed similarly to other devices. Overall, due to the purchase cost, the cost benefit of the tested wheelchair model was similar to aluminium wheelchairs.

• Implications for rehabilitation

• Carbon fibre wheelchair construction is a viable alternative to aluminium, titanium, or steel construction, and decreasing costs will continue to improve the benefits of carbon fibre over these models

• Carbon fibre wheelchair found to be more durable than aluminium models, but are also much more expensive. The additional cost may be justified for some users that need the increased durability, however

• Increased durability will reduce the number of repairs and warranty claims, potentially reducing the burden on a wheelchair user, and also improving their ability to travel and participate in their community

• The low weight of carbon fibre wheelchairs may increase the mobility of some users by allowing them to transfer more easily into and out of vehicles and manoeuvre throughout the environment