Neuroleptic malignant syndrome in users of risperidone

Neuroleptic malignant syndrome is a potentially life-threatening complication of neuroleptic therapy. Three nursing-home residents who suffered from multiple somatic disorders and dementia, two men aged 78 and 76 years respectively and a woman aged 72 years, developed neuroleptic malignant syndrome following the use of risperidone. The first two patients presented with severe muscular pain. Initially, none of them exhibited high fever and so it is debatable whether the diagnosis 'neuroleptic malignant syndrome' can be excluded in the absence of fever. A review of the literature indicates that the syndrome can easily be mistaken for an infection. Patients with extrapyramidal side effects as a result of earlier use of neuroleptics seem to be more vulnerable to developing neuroleptic malignant syndrome. Patients using neuroleptics who become ill with an altered level of consciousness, sweating and muscular rigidity, should at least have their blood tested for the level of creatine phosphokinase activity. Furthermore, pain might be an initial symptom. Treatment of the neuroleptic malignant syndrome failed in all three patients, and they died.     

Role of tumour necrosis factor gene polymorphisms (-308 and -238) in breast cancer susceptibility and severity

Introduction  

Genetic polymorphisms in the promoter region of the tumour necrosis factor (TNF) gene can regulate gene expression and have been associated with inflammatory and malignant conditions. We have investigated two polymorphisms in the promoter of the TNF gene (-308 G>A and -238 G>A) for their role in breast cancer susceptibility and severity by means of an allelic association study.     

Three-dimensional display modes for CT colonography: conventional 3D virtual colonoscopy versus unfolded cube projection

The authors compared a conventional two-directional three-dimensional (3D) display for computed tomography (CT) colonography with an alternative method they developed on the basis of time efficiency and surface visibility. With the conventional technique, 3D ante- and retrograde cine loops were obtained (hereafter, conventional 3D). With the alternative method, six projections were obtained at 90 degrees viewing angles (unfolded cube display). Mean evaluation time per patient with the conventional 3D display was significantly longer than that with the unfolded cube display. With the conventional 3D method, 93.8% of the colon surface came into view; with the unfolded cube method, 99.5% of the colon surface came into view. Sensitivity and specificity were not significantly different between the two methods. Agreements between observers were kappa = 0.605 for conventional 3D display and kappa = 0.692 for unfolded cube display. Consequently, the latter method enhances the 3D endoluminal display with improved time efficiency and higher surface visibility.     

Local recurrence of rectal cancer after total mesorectal excision without preoperative radiotherapy

Background: At this moment, it is still debatable whether all patients with mobile rectal cancer who undergo surgical removal of the tumor should be treated with preoperative radiotherapy, since it is likely that only certain patients will benefit from this strategy. In this study, patients with mobile rectal cancer were immediately operated upon and only those with positive nodes or with incomplete resection received adjuvant radiotherapy. Aims of the Study: To investigate the local recurrence rate after the use of a selective policy of adjuvant radiotherapy and to determine risk factors for local recurrence. Methods: In a 5-yr-period, 178 patients with rectal cancer were referred to our institute. A total of 131 patients with mobile rectal cancer were treated with curative intent, which implied a microscopically radical resection and no signs of distant metastasis at operation. A retrospective analysis was undertaken to investigate the incidence of local recurrence in this curative group and to determine risk factors for local recurrence. Results: The postoperative mortality in the curative group was 5.3%. Local recurrences were observed in 6 patients (4.6%) after a median period of 25 mo (range 11–37); two of them also had distant metastases detected at the same time. The highest local recurrence rates were seen in men (5.3%), in distal rectal cancers (6.9%), and in the node-positive group (8.7%). Conclusion: A low local recurrence rate can be achieved after total mesorectal excision (TME) without preoperative radiotherapy. Our results suggest using preoperative radiotherapy only for those patients who are at a higher risk for local recurrence. Staging techniques for selection of these patients are at this moment still inappropriate.     

Partial amino acid sequence of purified von Willebrand factor-cleaving protease

von Willebrand factor-cleaving protease (vWF-cp) is responsible for the continuous degradation of plasma vWF multimers released from endothelial cells. It is deficient in patients with thrombotic thrombocytopenic purpura, who show unusually large vWF multimers in plasma. Purified vWF-cp may be useful for replacement in these patients, who are now treated by plasma therapy. In this study, vWF-cp was purified from normal human plasma by affinity chromatography on the IgG fraction from a patient with autoantibodies to vWF-cp and by a series of further chromatographic procedures, including affinity chromatography on Protein G, Ig-TheraSorb, lentil lectin, and heparin. Four single-chain protein bands, separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under nonreducing conditions, showed M(r) of 150, 140, 130, and 110 kd and were found to share the same N-terminal amino acid sequence, suggesting that they were derived from the same polypeptide chain that had been partially degraded at the carboxy-terminal end. A hydrophobic sequence (Ala-Ala-Gly-Gly-Ile-Leu-His-Leu-Glu-Leu-Leu-Val-Ala-Val-Gly) of the first 15 residues was established. The protease migrates in gel filtration as a high-molecular-weight complex with clusterin, a 70-kd protein with chaperonelike activity. vWF-cp bound to clusterin is dissociated by the use of concentrated chaotropic salts. vWF-cp in normal human plasma or serum is not associated with clusterin, suggesting that the observed complex is due to vWF-cp denaturation during the purification procedure. Activity of vWF-cp is unusually stable during incubation at 37 degrees C; its in vitro half-life in citrated human plasma, heparin plasma, or serum is longer than 1 week. There was even a temporary increase in protease activity during the first 3 days of incubation.     

Conservative treatment for repetitive strain injury.

Various conservative treatment options for repetitive strain injury are widely used, despite questionable evidence of their effectiveness. This systematic review evaluates the effectiveness of these treatment options for relieving symptoms of repetitive strain injury and improving activities of daily living. Searches in Medline and Embase, with additional reference checking resulted in 15 eligible trials for this review. Methodological quality was assessed, and data-extraction was performed. With the use of a "best-evidence synthesis", no strong evidence was found for the effectiveness of any of the treatment options. There is limited evidence that multidisciplinary rehabilitation, ergonomic intervention measures, exercises, and spinal manipulation combined with soft tissue therapy are effective in providing symptom relief or improving activities of daily living. There is conflicting evidence for the effectiveness of behavioral therapy. In conclusion, little is known about the effectiveness of conservative treatment options for repetitive strain injury. To establish strong evidence, more high-quality trials are needed.     

Exposure of human vascular endothelial cells to sustained hydrostatic pressure stimulates proliferation. Involvement of the alphaV integrins

The present study investigated the effects of sustained hydrostatic pressure (SHP; up to 4 cm H2O) on human umbilical vein endothelial cell (HUVEC) proliferation, focal adhesion plaque (FAP) organization, and integrin expression. Exposure of HUVECs to SHP stimulated cell proliferation and a selective increase in the expression of integrin subunit alphaV. The increase in alphaV was observed as early as 4 hours after exposure to pressure and preceded detectable increases in the bromodeoxyuridine labeling index. Laser confocal microscopy studies demonstrated colocalization of the alphaV integrin to FAPs. The individual FAPs in pressure-treated cells demonstrated a reduced area and increased aspect ratio and were localized to both peripheral and more central regions of the cells, in contrast to the predilection for the cell periphery in cells maintained under control pressure conditions. The pressure-induced changes in alphaV distribution had functional consequences on the cells: adhesivity of the cells to vitronectin was increased, and alphaV antagonists blocked the pressure-induced proliferative response. Thus, the present study suggests a role for alphaV integrins in the mechanotransduction of pressure by endothelial cells.