Modification of Blood Vessel Diameter Following Perivascular Application of Botulinum Toxin-A

The purpose of this study was to demonstrate that perivascularly applied botulinum toxin-A (BTX) increases the diameter of treated blood vessels in a rat femoral vessel exposure model. Six adult Sprague–Dawley rats were used and bilateral femoral artery and vein exposures were performed. Five units of BTX were applied to the experimental side and an equal volume of sterile saline was applied to the control side. Digital images of the vessels were obtained at the following time points: pretreatment, immediately posttreatment, and postoperative days (POD) 1, 14, and 28. Vessel diameters were equivalent at baseline and immediately following application of BTX and saline. The BTX artery was significantly larger than the control artery on POD 1 and 14. The BTX treated artery was significantly larger than all other vessels on POD 14 (p < 0.05) as well as all prior time points (p < 0.01). Direct perivascular application of BTX increases the diameter of rat femoral vessels as early as POD 1. The affect is most robust on POD 14 where the artery was significantly larger than all other vessels at all time points. It is likely that the increased diameter of blood vessels results in an increased blood flow across the area of dilation. Such an increase in flow may serve to improve end-organ perfusion in microvascular procedures.     

Acute Cellular Rejection with CD20-Positive Lymphoid Clusters in Kidney Transplant Patients Following Lymphocyte Depletion

Lymphoid clusters (LC) containing CD20-positive B cells in kidney allografts undergoing acute cellular rejection (ACR) have been identified in small studies as a prognostic factor for glucocorticoid resistance and graft loss. Allograft biopsies obtained during the first episode of ACR in 120 recipients were evaluated for LC, immunostained with CD20 antibody, and correlated with conventional histopathologic criteria, response to treatment and outcome. LC were found in 71 (59%) of the 120 biopsies. All contained CD20 positive B cells that accounted for 5-90% of the LC leukocyte content. The incidence of LC was highest in the patients who had no lymphoid depletion or had been treated with Thymoglobulin preconditioning (79% vs. 75%, respectively) compared to 37% in patients pretreated with Campath (p = 0.0001). Banff 1a/1b ACR were more frequent in the LC-positive than the LC-negative group (96% vs. 80%, respectively; p = 0.0051). With a posttransplant follow-up of 953 +/- 430 days, no significant differences were detected between LC-postitive and LC-negative groups in time to ACR, steroid resistance, serum creatinine and graft loss. CD20+LC did not portend glucocorticoid resistance or worse short to medium term outcomes. CD20+LC may represent a heterogenous collection in which there may be a small still to be fully defined unfavorable subgroup.     

Enhanced chondrogenesis and Wnt signaling in PTH-treated fractures.

Studies have shown that systemic PTH treatment enhanced the rate of bone repair in rodent models. However, the mechanisms through which PTH affects bone repair have not been elucidated. In these studies we show that PTH primarily enhanced the earliest stages of endochondral bone repair by increasing chondrocyte recruitment and rate of differentiation. In coordination with these cellular events, we observed an increased level of canonical Wnt-signaling in PTH-treated bones at multiple time-points across the time-course of fracture repair, supporting the conclusion that PTH responses are at least in part mediated through Wnt signaling. INTRODUCTION: Since FDA approval of PTH [PTH(1-34); Forteo] as a treatment for osteoporosis, there has been interest in its use in other musculoskeletal conditions. Fracture repair is one area in which PTH may have a significant clinical impact. Multiple animal studies have shown that systemic PTH treatment of healing fractures increased both callus volume and return of mechanical competence in models of fracture healing. Whereas the potential for PTH has been established, the mechanism(s) by which PTH produces these effects remain elusive. MATERIALS AND METHODS: Closed femoral fractures were generated in 8-wk-old male C57Bl/6 mice followed by daily systemic injections of either saline (control) or 30 microg/kg PTH(1-34) for 14 days after fracture. Bones were harvested at days 2, 3, 5, 7, 10, 14, 21, and 28 after fracture and analyzed at the tissue level by radiography and histomorphometry and at the molecular and biochemical levels level by RNase protection assay (RPA), real-time PCR, and Western blot analysis. RESULTS: Quantitative muCT analysis showed that PTH treatment induced a larger callus cross-sectional area, length, and total volume compared with controls. Molecular analysis of the expression of extracellular matrix genes associated with chondrogenesis and osteogenesis showed that PTH treated fractures displayed a 3-fold greater increase in chondrogenesis relative to osteogenesis over the course of the repair process. In addition, chondrocyte hypertrophy occurred earlier in the PTH-treated callus tissues. Analysis of the expression of potential mediators of PTH actions showed that PTH treatment significantly induced the expression of Wnts 4, 5a, 5b, and 10b and increased levels of unphosphorylated, nuclear localized beta-catenin protein, a central feature of canonical Wnt signaling. CONCLUSIONS: These results showed that the PTH-mediated enhancement of fracture repair is primarily associated with an amplification of chondrocyte recruitment and maturation in the early fracture callus. Associated with these cellular effects, we observed an increase in canonical Wnt signaling supporting the conclusion that PTH effects on bone repair are mediated at least in part through the activation of Wnt-signaling pathways.     

Structural white matter abnormalities in patients with idiopathic dystonia

We investigated whether structural white matter abnormalities, in the form of disruption of axonal coherence and integrity as measured with diffusion tensor imaging (DTI), constitute an underlying pathological mechanism of idiopathic dystonia (ID), independent of genotype status. We studied seven subjects with ID: all had cervical dystonia as their main symptom (one patient also had spasmodic dysphonia and two patients had concurrent generalized dystonia, both DYT1‐negative). We compared DTI MR images of patients with 10 controls, evaluating differences in mean diffusivity (MD) and fractional anisotropy (FA). ID was associated with increased FA values in the thalamus and adjacent white matter, and in the white matter underlying the middle frontal gyrus. ID was also associated with increase in MD in adjacent white matter to the pallidum and putamen bilaterally, left caudate, and in subcortical hemispheric regions, including the postcentral gyrus. Abnormal FA and MD in patients with ID indicate that abnormal axonal coherence and integrity contribute to the pathophysiology of dystonia. These findings suggest that ID is not only a functional disorder, but also associated with structural brain changes. Impaired connectivity and disrupted flow of information may contribute to the impairment of motor planning and regulation in dystonia. © 2006 Movement Disorder Society     

Aprotinin does not inhibit the release of PGI2 or vWF from cultured human endothelial cells.

The release of prostacyclin (PGI2) and von Willebrand factor (vWF) from human umbilical vein endothelial cells (HUVEC) was examined to determine if aprotinin had any effects on these endothelial cell reactions. These end-points were chosen to indicate if this serine protease inhibitor caused alterations in the control of haemostatic function by endothelium, in the light of the improvement in haemostasis seen in patients given aprotinin therapy at the time of open heart surgery. Stimuli used to promote secretion of prostacyclin and vWF were human alpha-thrombin, histamine, protamine sulphate, poly-L-lysine and phorbol myristate acetate. Aprotinin (30 microMs) had no significant effect on the basal or stimulated release of PGI2 or vWF from HUVEC.     

The role of home-made ice cream as a vehicle of Salmonella enteritidis phage type 4 infection from fresh shell eggs.

A family outbreak of Salmonella enteritidis PT4 infection is described in which home-made ice cream was identified as the vehicle of infection. The ice cream contained approximately 10(5) S. enteritidis PT4 organisms per gm and was probably contaminated by an infected shell egg containing between 10(5)-10(8) organisms. The continued relevance of the Chief Medical Officer''s warning on the use of raw shell eggs is highlighted. Home-made ice cream using the same recipe as ice cream that had been incriminated as the cause of the family outbreak of S. enteritidis PT4 infection was used to study the growth of the organism that might have occurred in the 3-4 h it took to prepare the product. When the inoculum was in the stationary phase, as it would be from shell or other cross contamination, there was a lag phase of 3 h before growth occurred at room temperature. Even when actively multiplying organisms were introduced, as may be found in an infected egg, there was less than 3 log(10) increase in the salmonella count in 4 h at room temperature. It was, therefore, given the high S. enteritidis count, unlikely that the ice cream was cross-contaminated. By contrast, raspberry sorbet at pH 3.73 proved to be lethal to a large inoculum of S. enteritidis and may be a relatively safe raw egg containing product.     

Hepatic resections for primary and metastatic tumors using the ultrasonic surgical dissector.

We have previously described the development of new hepatic surgical techniques using the ultrasonic surgical dissector. With 10 years' experience, we have found that major liver resections have been simplified and that the technique is repeatable in hands other than our own. Thirty-three patients had 37 tumors, averaging 5.65 cm in size, resected with an average blood loss of only 1,020 mL per case, which included 5 right trisegmentectomies, 12 lobectomies, 15 segmental resections, and 4 subsegmental resections. Twenty-two patients had metastatic colorectal cancer. Blood transfusion requirements averaged only 2.24 units in long-term survivors, which was significantly less than the 3.5 units received by patients who have since died (p = 0.092). There were no operative deaths. The median survival of these 22 patients was 56 months, and the 5-year actuarial survival rate was 35%. All of the early deaths occurred in patients with more than four tumors, and no patient with less than four tumors died before 42 months with recurrent disease. Six patients had bilateral tumors, and the fact that patients survived into the fourth and fifth post-resectional year indicates that resection was worthwhile. All these patients had Dukes' C primary tumors, but we found no statistical difference in survival between patients with Dukes' B and Dukes' C lesions. The results indicate that hepatic resection with the ultrasonic surgical dissector decreases blood loss, requires few transfusions, is safe to perform, and is associated with excellent long-term survival.     

How negative are we to the idea of suicide prevention?

Assessment of attitudes amongst health care professionals to suicide prevention reveals a considerable degree of doubt with regards to its feasibility and appropriateness. The various professional groups may vary considerably in the degree of negative attitudes which they exhibit. Such findings suggest that there is an urgent need to ensure that health care professionals are fully informed about the key facts concerning suicide and preventive strategies. Key elements of clinical practice and service organization with regards to suicide prevention are discussed.