Low Molecular Weight Dextran Sulfate: A Strong Candidate Drug to Block IBMIR in Clinical Islet Transplantation

The instant blood-mediated inflammatory reaction (IBMIR) is triggered in clinical islet transplantation when human pancreatic islets come in contact with blood and may explain the initial tissue loss associated with this procedure. Low molecular weight dextran sulfate (LMW-DS; MM 5000), today available for clinical use, inhibits both complement and coagulation activation. In a tubing loop model, LMW-DS at concentrations ranging from 0.01 to 1 g/L showed a dose-dependent inhibition of IBMIR with an inhibition of coagulation and complement activation and less consumption of platelets and other blood cells. In blood or plasma APTT was demonstrated to be an excellent method for monitoring the LMW-DS concentration both in vitro and in vivo in a nonhuman primate model. The toxicity was assessed using a glucose challenge test and the pharmacokinetics was tested in the nonhuman primate model. Here, we present a tentative protocol for using LMW-DS in clinical islet transplantation.     

Do bisphosphonates reduce early micromotion and Periprosthetic bone loss in total knee arthroplasty? A review of the evidence

Early micromotion of implant components and periprosthetic bone loss in patients undergoing total knee arthroplasty are thought to contribute to late aseptic loosening. In the pursuit of longer implant survival, the administration of bisphosphonates may be advocated as a means to buffer implants against microinstability and periprosthetic bone loss. A bibliographic search identified one metaanalysis and two randomised controlled trials dealing with this topic. Current evidence supports the hypothesis that the inhibiting effects of bisphosphonates on bone resorption reduce implant micromotion and periprosthetic bone loss at the one-year follow-up. Tested bisphosphonates include clodronate, pamidronate and alendronate. However, a decline in periprosthetic BMD is observed at the three-year follow-up following a sixmonth course of bisphosphonate administration. Length of follow-up in available studies is currently too short to determine whether bisphosphonates increase the longevity of implants. Furthermore, the optimal dose, modality and length of bisphosphonate administration have yet to be determined.     

Ex Vivo Application of Carbon Monoxide in University of Wisconsin Solution to Prevent Intestinal Cold Ischemia/Reperfusion Injury

Carbon monoxide (CO), a byproduct of heme catalysis, was shown to have potent cytoprotective and anti-inflammatory effects. In vivo recipient CO inhalation at low concentrations prevented ischemia/reperfusion (I/R) injury associated with small intestinal transplantation (SITx). This study examined whether ex vivo delivery of CO in University of Wisconsin (UW) solution could ameliorate intestinal I/R injury. Orthotopic syngenic SITx was performed in Lewis rats after 6 h cold preservation in control UW or UW that was bubbled with CO gas (0.1-5%) (CO-UW). Recipient survival with intestinal grafts preserved in 5%, but not 0.1%, CO-UW improved to 86.7% (13/15) from 53% (9/17) with control UW. At 3 h after SITx, grafts stored in 5% CO-UW showed improved intestinal barrier function, less mucosal denudation and reduced inflammatory mediator upregulation compared to those in control UW. Preservation in CO-UW associated with reduced vascular resistance (end preservation), increased graft cyclic guanosine monophosphate levels (1 h), and improved graft blood flow (1 h). Protective effects of CO-UW were reversed by ODQ, an inhibitor of soluble guanylyl cyclase. In vitro culture experiment also showed better preservation of vascular endothelial cells with CO-UW. The study suggests that ex vivo CO delivery into UW solution would be a simple and innovative therapeutic strategy to prevent transplant-induced I/R injury.     

Sensitization Following LVAD Implantation Using Leucodepleted Blood Is Not Due to HLA Antibodies

Implantation of left ventricular assist devices (LVAD) is associated with HLA antibody sensitization. The objective of this study was to determine the specificity of antibodies produced by LVAD recipients using a combination of ELISA, Luminex and microcytotoxicity assays. Fifty-one LVAD patients were studied, from 44 to 838 days post-implantation. No patient developed HLA antibodies, although 24 produced IgG antibodies detectable in both ELISA and Luminex assays. These antibodies manifest as positive reactions with class I and class II wells of the ELISA and also blank wells. In Luminex assays, they produce high MFI readings with the negative control beads. Antibodies were detected 18 to 228 days after implantation. This reactivity was found to be directed against bovine serum albumin (BSA), commonly used to block non-specific binding in ELISA and Luminex assays; absorption of sera with BSA-coated beads completely abrogated reactivity in all solid phase assays, but did not eliminate anti-HLA antibodies in control sera. Ten of the 24 patients have proceeded to transplantation, with a 1-year graft survival of 69%. In conclusion, it appears that implantation of LVADS disrupts immunoregulatory pathways leading to production of anti-albumin antibodies. These can be misinterpreted as anti-HLA antibodies in solid phase assays.     

AFOREIGN SURGEON′s VIEW OF LAPAROSCOPIC SURGERY IN A DEVELOPMENT COUNTRY IN ASIA

InrecentcorrespondencewithasurgeonfriendfromChina ,IwastoldthatChinahaschangedconsid erablyinthepastdecade.Icanbelieveit.Theever presentpressuresofsocietyandpolitics,theworld widedemandsforcooperationansmutualassistance ,therecentwarsandthreatsthereof,theapparentin creasedincidenceofnaturaldisasters ,andmoststrikinglythequantumleapoftechnologyandcommunica tionovertherecentpasthaveaffectedeveryareaoflife .Onecansaywithoutequivocationthatthewholeworldhaschangeddramaticallyoverthepastdecade .Th…     

金黄色葡萄球菌在皮肤病医院对苯唑西林敏感性降低并无性系蔓延

2000年11月，作者得知从Aarhus大学医院皮肤科患者分离到的金黄色葡萄球菌对苯唑西林出现界线耐药（BORSA）。本文旨在描述其表型和基因型，并评估可能的传播途径以干预和阻止进一步蔓延。菌株由脉冲场凝胶电泳鉴定。几个感染控制方案的缺口显示患者间可直接或间接传播。皮肤屏障缺陷、皮肤病患者金黄色葡萄球菌的高携带率和院内双氯西林的高消耗率可促使传播。改善普通感染控制措施和重新评价院内抗生素政策后，该菌的暴发感染消失。     

Troubles psychotiques révélateurs de maladie de Creutzfeldt-Jakob sporadique

The onset of the sporadic Creutzfeldt-Jakob disease is usually characterized by dementia or neurological symptoms. We are reporting the case of a 31 year-old man with a sporadic Creutzfeldt-Jakob disease characterized by a schizophrenia-like onset. The schizophrenic symptoms developed for sixteen months before the neurological symptoms appeared. The psychiatric onset of the present case was linked with the early age of onset and the long duration of the disease and could have been influenced by polymorphism of the codon 129 of the prion protein gene (PRNP) and a type of pathological prion protein (PrPres).     

Hypohiderotic ectodermal dysplasia.

We report a case of a six years age girl who presented to our out patients department with the history and findings suggestive of recurrent respiratory tract infections. She was also noticed to have; non homogeneous hyper- pigmented patches on the face since three months of age, sparse hair on the scalp and eyebrows, conical peg like teeth and delayed dentition, prominent and low set ears, perpetually flexed third toe bilaterally. Axillary skin biopsy showed adenexal structures and eccrine glands in subcutaneous fat which were reduced in number. The diagnosis made was: Anhydrotic/ Hypohidrotic type of ectodermal dysplasia. Key words: Ectodermal Dysplasia, Anhidreotic, Hypohidrotic.