The effect of antibody against TNF alpha on cytokine response in Jarisch-Herxheimer reactions of louse-borne relapsing fever

Severe Jarisch Herxheimer reaction (J-HR) precipitated by antibiotic treatment of louse-borne relapsing fever (LBRF) is associated with a transient, marked rise in circulating tumour necrosis factor alpha (TNF alpha), interleukin 6 (IL-6) and interleukin 8 (IL-8). Ovine polyclonal anti-TNF alpha antibody fragments (Fab) were used in a randomized double blind placebo controlled trial in an attempt to prevent this reaction. Within 4 h after penicillin, in controls (n = 29), a several- fold rise in cytokines occurred, concomitant with a fall in spirochaetes and maximal clinical manifestations of the J-HR. An intravenous infusion of anti-TNF alpha Fab, 30 min before penicillin in 20 patients reduced peak plasma levels of IL-6 and IL-8 (but not IL-1 beta) compared with controls (p = 0.01 and < 0.001, respectively) and the incidence of the J-HR, indicating some neutralization of TNF alpha. An apparent fall in TNF alpha reflected interference of anti-TNF alpha in the immunoassay.      

Major complications after 400 continuous popliteal sciatic nerve blocks for post‐operative analgesia

Background: A continuous popliteal sciatic nerve block (CPSNB) has been performed with increasing frequency for post‐operative analgesia after foot surgery. Major complications associated with the placement of a perineural catheter remain rarely studied. The aim of this study was to prospectively determine the incidence of major complications (neurological and infectious) in post‐operative adult patients with a continuous popliteal catheter inserted by the anatomical posterior approach for analgesia after foot surgery. Methods: All popliteal catheters were placed pre‐operatively under sterile conditions with the aid of a nerve stimulator technique. The primary outcome measure was the incidence of major complications including infection and neuropathy. As a secondary outcome, adverse effects as well as other complications were also evaluated. Data were expressed as median [25th–75th percentiles]. Results: A total of 400 patients were included in the study during a 2‐year period. The median time the catheter remained indwelling was 47 h [23, 54]. Major complications included three events (0.75%) with one infection (0.25%) and two neuropathies (0.50%). Three blocks were unsuccessful and the catheter insertion was difficult in 12 patients (3%). During the CPSNB procedure, one patient reported slight paraesthesia during stimulation. Patient satisfaction was scored at 4 for 89%, 3 for 6% and 2 for 5% on the analogue scale. Conclusions: Major complications after the use of CPSN are not in fact rare. The incidence of severe neuropathy or infection complications is, respectively, 0.50% and 0.25%. However, the insertion of CPSN could be considered effective and is associated with only a few minor complications.     

De novo fragment assembly with short mate-paired reads: Does the read length matter?

Increasing read length is currently viewed as the crucial condition for fragment assembly with next-generation sequencing technologies. However, introducing mate-paired reads (separated by a gap of length, GapLength) opens a possibility to transform short mate-pairs into long mate-reads of length ≈ GapLength, and thus raises the question as to whether the read length (as opposed to GapLength) even matters. We describe a new tool, EULER-USR, for assembling mate-paired short reads and use it to analyze the question of whether the read length matters. We further complement the ongoing experimental efforts to maximize read length by a new computational approach for increasing the effective read length. While the common practice is to trim the error-prone tails of the reads, we present an approach that substitutes trimming with error correction using repeat graphs. An important and counterintuitive implication of this result is that one may extend sequencing reactions that degrade with length “past their prime” to where the error rate grows above what is normally acceptable for fragment assembly.     

胃重复畸形并胃胰腺损伤1例

1临床资料患儿,女性,4岁。因间断性腹痛1月加重伴黑便15d,呕吐2d入院。患儿病前无明确外伤史,其母于入院前15d发现左膝部有损伤痕,已愈合,行腹部B超检查,提示肝胆肾正常,胰大小正常,边界清,实质回声均匀,主胰管不扩张,肝前区肝肾夹角及脾肾夹角可见53mm的液性暗区,内见肠管蠕动     

Weight loss and incretin responsiveness improve glucose control independently after gastric bypass surgery

Background: The aim of the present study was to determine the mechanisms underlying Type 2 diabetes remission after gastric bypass (GBP) surgery by characterizing the short‐ and long‐term changes in hormonal determinants of blood glucose. Methods: Eleven morbidly obese women with diabetes were studied before and 1, 6, and 12 months after GBP; eight non‐diabetic morbidly obese women were used as controls. The incretin effect was measured as the difference in insulin levels in response to oral glucose and to an isoglycemic intravenous challenge. Outcome measures were glucose, insulin, C‐peptide, proinsulin, amylin, glucagon, glucose‐dependent insulinotropic polypeptide (GIP), glucagon‐like peptide‐1 (GLP‐1) levels and the incretin effect on insulin secretion. Results: The decrease in fasting glucose (r = 0.724) and insulin (r = 0.576) was associated with weight loss up to 12 months after GBP. In contrast, the blunted incretin effect (calculated at 22%) that improved at 1 month remained unchanged with further weight loss at 6 (52%) and 12 (52%) months. The blunted incretin (GLP‐1 and GIP) levels, early phase insulin secretion, and other parameters of β‐cell function (amylin, proinsulin/insulin) followed the same pattern, with rapid improvement at 1 month that remained unchanged at 1 year. Conclusions: The data suggest that weight loss and incretins may contribute independently to improved glucose levels in the first year after GBP surgery.     

Absence of linkage or association for osteoarthritis with the vitamin D receptor/type II collagen locus: the Framingham Osteoarthritis Study

OBJECTIVE: Studies have suggested that polymorphisms or mutations either in the COL2A1 or VDR gene. both on chromosome 12q, are associated with the occurrence of osteoarthritis (OA).We examined linkage and association between the VDR/COL2A1 locus and hand/knee OA in the Framingham Osteoarthritis Study (FOS). METHODS: Hand and knee joints were characterized radiographically in the FOS. An overall score for OA using the standard Kellgren and Lawrence grading scheme was determined, as well as scores for individual features of OA including osteophytes and joint space narrowing. For linkage studies, polymorphic microsatellite markers near the VDR-COL2AI genes on chromosome 12 were tested in a collection of 296 of the largest Framingham Heart Study families and the results analyzed using variance component linkage (SOLAR). For association studies, we characterized the allele status of a subset of subjects at the BsmI site of the VDR gene. RESULTS: Overall, we found no linkage or association between OA and the COL2A1/VDR locus for either knee or hand OA, nor did we find an association or linkage between COL2AI or VDR with any individual radiographic features of OA. CONCLUSION: Despite studies suggesting associations of OA with both COL2A1 and VDR loci, our results suggest that mutations at the COL2A1/VDR locus do not play an important role as a cause of common OA in the population at large.