Cephalosporin vs penicillin

Smaller individual series on the outcome of laparoscopic hernioplasty techniques have been reported. This study reports on the complications of 3,229 laparoscopic hernia repairs performed by the authors in 2,559 patients. The TAPP (transabdominal preperitoneal) technique was the most frequently performed: 1,944 (60%). The totally preperitoneal technique was performed 578 (18%) times. The IPOM (intraperitoneal onlay mesh) repair was performed 345 (11%) times. The plug-and-patch technique was used 286 (9%) times and simple closure of the hernia defect without mesh was used in 76 (2%) repairs. Overall, there were 336 (10%) complications: 17 (0.5%) major and 265 (8%) minor. There were 54 (1.6%) recurrences, with a mean follow-up of 22 months. The TAPP technique had 19 (1%) recurrences and 141 (7%) complications. There were four bowel obstructions in this subgroup from herniation of small bowel through the peritoneal closure and trocar sites. The totally preperitoneal technique had no recurrence and 60 (10%) complications. The IPOM group had 7 (2%) recurrences and 47 (14%) complications. The plug-and-patch technique had 26 (9%) recurrences and 24 (8%) complications. The simple closure of the internal ring had 2 (3%) recurrences and 10 (13%) complications. Laparoscopic hernioplasty is not without complications. Laparoscopic hernioplasty is not without complications. Training, experience, and attention to technique will prevent some of these complications.     

Inhibition of G protein-coupled receptor kinase subtypes by Ca2+/calmodulin

G protein-coupled receptor kinases (GRKs) are implicated in the homologous desensitization of G protein-coupled receptors. Six GRK subtypes have so far been identified, named GRK1 to GRK6. The functional state of the GRKs can be actively regulated in different ways. In particular, it was found that retinal rhodopsin kinase (GRK1), but not the ubiquitous betaARK1 (GRK2), can be inhibited by the photoreceptor-specific Ca2+-binding protein recoverin through direct binding. The present study was aimed to investigate regulation of other GRKs by alternative Ca2+-binding proteins such as calmodulin (CaM). We found that Gbetagamma-activated GRK2 and GRK3 were inhibited by CaM to similar extents (IC50 approximately 2 microM), while a 50-fold more potent inhibitory effect was observed on GRK5 (IC50 = 40 nM). Inhibition by CaM was strictly dependent on Ca2+ and was prevented by the CaM inhibitor CaMBd. Since Gbetagamma, which is a binding target of Ca2+/CaM, is critical for the activation of GRK2 and GRK3, it provides a possible site of interaction between these proteins. However, since GRK5 is Gbetagamma-independent, an alternative mechanism is conceivable. A direct interaction between GRK5 and Ca2+/CaM was revealed using CaM-conjugated Sepharose 4B. This binding does not influence the catalytic activity as demonstrated using the soluble GRK substrate casein. Instead, Ca2+/CaM significantly reduced GRK5 binding to the membrane. The mechanism of GRK5 inhibition appeared to be through direct binding to Ca2+/CaM, resulting in inhibition of membrane association and hence receptor phosphorylation. The present study provides the first evidence for a regulatory effect of Ca2+/CaM on some GRK subtypes, thus expanding the range of different mechanisms regulating the functional states of these kinases.     

Wound fluids and the pathogenesis of chronic wounds

PURPOSE: To describe two areas of ongoing investigation into analysis of wound fluids that may eventually lead to better understanding of pathophysiology of chronic wounds and to improved care and treatment. METHODS: Studies used Lowry protein assay, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Western blotting, and zymography to analyze fluids from acute and chronic wounds and serum samples collected from healthy and affected volunteers. SUBJECTS: Thirty-one subjects with ages ranging from 32 to 79 years participated in the research; fluid was collected from chronic wounds in 10 patients (two female, four male, and four unrecorded), fluid was collected from acute mastectomy wounds in 15 patients (all female); blister fluid and blood were collected from two volunteers (one male, one female); and blood for serum preparation was collected from four volunteers (two female, two male). PRIMARY OUTCOME VARIABLES: (1) Fibronectin degradation and (2) expression of matrix metalloproteinases. RESULTS: Fibronectin can be degraded in fluid from chronic wounds but remains intact in blood-derived serum, plasma-derived serum, blister fluid, and mastectomy wound fluid. Matrix metalloproteinases are overexpressed in fluid from chronic wounds compared with mastectomy wound fluid, blood-derived serum, and plasma-derived serum. Matrix metalloproteinases are also expressed of somewhat higher levels in mastectomy fluid than in blood-derived and plasma-derived serum. CONCLUSIONS: These studies identified two factors that may contribute to delayed healing of chronic wound: fibronectin degradation and overexpression of matrix metalioproteinases.