Plus Sutures for preventing surgical site infection: a systematic review of clinical outcomes with economic and environmental models.

BACKGROUND: Surgical site infections (SSIs) represent ~ 20% of all hospital-acquired infections in surgical patients and are associated with prolonged hospital stay, admission to intensive care, and mortality. We conducted a systematic review with economic and environmental models to assess whether triclosan-coated sutures (Plus Sutures) provide benefits over non-coated sutures in the reduction of SSI risk. METHODS: Searches were conducted in fifteen databases. A total of 1,991 records were retrieved. Following deduplication and screening by two independent reviewers, 31 randomized controlled trials in adults and children were included in the review. Similarity of the studies was assessed by narrative review and confirmed by quantitative assessment. A fixed effects meta-analysis of SSI incidence model including all groups of patients estimated a risk ratio of 0.71 (95% confidence interval: 0.64 to 0.79) indicating those in the Plus Sutures group had a 29% reduction in the risk of developing an SSI compared with those in the control group (p < 0.001). Safety outcomes were analysed qualitatively. RESULTS: The economic model estimated the use of Plus Sutures to result in average cost savings of £13.63 per patient. Plus Sutures remained cost-saving in all subgroup analyses with cost-savings ranging between £11 (clean wounds) and £140 (non-clean wounds). The environmental impact of SSI is substantial, and the model suggests that the introduction of Plus Sutures could result in potential environmental benefits. CONCLUSIONS: The evidence suggests that Plus Sutures are associated with a reduced incidence of SSI across all surgery types alongside cost savings when compared with standard sutures.

Changing epidemiology of Clostridium difficile infection following the introduction of a national ribotyping-based surveillance scheme in England.

BACKGROUND: Marked increases in Clostridium difficile infection (CDI) incidence, driven by epidemic strain spread, is a global phenomenon. METHODS: The Clostridium difficile Ribotyping Network (CDRN) was established in 2007 as part of enhanced CDI surveillance in England, to facilitate the recognition and control of epidemic strains. We report on changes in CDI epidemiology in England in the first 3 years of CDRN. RESULTS: CDRN received 12,603 fecal specimens, comprising significantly (P < .05) increasing numbers and proportions of national CDI cases in 2007-2008 (n = 2109, 3.8%), 2008-2009 (n = 4774, 13.2%), and 2009-2010 (n = 5720, 22.3%). The C. difficile recovery rate was 90%, yielding 11,294 isolates for ribotyping. Rates of 9 of the 10 most common ribotypes changed significantly (P < .05) during 2007-2010. Clostridium difficile ribotype 027 predominated, but decreased markedly from 55% to 36% and 21% in 2007-2008, 2008-2009, and 2009-2010, respectively. The largest regional variations in prevalence occurred for ribotypes 027, 002, 015, and 078. Cephalosporin and fluoroquinolone use in CDI cases was reported significantly (P < .05) less frequently during 2007-2010. Mortality data were subject to potential reporting bias, but there was a significant decrease in CDI-associated deaths during 2007-2010, which may have been due to multiple factors, including reduced prevalence of ribotype 027. CONCLUSIONS: Access to C. difficile ribotyping was associated with significant changes in the prevalence of epidemic strains, especially ribotype 027. These changes coincided with markedly reduced CDI incidence and related mortality in England. CDI control programs should include prospective access to C. difficile typing and analysis of risk factors for CDI and outcomes.

The four-variable modification of diet in renal disease formula underestimates glomerular filtration rate in obese type 2 diabetic individuals with chronic kidney disease.

AIMS/HYPOTHESIS: GFR is commonly estimated using the four-variable Modification of Diet in Renal Disease (MDRD) formula and this forms the basis for classification of chronic kidney disease (CKD). We investigated the effect of obesity on the estimation of glomerular filtration rate in type 2 diabetic participants with CKD. METHODS: We enrolled 111 patients with type 2 diabetes mellitus in different stages of CKD. GFR was measured using (51)Cr-labelled EDTA plasma clearance and was estimated using the four-variable MDRD formula. RESULTS: The bias between estimated and measured GFR was -22.4 (-33.8 to -11.0) p < 0.001 in the obese group compared with -6.04 (-17.6 to -5.5) p = 0.299 in the non-obese group. When GFR was indexed to body surface area of 1.73 m(2), the bias remained significant at -9.4 (-13.4 to -5.4) p < 0.001 in the obese participants. CONCLUSIONS/INTERPRETATION: This study suggests that the four-variable MDRD formula significantly underestimates GFR in obese type 2 diabetic participants with CKD.

Extended multilocus variable-number tandem-repeat analysis of Clostridium difficile correlates exactly with ribotyping and enables identification of hospital transmission.

PCR ribotyping is currently used in many countries for epidemiological investigation to track transmission and to identify emerging variants of Clostridium difficile. Although PCR ribotyping differentiates over 300 types, it is not always sufficiently discriminatory for epidemiological investigations particularly for common ribotypes, e.g., ribotypes 027, 106, and 017. Multilocus variable-number tandem-repeat analysis (MLVA) is a highly discriminatory molecular subtyping method that has been applied to a number of bacterial species for high-level subtyping. Two MLVA typing schemes for C. difficile have been previously published, each utilizing seven variable-number tandem-repeat (VNTR) loci on the genome with four loci common to both schemes. Although these schemes are good genotyping methods with the ability to discriminate between isolates, they do not identify the ribotype. We show here that increasing the number of VNTR loci to 15, creating the extended MLVA (eMLVA) scheme, we have successfully subtyped all clinically significant ribotypes while still clustering isolates in concordance with PCR ribotyping. The eMLVA scheme developed here provides insight into the genetic diversity of the C. difficile population at both global and cross-infection clusters in patient levels, with the possibility of replacing PCR ribotyping.

Human gamma interferon strongly upregulates its own gene expression in peripheral blood lymphocytes.

The product of the human IFN-gamma gene was found to be a powerful upregulatory stimulus for its own gene expression in lectin-activated human PBMC. The INF-gamma autosuperinduction response was further enhanced by "priming" PBMC with IFN-gamma. Primed cells maximally upregulated their levels of IFN-gamma specific mRNA 4-fold faster and more than 20-fold higher than mock-stimulated cells. High mRNA levels persisted for several days after stimulation, and enhanced secretion of biologically active IFN-gamma paralleled the observed upregulation of gene expression. Producer cells demonstrating this response were found to be primarily localized to the rosette E- (leu 11+) fraction of PBMC and appear to be of the LGL/NK variety. Whether the autosuperinduction phenomenon occurs through direct or indirect effects of IFN-gamma on producer cells is still unclear. These results may be important both to an understanding of the pathogenesis of immune dysfunction and to the design of more effective immunotherapy.

A model of human cytokine regulation based on transfection of gamma interferon gene fragments directly into isolated peripheral blood T lymphocytes.

An approach has been optimized permitting measurement of human cytokine reporter gene expression after transient transfection directly into purified human peripheral blood T lymphocytes. Comparing the expression of interleukin 2 (IL-2) CAT with a series of specially engineered gamma interferon (IFN-gamma) constructs, a fundamental difference in the molecular mechanisms regulating these two cytokines has been suggested. A potent, tissue-specific, constitutive-acting positive regulatory element was located between sequences -215 and -53 in the human IFN-gamma gene. Deletion analyses suggested that sequences slightly upstream, between positions -251 to -215, exerted a powerful dominant suppressive influence over that positive element. Negative elements appear to play a major role in controlling the regulation of human IFN-gamma gene expression. We thus propose a model of cytokine gene regulation in which selective derepression may be an important fundamental mechanism of induction and/or positive modulation.

Intranuclear localization of mercury in vivo.

Purified nuclei isolated from mice challenged with nonlethal levels of mercury chloride (10-(3)M) in drinking water for 4 to 7 weeks (experimental) and from animals given deionized water (control) were fractionated and the subsequent fractions were analyzed for mercury by flameless atomic absorption. Control (active) euchromatin contained 1.75 +/- 0.53 micrograms of mercury per milligram of DNA. There was a 12- to 15-fold enrichment of mercury in the euchromatin fraction of challenged animals. Mercury was not detected in control (inactive) heterochromatin, and only trace levels (parts per billion) appeared in experimental heterochromatin. It seems likely that mercury can be incorporated into chromatin as a metal-protein complex, but the possibility of protein-mercury-DNA or mercury-DNA complexes within euchromatin cannot be excluded.

Differential effect of cyclosporin A on activation signaling in human T cell lines.

Different T cell lines, which can be induced to secrete interleukin 2 (IL-2) in vitro, were used to dissect the effect of cyclosporin A (CsA). The T leukemia cell Jurkat requires an increase in cytoplasmic calcium concentration ([Ca++]i) and phorbol myristate acetate (PMA) for the induction of IL-2 production, which is completely blocked by CsA. Another T cell line, HUT 78, also produces IL-2 in response to a rise in [Ca++]i and PMA; however, in HUT 78, PMA alone induces low levels of IL-2 production that is not blocked by CsA. After treatment with 5-azacytidine, HUT 78 cells produced maximal levels of IL-2 in response to PMA alone without requiring [Ca++]i increasing stimuli. In these cells no inhibitory effect of CsA on PMA-induced activation could be demonstrated. In addition, CsA does not inhibit PMA-induced translocation of protein kinase C. These data suggest that CsA does not globally inhibit IL-2 gene expression, but rather interferes with signaling events of T cell activation.

Subtyping of ST22-MRSA-IV (Barnim epidemic MRSA strain) at a university clinic in Germany from 2002 to 2005.

Emergence of the meticillin-resistant Staphylococcus aureus (MRSA) Barnim epidemic strain (ST22-MRSA-IV) was demonstrated recently at University Hospital in Magdeburg, Germany. To aid the study of transmission events, it is important to have an epidemiological typing method with the ability to distinguish among MRSA isolates. The aim of this study was to determine the ability of phenotypic and genotypic methods to type ST22-MRSA-IV strains within a hospital for microevolution events. Forty-two ST22-MRSA-IV strains collected from 2002 to 2005 were analysed using antimicrobial testing, toxin gene analysis, PFGE, spa typing, fluorescent amplified fragment length polymorphism (fAFLP) and determination of staphylococcal interspersed repeat units (SIRUs). Four different antimicrobial patterns were observed. The majority of the isolates (n=31) were resistant towards erythromycin, ciprofloxacin and clindamycin, in addition to penicillin and oxacillin. All strains harboured the sec gene and showed a homogeneous profile of toxin genes. One isolate was typed as spa t022, two as spa t474 and the remainder belonged to spa type t032. PFGE yielded eight profiles and SIRU typing resulted in six different patterns. The fAFLP technique subdivided the individual PFGE profiles, but the grouping of isolates differed from that obtained by PFGE or SIRU typing. These results showed a diversity of ST22-MRSA-IV strains within a narrow clinical setting, indicating microevolution of the Barnim MRSA clone. The ability to distinguish among MRSA strains within an endemic setting will lead to a greater understanding of the transmission of MRSA and is necessary to be able to control the spread of various clones.

Rapid recontamination with MRSA of the environment of an intensive care unit after decontamination with hydrogen peroxide vapour.

Meticillin-resistant Staphylococcus aureus (MRSA) persists in the hospital environment and conventional cleaning procedures do not necessarily eliminate contamination. A prospective study was conducted on an intensive care unit to establish the level of environmental contamination with MRSA, assess the effectiveness of hydrogen peroxide vapour (HPV) decontamination and determine the rate of environmental recontamination. MRSA was isolated from 11.2% of environmental sites in the three months preceding the use of HPV and epidemiological typing revealed that the types circulating within the environment were similar to those colonising patients. After patient discharge and terminal cleaning using conventional methods, MRSA was isolated from five sites (17.2%). After HPV decontamination but before the readmission of patients, MRSA was not isolated from the environment. Twenty-four hours after readmitting patients, including two colonized with MRSA, the organism was isolated from five sites. The strains were indistinguishable from a strain with which a patient was colonized but were not all confined to the immediate vicinity of the colonized patient. In the eight weeks after the use of HPV, the environment was sampled on a weekly basis and MRSA was isolated from 16.3% sites. Hydrogen peroxide vapour is effective in eliminating bacteria from the environment but the rapid rate of recontamination suggests that it is not an effective means of maintaining low levels of environmental contamination in an open-plan intensive care unit.

Chromatin structure of the HLA-DR alpha gene in different functional states of major histocompatibility complex class II gene expression.

We utilized DNase I hypersensitivity mapping to study chromatin structure within the HLA-DR alpha gene. We found a single DNase I-hypersensitive site coinciding with the HLA-DR alpha gene promoter in all cells studied. Moreover, in cells that constitutively express HLA-DR, two additional DNase I-hypersensitive sites were observed. These lie within the first intron of the HLA-DR alpha gene and encompass DNA sequences that share homologies with regulatory loci of the immunoglobulin and immune response genes, as well as with core enhancer consensus sequences.

Investigation of community carriage rates of Clostridium difficile and Hungatella hathewayi in healthy volunteers from four regions of England.

Faecal samples from 1365 healthy asymptomatic volunteers from four regions in England were screened for the presence of Clostridium difficile between December 2013 and July 2014. The carriage rate of C. difficile in healthy patients was 0.5%, which is lower than reported previously. This study demonstrates that the true community reservoir of C. difficile in the healthy UK population is very low and is, therefore, unlikely to be a reservoir for infections diagnosed in the hospital setting.

The cyclic AMP response to glucagon. Comparison of tissue and plasma cyclic AMP levels in the rabbit.

The effects of glucagon on tissue and plasma cyclic AMP levels have been investigated in rabbits anesthetized with urethane. Glucagon (2 nmole/kg.) caused at least a twofold increase in hepatic cyclic AMP, which reached a peak within two minutes and declined to basal values after 40 minutes. Plasma cyclic AMP also increased at least twofold, reaching a peak at 10 minutes and declining to basal values after 60 minutes. Glucagon (20 nmole/kg.) stimulated hepatic and plasma cyclic AMP in a manner indistinguishable from that observed at the lower dose. Hepatectomy abolished the plasma cyclic AMP responses to glucagon, and no significant stimulation of cyclic AMP concentration was noted in the heart, adipose tissue, small bowel, or kidney. Cyclic AMP hydrolysis was estimated in blood taken before and after administration of glucagon. Glucagon (2 nmole/kg.) increased cyclic AMP hydrolysis slightly, but this was explained by the raised cyclic AMP levels. By contrast, cyclic AMP hydrolysis increased two-to-threefold in blood taken 20 and 40 minutes after glucagon (20 nmole/kg.). The higher dose of glucagon also stimulated cyclic AMP hydrolysis in crude liver homogenate, which could not be explained by increases in cyclic AMP concentration. The increase in cyclic AMP hydrolysis observed in blood and liver may partly explain the failure to show additional stimulation of hepatic and plasma cyclic AMP levels with the higher dose of glucagon. Despite the changes in cyclic AMP hydrolysis, a highly significant correlation was observed in individual rabbits between the hepatic and plasma cyclic AMP responses to glucagon (2 and 20 nmole/kg.), when these were calculated as incremental areas above mean basal levels. It is suggested that measurement of plasma cyclic AMP levels after stimulation by glucagon may be an accurate index of the hepatic cyclic AMP response to glucagon in vivo.

Role of interferon-gamma in immune cell regulation.

In 1965 Wheelock reported that phytohemagglutinin could induce from human leukocytes an interferon-like virus inhibitor [1]. This substance, which turned out to be interferon-gamma (IFN-gamma), has been the subject, directly or indirectly, of thousands of scientific publications since that initial report. Past research has led to the general conclusion that IFN-gamma is much more than an interferon in that it has broader effects on the various arms of the immune system than most any other lymphokine or cytokine. In this review we discuss the effects of IFN-gamma on the various cell lineages of the immune system, focusing on the biology of its actions. In addition, we summarize research focused on the consequences of introducing IFN-gamma cDNA into tumor cells, aberrant IFN-gamma production in transgenic animals, and inhibition of IFN-gamma effects by knocking out either the IFN-gamma gene itself or the IFN-gamma receptor gene.

Severe insulin-induced lipohypertrophy successfully treated by liposuction.

OBJECTIVE: To examine the usefulness of liposuction surgery on diabetic patients with lipohypertrophy. RESEARCH DESIGN AND METHODS: We treated a diabetic patient who suffered from severe localized thigh lipohypertrophy. When she did not respond to conventional treatment of resting the injection site, we recommended liposuction surgery. RESULTS: Our patient's lipohypertrophy was immediately cured by the liposuction procedure. CONCLUSIONS: Liposuction surgery could be useful in patients with diabetic lipohypertrophy who do not respond to more conservative treatments.

A treatable cause of recurrent severe hypoglycemia.

OBJECTIVE: To see if glucocorticoid deficiency might explain increased insulin sensitivity causing severe brittle diabetes in two type I diabetic patients. CASES: We describe two patients who developed brittle diabetes characterized by recurrent severe hypoglycemia on small daily insulin doses with severe hyperglycemia on further insulin dose reduction. In both patients, insulin requirements had fallen markedly. RESULTS: Both patients were found to have glucocorticoid deficiency. In one patient, this was a result of hypopituitarism, in which hypoglycemia was aggravated by growth hormone deficiency. In the other patient, glucocorticoid deficiency was the result of primary adrenal failure. Resolution of brittle diabetes and restoration of normal insulin doses followed steroid replacement therapy in both patients. CONCLUSIONS: These patients emphasize the importance of seeking an organic cause for recurrent severe hypoglycemia. Increasing insulin sensitivity in type I diabetic patients should alert clinicians to the possibility of glucocorticoid deficiency.

Diabetic nephropathy is associated with an increased familial risk of stroke.

OBJECTIVE: To test the hypothesis that genetic susceptibility to diabetic nephropathy is associated with an increased familial risk of vascular disease, we have examined the causes and rates of death of parents of individuals with type 1 diabetes complicated by diabetic nephropathy compared with the causes and rates of death of parents of control subjects with diabetes uncomplicated by nephropathy. RESEARCH DESIGN AND METHODS: Individuals with at least a 14-year duration of type 1 diabetes complicated by diabetic nephropathy were identified and matched for age, sex, and duration of diabetes to control subjects. A total of 118 patients and 118 matched control subjects were identified and approached to obtain information on parental age and cause of death. For parents who had died, the cause of death was ascertained from the death certificate. RESULTS: Kaplan-Meier curves showed that parents of subjects with nephropathy (PN) had reduced survival compared with parents of diabetic subjects without nephropathy (PC) (log rank test P < 0.05). There was an excess of all vascular deaths and, in particular, strokes in the parents of subjects with nephropathy (PN: 20 of 103 deaths, 19% vs. PC: 3 of 66 deaths, 4%; Fisher's exact test P < 0.01). CONCLUSIONS: Parents of diabetic patients with nephropathy have reduced survival. This seems to be largely explained by an increase in vascular deaths and, in particular, a four-fold increase in the number of strokes. This supports the hypothesis that a common hereditary risk factor predisposes to both vascular death and diabetic renal disease.

Effect of sodium loading and ACTH on blood pressure of sheep with reduced renal mass.

Sodium chloride loading produced a rise in blood pressure in intact sheep which was potentiated by reduction in renal mass. ACTH induced hypertension was also potentiated by reduced renal mass, suggesting a volume component for the hypertension when renal excretory capacity for salt and water is reduced.