Efficacy of Negative Pressure Wound Treatment in Preventing Surgical Site Infections after Whipple Procedures.

Surgical site infections (SSIs) occur at an average rate of 21.1 per cent after Whipple procedures per NSQIP data. In the setting of adherence to standard National Surgery Quality Improvement Program (NSQIP) Hepatopancreatobiliary recommendations including wound protector use and glove change before closing, this study seeks to evaluate the efficacy of using negative pressure wound treatment (NPWT) over closed incision sites after a Whipple procedure to prevent SSI formation.

Experience matters more than specialty for carotid stenting outcomes.

Objective: The introduction of carotid stenting has led to a rapid rise in the number of vascular specialists performing this procedure. The Carotid Revascularization Endarterectomy vs Stenting Trial (CREST) has shown that carotid stenting can be performed with an equivalent major event rate compared with carotid endarterectomy. However, there is still controversy about the appropriate training and experience required to safely perform this procedure.

Oral green tea catechin metabolites are incorporated into human skin and protect against UV radiation-induced cutaneous inflammation in association with reduced production of pro-inflammatory eicosanoid 12-hydroxyeicosatetraenoic acid.

Green tea catechins (GTC) reduce UV radiation (UVR)-induced inflammation in experimental models, but human studies are scarce and their cutaneous bioavailability and mechanism of photoprotection are unknown. We aimed to examine oral GTC cutaneous uptake, ability to protect human skin against erythema induced by a UVR dose range and impact on potent cyclo-oxygenase- and lipoxygenase-produced mediators of UVR inflammation, PGE2 and 12-hydroxyeicosatetraenoic acid (12-HETE), respectively. In an open oral intervention study, sixteen healthy human subjects (phototype I/II) were given low-dose GTC (540 mg) with vitamin C (50 mg) daily for 12 weeks.

Time-travelling and mind-travelling: examining individual differences in self-projection.

It has recently been suggested that memory and theory of mind may share the characteristic of mentally projecting oneself into another time or place to imagine alternative perspectives. This study examines this possible relationship by investigating individual differences in performance on a reality monitoring task and two mentalising tasks: the faux pas task and the reading the mind in the eyes test. Consistent with recent functional neuroimaging studies that have observed activity during reality monitoring tasks in the same region of prefrontal cortex that was activated in previous mentalising studies, a significant positive correlation in performance was observed between memory for agency and faux-pas recognition.

Characterization of a neurovirulent aciclovir-resistant variant of herpes simplex virus.

A clinical isolate of herpes simplex virus type 1 that is aciclovir resistant but neurovirulent in mice was described previously. The mutation in this virus is a double G insertion in a run of seven G residues that has been shown previously to be a mutational hotspot. Using a sensitive assay, it has been demonstrated that preparations of this virus are able to induce low but consistent levels of thymidine kinase (TK) activity.

Phenotypic and genotypic characterization of clinical isolates of herpes simplex virus resistant to aciclovir.

A panel of 10 clinical isolates of herpes simplex virus (HSV) deficient in the expression of thymidine kinase (TK) and phenotypically resistant to aciclovir was characterized. Sequence analysis revealed a variety of mutations in TK (nucleotide substitutions, insertions and deletions), most of which resulted in truncated TK polypeptides. In line with previous reports, the most common mutation was a single G insertion in the 'G-string' motif.

Predicting the emergence of drug-resistant HSV-2: new predictions.

Background: Mathematical models can be used to predict the emergence and transmission of antiviral resistance. Previously it has been predicted that high usage of antivirals (in immunocompetent populations) to treat Herpes Simplex Virus type 2 (HSV-2) would only lead to fairly low levels of antiviral resistance. The HSV-2 predictions were based upon the assumption that drug-resistant strains of HSV-2 would be less infectious than drug-sensitive strains but that the drug-resistant strains would not be impaired in their ability to reactivate.

Apolipoprotein A-I in bile inhibits cholesterol crystallization and modifies transcellular lipid transfer through cultured human gall-bladder epithelial cells.

Background: Apolipoprotein A-I (Apo A-I), conventionally purified by several steps including organic solvent-delipidation from plasma, inhibits cholesterol crystallization in bile. To observe a significant effect in vitro, however, supraphysiological concentrations above 100 microg/mL are required. For this reason, this protein has not been considered to play a physiological role in vivo.

Predicting and preventing the emergence of antiviral drug resistance in HSV-2.

Genital herpes, caused by herpes simplex virus, is the most prevalent sexually transmitted disease worldwide. In many developing countries genital herpes is untreated, and in the United States only 10% of cases are treated. We present a mathematical model that we use as a health policy tool to predict the levels of antiviral drug resistance that would emerge, if treatment rates were increased, and to identify the key factors in determining the emergence of drug resistance.

Survey of resistance of herpes simplex virus to acyclovir in northwest England.

Acyclovir (ACV) has been used for more than 15 years in the management of herpes simplex virus (HSV) and varicella-zoster virus (VZV) disease. The present survey was undertaken to assess the level of ACV resistance in the population. More than 2,000 HSV isolates from both immunocompetent and immunocompromised patients in northwest England were collected over a 2-year period and tested for sensitivity to ACV.

Human immunodeficiency virus. Mutations in the viral protease that confer resistance to saquinavir increase the dissociation rate constant of the protease-saquinavir complex.

Mutations in the human immunodeficiency virus (HIV) protease (L90M, G48V, and L90M/G48V) arise when HIV is passaged in the presence of the HIV protease inhibitor saquinavir. These mutations yield a virus with less sensitivity to the drug (L90M > G48V >> L90M/G48V). L90M, G48V, and L90M/G48V proteases have 1/20, 1/160, and 1/1000 the affinity for saquinavir compared to WT protease, respectively.

Construction of a herpes simplex virus/varicella-zoster virus (HSV/VZV) thymidine kinase recombinant with the pathogenic potential of HSV and a drug sensitivity profile resembling that of VZV.

A recombinant of herpes simplex virus (HSV) was constructed in which the HSV thymidine kinase (TK) gene was deleted and the varicella-zoster virus (VZV) TK gene was introduced into the US5 region under the control of the human cytomegalovirus IE promoter. Infection with the recombinant (R18) led to the induction of TK although the kinetics of synthesis resembled those of a 'late' gene product. The recombinant was virulent in the zosteriform mouse model with the pattern of pathogenesis similar to that of wild-type HSV-1.

High resolution structures of HIV-1 RT from four RT-inhibitor complexes.

We have determined the structures of four complexes of HIV-1 reverse transcriptase with non-nucleoside inhibitors, three fully refined at high resolution. The highest resolution structure is of the RT-nevirapine complex which has an R-factor of 0.186 and a root-mean-square bond length deviation of 0.

Acyclovir--and beyond.

Over the past 15 years, acyclovir has become established as standard therapy for the management of herpes simplex virus infections, but there are areas where improvements might be made. Acyclovir has a relatively low oral bioavailability. As a result, valaciclovir, the L-valine ester of acyclovir, is being developed.

Review of research leading to new anti-herpesvirus agents in clinical development: valaciclovir hydrochloride (256U, the L-valyl ester of acyclovir) and 882C, a specific agent for varicella zoster virus.

Research leading to the new anti-herpesvirus compounds discussed here has come from three approaches. The first approach was directed towards improving the bioavailability of acyclovir by examining the potential of a variety of prodrugs, leading to the new compound valaciclovir hydrochloride. The second approach was to examine a large number of 5-substituted pyrimidines for activity against those viruses which were not as potently inhibited by acyclovir as are herpes simplex viruses, i.

The acyclovir legacy: its contribution to antiviral drug discovery.

The discovery of acyclovir marked the beginning of an exciting era in antiviral research. Early studies on the novel mode of action explained the selectivity of the compound and the remarkably narrow spectrum of activity against a subset of the herpesviruses. Throughout the past decade many clinical trials have demonstrated the efficacy and safety of this drug.

The multifunctional folic acid synthesis fas gene of Pneumocystis carinii appears to encode dihydropteroate synthase and hydroxymethyldihydropterin pyrophosphokinase.

We describe the cloning of a multifunctional folic acid synthesis (fas) gene from Pneumocystis carinii. The nucleotide sequence contains an open reading frame interrupted by three introns, that encodes a protein of 740 amino acids with an Mr of 97,278. The predicted Fas protein has homology to two enzyme domains, dihydropteroate synthase and 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase, both of which are involved in folate synthesis, and at least one other region of unknown function.

Ordered appearance of zidovudine resistance mutations during treatment of 18 human immunodeficiency virus-positive subjects.

The order of appearance in the reverse transcriptase gene of four mutations implicated in the development of resistance to zidovudine was investigated by selective polymerase chain reaction. Serial human immunodeficiency virus isolates were studied from 18 initially asymptomatic individuals who had been treated with zidovudine for 2 years. Most subjects had similar patterns.

Zidovudine sensitivity of human immunodeficiency viruses from high-risk, symptom-free individuals during therapy.

Human immunodeficiency type 1 isolates from 18 initially symptom-free men who were treated with zidovudine for 2 years were investigated for drug sensitivity. At the start all the men had persistent core antigenaemia; the acquired immunodeficiency syndrome developed in 6 during the study. The polymerase chain reaction was used to detect mutations at residue 215 of reverse transcriptase, a mutation associated with reduced drug sensitivity.

The role of herpes simplex virus type 1 thymidine kinase in pathogenesis.

A genetically engineered herpes simplex virus type 1 (HSV-1)thymidine kinase (TK) deletion mutant has been constructed and used to investigate the role of this gene in pathogenesis. Inoculation of mice with the HSV TK deletion mutant resulted in the establishment of latent ganglionic infection as demonstrated by superinfection of explanted ganglia with wild-type (wt) virus but not by routine explant culture suggesting that the virus-encoded TK is not essential for the establishment of latent infection but may be necessary for either reactivation or virus replication following reactivation. In addition, Southern blot hybridization has been used to demonstrate in vivo complementation of this mutant by wt virus in both peripheral and central nervous system tissues of mice during acute infection and to show that such complementation can result in the establishment and reactivation of latent TK- infection.

HIV with reduced sensitivity to zidovudine (AZT) isolated during prolonged therapy.

The drug sensitivities of human immunodeficiency virus (HIV) isolates from a group of patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC) who were receiving zidovudine (3'-azido-3'-deoythymidine, AZT) therapy were tested by means of a newly developed plaque assay in CD4+ HeLa cells. Fifty percent inhibitory dose (ID50) values of 18 isolates from untreated individuals ranged between 0.01 microM and 0.

Characterization of a DNA polymerase mutant of herpes simplex virus from a severely immunocompromised patient receiving acyclovir.

A series of herpes simplex virus isolates were recovered from a bone marrow transplant patient who received prolonged acyclovir therapy for indolent herpes simplex mouth and throat ulceration. Of 14 isolates received 10 were resistant to acyclovir and partially resistant to phosphonoacetic acid. Biochemical characterization revealed that resistance was due to an alteration in the virus DNA polymerase.