Vancomycin-resistant enterococcal bacteremia: comparison of clinical features and outcome between Enterococcus faecium and Enterococcus faecalis.

BACKGROUND AND PURPOSE: Vancomycin-resistant enterococci (VRE) have emerged as important nosocomial pathogens. This study was conducted to clarify the clinical features and outcome of patients with vancomycin-resistant enterococcal bacteremia. METHODS: Patients with vancomycin-resistant enterococcal bacteremia treated at a medical center in northern Taiwan between November 1998 and July 2006 were reviewed. Clinical and bacteriological characteristics of Enterococcus faecium and Enterococcus faecalis were compared. RESULTS: Twelve patients (6 males and 6 females) were included for analyses. The mean age was 69.3 years (range, 40 to 86 years), and 8 cases (66.7%) were older than 65 years. All patients had underlying disease. Two patients received total hip replacement before development of VRE bacteremia. Twelve patients had prior exposure to broad-spectrum antimicrobial therapy. Ten patients had prior intensive care unit stay and prior mechanical ventilation before VRE bacteremia. All of the patients (n = 12) had an intravascular catheter in place. Bacteremia was caused by E. faecalis in 4 patients and by E. faecium in eight. The portals of entry included urinary tract (8.3%), skin, soft tissue and bone (41.7%) and unknown sources (50.0%). E. faecium showed a higher rate of resistance to ampicillin and teicoplanin than E. faecalis (87.5% vs 0.0%, p=0.01). The 60-day mortality rate was higher in patients with E. faecium bacteremia than E. faecalis bacteremia (62.5% vs 0.0%), although statistical significance was not obtained (p=0.08). CONCLUSIONS: VRE bacteremia may have an impact on the mortality and morbidity of hospitalized patients. Patients with bacteremia caused by vancomycin-resistant E. faecium had a grave prognosis, especially immunosuppressed patients. The prudent use of antibiotics and strict enforcement of infection control may prevent further emergence and spread of VRE.     

Altered GABAB receptor immunoreactivity in the gerbil hippocampus induced by baclofen and phaclofen, not seizure activity

The present study was performed to determine whether the effects induced by GABA(B) receptor-acting drugs would be related with the alteration in GABA(B) receptor expression in the hippocampus using Mongolian gerbil, a genetic epilepsy model. The distribution patterns of both GABA(B) receptor 1A/B and GABA(B)receptor 2 immunoreactivities were similarly detected in the hippocampi of normal and seizure-prone gerbils. Following baclofen (GABA(B) receptor agonist) or phaclofen (GABA(B) receptor antagonist) treatment, GABA(B) receptor immunoreactivities were decreased or increased by dose-dependent manners, respectively. Vigabatrin (GABA transaminase inhibitor) or 3-mercaptopropionic acid (GAD inhibitor) treatment did not affect GABA(B) receptor expressions. These findings suggest that GABA(B) receptor expression in the gerbil hippocampus may be altered by baclofen or phaclofen treatment.     

Anti-nociceptive and anti-inflammatory effects of the ethanolic extract of potato (Solanum tuberlosum)

The ethanol extract of potato tubers (Solanum tuberlosum L.) has been evaluated for antinociceptive and anti-inflammatory activities in mice. The acute treatment of mice with an ethanolic extract from the potato tuber at doses of 100 and 200 mg/kg, by oral administration, produced a significant anti-nociceptive effect in the acetic acid-induced writhing, formalin-induced pain licking and hot plate-induced pain. Also, the ethanolic extract of potato tubers significantly inhibited both carrageenan- and formalin-induced inflammation in mice as well as arachidonic acid-induced ear edema in mice. These inhibitions were statistically significant (p<0.05). These results provide support for the use of the ethanol extract of potato tuber in relieving inflammatory pain, and insight into the development of new agents for treating inflammatory diseases.     

Role of Drosophila IKK gamma in a toll-independent antibacterial immune response

We have generated, by ethylmethane sulfonate mutagenesis, loss-of-function mutants in the Drosophila homolog of the mammalian I-kappa B kinase (IKK) complex component IKK gamma (also called NEMO). Our data show that Drosophila IKK gamma is required for the Relish-dependent immune induction of the genes encoding antibacterial peptides and for resistance to infections by Escherichia coli. However, it is not required for the Toll-DIF-dependent antifungal host defense. The results indicate distinct control mechanisms of the Rel-like transactivators DIF and Relish in the Drosophila innate immune response and show that Drosophila Toll does not signal through a IKK gamma-dependent signaling complex. Thus, in contrast to the vertebrate inflammatory response, IKK gamma is required for the activation of only one immune signaling pathway in Drosophila.     

Early rehabilitation program in postmastectomy patients: a prospective clinical trial

The purpose of this study was to determine whether 20 patients who received an early postmastectomy rehabilitation treatment program showed more improvement in range of shoulder motion and functional activities than 13 patients who received instruction for exercise only. Data were obtained at preoperatively, three days after operation, at discharge and at postdischarge one month for each patient on parameters such as range of motion of the ipsilateral shoulder joint, upper extremity circumferential measurements, as well as 10 elements of shoulder function. Postoperatively, both groups showed an increased range of motion of the shoulder joint and improved functional activities, but the group that received postoperative rehabilitation management had a better range of shoulder motion and less difficulty in five items for functional assessment. This study also showed that an early rehabilitation program did not increase postoperative complications. We concluded that an early rehabilitation program or intensive instruction program only by a well-trained physical therapist or physiatrist was beneficial to postmastectomy patients in regaining the function and range of shoulder motion, and significantly better in a rehabilitation group.     

The cytoplasmic membrane is a primary target for the staphylocidal action of thrombin-induced platelet microbicidal protein.

Thrombin-induced platelet microbicidal protein (tPMP-1) is a small, cationic peptide released from rabbit platelets exposed to thrombin in vitro. tPMP-1 is microbicidal against a broad spectrum of bloodstream pathogens, including Staphylococcus aureus. Preliminary evidence suggests that tPMP-1 targets and disrupts the staphylococcal cytoplasmic membrane. However, it is not clear if the cytoplasmic membrane is a direct or indirect target of tPMP-1. Therefore, we assessed the in vitro activity of tPMP-1 versus protoplasts prepared from logarithmic-phase (LOG) or stationary-phase (STAT) cells of the genetically related S. aureus strains 19S and 19R (tPMP-1 susceptible and resistant, respectively). Protoplasts exposed to tPMP-1 (2 microg/ml) for 2 h at 37 degrees C were monitored for lysis (decrease in optical density at 420 nm) and ultrastructural alterations (by transmission electron microscopy [TEM]). Exposure to tPMP-1 resulted in substantial lysis of LOG but not STAT protoplasts of 19S, coinciding with protoplast membrane disruption observed by TEM. Thus, it appears that tPMP-1-induced membrane damage is influenced by the bacterial growth phase but is independent of the staphylococcal cell wall. In contrast to 19S, neither LOG nor STAT protoplasts of 19R were lysed by tPMP-1. tPMP-1-induced membrane damage was further characterized with anionic planar lipid bilayers subjected to various trans-negative voltages. tPMP-1 increased conductance across bilayers at -90 mV but not at -30 mV. Once initiated, a reduction in voltage from -90 to -30 mV diminished conductance magnitude but did not eliminate tPMP-1-mediated membrane permeabilization. Therefore, tPMP-1 appears to directly target the staphylococcal cytoplasmic membrane as a primary event in its mechanism of action. Specifically, tPMP-1 likely leads to staphylococcal death, at least in part by permeabilizing the bacterial membrane in a voltage-dependent manner.     

Lipooligosaccharide of Campylobacter jejuni prevents myelin-specific enteral tolerance to autoimmune neuritis--a potential mechanism in Guillain-Barre syndrome?

Campylobacter jejuni-induced enteritis is the most common infection preceding Guillain-Barre syndrome (GBS), an immune-mediated polyradiculoneuritis. The acute autoimmune attack is thought to be based on C. jejuni antigens which may mimick antigens of the peripheral nervous system. Additional pathomechanisms, like disturbance of natural T cell immunoregulation by C. jejuni, have not been evaluated so far. In experimental autoimmune neuritis (EAN), a T lymphocyte-mediated animal model of human GBS, tolerance to myelin-derived autoantigens can be induced by oral feeding of the respective antigen. Here we investigated whether the lipooligosaccharide (LOS) fraction of C. jejuni may directly alter immunologic tolerance through gastrointestinal pathways. While EAN, actively induced by immunization with bovine peripheral nerve myelin could be ameliorated by precedent feeding of myelin, feeding of C. jejuni LOS along with the myelin antigen not only prevented the tolerizing effects of oral myelin but even accelerated the onset of overt EAN and augmented the myelin-specific B cell response. These findings provide evidence that LOS of C. jejuni, as produced in the gut during C. jejuni-induced enteritis, can disturb natural tolerance to definite proteins which may be or may mimic peripheral nerve antigens. In human patients this may be one of the potential mechanisms to explain why C. jejuni enteritis is a common trigger of GBS.     

An IFN-beta-albumin fusion protein that displays improved pharmacokinetic and pharmacodynamic properties in nonhuman primates.

The long half-life and stability of human serum albumin (HSA) make it an attractive candidate for fusion to short-lived therapeutic proteins. Albuferon (Human Genome Sciences [HGS], Inc., Rockville, MD) beta is a novel recombinant protein derived from a gene fusion of interferon-beta (IFN-beta ) and HSA. In vitro, Albuferon beta displays antiviral and antiproliferative activities and triggers the IFN-stimulated response element (ISRE) signal transduction pathway. Array analysis of 5694 independent genes in Daudi-treated cells revealed that Albuferon beta and IFN-beta induce the expression of an identical set of 30 genes, including 9 previously not identified. In rhesus monkeys administered a dose of 50 microg/kg intravenously (i.v.) or subcutaneously (s.c.) or 300 microg/kg s.c., Albuferon beta demonstrated favorable pharmacokinetic properties. Subcutaneous bioavailability was 87%, plasma clearance at 4.7-5.7 ml/h/kg was approximately 140-fold lower than that of IFN-beta, and the terminal half-life was 36-40 h compared with 8 h for IFN-beta. Importantly, Albuferon beta induced sustained increases in serum neopterin levels and 2',5' mRNA expression. At a molar dose equivalent to one-half the dose of IFN-beta, Albuferon beta elicited comparable neopterin responses and significantly higher 2',5'-OAS mRNA levels in rhesus monkeys. The enhanced in vivo pharmacologic properties of IFN-beta when fused to serum albumin suggest a clinical opportunity for improved IFN-beta therapy.     

PCR-RFLP based molecular typing of enteroviruses isolated from patients with aseptic meningitis in Korea

Summary.  We have evaluated PCR–RFLP as a practical method for rapid typing of enteroviruses causing aseptic meningitis in Korea. Through blind examination of 80 clinical isolates from patients with aseptic meningitis, we have compared the results of conventional serotyping with PCR–RFLP based genotyping, which was developed for this study. Among the 80 case isolates, which had been previously typed by routine neutralization test, only 42 cases (52.5%) were matched with typing by PCR–RFLP. The result clearly demonstrated that the enterovirus serotype does not coincide with the genotype. Therefore, the classification of enteroviruses by genotyping with PCR–RFLP, although rapid and simple, may be complicated by regional or seasonal differences. However, the PCR–RFLP method developed in this study is applicable to the epidemiological study of enteroviruses when regional or seasonal differences exist, and is useful in identifying the source of an infection. Received August 6, 2001; accepted April 15, 2002 Published online July 10, 2002     

Regulation of L-carnitine metabolism in Escherichia coli

The metabolization of L-carnitine was studied using whole cells of Escherichia coli 044 K74. It showed features of an epigenetical control. L-carnitine and crotonobetaine were able to induce the carnitine-reducing system. Oxygen and nitrate as electron acceptors, gamma-butyrobetaine as final product of carnitine transformation in E. coli as well as glucose repress the carnitine metabolization. Other betaines and structurally related compounds did not show any effect neither as inductors nor as repressors.