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Biomedical subjects

R Finkelstein

Publications and source records attributed to R Finkelstein.

At least 19 recordsLinked to original sources

Clinical and epidemiologic significance of coagulase-negative staphylococci bacteremia in a tertiary care university Israeli hospital.

OBJECTIVES: To characterize the clinical significance of coagulase-negative staphylococci (CNS) bacteremia. DESIGN: Prospective cohort study. SETTING: A 900-bed hospital in Haifa, Israel, from November 1996 to March 1997. RESULTS: Of 137 episodes of positive blood cultures for CNS, 41 (30%) were considered as true infection. Twenty-seven of 119 episodes associated with only 1 blood culture positive for CNS (23%) met the definition of infection as compared with 14 of 18 episodes (78%) associated with 2 or more blood cultures positive for CNS (P <.001). Methicillin resistance was significantly more frequent among Staphylococcus epidermidis isolates of episodes of true bacteremia than of episodes of contamination (15 of 22 [68%] vs. 11 of 33 [33%], respectively; P =.02). S hominis was isolated only in episodes considered as contamination (P =.01). It was estimated that CNS represents 24% of all nosocomial bloodstream pathogens. When CNS were isolated in the first 48 hours of hospitalization, an intravascular device was more frequently associated with episodes of true bacteremia than in those considered as contamination (7 of 7 [100%] vs. 10 of 57 [18%], respectively; P <.001). The mortality rate among patients with true CNS bacteremia was 16%. CONCLUSION: Some laboratory parameters may help identify episodes of true CNS bacteremia, which appears to be more common than previously considered.

Adult↗

Vancomycin versus cefazolin prophylaxis for cardiac surgery in the setting of a high prevalence of methicillin-resistant staphylococcal infections.

OBJECTIVE: This study was undertaken to compare the efficacy of vancomycin prophylaxis with that of cefazolin in preventing surgical site infections in a tertiary medical center with a high prevalence of methicillin-resistant staphylococcal infections. METHODS: All adult patients (> or = 18 years) scheduled for cardiac surgery requiring sternotomy were randomly assigned to receive vancomycin (1 g every 12 hours) or cefazolin (1 g every 8 hours). Prophylaxis was started during the induction of anesthesia and continued for only 24 hours. Patients were followed up for at least 30 days (1 year for those receiving a cardiac implant). Surgical site infections were stratified according to the National Nosocomial Infections Surveillance System risk index. RESULTS: Of the 885 patients included in the study, 452 received vancomycin and 433 received cefazolin. The overall surgical site infection rates were similar in the two groups (43 cases in the vancomycin group, 9.5%, vs 39 cases in the cefazolin group, 9.0%, P =.8). Superficial and deep incisional surgical site infection rates were also similar in the two groups. There was a trend toward more frequent organ-space infections and infections with beta-lactam-resistant organisms among patients receiving cefazolin, but this trend did not reach statistical significance. In contrast, surgical site infections caused by methicillin-susceptible staphylococci were significantly more common in the vancomycin group (17 cases, 3.7%, vs 6 cases, 1.3%, P =.04). The durations of postoperative hospitalization and the mortalities were similar in the two groups. CONCLUSIONS: This trial suggests that vancomycin and cefazolin have similar efficacy in preventing surgical site infections in cardiac surgery.

Adult↗

Invasive pulmonary aspergillosis in neutropenic patients during hospital construction: before and after chemoprophylaxis and institution of HEPA filters.

Between September 1993 and December 1993, during extensive hospital construction and indoor renovation, a nosocomial outbreak of invasive pulmonary aspergillosis occurred in acute leukemia patients treated in a regular ward that has only natural ventilation. The observed infection rate was 50%. Chemoprophylaxis with intravenous continuous low-dose amphotericin B was then instituted as a preventive measure. During the next 18 months invasive pulmonary aspergillosis developed in 43% of acute leukemia patients. After that period a new hematology ward was opened with an air filtration system through high-efficiency particulate air filtration (HEPA) filters, and a bone marrow transplantation program was started on the hematology service. During the following three years, none of the acute leukemia or bone marrow transplantation patients who were hospitalized exclusively in the hematology ward developed invasive pulmonary aspergillosis, although 29% of acute leukemia patients who were housed in a regular ward, because of shortage of space in the new facility, still contracted invasive pulmonary aspergillosis. Overall, 31 patients were diagnosed with invasive pulmonary aspergillosis during almost five years: 74% of patients recovered from invasive pulmonary aspergillosis, and 42% are long-term survivors; 26% of patients died of resistant leukemia with aspergillosis, but no one died of invasive pulmonary aspergillosis alone. In conclusion, during an on-going construction period, an extremely high incidence rate of invasive pulmonary aspergillosis in acute leukemia patients undergoing intensive chemotherapy was observed. Institution of low-dose intravenous amphotericin B prophylaxis marginally reduced the incidence rate of invasive pulmonary aspergillosis. Keeping patients in a special ward with air filtration through a HEPA system eliminated invasive pulmonary aspergillosis completely. Among patients who developed invasive pulmonary aspergillosis, early diagnosis and treatment are probably the explanation for the favorable outcome.

Adult↗

Device-associated, device-day infection rates in an Israeli adult general intensive care unit.

Surveillance is an essential element of hospital infection control programs. Previous studies have shown that interhospital comparison of intensive care unit (ICU) nosocomial infections (NI) may be best made by comparing ICU-type-specific, device-associated infection rates and that these adjusted rates vary by ICU type. The aim of this study was to evaluate whether significant structural improvements introduced in an adult general ICU were associated with changes in the NI rates in this unit. In addition, we compared these rates with those of ICUs reported by the National Nosocomial Infections Surveillance (NNIS) System of the Centers for Diseases Control and Prevention. During a 12-month period 337 patients were surveyed. There were 20 ventilator-associated pneumonias (VAP)/1000 ventilator (VEN)-days, 12 bloodstream infections (BSI)/1000 central vascular catheter (CVC)-days and 14 urinary tract infection (UTI)/1000 indwelling urinary catheter (IUC)-days. Structural changes and reduction in device utilization ratios were not followed by change in NI rates in this unit. VAP and BSI rates were comparable to those reported for neurosurgical and burn ICUs, respectively, in the NNIS System, despite a much higher device utilization ratios. The present study provides specific surveillance data for further interhospital comparison with similar types of ICUs.

Adult↗

Epidermal growth factor receptor signaling activates orthodenticle expression during Drosophila head development.

The relation between signal transduction pathways and the genes that specify regional identity remains poorly understood. We investigated the interaction between the epidermal growth factor receptor (EGFR) pathway and the homeobox gene orthodenticle (otd), which specifies cell fate during head development. Previous studies of head formation in Drosophila melanogaster demonstrated that reducing either EGFR signaling or otd expression in the imaginal primordium of the dorsal head capsule eliminates the ocelli and other dorsal head structures. Here, we show that blocking EGFR signaling reduces otd expression and that activating EGFR signaling outside this primordium induces ectopic otd expression. We also demonstrate that loss of EGFR can be rescued by constitutive otd expression. Our results indicate that otd is a downstream target of the EGFR pathway during head development.

Animals↗

Clinical, epidemiological, and microbiological features of Vibrio vulnificus biogroup 3 causing outbreaks of wound infection and bacteraemia in Israel. Israel Vibrio Study Group.

BACKGROUND: Vibrio vulnificus is a gram-negative bacterium that causes septicaemia and wound infection. Cases occur sporadically, and no previous outbreaks due to a common source or a clonal strain have been reported. In the summer and autumn of 1996 and 1997, an outbreak of invasive V. vulnificus infection occurred in Israel in people who had recently handled fresh, whole fish purchased from artificial fish-ponds. METHODS: We reviewed clinical and epidemiological information, and undertook an environmental investigation to assess disease characteristics, modes of transmission, phenotypic characteristics of the bacterium, and fish-marketing policy. The clonal nature of 19 isolates was studied by biotyping, pulsed-field gel electrophoresis, and restriction-fragment length polymorphism (RFLP) analysis of a PCR fragment. FINDINGS: During 1996-97, 62 cases of wound infection and bacteraemia occurred. 57 patients developed cellulitis, four had necrotising fasciitis, and one developed osteomyelitis. In all cases, the fish were cultivated in inland fish-ponds. In the summer of 1996, fish-pond managers initiated a new marketing policy, in which fish were sold alive instead of being packed in ice. Phenotypically, the isolates had five atypical biochemical test results. The isolates were non-typeable by pulsed-field gel electrophoresis, and all had the same PCR-RFLP pattern which had not been seen previously. INTERPRETATION: The cause of the outbreak was a new strain of V. vulnificus, classified as biogroup 3. A new fish-marketing policy that began in 1996 may have exposed susceptible people to the organism.

Adolescent↗

Evaluating supervised HAART in late-stage HIV among drug users: a preliminary report.

OBJECTIVE: To examine response to highly active antiretroviral therapy (HAART) among a sample of treatment-experienced patients in the late stage of human immunodeficiency virus (HIV) infection in residential health care facilities (RHCFs) in New York City facilities designated for HIV/AIDS (acquired immunodeficiency syndrome) when access and adherence are maximized. METHODS: Medical record review of 111 patients. RESULTS: Demographics were mean age 42 years; 58% male; 60% African-American; 31% Hispanic; 57% injection drug users (IDUs); 23% with history of dementia; 52% hepatitis C virus (HCV) antibody seropositive; 80% on HAART, of whom 18% had lipodystrophy. Of 88 patients on HAART, 52% had a decreased viral load (>1/2 log) versus 13% of 23 not on HAART (P<.05); a >1/2 log viral load increase was seen in 8% and 35%, respectively (P<.05). Those with viral load increase were more likely than those with stable/decreased viral load to be IDUs (71% vs. 64%) and to have HCV seropositivity (86% vs. 53%), even with similar initial CD4+ cell count, viral load, and follow-up time. CONCLUSION: In a predominantly minority IDU population who are treatment experienced, 50% of the patients successfully responded to treatment with supervised therapy. The RHCFs in New York City provide a unique opportunity to examine further factors associated with response to HAART in an environment in which medication administration and adherence are maximized and monitored carefully.

Adult↗

Identification of a Drosophila prolyl endopeptidase and analysis of its expression.

Prolyl endopeptidases (PEPs) are believed to be involved in the metabolism of neuropeptide hormones (reviewed in Mentlein [1988]). Genes encoding PEPs have been isolated from various species, but their expression patterns during development have not been determined. In this study, we isolated a gene encoding a predicted PEP from the fruitfly Drosophila melanogaster. The gene encodes a predicted 756-amino acid protein having extensive sequence similarity to human PEP. We demonstrated that the Drosophila gene (DPEP) is expressed in a spatially restricted pattern in imaginal discs and the larval brain. Our results suggest a role for DPEP in the regional specification of larval tissues. They also provide a starting point for a genetic analysis of the function of this enzyme during development.

Amino Acid Sequence↗

Hedgehog activates the EGF receptor pathway during Drosophila head development.

The Hedgehog (Hh) and Epidermal growth factor receptor (EGFR) signaling pathways play critical roles in pattern formation and cell proliferation in invertebrates and vertebrates. In this study, we demonstrate a direct link between these two pathways in Drosophila melanogaster. Hh and EGFR signaling are each required for the formation of a specific region of the head of the adult fruitfly. We show that hh and vein (vn), which encodes a ligand of the Drosophila EGFR (Schnepp, B., Grumbling, G., Donaldson, T. and Simcox, A. (1996) Genes Dev. 10, 2302-13), are expressed in adjacent domains within the imaginal primordium of this region. Using loss- and gain-of-function approaches, we demonstrate that Hh activates vn expression. We also show that Hh activation of vn is mediated through the gene cubitus interruptus (ci) and that this activation requires the C-terminal region of the Ci protein. Finally, we demonstrate that wingless (wg) represses vn expression, thereby limiting the domain of EGFR signaling.

Animals↗

[Empirical treatment of urinary tract infections in the delivery room--findings and desires].

Urinary tract infection (UTI) is the most common bacterial infection during pregnancy. In prenatal and delivery wards treatment is usually started at once in pregnant women with symptoms suggesting UTI, but there is no uniformity as to treatment. We surveyed such treatment in the delivery rooms throughout Israel, and whether the treatment differed in simple cystitis as opposed to pyelonephritis. Results of positive urine cultures from symptomatic parturients admitted here during 1995-1996 were examined. There were 17 different empiric treatment protocols in 28 delivery rooms, whose daily cost ranged from 1-119 NIS. We present the antimicrobial sensitivity of 156 bacteria isolated from the urinary cultures from pregnant women in our prenatal ward. Based upon urinary flora, sensitivity and daily cost, we suggest a protocol for empiric treatment. We recommend first and second generation cephalosporins for treatment of simple lower (UTIs), while gentamicin is suggested for treatment of clinical pyelonephritis during pregnancy. There is no medical nor economic justification for the multiplicity of empiric treatment protocols currently used. Considering our results, our protocol is cost-effective for the empiric treatment of UTI in hospitalized parturients and in the community as well.

Anti-Bacterial Agents↗

Ectopic orthodenticle expression alters segment polarity gene expression but not head segment identity in the Drosophila embryo.

The cephalic gap genes specify anterior head development in the Drosophila embryo. However, the mechanisms of action of these genes remain poorly understood. Here, we focused on the cephalic gap gene orthodenticle (otd), which establishes a specific region of the anterior head. It has been proposed that otd acts in a combinatorial fashion with the cephalic gap genes empty spiracles (ems) and buttonhead (btd) to assign segmental identities in this region. To test this model, we used a heat-inducible transgene to generate pulses of ubiquitous otd expression during embryonic development. Ectopic otd expression caused significant defects in head formation, including the duplication of sensory structures derived from otd-dependent segments. However, these defects do not appear to result from the transformation of head segment identities predicted by the combinatorial model. Instead, they correlate with specific regulatory effects of otd on the expression of the segment polarity genes engrailed (en) and wingless (wg). Ectopic otd expression also caused the loss of head structures derived from the maxillary segment, which lies posterior to the otd domain. We show that this effect is associated with otd repression of the homeotic selector gene Deformed (Dfd).

Animals↗

Developmental rescue of Drosophila cephalic defects by the human Otx genes.

The molecular mechanisms of head development are a central question in vertebrate and invertebrate developmental biology. The anteriorly expressed homeobox gene otd in Drosophila and its homolog Otx in mouse are required for the early development of the most anterior part of the body, suggesting that a fundamental genetic program of cephalic development might be conserved between vertebrates and invertebrates. We have examined this hypothesis by introducing the human Otx genes into flies. By inducing expression of the human Otx homologs with a heat shock promoter, we found that both Otx1 and Otx2 functionally complement the cephalic defects of a fly otd mutant through specific activation and inactivation of downstream genes. Combined with previous morphological studies, these results are consistent with the view that a common molecular ground plan of cephalization was invented before the diversification of the protostome and the deuterostome in the course of metazoan evolution.

Amino Acid Sequence↗

A homologue of the calcium-binding disulfide isomerase CaBP1 is expressed in the developing CNS of Drosophila melanogaster.

Previous studies identified a group of proteins localized to the endoplasmic reticulum (ER) that bind calcium and direct protein folding. Three of these proteins, CaBP1, CaBP2, and protein disulfide isomerase, have been purified from rat microsomes and analyzed biochemically. However, their function in vivo has not been determined. Here, we report the isolation of a homologue of the CaBP1 gene from the fruitfly Drosophila melanogaster (DmCaBP1). The predicted sequence of the Drosophila protein is very similar to that of rat CaBP1 and retains motifs thought to be functionally important in the mammalian protein. We show that DmCaBP1 is expressed in a specific spatiotemporal pattern during embryogenesis. In particular, it is expressed in midline precursor cells in the developing CNS. This is the first demonstration of tissue-specific expression for a member of this group of ER proteins and suggests a possible role for DmCABP1 as a molecular chaperone involved in nervous system development. The identification of the DmCaBP1 gene provides a basis for future genetic studies of its function.

Amino Acid Sequence↗

Community-acquired urinary tract infection in adults: a hospital viewpoint.

The clinical and epidemiologic spectrum of 175 cases of community-acquired urinary tract infection (UTI) were evaluated at a university hospital. Patients were grouped in five different categories of which complicated UTI was the most common (39%). Bacteraemia was detected in eight patients (18%) of this group and in five (12%) with acute uncomplicated pyelonephritis. A single organism was isolated in 166 cases (95%). The rate of Escherichia coli bacteriuria ranged from 60% (asymptomatic bacteriuria) to 94% (uncomplicated cystitis). Of the 184 isolates, 92% were susceptible to ciprofloxacin and significantly high rates of resistance were found for ampicillin, cefazolin, cefuroxime, and co-trimoxazole. Isolates causing uncomplicated UTI had significantly high rates of resistance to ampicillin, amoxycillin-clavulanate and co-trimoxazole and those causing complicated UTI, had significantly high rates of resistance to most oral antibiotics tested, except quinolones and nitrofurantoine. Community-acquired UTI requiring hospital evaluation occurs in a complex group of patients, and current patterns of antibiotic resistance make it difficult to suggest empiric oral treatments in this setting.

Acute Disease↗