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Biomedical subjects

Y Schlesinger

Publications and source records attributed to Y Schlesinger.

At least 37 records · Page 2Linked to original sources

MR imaging of herpes simplex type 1 encephalitis in infants and young children: a separate pattern of findings.

OBJECTIVE: We sought to identify the initial MR findings of herpes simplex encephalitis in infants and young children. CONCLUSION: MR imaging findings of herpes encephalitis in infants and young children appear to differ from those seen in neonates, older children, and adults. Appreciation of this MR imaging pattern coupled with a strong clinical suspicion of herpes helps to ensure the correct diagnosis is made.

Brain↗

Cefuroxime utilization evaluation: impact of physician education on prescribing patterns.

BACKGROUND: Cefuroxime is a second-generation cephalosporin antibiotic used widely for the treatment of various infections. OBJECTIVES: To assess the appropriateness of cefuroxime usage as well as the long-term impact of re-feeding the results to prescribing physicians. METHODS: Drug utilization evaluation involved three data-collecting periods, each comprising 6 weeks, during which all patients receiving cefuroxime were evaluated. Results of phase I were distributed to all physicians in a newsletter and departmental lectures; phase II was announced and conducted 6 months later. An identical phase III was unannounced and conducted one year after phase II. The study included all patients receiving cefuroxime during the three phases. The main outcome measure was appropriateness of initiation, and continuation beyond 3 days, of empirical treatment. Appropriateness was determined according to a prepared list of indications based on the literature and the hospital's protocols. RESULTS: Cefuroxime was initiated appropriately in 104 of 134 patients (78%) in phase I, in 85 of 100 (85%) in phase II, and in 93 of 100 (93%) in phase III (P < 0.001). Cefuroxime was continued appropriately after 3 days in 58/134 (43%), 57/100 (57%) and 70/100 (70%) respectively (P < 0.001). The total number of appropriate treatment days out of all treatment days increased from 516 of 635 (81%) in phase I, to 450 of 510 (88%) in phase II, to 485 of 509 (95%) in phase III (P < 0.001). The principal reason for cefuroxime usage was community-acquired respiratory tract infection. CONCLUSION: Drug utilization evaluation may provide valuable data on the usage of a particular drug. This information, once re-fed to physicians, may improve utilization of the particular drug. This positive effect may be prolonged beyond the immediate period of observation.

Cefuroxime↗

Novel human gene transfer vectors: evaluation of wild-type and recombinant animal adenoviruses in human-derived cells.

Major disadvantages of human adenovirus (hAd) vectors in gene therapy include preexisting or induced immune responses, and possible coreplication of recombinant hAd in the presence of wild-type hAds. These disadvantages may be overcome by using nonhuman, animal adenoviruses (aAds). We evaluated four different aAds for their potential use as viral vectors. The canine adenovirus type 2 (CAV2) and bovine adenovirus type 3 (BAV3) appeared to be suitable systems, as they infect human cells. CAV2, but not BAV3, caused cytotoxicity, and only limited (CAV2) or no (BAV3) production of infectious virus particles was observed after infection of human cell lines. CAV2 showed higher expression of endogenous genes than did BAV3 in the tested human cells. No interference between hAd and CAV2 or BAV3, such as recombination of DNA or cross-activation of virus replication, was observed in up to five passages in double-infected human cells. Transfection of cloned genomic CAV2 or BAV3 DNA into appropriate permissive cell lines rescued infectious virus. Furthermore, we produced a recombinant E1-deleted BAV3, and showed that it could infect and express a reporter gene in various human cell types. The goal was to construct and evaluate recombinant (E1-deleted) animal adenoviruses (aAds) as new vector systems for human gene therapy. The rationale for developing aAds for human use is the potential higher safety and efficiency, as compared with human adenoviruses (hAds). Coreplication and recombination with preexisting hAds should not be possible owing to lack of homology, and preexisting immunity in the general population should be limited. Of the four aAds we evaluated, BAV3 appeared to be the best candidate. It infects human cells without showing growth or cytotoxic effects, viral gene expression was barely detectable, and no trans-activation of either virus was detected in coinfections with hAd5. Rescue of virus in permissive cells, from plasmids containing the CAV2 or BAV3 genome, confirmed our approach. Furthermore, an E1-deleted recombinant BAV3 was constructed and shown to transduce and express the lacZ reporter gene in human cells.

Adenoviridae↗

In-vitro activity of cefepime and other broad-spectrum antimicrobials against several groups of gram-negative bacilli and Staphylococcus aureus.

The in vitro activity of cefepime was compared with that of amikacin, ceftazidime, imipenem, ciprofloxacin, and piperacillin-tazobactam by using the E-test against five groups of carefully selected organisms: Klebsiella pneumoniae (68 isololates), Pseudomonas aeruginosa (62), methicillin-susceptible Staphylococcus aureus (MSSA) (60), and two groups of Enterobacteriaceae (60 and 62 isolates, respectively). The bacteria were subdivided according to whether the infection was nosocomial or community-acquired, applying accepted and predefined criteria. These isolates were obtained from patients admitted to our medical center throughout 1998. We retrospectively compared antimicrobial susceptibilities of the study sample with those of the +/- 3000 bacterial strains isolated from blood stream infections since 1990: the study sample appeared to represent adequately the clinical databank. Presence of extended-spectrum beta-lactamase (ESBL) was determined in all groups of Enterobacteriaceae with the ESBL screening E-test strip. Of the 252 Gram-negative bacilli tested, 242 (96%) were susceptible to cefepime, whereas only 168 (67%) were susceptible to ceftazidime, 211 (84%) to amikacin, and 220 (87%) to piperacillin-tazobactam (p < 0.001). Imipenem was slightly superior to cefepime with only seven isolates resistant (3%), six of which were P. aeruginosa. Cefepime was more active against Enterobacteriaceae than ceftazidime (93% vs. 72%, p < 0.001). This superiority was most evident against nosocomial strains of K. pneumoniae, against which cefepime was > three times more active than ceftazidime. The high level of resistance seen in nosocomial isolates of K. pneumoniae is consistent with high rates of ESBL production (69%, compared with 15-26% in other Enterobacteriaceae). The MIC90 of cefepime to methicillin-sensitive S. aureus was 1.5 micrograms/mL, whereas that of ceftazidime was 4 micrograms/mL; the susceptibility rate of both was 100%. In conclusion, cefepime possesses in vitro potencies against MSSA and current clinical strains of Gram-negative bacilli, many of which harbor resistance to other antimicrobial agents. Hence, it seems very suitable for empiric coverage of serious nosocomial infections.

Cefepime↗

Cost-effectiveness of blood cultures for adult patients with cellulitis.

To assess the cost-effectiveness of blood cultures for patients with cellulitis, a retrospective review was conducted of clinical and microbiological data for all 757 patients admitted to a medical center because of community-acquired cellulitis during a 41-month period. Blood cultures were performed for 553 patients (73%); there were a total of 710 blood samples (i.e., a mean of 1.3 cultures were performed per patient). In only 11 cases (2.0%) was a significant patient-specific microbial strain isolated, mainly beta-hemolytic streptococci (8 patients [73%]). An organism that was considered a contaminant was isolated from an additional 20 culture bottles (3. 6%). The cost of laboratory workup of the 710 culture sets was $36, 050. Isolation of streptococci led to a change from empirical treatment with cefazolin to penicillin therapy for 8 patients. All patients recovered. In conclusion, the yield of blood cultures is very low, has a marginal impact on clinical management, and does not appear to be cost-effective for most patients with cellulitis.

Adolescent↗

Surveillance of antimicrobial prophylaxis for surgical procedures.

OBJECTIVE: To assess the practice of antimicrobial prophylaxis for surgical procedures in eight surgical departments in a 550-bed teaching hospital. METHODS: A list of all major procedures performed in our hospital, with recommendations for prophylaxis based upon the literature, has been distributed since 1993 and is updated periodically. The practice of surgical prophylaxis between January 1 and March 31, 1996, was examined by assessing four variables: (1) Did the particular procedure justify prophylaxis, and was it provided? (2) Was timing optimal, ie, within 1 hour prior to surgery? (3) Was the appropriate antimicrobial selected? (4) Was duration optimal, ie, < or =24 hours? RESULTS: During the study period, 2,117 operations were performed, of which 1,631 (77%) were reviewed. Sixty-six percent were clean surgery, 28% clean-contaminated, and 6% contaminated; 72% of procedures were elective, 28% emergencies. Of 1,631 operations requiring prophylaxis, 1,142 (70%) received it, 489 (30%) did not. Of 1,631 patients, 1,392 (85%) received appropriate care: 929 (67%) appropriately received prophylaxis, and 463 (33%) appropriately did not receive prophylaxis. Of 955 patients who received prophylaxis, 26 (3%) did so inappropriately. Of 1,142 patients who should have received prophylaxis, 213 (19%) did not receive it. Female gender, clean surgery, elective operations, and infrequently performed procedures were all significant indicators of inappropriately withheld prophylaxis (P<.001). In addition, the rate of appropriately provided prophylaxis varied between departments from 71% to 97% (P<.001). Assessment of the 929 procedures for which prophylaxis was justified and given revealed that 100% of patients received it on time, the choice of antimicrobial was appropriate in 95% of cases, and duration was < or =24 hours in 91%. CONCLUSIONS: Audits of surgical prophylaxis are expected to detect different errors in different institutions. Conducting audits of surgical prophylaxis probably should be part of the routine activity of infection control teams. Feeding the information back to surgeons could improve adherence to recommended guidelines and might contribute to reduced wound infection rates.

Adult↗

Fiberless recombinant adenoviruses: virus maturation and infectivity in the absence of fiber.

In vivo targeting of therapeutic genes to specific tissues has become a major issue in gene therapy, in particular when recombinant adenovirus vectors are used. Restriction of the viral tropism to selected cell types requires the abrogation of the interaction between the viral fiber and its natural cellular receptors and the introduction of a new binding specificity into the virion. In this context, fiberless adenoviruses are attractive vectors, since they may be used as substrates for the insertion of a new ligand in other capsid proteins. In this study, we confirm by using cloned full-length adenovirus genomes with the fiber gene deleted that efficient virus particle formation can occur in the absence of fiber. As expected, the infectivity of such fiberless viruses was severely reduced, but it could be only partially restored when the viruses were produced in cells stably providing the fiber in trans. Although incorporation of penton base into the fiberless particles was normal and binding of the particles to the cellular integrins was functional, several pieces of experimental evidence suggest that later steps in the cell entry process are impaired in correlation with an incorrect maturation of several structural proteins of the fiberless particles. These observations support the hypothesis that the fiber protein may have additional biological functions besides its role in cell binding. Together with the fiber complementation cells, such fiberless vectors constitute unique tools to investigate the role of the fiber in virus assembly, maturation, and cell entry and to explore the possibility of deriving gene transfer vectors with novel target specificities.

Adenoviruses, Human↗

Fatal pneumococcal sepsis following flexible bronchoscopy in an immunocompromised infant.

A 5-month-old boy who suffered from a leukocyte chemotactic defect underwent flexible bronchoscopy for persistent right upper lobe atelectasis and tachypnea. Ten hours after the procedure he developed fulminant sepsis, and he died 16 hrs after bronchoscopy. Streptococcus pneumoniae (serotype 23) grew from the bronchoalveolar lavage fluid and from the blood culture taken during the sepsis work-up. We, therefore, suggest administering prophylactic antimicrobial therapy immediately following bronchoscopy to immunosuppressed children, even when an acute respiratory infection is not suspected, in order to prevent bacteremia and sepsis.

Bronchoscopy↗

Infective endocarditis due to Stenotrophomonas (Xanthomonas) maltophilia.

Stenotrophomonas maltophilia (formerly Xanthomonas maltophilia) is a gram-negative bacillus increasingly associated with serious nosocomial infections. Here, the case of a 69-year-old female patient who developed prosthetic valve endocarditis associated with this organism is described. A review of the literature revealed only 18 previous reports; eight involved native valves, the remainder prosthetic valves. Most cases were associated with risk factors, including intravenous drug abuse (6 patients), infected intravenous lines (4 patients) or a recent invasive procedure (3 patients). The course of the disease appears to be indolent, but is otherwise similar to infective endocarditis associated with other gram-negative organisms. Antimicrobial therapy is complicated by multiple drug resistance of the organism; cotrimoxazole may be beneficial, if the isolate is susceptible, in combination with another agent. Five of nine (55%) patients who underwent valve replacement survived, as compared to three of seven (43%) who received antibiotic therapy only. Hence, surgery is not essential for survival in every case and depends as much on the individual patient's course as on established criteria for valve replacement in prosthetic valve endocarditis.

Anti-Bacterial Agents↗

Analysis and impact of infectious disease consultations in a general hospital.

During an 18-month period, data from all patients in whose care our infectious diseases (ID) service was involved, were recorded in a computerized database. A total of 4184 new consultations was recorded. The consultations were solicited by the patients' physicians in 3326 cases (80%) and initiated by the ID service in the remainder. The purpose of the consultations was diagnosis (14%), therapy (39%), both diagnosis and therapy (40%), and prophylaxis (6%). Two thousand and ninety-four consultations (50%) were performed at the bedside, and the others by personal or telephone discussion. ID consultation was given in more than 10% of admitted patients in six departments, 46% of the admissions in the ICU, and 6.9/100 hospitalized patients. Recommendations included: antibiotic manipulation (i.e., initiation, change or discontinuation of antibiotic treatment) (51%); performance of tests (13%); performance of diagnostic or therapeutic procedures (5%); prophylaxis (4%) or no change in management (26%). Analysis of the solicited vs unsolicited consultations and of the bedside vs telephone consultations revealed that sub-groups of consultations differ significantly from each other in many aspects. Recording of consultations enables the ID service to evaluate its activity and to direct efforts to departments with high rates of infectious diseases and/or antimicrobial usage.

Communicable Diseases↗

Analysis of 5 years of bacteraemias: importance of stratification of microbial susceptibilities by source of patients.

Many factors need to be considered when selecting empiric antimicrobial treatment for infections; foremost are the principal pathogens causing the diagnosed infection and their antimicrobial susceptibility patterns. These susceptibilities are location specific. This study analyses blood cultures of a 5-year period (1990-94) at a 550 bed community hospital and stratifies antimicrobial susceptibilities by source of patients. Data included: date of culture, patient location, number of positive bottles with the same organism over a period of 2 weeks and results of susceptibility testing. Positive cultures from patients in the Emergency Department were deemed to reflect community-acquired strains: positive cultures from patients in the Intensive Care Unit were considered nosocomial organisms. During the study period 52055 blood cultures were drawn; 5652 (11%) from 2742 patients grew at least one organism, excluding skin contaminants. Organisms cultured most frequently were: Enterobacteriaceae: 1162 patients (42%); Staphylococcus aureus: 442 (16%); Enterococcus; 429 (16%); and Pseudomonas: 196 (7%). Antimicrobial susceptibility percentages of Enterobacteriaceae from Emergency Room patients (n = 370) were significantly greater to all tested antimicrobials than from ICC patients (n = 161) (P < 0.001). Overall, 143 isolates of S. aureus from 442 patients (32%) were methicillin resistant (MR); stratification by department revealed a range of 20/142 (14%) MR in community acquired strains to 49/67 (73%) from ICU patients (P < 0.001). Detailed tables with antimicrobial susceptibilities according to strains, and stratified by source of patients are presented. When selecting empiric antimicrobial therapy for patients with bacterial infections, it is crucially important to physicians to have access to antimicrobial susceptibility percentages, stratified by source of patients.

Anti-Bacterial Agents↗

Jewish responses to AIDS.

Theoretically, Judaism treats AIDS, an illness, with compassion. Yet because of its link to homosexuality, AIDS and its stigma are often concealed. Neither homosexuality nor AIDS can be fully concealed, even by those who most denounce them, nor can they be completely open, even by those who most fully accept them. The implications of rejection and acceptance (a continuum) are discussed. In spite of the biblical rejection of homosexuality, The Gay Synagogue offers the most meaningful support to those who suffer from AIDS and to their loved ones. Paradoxically, the most successful programs are those adhering to the formal religious practices which provide the basic structure to every Jewish synagogue.

Acquired Immunodeficiency Syndrome↗

Emergence of drug-resistant tuberculosis in Jerusalem: ten-year retrospective review.

Drug-resistant tuberculosis (TB) has emerged as a worldwide problem. The annual incidence of TB has increased in Israel in the last decade, mainly due to successive waves of immigration. Few data are available on drug-resistant TB in Israel A 10-year retrospective review was conducted on all patients who had been infected with culture-proven Mycobacterium tuberculosis and had been admitted to our hospital. Forty-seven patients had culture-positive TB; 27 (57%) were male, 20 (43%) were female; mean age (+/- SD) was 56 +/- 23 years. Twenty patients (43%) had pulmonary TB. Three patients (6.4%) had single-drug resistance; 4 patients (8.5%) had multi-drug resistance. Six of the seven patients (86%) with drug-resistant TB had been diagnosed after 1990. Six of the 20 patients (30%) with pulmonary TB had drug-resistant organisms. Six of the 7 patients (86%) with drug-resistant TB had pulmonary infection, as compared to 15/40 (37%) of the patients with drug-susceptible TB (p < 0.001). Six of the 7 patients (86%) with drug-resistant TB had a history of TB. Fifteen percent (14.9%) of all new cases diagnosed with TB in our hospital in the last 10 years had drug-resistant M. tuberculosis. Thirty percent of patients with pulmonary TB had drug-resistant organisms. Drug-resistant TB has evidently emerged in Israel and poses a serious clinical and social threat. A strong case for directly-observed treatment in Israel should be made, especially since the incidence of TB here is still small.

Adolescent↗

Epstein-Barr virus DNA in peripheral blood leukocytes of patients with posttransplant lymphoproliferative disease.

We tested the hypotheses that Epstein-Barr virus (EBV) DNA levels in peripheral blood leukocytes (PBL) of transplant recipients with posttransplant lymphoproliferative disease (PTLD) (1) exceed those of patients without PTLD, (2) rise with or before clinical detection of the disease, and (3) fall with effective therapy. Using the polymerase chain reaction (PCR) and an endpoint dilution technique, we compared EBV DNA levels in sequential specimens from 5 patients with PTLD, 16 solid organ transplant recipients without PTLD, and 5 young adults with primary infectious mononucleosis (IM), and in single specimens from 21 healthy seropositive subjects. EBV DNA levels in the first two groups rose with induction of immunosuppression despite prophylactic acyclovir. Markedly elevated levels of EBV DNA were seen in 4 of 5 patients with PTLD at or before clinical diagnosis. The peak levels in these patients exceeded those of transplant recipients without PTLD (P = 0.02) and healthy adults with IM (P = 0.02). EBV DNA levels fell dramatically with effective therapy. Four of 21 healthy seropositive subjects demonstrated low levels of EBV DNA, similar to levels seen late in the course of patients with IM. We conclude that a semiquantitative PCR assay for EBV DNA in PBL can assist in the detection of PTLD and in monitoring the effect of therapy.

Adolescent↗

Sequence analysis of the canine adenovirus 2 fiber-encoding gene.

The gene coding for the fiber protein (Fip) of canine adenovirus type 2 (CAV-2) has been cloned and sequenced. The putative protein has 80% sequence similarity with the CAV-1 Fip. The observed differences may contribute to the known differences in cell tropism and virulence of the two types of CAV.

Adenoviruses, Canine↗

Expanded spectrum of herpes simplex encephalitis in childhood.

We designed a polymerase chain reaction method to detect herpes simplex virus (HSV) DNA in spinal fluid from patients with encephalitis. The polymerase chain reaction amplified a 211 base-pair segment of the HSV DNA polymerase gene. Applying this method, we diagnosed HSV type 1 infection in three young children, aged 7 to 13 months, who had atypical forms of the illness. On the basis of magnetic resonance imaging, their disease was diffuse or multifocal in two cases and, in all three, lacked the temporal lobe involvement considered characteristic of HSV encephalitis beyond the neonatal period. Most of the diffuse or multifocal abnormalities detected by magnetic resonance imaging were not apparent by computed tomography. Restriction enzyme analysis of the polymerase chain reaction products from all three patients indicated that their disease was caused by HSV type 1. We conclude that in preschool-age children beyond the neonatal period, the spectrum of HSV encephalitis includes multifocal or diffuse involvement of the brain, which may be detected most efficiently by magnetic resonance imaging. The polymerase chain reaction method has the potential for providing an early diagnosis, but further studies are required to define the sensitivity and specificity of the polymerase chain reaction before it can be used for routine clinical decision making.

Antibodies, Viral↗

Herpes simplex virus type 2 meningitis in the absence of genital lesions: improved recognition with use of the polymerase chain reaction.

Herpes simplex virus type 2 (HSV-2) is known to cause aseptic meningitis, which can be recurrent. The diagnosis of HSV-2 infection is suggested when meningitis occurs simultaneously with genital lesions but may be obscure if genital lesions are not present or are not appreciated. Viral culture of the CSF is sometimes positive, but it may also be negative, especially in cases of recurrent disease. We report three cases of HSV meningitis in young women who did not have a history of genital herpetic lesions and for whom genital lesions were not noted on presentation. With use of the polymerase chain reaction (PCR), HSV DNA was detected in CSF from all three patients. The diagnosis of HSV meningitis was further confirmed by a positive culture of CSF in one patient's case and by demonstration of intrathecal synthesis of HSV antibodies in a second patient's case. The use of PCR can improve the recognition of HSV meningitis in adults presenting with aseptic meningitis, even in the absence of herpetic lesions.

Adult↗