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Biomedical subjects

R Raz

Publications and source records attributed to R Raz.

At least 73 records · Page 4Linked to original sources

Pneumococcal bacteremia in hospitalized Israeli adults: epidemiology and resistance to penicillin. Israeli Adult Pneumococcal Bacteremia Group.

In April 1993 a national survey of pneumococcal bacteremia in hospitalized Israeli adults was started, and this survey covered 23 of the 24 Israeli medical centers. During the first 2 years, 603 episodes of pneumococcal bacteremia were recorded. The overall annual incidence of pneumococcal bacteremia in Israeli adults was 14.5 episodes per 100,000 inhabitants, and the overall mortality rate was 27.8%. Pneumonia was the source of bacteremia in 70.8% of cases, primary bacteremia was the source in 17.5%, meningitis was the source in 7.5%, and otitis media/sinusitis was the source in 4.2%. Of the 258 pneumococcal isolates for which an MIC was determined, 88.8% were susceptible to penicillin, 9.3% were partially resistant, and only 1.9% were highly resistant. Twenty-four serogroups were identified from 398 strains tested. The highest percentage of penicillin-resistant strains belonged to serogroups 23, 19, 9, 4, and 6. Although only 13 of these 24 serogroups correspond to the serotypes included in the 23-valent pneumococcal vaccine, they accounted for 94% of all isolates.

Adolescent↗

Safety and immunogenicity of a novel mammalian cell-derived recombinant hepatitis B vaccine containing Pre-S1 and Pre-S2 antigens in neonates.

BACKGROUND: Most of the licensed hepatitis B vaccines produced by recombinant DNA contain the S protein component of the hepatitis B virus surface antigen particle but lack two important components, Pre-S1 and Pre-S2. These components have recently been shown to play an important immunogenic role by enhancing the hepatitis B surface antibody (anti-HBs) titers, stimulating response and circumventing genetic nonresponsiveness. OBJECTIVE: To assess safety, tolerability and immunogenicity in neonates of a novel recombinant HBV vaccine (Bio-Hep-B) containing the S, Pre-S1 and Pre-S2 components compared with a licensed recombinant vaccine (Engerix-B) containing the S component only. METHODS: Healthy neonates were randomized to receive either Bio-Hep-B (2.5 micrograms/dose) or Engerix-B (10 micrograms/dose) at ages < 24 h, 1 month and 6 months. Blood was obtained at ages 0, 1, 7 and 12 months. Tolerability was assessed by diary cards filled by the parents for 5 successive days after immunization. Immunogenicity was assessed by determination of anti-HBs antibody. RESULTS: Of 205 neonates 153 were in the Bio-Hep-B group and 52 were in the Engerix-B group. Both vaccines were well-tolerated and all infants became seroprotected (anti-HBs > 10 mIU/ml). After the first dose a significantly higher proportion of neonates seroconverted in the Bio-Hep-B group than in the Engerix-B group (83% vs. 34%; P < 0.001); this difference in seroresponse was even more pronounced for those achieving seroprotective concentrations (> 10.0 mIU/ml) after the first dose: 54% vs. 7%, respectively (P < 0.001). Geometric mean concentrations were significantly higher at all points in the Bio-Hep-B group. CONCLUSION: Both vaccines were well-tolerated and immunogenic. Bio-Hep-B, despite its low dose, was significantly more immunogenic and elicited more rapid antibody response. This finding has implication for future vaccine programs in regions where maternal screening for hepatitis B virus surface antigen and administration of hepatitis B immunoglobulin are not routinely practiced at birth for infants of hepatitis B virus carrier mothers.

Female↗

Cost-minimisation analysis of sequential treatment with ofloxacin or ciprofloxacin in hospitalised patients.

This study evaluated the cost of sequential treatment with once-daily ofloxacin or twice-daily ciprofloxacin in 474 hospitalised patients in different countries. The patients were treated intravenously for at least 3 days, then orally for 7 to 10 days or for 3 days beyond the disappearance of infection-related symptoms. The overall clinical cure rate (86.8% with ofloxacin and 89.6% with ciprofloxacin) and the overall bacteriological response rate (89.9 and 89.0%, respectively) were similar, and a cost-minimisation analysis was conducted. The acquisition costs for ofloxacin and ciprofloxacin in Greece, Israel, Slovenia and Turkey were used and converted to Deutschmarks (DM), and the costs of administration were analysed for each hospital. The different cost categories for oral and intravenous (IV) treatment (e.g. antimicrobial acquisition, drug monitoring, drug delivery costs) were used to identify any differences. The total costs per patient varied between the countries involved, but were higher for ciprofloxacin (ofloxacin: DM239 to DM724; ciprofloxacin: DM540 to DM976). In a sensitivity analysis using identical daily acquisition costs for the 2 fluoroquinolones, the total cost of treatment was higher for ciprofloxacin, as a result of the lower cost of administration of ofloxacin in the once-daily regimen. Continuing IV therapy would be approximately 50% more expensive than switching to oral administration; however, whenever possible, both drugs can be switched from IV to oral treatment.

Anti-Infective Agents↗

A 1-year trial of nasal mupirocin in the prevention of recurrent staphylococcal nasal colonization and skin infection.

BACKGROUND: The usefulness of nasal mupirocin in preventing recurrent staphylococcal nasal colonization and skin infection has been examined in immunodeficient patients and in healthy staphylococcal carriers but not in immunocompetent staphylococcal carriers who experience recurrent skin infections. We studied 34 such patients. METHODS: After an initial 5-day course of nasal mupirocin ointment for all patients, 17 patients continued to apply a 5-day course of nasal mupirocin every month for 1 year, and the other 17 patients applied a placebo ointment. Nasal cultures were obtained monthly, and all episodes of skin infection were recorded. RESULTS: The overall number of positive nasal cultures was 22 in the mupirocin group and 83 in the placebo group (P < .001), and the number of skin infections was 26 and 62, respectively (P < .002). Eight of the 17 mupirocin-treated patients but only 2 in the placebo group remained free of positive staphylococcal nasal cultures. One of the 10 patients who were free of colonization during the 12-month treatment period had skin infections, in contrast to all 24 of the patients with positive cultures (P < .01). Staphylococci resistant to mupirocin were observed in 1 patient. No adverse effects were reported. CONCLUSIONS: A monthly application of mupirocin ointment in staphylococcal carriers reduces the incidence of nasal colonization, which in turn lowers the risk of skin infection.

Administration, Topical↗

Two rules for early prediction of bacteremia: testing in a university and a community hospital.

BACKGROUND: Two rules (model 1 and model 2) were previously derived and prospectively validated at the same institution to predict the likelihood of bacteremia. The objective of the present study was to test and compare the performance of the rules in patients admitted to two sites of inpatient care: a university hospital and a community hospital. METHODS: Clinical and laboratory data (including the variables contained in the two models) were collected within 24 hours in all patients admitted to the Department of Medicine of the Beilinson Medical Center, a university hospital in central Israel, and Emek Hospital, a community hospital in northern Israel, because of an acute infectious disease. The scores of the models were compared with the results of blood cultures. RESULTS: The percentage of bacteremia was 15% in the university and 18.5% in the community hospital. The area under the receiver-operating characteristic curve was 0.56 + or - 0.04 SE for model 1, and 0.67 + or - 0.04 SE for model 2 in the university hospital; and 0.59 + or - 0.05 SE versus 0.63 + or - 0.04 SE, respectively, in the community hospital. At the best calibration, model 1 defined low-risk groups of 205 patients in the university hospital, and 66 patients in the community hospital, with prevalences of bacteremia of 13% and 15%. The high-risk groups defined by model 1 had prevalences of 30% and 32%. Model 2 defined low-risk groups with prevalences of bacteremia of 7% (8 of 114) and 8% (6 of 76); and high-risk groups with percentages of 29% and 38%. CONCLUSIONS: The overall accuracy of the two models deteriorated significantly. Both models defined groups at high risk of bacteremia, but the percentages of bacteremia and of death in the low-risk groups do not encourage withholding blood cultures in these patients. The failure of the two models points toward the need for external validation, and for monitoring performance of prediction models over time.

Adolescent↗

Safety and immunogenicity of a novel mammalian cell-derived recombinant hepatitis B vaccine containing Pre-S1 and Pre-S2 antigens in children.

We tested the safety and immunogenicity of the new recombinant hepatitis B virus (HBV) vaccine produced via expression of the Pre-S1, Pre-S2 and S protein components of the hepatitis B surface antigen (HBsAg). A reduced dose (2.5 micrograms) of the vaccine (Bio-Hep-B) was tested in children aged 4-9 years and was compared to a 10 microgram dose of a licensed vaccine (Engerix-B) in a randomized manner. Both vaccines were administered in 3 doses (0, 1 and 6 month intervals). Adverse events were collected 5 days following each vaccination by a diary card provided to the parents. Immunogenicity was tested by measuring anti-hepatitis B surface antibody (anti-HBs). A total of 217 children were enrolled (162 in the Bio-Hep-B group and 55 in the Engerix-B group). Total adverse events were observed in 35% of the Bio-Hep-B group and 33% of the Engerix-B group, with no differences when each of the potential adverse events was considered. Titers were within the expected range (geometric mean titers post dose 1, 2 and 3 were 45.8, 8360.2 and 1445.7, respectively, for Bio-Hep-B and 36.3, 10316.1 and 1898.7, respectively, for Engerix-B). A trend toward better immunogenicity with Bio-Hep-B was observed at early visits when measured by both seroconversion (anti-HBs > or = 2.1 mIU ml-1) rate and seroprotection (anti-HBs > or = 10 mIU ml-1) rate; however, statistical significance was not reached. We conclude that in children, Bio-Hep-B vaccine at a reduced dose was as safe and as immunogenic as Engerix-B given at the regular pediatric dosage.

Child↗

Activation of the JAK-STAT signal transduction pathway by oncostatin-M cultured human and mouse osteoblastic cells.

Oncastatin M (OSM) is one member of the leukemia inhibitory factor/interleukin-6 family of cytokines that has been shown to be a growth regulatory molecule. In osteoblastic cultures, OSM causes marked phenotypic changes and the enhanced secretion of interleukin-6. In this study, we have shown that stimulation of murine and human osteoblastic cultures and a human osteosarcoma cell line with OSM resulted in the tyrosine phosphorylation of a number of cellular proteins including members of both the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) family of signaling proteins. The JAKs, a family of intracellular kinases, and the STATs, a family of transcription factors, have both previously been shown to be tyrosine phosphorylated and activated in response to various cytokines, interferons, and growth factors in cells of non-skeletal origin. Using three different sources of cells of the osteoblast lineage, we demonstrate that OSM induces a rapid but transient tyrosine phosphorylation of the three JAK family members tested, JAK1, JAK2 and Tyk2. In addition, two members of the STAT family, Stat1alpha and Stat3, are tyrosine phosphorylated in osteoblastic cells in culture in response to OSM. OSM activation of this pathway in cells of the osteoblast lineage will result in the transcription of specific genes that ultimately may be associated with osteoblast function.

Animals↗

Molecular analysis of a putative transposable retroelement from the Zea genus with internal clusters of tandem repeats.

The molecular characterization of a recently discovered family of long repetitive sequences, termed ZLRS, is described. These elements belong to the class of moderate dispersed repetitive DNA and are specific to the Zea genus. An 8089-bp sequence from a Zea diploperennis ZLRS element have been elucidated. Sequence analysis reveals the presence of a long terminal repeat-like region, two clusters of different tandem repeats and several ORFs. On these grounds, ZLRS could be considered a new member of the superfamily of transposable retroelements. Tandems are present in the majority of ZLRS elements, they show an important stem-loop secondary structure predicted by the computer and their sequence conservation suggests a functional role.

Amino Acid Sequence↗

Activation of acute phase response factor (APRF)/Stat3 transcription factor by growth hormone.

The mechanism by which the binding of growth hormone (GH) to its cell surface receptor elicits changes in gene transcription are largely unknown. The transcription factor Stat1/p91 has been shown to be activated by GH. Here we show that acute phase response factor or Stat3 f1p4an antigenically related protein), is also activated by GH. Stat3 has been implicated in the interleukin-6-dependent induction of acute phase response genes. GH promotes in 3T3-F442A fibroblasts the tyrosyl phosphorylation of a protein immunoprecipitated by antibodies to Stat3. This protein co-migrates with a tyrosyl phosphorylated protein from cells treated with leukemia inhibitory factor, a cytokine known to activate Stat3. Tyrosyl phosphorylated Stat3 is also observed in response to interferon-gamma. Stat3 is present in GH-inducible DNA-binding complexes that bind the sis-inducible element in the c-fos promoter and the acute phase response element in the alpha 2-macroglobulin promoter. The ability of GH to activate both Stat1 and Stat3 (i.e. increase their tyrosyl phosphorylation and ability to bind to DNA) suggests that gene regulation by GH involves multiple Stat proteins. Shared transcription factors among hormones and cytokines that activate JAK kinases provide an explanation for shared responses, while the ability of the different ligands to differentially recruit various Stat family members suggests mechanisms by which specificity in gene regulation could be achieved.

3T3 Cells↗

Cytoplasmic transcription factors: mediators of cytokine signaling.

The distinct pattern of transcriptional responses of cells to different extracellular signals requires a signal transduction pathway that provides rapid, accurate, and faithful transmission of information from the cell surface to the nucleus. One mechanism exploited by many cytokines, exemplified by interferons (IFN) but also used by many interleukins and growth factors, uses a family of cytoplasmic transcription factors that are activated by tyrosine phosphorylation. Once phosphorylated by receptor-associated tyrosine kinases, these proteins assemble into multimeric transcription factors, translocate to the nucleus, and bind specific DNA sequence elements in the promoters of target genes.

Cytokines↗

Double-blind randomized study of 1 g versus 2 g intravenous ceftriaxone daily in the therapy of community-acquired infections.

In a multicentre, double-blind, randomized study involving four general hospitals in Israel, the efficacy and safety of ceftriaxone 1 g/day i.v. was compared to that of 2 g/day i.v. in the treatment of moderate to severe community-acquired infections requiring hospitalization. Two hundred and twenty-two patients were enrolled; 112 received intravenous ceftriaxone 1 g/day, and 110 received 2 g/day. The two groups were matched demographically, and their mean APACHE II score (10 points) and mean duration of successful therapy (7 days) were identical. The sites of infection in the 1 g and 2 g groups respectively were lower respiratory tract in 57 versus 51 patients, urinary tract in 31 versus 40 patients, and soft tissue in 24 versus 19 patients. There were no significant differences in clinical outcome between the 1 g and 2 g groups, the outcome being cure in 91% versus 86% of patients, improvement in 3% versus 3% of patients, failure in 3% versus 8% of patients, and relapse in 3% versus 3% of patients. The findings of this study indicate that ceftriaxone 1 g/day is as effective as 2 g/day in the treatment of moderate to severe community-acquired infections. The low-dose form is a more economical means of treating these infections.

Adult↗

Intravenous administration of gentamicin once daily versus thrice daily in adults.

The efficacy and safety of intravenous gentamicin administered once daily versus thrice daily was evaluated in adults. Patients over 16 years of age with a suspected or documented gram-negative infection were randomly divided into two groups: one group received gentamicin intravenously 4.5 mg/kg once daily (n = 48), and the other received 1.5 mg/kg every eight hours (n = 52). Baseline characteristics were comparable in the two groups. The mean peak level of gentamicin in the once daily group was significantly higher than that in the thrice daily group, 8.7 +/- 2.3 mg/l versus 4.6 +/- 1.2 mg/l (p < 0.005), and the trough level lower, 0.7 +/- 0.3 mg/l versus 1.1 +/- 0.9 mg/l (p < 0.005). The clinical cure rate was significantly higher in the once daily group, 42 of 48 (87.5%) versus 36 of 52 (69.2%). The microbiological cure rate was also better in the once daily group than in the thrice daily group (31 of 36 versus 28 of 38 patients evaluated), although this difference was insignificant. Nephrotoxicity was not observed in either group, but ototoxicity was present in three of the patients treated thrice daily. A once daily dosing regimen of gentamicin is more effective and less ototoxic than a thrice daily regimen.

Adolescent↗

Three distinct loci on human chromosome 21 contribute to interferon-alpha/beta responsiveness.

The species specificity of interferons (IFNs) depends on restricted recognition of these ligands by multisubunit cell surface receptors. Expression of the human receptor subunit IFNAR in mouse cells conferred sensitivity only to one subtype of human IFN, IFN-alpha B. Other genes on human chromosome 21 were required for responses to other subtypes of type I IFN. In contrast, IFNAR expression in hamster cells did not confer sensitivity to any human IFN tested, including IFN-alpha B. Using human-hamster somatic cell hybrids, we mapped the Ifnabr gene, encoding a ligand-binding subunit of the IFN-alpha/beta (type I) receptor, to human chromosome 21. Ifnabr colocalized with Ifnar to the distal region of q22.1. The presence of a chromosomal fragment encoding IFNABR and IFNAR was also not sufficient to confer sensitivity to human IFN. In contrast, hybrids carrying in addition the region 21q22.2 showed a full response to human IFN-alpha B, suggesting that a gene located in this region encodes a third factor required for type I IFN receptor activity.

Animals↗

Oral ciprofloxacin for treatment of infection following nail puncture wounds of the foot.

From January 1990 to December 1993, 23 adults were hospitalized at our institution for treatment of foot infections that occurred following nail puncture wounds. All 23 patients had cellulitis, and 14 had signs of osteochondritis on a roentgenogram or a 99mTc bone scan. After undergoing surgical intervention that consisted of debridement, drainage of the pus, and exploration of the bones, patients received intravenous ciprofloxacin (400 mg b.i.d.) for 24 hours, followed by an oral regimen (750 mg b.i.d.). Nine patients with cellulitis received oral therapy for 7 days, and the 14 patients with osteochondritis received oral therapy for 14 days. Isolates that were recovered included Pseudomonas aeruginosa (18 patients) and Staphylococcus aureus (2 patients); one patient had a mixed infection, and in two cases no pathogens were recovered. All of the isolates were susceptible to ciprofloxacin. All patients were cured, and none had reinfection. Our results show that foot infection following a nail puncture wound may be treated with oral ciprofloxacin (750 mg b.i.d.) for 7-14 days, provided that surgery is performed first.

Administration, Oral↗

Gentamicin once-daily versus thrice-daily in children.

Fifty children aged 3 months--16 y with Gram-negative bacterial infections, were evaluated in this open randomized study; 26 received gentamicin 4.5 mg/kg/day, once daily, and 24 received the same daily dosage, in three divided doses. The groups had similar demographic and clinical characteristics. Serum trough gentamicin concentrations were significantly lower in the od group than in the tds group, while peak concentration were significantly higher in the od group. Clinical cure was obtained in 23 of the 26 (88.8%) children who received gentamicin once daily, and in 22/24 (91%) children treated thrice daily. Microbiological cure was obtained in 10/10 (100%) and 12/13 (92%) of the evaluated cases. Nephrotoxicity was not observed but ototoxicity occurred in two children in each group. These results, although obtained from a small number of patients, showed a similar outcome in children receiving gentamicin 4.5 mg/kg/day whether administered once or thrice daily.

Adolescent↗

Bacteraemia in a community and a university hospital.

Four hundred and forty-one and 1048 episodes of bacteraemia were prospectively surveyed over a period of 18 months in two hospitals, a 450 bed community hospital and a 900 bed tertiary care urban university hospital. Incidence of bacteraemia was 2.18 per 1000 hospitalization days (10.1 per 1000 admissions) in the community hospital and 2.64 per 1000 hospitalization days (12.0 per 1000 admissions (P < 0.004)) in the university hospital. Sixty six and 62% of episodes of bacteraemia were community acquired. The majority of bacteraemic episodes originated on the internal medicine wards of both hospital--46.7% and 58.7% respectively; the incidence of bacteraemia in the medical divisions of both hospitals was 23.1 and 17.5 per 1000 admissions respectively (P < 0.01). Overall mortality rates were 22% and 26.7% respectively. 39.9% and 44% of all isolates were Gram-positive pathogens. Escherichia coli was the commonest Gram-negative pathogen in both hospitals, particularly the community hospital--47.5% vs 32.8% (P < 0.005) of all Gram-negative pathogens, while Pseudomonas spp. were significantly more common in the university hospital--18.5% vs 11.8% (P < 0.02). Non-enterococcal streptococci were more common in the community hospital while enterococci were far more common at the university hospital--15.1% vs 1% of all Gram-positive pathogens (P < 0.05). Staphylococcus epidermidis was more common among the community hospital Gram-positive bacteraemias--31.1% vs 18.6% (P < 0.005). For almost all genera and species, antibiotic resistance was higher at the university hospital. Twenty nine point four per cent of Staphylococcus aureus isolates from the university hospital were methicillin resistant compared to 2.4% at the community hospital (P < 0.005). 29.4% of all Streptococcus pneumoniae isolates at the university hospital were penicillin resistant while no resistance was found at the community hospital. A high resistance rate to ofloxacin was found at the university hospital among S. aureus and Pseudomonas sp. Sources of bacteraemia did not differ significantly between the two hospitals. In conclusion, although outcome did not differ significantly for the two hospitals, there were significant differences between blood culture isolates in these two different settings. These differences may influence clinical decision-making about antibiotic therapy for patients in these hospitals.

Adult↗