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Biomedical subjects

S Ashkenazi

Publications and source records attributed to S Ashkenazi.

At least 19 recordsLinked to original sources

Long-term outcome of infective endocarditis: the impact of early surgical intervention.

To determine the impact of early surgical intervention on long-term survival in patients with infective endocarditis (IE), charts of all patients who had IE from January 1987 through December 1996 were reviewed. A total of 252 patients with definite or possible IE were included. Forty-four patients (17.5%) had early surgery on median hospital day 2 (range, 0-30 days), and 208 patients (82.5%) received medical treatment alone. On multivariate analysis, several variables, including early surgical intervention, improved long-term survival rates (hazard ratio, 1.5; P=.03), mainly in patients with Staphylococcus aureus etiology (P=.04). When patients with prosthetic devices were excluded, the median duration of survival for patients who had early surgery was >150 months, compared with 61.5 months for patients in the medical group (P=.1). Early surgical intervention compared with medical therapy alone is associated with increased short- and long-term survival rates in patients with IE, primarily when IE is caused by S. aureus.

Adolescent↗

Early responses to nonconjugated polyribosylribitol phosphate challenge as evidence of immune memory after combined diphtheria-tetanus-pertussis-polio-Haemophilus influenzae type b primary vaccination.

OBJECTIVES: A high risk of invasive Haemophilus influenzae type b (Hib) disease exists in the first few years of life. A reduction in anti-polyribosylribitol phosphate (PRP) antibody concentrations follows the administration of certain diphtheria-tetanus-acellular pertussis (DTPa)-based Hib conjugate combined vaccines. However, these combined vaccines prime the immune memory, which is an important factor in protection. As yet there is no direct evidence of the time scale involved in the development of the immune memory post-primary vaccination. In this report we investigated the presence of immune memory at 10 and 12 months of age, 4 and 6 months after primary vaccination of young infants with a pentavalent combination of DTPa, inactivated poliovirus vaccine (IPV) and Hib (DTPa-IPV/Hib) vaccine. METHODS: In two trials (A and B) infants received DTPa-IPV combined with Hib-tetanus conjugate (PRP-T) vaccine at 2, 4 and 6 months of age. The presence of immune memory was assessed by measuring anti-PRP concentrations 7 to 10 days after a nonconjugated PRP challenge given at 10 months in Trial A and at 12 months in Trial B. RESULTS: Administration of a nonconjugated PRP challenge 4 and 6 months after primary vaccination in Trials A and B, respectively, elicited an increase in anti-PRP geometric mean concentrations (4.5 and 5.8 microg/ml, respectively) within 7 to 10 days. These concentrations exceed those reported in the literature involving unprimed children who had received a single dose of nonconjugated PRP at the same age. CONCLUSION: The results demonstrate the development of anti-PRP immune memory at an early age, 4 and 6 months after completion of a three dose primary vaccination course of combined DTPa-IPV/Hib vaccine. The ability of primed infants to mount a rapid response is an important observation given the high risk of Hib infection at this critical age.

Antibodies, Bacterial↗

Mycetoma of the renal pelvis caused by Fusarium species.

A preterm infant, with posterior urethral valves had a mycetoma of the renal pelvis caused by Fusarium species. Prolonged treatment with amphotericin B alone or with flucytosine failed. Combined surgical drainage and medical therapy resulted in full resolution.

Adult↗

Emergence of multiple human cytomegalovirus ganciclovir-resistant mutants with deletions and substitutions within the UL97 gene in a patient with severe combined immunodeficiency.

Infection with multiple ganciclovir-resistant human cytomegalovirus mutants, containing different substitutions and deletions in the UL97 gene, was found in a patient with severe combined immunodeficiency (SCID) within 3 weeks of ganciclovir therapy. A novel 11-codon deletion at positions 590 to 600 was identified. These unique findings may be related to the nature of the immunodeficiency in the SCID patient.

Amino Acid Substitution↗

Safety and immunogenicity of improved Shigella O-specific polysaccharide-protein conjugate vaccines in adults in Israel.

Data suggest that the O-specific polysaccharide (O-SP) domain of the lipopolysaccharide (LPS) of Shigella species is both an essential virulence factor and a protective antigen and that a critical level of serum immunoglobulin G (IgG) to this antigen will confer immunity to shigellosis. Because covalent attachment of polysaccharides to proteins increases their immunogenicity, especially in infants and in young children, the O-SP of Shigella species were bound to medically useful proteins, and the safety and immunogenicity of the resultant conjugates were confirmed in adults and 4- to 7-year-old children. Succinylation of the carrier protein improved the immunogenicity of Shigella conjugates in mice and increased their yield. Based on these results, a clinical trial of O-SP conjugates of Shigella sonnei and Shigella flexneri 2a bound to succinylated mutant Pseudomonas aeruginosa exotoxin A (rEPAsucc) or native or succinylated Corynebacterium diphtheriae toxin mutant (CRM9 or CRM9succ) was conducted in healthy adults. The conjugates were safe and immunogenic. S. sonnei-CRM9, S. sonnei-CRM9succ, and S. sonnei-rEPAsucc elicited significant rises of geometric mean (GM) IgG anti-LPS within 1 week of injection (P < 0.001). At 26 weeks, the GM anti-LPS levels elicited by these three conjugates were similar and higher than their prevaccination levels (P < 0.0001). GM IgG anti-LPS levels elicited by S. flexneri 2a-rEPAsucc were significantly higher than those elicited by S. flexneri 2a-rCRM9succ at all intervals after injection. At 26 weeks, the levels of IgG anti-LPS in vaccinees were higher than their prevaccination levels (P < 0.0001). The serum antibody responses were specific, as there was no significant rise of anti-LPS to the heterologous O-SP in any vaccinee. Both conjugates elicited statistically significant rises of serum antibodies to the injected carrier protein. At 6 months, these five Shigella conjugates elicited higher fold rises than similar conjugates (D. N. Taylor et al., Infect. Immun. 61:3678-3687, 1993). Based on these data, we chose S. sonnei-CRM9 and S. flexneri 2a-rEPAsucc for evaluation in children.

Adolescent↗

Successful treatment of antiepileptic drug hypersensitivity syndrome with intravenous immune globulin.

Intravenous immune globulin (IVIG) has proved beneficial for severe immunologically related cutaneous adverse reactions. We report a child with severe antiepileptic drug hypersensitivity syndrome who was successfully treated with IVIG. IVIG should be considered in the pharmacologic armamentarium of severe antiepileptic drug hypersensitivity syndrome. antiepileptic drugs, hypersensitivity, immune globulin.

Anticonvulsants↗

Cost-benefit analysis of active vaccination campaigns against hepatitis A among daycare centre personnel in Israel.

OBJECTIVE: To evaluate, in economic terms, active vaccination campaigns against hepatitis A in comparison with the use of nonspecific immune globulin for the prevention of the disease among daycare centre employees in Israel. SETTING: Hypothetical analysis of the costs and benefits related to vaccination campaigns of workers currently employed in daycare centres in Israel. METHODS: A cost-benefit analysis was performed, comparing mass and selective active vaccination strategies for the daycare centre working force. Direct and indirect costs of diagnosis, treatment and immunisation as well as productivity loss were considered. A Markov-based model was developed using data from previous epidemiological studies and literature. RESULTS: The benefit-to-cost ratios of selective and mass active vaccination strategies were 1.50 [net present value (NPV) $US606 396] and 0.04 (NPV-$US2.36 million), respectively (2000 values). CONCLUSION: Under these study assumptions, the practice of administering hepatitis A active vaccine to serologically proven non-immune daycare centre workers has a cost-benefit justification, and should be widely considered in countries with a similar hepatitis A epidemiology to that in this study.

Adolescent↗

Severe allergic bronchopulmonary aspergillosis in an infant with cystic fibrosis and her asthmatic father.

An infant with cystic fibrosis and her asthmatic father were diagnosed as suffering from allergic bronchopulmonary aspergillosis (ABPA). Cystic fibrosis was diagnosed in the infant at 6 weeks of age, and gene mutations were W1282X/G542X. She was diagnosed definitively as suffering from ABPA at age 3.5 years, but had suggestive symptoms from age 11 months. This may be the youngest age described to date for ABPA. The child responded well to systemic steroid therapy, but remained steroid-dependent over the next 4 years. Treatment with itraconazole enabled a marked reduction in steroid dosage. The father was an asthmatic, and a heterozygote for the cystic fibrosis transmembrane regulator (CFTR) mutation W1282X. He had a normal sweat test, atopy, and moderate reversible airway obstruction. There was no proven exposure to Aspergillus in the home environment. The importance of considering the diagnosis of ABPA even in infancy, the therapeutic dilemmas, and the possible role of abnormal CFTR function in the development of ABPA are discussed.

Adult↗

Seven-year study of bacteraemic pneumonia in a single institution.

In order to enhance current knowledge of nosocomial and community-acquired bacteraemic pneumonia in a single tertiary hospital in Israel, a 7-year study was conducted. Using a computerised database, all patients who had bacteraemic pneumonia from March 1988 to August 1995 were studied. During the study period, pneumonia was the source of bacteraemia in 319 of 4,548 (7%) episodes, occurring in 295 patients; 211 (66%) episodes were community-acquired and 108 (34%) were nosocomial. The microoroganisms isolated most frequently from patients with community-acquired bacteraemic pneumonia were Streptococcus pneumoniae (46%), Staphylococcus aureus (10%) and Haemophilus influenzae (8%); while Pseudomonas spp. (17%), Klebsiella spp. (11%) and Staphylococcus aureus (10%) were isolated most often from the patients with nosocomial bacteraemic pneumonia. The median age of patients was 68 years (range, 0.003-100). The overall mortality was 34%. No significant difference was found between the mortality rates of patients with community-acquired (31%) and nosocomial (40%) bacteraemic pneumonia (P=0.1). Multivariate analysis showed that hypothermia, respiratory failure, impaired consciousness, tracheal intubation, Staphylococcus aureus aetiology, septic shock, inappropriate empiric antibiotic treatment and age significantly increased mortality.

Aged↗

Clinical and laboratory impact of coagulase-negative staphylococci bacteremia in preterm infants.

UNLABELLED: A retrospective evaluation of the clinical and laboratory impact of coagulase-negative staphylococci (CONS) bacteremia in preterm infants was carried out. The study population included all preterm infants (n = 31) in whom two or more blood cultures were positive for CONS within a period of 4 d, with negative blood cultures 1 wk before and 1 wk after the CONS bacteremia. Clinical manifestations and the results of laboratory tests 7 d before and after the positive blood cultures, and on the first day of sepsis, were recorded and compared. During CONS bacteremia, the infants demonstrated apnoea and bradycardia (88%) and a need for oxygen (59%) and ventilatory support (69%). Significant laboratory findings were leukopenia below 5,000 cells/mm3 (12%), leukocytosis above 30,000 cells/mm3 (39%), and thrombocytopenia below 150,000/mm3 (25%). These clinical and laboratory manifestations differed significantly during the bacteremia infection compared with the week before and after. CONCLUSION: CONS bacteremia is a clinically significant infection in preterm infants, causing episodes of apnoea and bradycardia, and a need for ventilatory support.

Anti-Bacterial Agents↗

Liver enzyme abnormalities in gram-negative bacteremia of premature infants.

BACKGROUND: Hyperbilirubinemia and liver enzyme abnormalities are commonly observed in sepsis. However, the frequency in premature neonates and the specific relation to gram-negative bacteria are not known. PATIENTS AND METHODS: Charts of all preterm infants who had positive blood cultures for either gram-negative bacteria or coagulase-negative staphylococci were reviewed. Neonates with gram-negative bacteremia (n = 54) were compared with neonates with coagulase-negative staphylococcal bacteremia (n = 31). In addition infants with gram-negative bacteremia and elevated liver enzymes (n = 25) were compared with infants with gram-negative bacteremia and normal liver enzymes (n = 29). RESULTS: Liver enzyme abnormalities accompanied 46.3% (25 of 54) of gram-negative bacteremia and 12.9% (4 of 31) of episodes of coagulase-negative staphylococcal bacteremia (P = 0.002). Serum concentrations of liver enzymes were significantly higher in infants with gram-negative bacteremia than in those with coagulase-negative staphylococcal bacteremia (P < 0.0001), but no difference in alkaline phosphatase serum values was observed. Infants with gram-negative bacteremia and elevated liver enzymes were not fed for a longer period than infants with gram-negative bacteremia and normal liver enzymes (7.3 +/- 6.3 days vs. 4.0 +/- 4.3 days, P = 0.03), and this was accompanied by significant conjugated hyperbilirubinemia (P < 0.0001). Ventilation, total parenteral nutrition and medications were not responsible for the observed differences. Klebsiella pneumoniae bacteremia was commonly associated with elevated liver enzymes (12 of 18), whereas none of the infants with Pseudomonas aeruginosa bacteremia had elevated liver enzymes. CONCLUSIONS: Gram-negative bacteremia is commonly associated with cholestasis in premature neonates. Liver enzyme abnormalities are more common than elevated conjugated bilirubin, not all gram-negative bacteria have the same effect and the lack of enteral feeding seems to play a more significant role than the administration of parenteral nutrition.

Bacteremia↗

Immunization against hepatitis A in the first year of life: priming despite the presence of maternal antibody.

BACKGROUND: Maternal antibodies interfere with hepatitis A vaccination in young infants. We examined the response to a high dose hepatitis A vaccine administered concomitantly with a combination of diphtheria-tetanus toxoids-acellular pertussis-inactivated poliovirus vaccine/Haemophilus influenzae type b vaccine to initially seropositive vs. initially seronegative infants. METHODS: Three hundred subjects were originally planned to be enrolled at age 6 to 10 weeks and received hepatitis A vaccine (formalin-inactivated vaccine, SB-Bio, 720 enzyme-linked immunosorbent assay units) at 2, 4 and 6 months concomitantly with a diphtheria-tetanus toxoids-acellular pertussis-inactivated poliovirus vaccine/H. influenzae type b vaccine. Children initially seropositive received a booster dose at 12 months of age. An additional 100 twelve-month-old infants previously not vaccinated with hepatitis A vaccine were given 1 dose, to observe the primary response at that age. Reactogenicity was recorded on diary cards for the 3 subsequent days. Immunogenicity was measured at Months 2, 4, 5, 10 and 11 after administration of the first vaccine dose. For the subjects enrolled at 12 months, blood was drawn before and 1 month after the first vaccination. RESULTS: Of 297 initially enrolled infants 36% were seronegative before vaccination (Group A). The geometric mean concentration (GMC) (milli-International Units/ml) of the seropositive infants (Group B) before immunization was 2587. The GMCs of Group A infants 1 month after each dose and at 12 months of age were 93, 518, 1656 and 786, respectively. For Group B infants, the respective GMCs were 1165, 460, 508 and 167. One hundred subjects of Group B received a booster dose at age 12 months; at Month 13 all were seropositive with a GMC of 1902. For comparison, a third group of 100 not previously immunized 12-month-old infants (Group C) were enrolled and received 1 dose of hepatitis A vaccine with pre- and postimmunization GMCs of 52 and 120, respectively. CONCLUSIONS: Our results suggest that the initially seropositive infants were primed despite maternal antibody interference. The hepatitis A vaccine was well-tolerated in this population of young infants.

Female↗

Safety and immunogenicity of two different lots of the oral, killed enterotoxigenic escherichia coli-cholera toxin B subunit vaccine in Israeli young adults.

Enterotoxigenic Escherichia coli (ETEC) is one of the leading causes of diarrhea among Israeli soldiers serving in field units. Two double-blind placebo-controlled, randomized trials were performed among 155 healthy volunteers to evaluate the safety and immunogenicity of different lots of the oral, killed ETEC vaccine consisting of two doses of whole cells plus recombinantly produced cholera toxin B subunit (rCTB). The two doses of vaccine lot E005 and the first dose of vaccine lot E003 were well tolerated by the volunteers. However, 5 (17%) vaccinees reported an episode of vomiting a few hours after the second dose of lot E003; none of the placebo recipients reported similar symptoms. Both lots of vaccine stimulated a rate of significant antibody-secreting cell (ASC) response to CTB and to colonization factor antigen I (CFA/I) after one or two doses, ranging from 85 to 100% and from 81 to 100%, respectively. The rate of ASC response to CS2, CS4, and CS5 was slightly lower than the rate of ASC response induced to CTB, CFA/I, and CS1. The second vaccine dose enhanced the response to CTB but did not increase the frequencies or magnitude of ASC responses to the other antigens. The two lots of the ETEC vaccine induced similar rates of serum antibody responses to CTB and CFA/I which were less frequent than the ASC responses to the same antigens. Based on these safety and immunogenicity data, an efficacy study of the ETEC vaccine is under way in the Israel Defense Force.

Administration, Oral↗

Selected abstracts

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Journal Article↗

Induction of mRNA for tumor necrosis factor-alpha and interleukin-1 beta in mice brain, spleen and liver in an animal model of Shigella-related seizures.

BACKGROUND: The pathogenesis of neurological symptoms, the most common extraintestinal complication of childhood shigellosis, is unclear. To elucidate the mechanisms involved, we developed an animal model and demonstrated that TNF alpha and IL-1 beta play a role. OBJECTIVES: To determine whether TNF alpha and IL-1 beta genes are expressed in the brain following peripheral administration of Shigella dysenteriae 60R. METHODS: Expression of mRNA for TNF alpha and IL-1 beta was examined in the brain structures (hypothalamus and hippocampus) and peripheral organs by reverse transcriptase polymerase chain reaction, at different time points after intraperitoneal injection of S. dysenteriae sonicate. RESULTS: In our animal model of Shigella-related seizures, TNF alpha and IL-1 beta mRNA were induced in the brain, spleen and liver already 1 hour after injection of S. dysenteriae sonicate. The expression of TNF alpha and IL-1 beta mRNA in spleen, hippocampus and hypothalamus decreased after 6 h and increased again at 18 h post-injection. CONCLUSIONS: Local production of TNF alpha and IL-1 beta in the brain may be involved in the enhanced seizure response of mice after administration of S. dysenteriae. It is possible that intracerebral production of TNF alpha and IL-1 beta plays a role in neurological disturbances of human shigellosis.

Animals↗

The diagnostic and therapeutic approach to acute bronchiolitis in hospitalized children in Israel: a nationwide survey.

BACKGROUND: Bronchiolitis caused by respiratory syncytial virus is one of the major causes of hospitalization in young children, especially during the winter. Recent evidence has shown that pharmacological treatment, especially nebulized epinephrine, in addition to the traditional supportive treatment, can alleviate symptoms and shorten hospitalization, but this approach is not yet widespread. OBJECTIVES: To determine whether the management of bronchiolitis in Israel is moving toward a stronger emphasis on pharmacological care. METHODS: A questionnaire on the diagnosis and management of bronchiolitis was completed by 27 heads of pediatric departments throughout Israel. The questionnaire dealt with the frequency of usage of diagnostic and selected therapeutic procedures. RESULTS: Chest X-ray and arterial blood gases are commonly used as a diagnostic aid in more than 75% of the departments, and antibiotics are prescribed routinely in 24%. Corticosteroids are still in use: 48% use systemic steroids, and 19% nebulized steroids. Nebulized epinephrine is used in 22% of the departments, while nebulized beta-agonists are used frequently in two-thirds of the departments. CONCLUSIONS: Despite convincing data that beta-agonists and steroids have no positive effect on the outcome of bronchiolitis on the one hand, and that nebulized epinephrine has advantages in children on the other, we found significant use of the former two agents and sparse use of the latter. Greater awareness is needed among pediatricians, and measures should be introduced to incorporate the new recommendations, with further study of the effect of the old and new drugs on bronchiolitis.

Administration, Inhalation↗