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Biomedical subjects

G W Fischer

Publications and source records attributed to G W Fischer.

At least 19 recordsLinked to original sources

Nonallergic individuals recognize the same T cell epitopes of Bet v 1, the major birch pollen allergen, as atopic patients.

The immune response toward allergens in nonallergic healthy individuals was investigated. To boost immune responses, two injections of birch pollen extract were administered to five nonallergic volunteers. T cell lines (TCL) with specificity for Bet v 1, the major birch pollen allergen, were established and analyzed for epitope specificity using overlapping peptides. Forty-nine T cell clones (TCC) specific for Bet v 1 were isolated from TCLs. Comparison with TCL and TCC established from birch pollen-allergic patients was performed. All TCC revealed the Th phenotype. Epitope specificities of TCL and TCC from nonatopics were identical to those found in allergic individuals. No association between MHC class II molecules and particular epitopes could be observed. In nonallergic as well as in allergic individuals, cytokine production in response to specific stimulation revealed a majority of Th-clones producing IL-4 and IFN-gamma. However, TCC derived from atopic individuals revealed a higher IL-4/IFN-gamma ratio. Immunoblot and ELISA revealed Bet v 1-specific IgG in nonallergic individuals before and after booster injections, but no IgE could be detected. High levels of Bet v 1-specific IgG and IgE could be detected in birch pollen-allergic patients. It can be concluded, that nonatopic and allergic individuals display the same repertoire of T cell specificities. In allergic individuals, the activation of allergen-specific TCC leads to a higher ratio of produced IL-4 vs IFN-gamma, which is responsible for enhanced IgE production.

Allergens

Opsonic antibodies to Staphylococcus epidermidis: in vitro and in vivo studies using human intravenous immune globulin.

Staphylococcus epidermidis is a major cause of nosocomial infections, including sepsis in premature infants. Intravenous immune globulin (IVIG) has been used to prevent neonatal sepsis, but efficacy has varied in different clinical trials. The role of IgG antibody in immunity to S. epidermidis was studied using an opsonophagocytic assay and a lipid-emulsion-induced lethal model of neonatal S. epidermidis sepsis. Opsonic antibody to S. epidermidis varied between IVIG preparations and between lots: Lots with > or = 90% opsonic activity promoted bacterial clearance from blood and significantly enhanced survival when compared with lots with < or = 50% opsonic activity. Absorption of IVIG with S. epidermidis removed in vitro opsonic and in vivo protective activity. These studies suggest that opsonic antibody may play an important role in S. epidermidis immunity in immunocompromised patients, such as premature infants. Standard IVIG, however, may not provide therapy effective in preventing S. epidermidis infections, as many IVIG lots contain insufficient levels of opsonic S. epidermidis antibody.

Animals

Opsonic activity of commercially available standard intravenous immunoglobulin preparations.

Several standard intravenous immunoglobulin G (IVIG) products are available in the United States and have been used with the intent to treat or prevent infections in neonates. We evaluated more than 100 lots of IVIG, from 6 products, to determine the amount of opsonic antibody against neonatal pathogens. Neutrophil-mediated opsonophagocytosis was used to determine opsonic activity in these preparations for Staphylococcus epidermidis; Haemophilus influenzae type b; Streptococcus pneumoniae serotypes 3, 14 and 19; Group B Streptococcus serotypes Ia, Ib, Ia/c, II and III; and Escherichia coli (K1). Pathogen-specific opsonic activity of the lots tested ranged from undetectable to 1:80 and was detectable in < 10% to > 90% of lots tested depending on the organism and manufacturer. Within an IVIG lot there was variable opsonic activity against different strains or serotypes of the same organism. Opsonic activity was significantly (P < or = 0.05) affected by the manufacturer's donor pool and less so by the manufacturing method. We conclude that the pathogen-specific opsonic antibody activity of an IVIG lot is: (1) highly variable for several common neonatal pathogens; (2) predominantly dependent on the donor pool and not the manufacturing method. Clinicians may more appropriately select therapy if the pathogen-specific antibody content of IVIG products by lot are known. In the future neonatal IVIG research should focus on using preparations with known pathogen-specific antibody activity.

Analysis of Variance

Use of intravenous immune globulin in newborn infants.

Bacterial infections remain a major cause of morbidity and mortality in neonates. Intravenous immune globulin (IVIG) may enhance immunity to neonatal bacterial pathogens by facilitating opsonophagocytosis. In early-onset neonatal sepsis, antibody has improved survival when used therapeutically in combination with antibiotics. However, some IVIG lots may not contain sufficient pathogen-specific antibody to provide effective therapy. Antibody prophylaxis has not provided protection from late-onset (nosocomial) sepsis consistently. Failure of antibody prophylaxis may also be related to variable levels of opsonic antibodies to nosocomial bacteria in IVIG preparations. Staphylococci (particularly Staphylococcus epidermidis) have become a major cause of late-onset sepsis. IVIG preparations contain variable levels of antibody to S. epidermidis, with many lots having nearly undetectable anti-staphylococcal antibody titres. This absence of antibodies to staphylococci may explain why antibody prophylaxis of neonatal sepsis has not been consistently effective. In future studies, IVIG preparations or monoclonal antibodies that possess specific antibodies to key neonatal pathogens will be needed.

Animals

Age-adjusted CD4+ lymphocyte parameters in healthy children at risk for infection with the human immunodeficiency virus. The Military Pediatric HIV Consortium.

Values for CD4+ lymphocytes are reported to vary by age. We evaluated an ethnically diverse population of healthy children at risk for human immunodeficiency virus infection to establish normal ranges for age-adjusted CD4+ lymphocyte parameters. We identified a threshold of approximately 30% CD4+ lymphocytes which corresponded to a 5th percentile for all ages. It is important that no significant differences in absolute CD4+ lymphocyte counts on the basis of ethnic group were found.

Age Factors

False-negative urine latex particle agglutination testing in neonates with group B streptococcal bacteremia. A function of improper test implementation?

Although blood cultures remain the most specific indicator of Group B streptococcus (GBS) sepsis, a potentially life-threatening infection in neonates, test results may not be available for 24 to 48 hours. Detection of GBS antigen in the urine by latex particle agglutination (LPA) may speed diagnosis. This study analyzed the sensitivity of the GBS urine LPA assay under clinical conditions. The urine of neonates with early-onset GBS bacteremia was analyzed for GBS antigen over a three-year period at six military medical centers. Overall, 53.5% (38/71) of infants with positive blood cultures had a positive urine LPA test. Only one medical center routinely followed manufacturer's recommendations to concentrate urine specimens before testing. These data suggest that the sensitivity for the urine LPA assay, when performed on unconcentrated urine, is lower than previously reported. Clinicians should insist that the laboratory maximize sensitivity by concentrating urine prior to GBS LPA testing.

Antigens, Bacterial

Directed immune globulin for the prevention or treatment of neonatal group B streptococcal infections: a review.

Intravenous immune globulin (IVIG) is now used in many nurseries to prevent or treat neonatal infections. The most common cause of early-onset neonatal sepsis is the group B streptococcus (GBS). Commercially available IVIG preparations have variable levels of specific antibody directed against GBS. Therefore, to ensure high levels of anti-GBS antibody, we developed a polyvalent IVIG directed against GBS (GBS-IVIG) by immunizing plasma donors. This GBS-IVIG was superior to standard IVIG both in vitro using opsonic studies and in vivo using a lethal suckling rat model of GBS sepsis. GBS-IVIG also protected neonatal rhesus monkeys in a GBS sepsis model. Safety and pharmacokinetic studies have been completed in 20 neonates with suspected sepsis. Fifteen infants were randomized to receive 500, 250, or 100 mg/kg of GBS-IVIG and were compared with 5 infants given 500 mg/kg of standard IVIG. No adverse effects of standard IVIG or GBS-IVIG were observed. While total serum IgG and IgG subclasses reflected the dose administered, the specific GBS antibody reflected both the dose and IVIG preparation utilized. At 500 mg/kg, the GBS-specific antibody rises more than fourfold above baseline in all babies that were observed for greater than 42 days postinfusion, while standard IVIG provided a fourfold rise in less than 20% of babies for less than 1 day. These studies suggest that GBS-IVIG can effectively and reliably elevate GBS-specific antibody levels in neonates. Clinical trials are needed to evaluate the efficacy of GBS-IVIG in preventing or treating neonatal GBS infections.

Adult

Investigations of the acute toxic, cytogenetic, and embryotoxic activity of buminafos.

The organophosphorus herbicide buminafos (O,O-dibutyl-(1-butylaminocyclohexyl)-phosphonate) was tested for its acute toxic, cytogenetic, and embryotoxic activity on different strains of mice. The oral LD50 value for male NMRI mice was determined to be 3500 mg/kg. Single oral doses of 175, 1000, and 2000 mg/kg did not cause any significant enhancement in the percentage of chromosome aberrations in bone marrow cells of male NMRI mice. After oral administration of 500 and 1000 mg/kg buminafos to pregnant Halle:DBA and Halle:AB mice at Days 6-15 of gestation no embryotoxic effects were observed. The cytogenetic inactivity of buminafos in the bone marrow chromosome assay corresponds to negative findings in other mutagenicity tests.

Animals

Comparison of standard and quantitative blood cultures in the evaluation of children with suspected central venous line sepsis.

We reviewed our experience with paired quantitative and standard blood cultures in the evaluation of children with suspected central-line sepsis with the hypothesis that by employing both systems we would increase our yield of pathogenic isolates. A total of 913 paired cultures were reviewed, representing 267 pathogenic isolates and 58 individual episodes of sepsis. The isolates were analyzed for recovery rates for each system and by combining both systems. The Isolator system proved to be equal to the BACTEC system for the recovery of all groups of pathogenic isolates. The combined use of both the quantitative and the standard culture systems demonstrated a statistically significant advantage (p less than 0.001) for the recovery of pathogens as compared with either system alone. The use of either system alone would have missed 15% of the total pathogenic isolates. Quantitative colony counts were helpful in identifying the line as the source of infection in 35 to 58 episodes of sepsis and were often beneficial in the clinical management central venous line infection. We recommend the use of the Isolator 1.5 ml combined with a conventional broth-bottle system in selected pediatric patients to enhance the recovery of pathogenic organisms.

Bacteremia

Early-onset group B streptococcal sepsis: a current assessment.

Group B streptococcus (GBS) is a common cause of early-onset sepsis in neonates. The most recent reviews describing incidence, diagnosis, treatment, and outcome evaluated data on patients from the early 1980s. To obtain current information about this disease, we retrospectively evaluated data on neonates with GBS early-onset sepsis from nine hospitals in the United States between Jan. 1, 1987, and Dec. 31, 1989. There were 245 infants with GBS bacteremia identified among 61,809 live births, resulting in an incidence of 0.32%. Ninety-six infants (39%) were preterm (less than 38 weeks of gestational age). Maternal risk factors for infected preterm and term infants were similar. Antibiotics were administered during parturition in 10% of infants with bacteremia. Mothers of preterm infants received antibiotics up to 48 hours before delivery; mothers of term infants received antibiotics less than 4 hours before delivery. All preterm infants with bacteremia had symptoms; 22% of term infants with bacteremia had no symptoms. Group B streptococcal meningitis was confirmed in 6.3% of infants. Although 86% survived, GBS sepsis increased the birth weight-specific mortality rate up to eightfold in preterm infants and more than 40-fold in term infants. Although the incidence of GBS early-onset sepsis is not changing, we speculate that the improved birth weight-specific survival rate and the changing clinical presentation are due to improved intrapartum and neonatal management.

Bacteremia

Catheter-associated sepsis caused by Ochrobactrum anthropi: report of a case and review of related nonfermentative bacteria.

Ochrobactrum anthropi, formerly known as CDC group Vd, is an oxidase-producing, gram-negative, non-lactose-fermenting bacillus that oxidizes glucose and grows readily on MacConkey agar. Only occasionally isolated from human clinical specimens, this organism has rarely been found to be pathogenic. We describe the first reported case of infection due to O. anthropi in a child, that of bacteremia in a 3-year-old girl undergoing chemotherapy for retinoblastoma. In addition, we review the literature concerning cases of infection due to this and closely related bacterial species, namely Alcaligenes xylosoxidans subspecies xylosoxidans, Agrobacterium radiobacter, and "Achromobacter" group B. Finally, we attempt to clarify the confusing history and taxonomy of these organisms as well as make recommendations regarding antimicrobial therapy for infections caused by them.

Anti-Bacterial Agents

Risk perception and the value of safety.

This paper examines the relationship between perceived risk and willingness-to-pay (WTP) for increased safety from technological hazards in both conceptual and empirical terms. A conceptual model is developed in which a given household's WTP for risk reductions is a function of traditional socioeconomic variables (i.e., income and base level of risk) and perceived characteristics of the hazards (i.e., dread, knowledge, and exposure). Data to estimate the model are obtained through a combined contingent valuation and risk perception survey that considers 10 technological hazards, five of which are well-defined (e.g., death rates are known and the risks are relatively common) and five are less well-defined. Econometric results, using TOBIT estimation procedures, support the importance of both types of variables in explaining WTP across all 10 hazards. When the risks are split into two groups, the results show that WTP for well-defined hazards is most influenced by perceived personal exposure, while WTP for less well-defined risks is most influenced by levels of dread and severity.

Data Collection

Immunoglobulin therapy in older infants and children.

The availability of intravenous immunoglobulin preparations and human monoclonal antibodies has broadened the potential utility of antibody therapy to include treatment of viral infections such as cytomegalovirus and respiratory syncytial virus and prevention and treatment of serious bacterial infections such as endotoxic shock and pneumonia in children with acquired immunodeficiency syndrome. As new polyclonal and monoclonal immunoglobulin preparations are developed for specific organisms or clinical settings, immunoglobulin therapy is likely to become an increasingly important component of the clinician's armamentarium.

Bacterial Infections

Preferences for separating or combining events.

This research investigates people's preferences for temporally separating or combining emotionally impactful events. For instance, do people prefer to experience 2 negative events (e.g., manuscript rejections) on the same day or on different days? Do people prefer to experience 2 positive events (e.g., manuscript acceptances) on the same or different days? This article proposes a renewable resources model that combines elements of decision-making models (prospect theory) with the notion that people possess limited but renewable physiological, cognitive, and social resources for dealing with emotionally impactful events. As predicted, Ss preferred to separate 2 positive events (the gain-savoring hypothesis), to separate 2 negative events (the multiple-loss-avoidance hypothesis), and to combine a positive and a negative event (the loss-buffering hypothesis). Ss displayed identical preferences for events from the academic, financial, and social domains.

Activities of Daily Living