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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

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

Comparative protective activity of human monoclonal and hyperimmune polyclonal antibody against group B streptococci.

Group B streptococcal (GBS) infections cause significant morbidity and mortality in neonates and compromised hosts, who usually lack opsonic antibody to their infecting strain. Unfortunately, most conventional immunoglobulin preparations possess little GBS antibody. The protective activity of a human monoclonal antibody (HuMAb) and a human hyperimmune intravenous immunoglobulin (HivIg) were evaluated against these organisms and compared with a conventional intravenous immunoglobulin (ivIg). The HuMAb and the HivIg possessed significant protective activity (50%-95%) against extremely virulent strains of types I, II, and III GBS in doses as low as 4-20 mg/kg. In contrast, the conventional ivIg had little protective activity against some of these strains in doses as high as 500 mg/kg. The opsonic activity of the HuMAb and HivIg also usually exceeded that of the conventional ivIg. These studies suggest HivIg or HuMAb with markedly enhanced specific activity may provide optimal immunotherapy for GBS infections.

Animals

Comparison of commercially available group B streptococcal latex agglutination assays.

Detection of group B streptococcus (GBS) antigen in urine by latex particle agglutination (LPA) may facilitate the rapid diagnosis of GBS sepsis. We sought to compare three commercial LPA assays with specimens that were spiked with type-specific antigen, group-specific antigen, or type III organisms. There were sensitivity differences between the assays, but the Bactigen assay performed best, detecting as little as 1 ng of GBS group-specific antigen per ml in urine and as few as 10(5) CFU of GBS type III organisms per ml in urine, serum, and cerebrospinal fluid.

Adult

Immunoprecipitation and opsonic cross-reaction between type-14 pneumococcus and group-B streptococcus type III.

Antisera directed against type-14 pneumococcus was opsonic for several strains of type-III group-B streptococcus. Furthermore, the polysaccharide antigen in the polyvalent pneumococcal vaccine reacted to form precipitation lines with antisera directed against type-14 pneumococcus and group-B streptococcus type III Immunisation with currently available pneumococcal vaccine may provide opsonic antibody against group-B streptococci and provide a method of preventing neonatal group-B streptococcal infections.

Animals

Immunochemical cross-reactions between type III group B Streptococcus and type 14 Streptococcus pneumoniae.

Serological cross-reactions between certain streptococci and some serotypes of Streptococcus pneumoniae have been reported. These studies detail the serological cross-reactivity observed between hot HCl-extracted group b streptococcus type III (GBS III) antigens and S. pneumoniae type 14 (Pn 14) polysaccharide. Similar electrophoretic migration patterns of GBS III and Pn 14 were observed when either type-specific BGS III antisera or pneumococcal omniserum was utilized to precipitate these antigens. Both the GBS III antigen and the Pn 14 polysaccharide migrated toward the cathode, whereas all other pneumococcal polysaccharides migrated toward the anode. No cross-reactions were observed between GBS III antisera and the 11 other types of pneumococcal polysaccharides. Lines of identity were observed between type-specific GBS III antisera and monospecific Pn 14 antiserum with either GBS III antigens or purified Pn 14 polysaccharide. The cross-reacting antigens of GBS III and Pn 14 appear to be identical by immunodiffusion and immunoelectrophoresis.

Antigens, Bacterial

Demonstration of opsonic activity and in vivo protection against group B streptococci type III by Streptococcus pneumoniae type 14 antisera.

The present studies demonstrate that antisera directed against Streptococcus pneumoniae type 14 is opsonic for group B streptococci type III in a neutrophile-mediated bactericidal assay. Specificity was demonstrated by the observations that group B streptococci type III and S. pneumoniae type 14 adsorbed the opsonic activity of anti-S. pneumoniae type 14 antisera. Group B streptococci strain 090R (devoid of type antigens) and S. pneumoniae type 3, did not remove the opsonic activity of anti-S. pneumoniae type 14 serum. In vivo studies using a suckling rat model of neonatal group B streptococcal type III sepsis demonstrated that antisera directed against S. pneumoniae type 14 was highly protective.

Animals

Oral polio vaccine. Effect of booster vaccination one to 14 years after primary series.

We studied the persistence of antibody after vaccination and the response to booster revaccination with trivalent oral polio vaccine (TOPV) administered at varied intervals after the primary series in a large group of children. Decline in antibody was related to intervals since last vaccination, and not to sex, age, age at primary vaccination, or type and number of previous administrations. Geometric mean titers of neutralizing antibody were 11.3 for type 1 and 8.0 for types 2 and 3 poliovirus when vaccine had been given within the previous year, declining to 3.2, 3.0, and 2.1 for types 1, 2, and 3 after nine years. Most children with an initial titer of 4 or less responded to revaccination with a fourfold or greater increase in titer of IgG. Geometric mean titers for all three types of polio dropped to this level when last TOPV administration had been five to six years or more.

Adolescent

Evaluation of miconazole therapy in experimental disseminated candidiasis in laboratory rats.

Miconazole, a broad-spectrum antimycotic agent with some antibacterial activity, has recently become available for experimental parenteral use in the United States. Its efficacy as an anticandidal drug was tested in adult Wistar rats. A previously established infectious dose of 5 x 10(6)Candida albicans was intravenously injected into 250- to 300-g animals. This dose was fatal to 95% (20/21) of placebo-treated control animals within the 2-week postinfection observation period. Only 4% (2/53) of rats receiving intramuscular miconazole treatment died. Miconazole therapy in Candida-infected rats at a dosage of 50 mg/kg per day resulted in 85% survival, and, although 100 mg/kg per day was 100% efficacious, it was a relatively large volume to give intramuscularly to a rat. Therefore, 75 mg/kg per day was used as a therapeutic dose, and it gave favorable results in this study. Histological examination of all placebo-treated animals revealed C. albicans and a marked inflammatory response in the kidney, brain, and heart. C. albicans organisms were observed to be very prominent in these tissues by using the Gomori methenamine silver stain, and were cultured from these organs. Miconazole-treated rats that were killed after surviving the 2-week observation period had minimal histopathological changes, and the organisms present did not exhibit the same staining characteristics, nor were they isolated like those in the placebo-treated group. Miconazole appears to be an efficacious drug for parenteral therapy, as demonstrated in this reproducible model of disseminated candidiasis in laboratory rats, and more extensive experimental studies are indicated.

Animals

Effect of levamisole on metabolism of phagocytic cells.

The effect of levamisole (LMS) on glucose metabolism was studied using a protozoan phagocytic model and human leukocytes. At concentrations of greater than 10 microgram/ml, LMS inhibited glucose metabolism in the protozoan phagocytic model. Glucose metabolism in both the phagocytic model and normal peripheral blood leukocytes was, however, minimally altered when exposed to levels of LMS of less than 10 microgram/ml. In contrast, myeloblasts from a child with leukemia seemed to have increased metabolic activity and 5 microgram/ml of LMS markedly reduced the glucose metabolism. These preliminary studies suggest that LMS can alter glucose metabolism of certain cells and that some malignant cells may be directly inhibited metabolically by LMS.

Child