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Biomedical subjects

G W Fischer

Publications and source records attributed to G W Fischer.

At least 55 records · Page 3Linked to original sources

Cytogenetic, genetic, and embryotoxicity studies with dimethyl 2,2,2-trichloro-1-(2,2,2-trichloro-1-hydroxyethoxy)-ethylphosphonat e, a hypothetical impurity in technical grade trichlorfon.

The hemiacetal (CH3O)2P(O)CHOCHOHCCl3)CCl3, a hypothetical contaminant in technical preparations of the organophosphorus pesticide trichlorfon, was tested for cytogenetic, mutagenic, and embryotoxic activity after ip administration to mice of different strains. A single dose of 81 mg/kg (0.2 mmol/kg) caused a significant enhancement in the percentage of chromosome aberrations in bone marrow cells of CFLP mice; a similar effect was induced by an equimolar single dose of chemically pure trichlorfon (51.5 mg/kg). At the same dosage level, the hemiacetal proved to be ineffective in the micronucleus test on fetal blood of DBA and AB Jena/Halle mice. In the dominant lethal mutation assay, a single dose of 81 mg/kg hemiacetal to males resulted in a slight increase in the fetal mortality of DBA mice, whereas AB Jena/Halle mice did not respond under these conditions. Four consecutive doses of 81 mg/kg hemiacetal to pregnant AB Jena/Halle mice at Days 2, 3, 4, and 5 of gestation caused only a very weak embryotoxic effect comparable to that of trichlorfon at equimolar dosage. On the basis of these results the hemiacetal tested may not be considered to represent a potential risk factor in technical grade trichlorfon.

Animals↗

Antimicrobial therapy of Broviac catheter infections in pediatric hematology oncology patients.

Long-term therapy of pediatric oncology patients has been facilitated by permanent indwelling venous catheters. Over a 3-year period, 54 Broviac catheters were placed in 43 oncology patients and two hemophiliacs. There were 20 episodes of sepsis in 14 patients and the most common bacteria were S epidermidis (4), S aureus (4), and K pneumoniae (3). Catheter exit site infections occurred ten times in six patients; S aureus eight of ten. Antibiotic therapy without catheter removal was successful in 18 of 20 children with catheter sepsis and 8 of 10 patients with exit site infections. These data strongly suggest that although catheter-related infections are common, removal of Broviac catheters is not required for successful treatment of the infection.

Anti-Bacterial Agents↗

Rapid detection of group B streptococcal antigen in human amniotic fluid.

Infants exposed in utero to group B streptococcus (GBS)-infected human amniotic fluid (HAF) are at high risk for serious infection. Latex particle agglutination (LPA) tests are not approved for detection of GBS in HAF. Two LPA systems, Patho-Dx Strep B and Wellcogen Strep B, were used to test unfiltered sterile HAF and filtered HAF containing concentrations of GBS carbohydrate from 0.2 to 100 micrograms/ml. Four different processing techniques were used to prevent nonspecific LPA: EDTA, nitrous acid, enzyme, and nitrous acid-heat. GBS (10(2) CFU/ml) was inoculated into filtered HAF, incubated, sampled serially, processed with enzyme, and tested by LPA. Unprocessed, unfiltered HAF showed 33% nonspecific agglutination when tested by LPA. Processing of HAF removed nonspecific agglutination and improved GBS antigen detection. Without processing, LPA could not detect less than 100 micrograms of GBS carbohydrate per ml. With nitrous acid or enzyme processing, as little as 0.2 microgram/ml could be detected. Results were easier to read after enzyme processing than after nitrous acid processing. Although both LPA systems were equally efficient, testing was easier with the Patho-Dx system. After enzyme processing, LPA could detect as few as 10(4) CFU/ml when agglutination was read with a 4 X hand lens. Substances in HAF induce false-positive reactions during LPA testing. Processing removes the interference and improves the detection of GBS. LPA testing of HAF may allow earlier identification and treatment of infants at risk for serious GBS infection.

Amniotic Fluid↗

A group B streptococcal extract reduces neutrophil counts and induces neutrophil aggregation.

The possibility that group B streptococci (GBS) may induce neonatal neutropenia by promoting neutrophil aggregation and the entrapment of aggregates in the lung was studied in vivo and in vitro utilizing a cell free GBS extract [(GBS)-trichloroacetic acid (TCA)]. The intravenous infusion of the extract into neonatal lambs induced reductions of circulating white blood cells (0 time, 3.1 X 10(3)/mm3 +/- 0.5 versus 2.2 X 10(3)/mm3 +/- 0.7) 5 min after infusion (p less than 0.01). At necropsy these lambs had prominent accumulation of polymorphonuclear leukocytes in their pulmonary interstitium. Subsequently, neutrophil aggregation was studied by incubating GBS-TCA in human serum or phosphate-buffered saline with subsequent addition to human polymorphonuclear leukocytes in an aggregometer. GBS-TCA incubated in human serum induced prompt polymorphonuclear leukocyte aggregation (mean delta T 12.3% +/- 2.8 in human serum versus delta T 2.5% +/- 2.1 in phosphate-buffered saline, p less than 0.001). Preincubation of GBS-TCA followed by incubation in human serum with human GBS hyperimmune IgG significantly reduced aggregation (GBS-TCA in serum mean delta T 14.9 +/- 2.44 versus 5.42 +/- 1.80, p = 0.002). Cell-free GBS products may induce polymorphonuclear leukocyte aggregation in the presence of whole serum. This phenomenon might contribute to the pulmonary injury experienced by infants with GBS pneumonia and sepsis.

Animals↗

Cytogenetic and embryotoxic effects of bromophos and demethylbromophos.

The organophosphorus pesticide bromophos and the tetramethylammonium and sodium salts of demethylbromophos were tested for cytogenetic and embryotoxic activity on mice of different strains. Single intraperitoneal (ip) doses of 183.0 mg/kg (0.5 mmol/kg) and 73.2 mg/kg (0.2 mmol/kg) bromophos caused a significant enhancement in the percentage of chromosome aberrations in bone marrow cells of CFLP mice; similar effects were produced by a single dose of 0.2 mmol/kg demethylbromophos tetramethylammonium salt and demethylbromophos sodium salt trihydrate, respectively, indicating that the cytogenetic activity of bromophos is not connected with its alkylating properties. After repeated ip or oral administration to pregnant mice of strains AB Jena/Halle and DBA, none of the tested compounds showed a marked influence on the total implantation losses, although in some cases the postimplantation losses were significantly increased.

Animals↗

Opsonic and protective activity of immunoglobulin, modified immunoglobulin, and serum against neonatal Escherichia coli K1 infection.

Because modified immune serum globulin (M-ISG) has been proposed for therapy in neonatal bacterial sepsis, we evaluated it in a suckling rat model of Escherichia coli K1 sepsis. We compared a M-ISG preparation (lot 2581), which was protective against group B streptococcal (GBS) sepsis, with other M-ISG, standard ISG preparations and with adult and cord serum. All immune serum preparations and sera demonstrated opsonic activity against E. coli K1 and were superior to saline in protecting against death due to E. coli K1 sepsis. Survival rates were higher for one M-ISG preparation (lot 2581) than for randomly selected standard immune serum globulin and cord sera but were similar to adult sera in these protection studies. Therapeutic and opsonic activity of standard immune serum globulin and M-ISG prepared from the same donors were similar, suggesting that the different processes used for their manufacture did not affect these activities. Because the M-ISG preparation studied showed protective activity to both GBS and E. coli K1, we studied it further by adsorbing the preparation with GBS and E. coli K1. Opsonic activity to E. coli K1 was removed by E. coli adsorption but not by adsorption with GBS, indicating that this activity was not due to a single cross-reacting antibody. Empirical therapy with M-ISG prescreened for opsonic activity to both E. coli K1 and GBS may be of clinical value. Trials appear warranted to study the pharmacology and efficacy of M-ISG in septic newborns.

Animals↗

Rapid in vitro replication of group B streptococcus in term human amniotic fluid.

4-hour in vitro growth curves of a type III group B streptococcus (GBS) and Escherichia coli were examined in sterile term human amniotic fluid specimens. Both bacterial strains proliferated despite ratios of phosphate to elemental zinc in the range reportedly inhibitory for E. coli. After 4 h of incubation, despite comparable inocula, GBS numbers exceeded those of E. coli by 10-fold. The strikingly rapid growth of some GBS strains in amniotic fluid may represent yet another factor responsible for perinatal GBS infection of the human neonate.

Amniotic Fluid↗

Avoidance of false-negative blood culture results by rapid detection of pneumococcal antigen.

False-negative blood culture results may occur in children with pneumococcal bacteremia due to bacterial autolysis. We describe four patients with pneumococcal bacteremia whose aerobic blood cultures showed partial or complete autolysis of the pneumococci. Pneumococcal antigen, however, was rapidly detected in media from the blood culture bottles, using an agglutination assay. Processing of the media before analysis was necessary to prevent nonspecific agglutination and to allow the detection of a specific reaction. It is important that physicians and laboratory personnel be aware that pneumococci may rapidly autolyze during incubation, yielding false-negative culture results. Antigen detection methods may provide rapid and specific identification of the etiologic agent.

Agglutination Tests↗