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Biomedical subjects

B R Smith

Publications and source records attributed to B R Smith.

At least 235 records · Page 13Linked to original sources

In vitro activity of A-56619 and A56620, two new aryl-fluoroquinolone antimicrobial agents.

The in vitro antimicrobial activity of two new aryl-fluoroquinolone antibiotics, A-56619 and A-56620, was compared with those of norfloxacin and several other antibiotics against 448 bacterial isolates. A-56620 was the most active agent tested. The usual 90% MIC of A-56620 was less than or equal to 2 micrograms/ml, except for enterococci, gentamicin-resistant Serratia marcescens, and gentamicin-resistant Pseudomonas aeruginosa, for which the 90% MIC was 4 micrograms/ml. A-56619 and norfloxacin were generally severalfold less active than A-56620. Cross resistance was observed between the quinolone antibiotics and other unrelated antibiotic classes.

Anti-Bacterial Agents↗

Cefotetan pharmacokinetics in volunteers with various degrees of renal function.

Twenty-six volunteers with various degrees of renal function were given a single 1-g dose of cefotetan intravenously over 30 min. Concentrations of cefotetan and cefotetan tautomer in plasma and urine were determined by high-performance liquid chromatography. The pharmacokinetic parameters for cefotetan were calculated according to a two-compartment open model. The mean plasma cefotetan concentration at the end of the intravenous infusion did not vary with renal function and ranged between 122 and 126 micrograms/ml. The mean terminal half-life was 4.2 h in normal volunteers and 9.9 h in volunteers with moderate renal impairment. There was a significant linear correlation between the systemic clearance of cefotetan and creatinine clearance. The cumulative amount of cefotetan excreted in the urine over 24 h in normal volunteers was approximately 49% of the dose, but this was reduced in volunteers with moderate renal impairment. The mean urinary cefotetan concentrations generally peaked during the 2- to 4-h interval after dosing. Cefotetan tautomer was sporadically detected in the plasma and urine of approximately 50% of the volunteers. The mean plasma cefotetan tautomer concentrations and mean total cumulative urinary recoveries of cefotetan tautomer were only minimal compared with those for cefotetan. The mean percentage of the dose excreted in the urine as cefotetan tautomer was not significantly affected by the degree of renal impairment. Recommendations for the dosing of cefotetan in renal-impaired patients are given.

Adolescent↗

Osteolytic phaeohyphomycosis in a German shepherd dog caused by Phialemonium obovatum.

Phialemonium obovatum was found to be the cause of osteomyelitis in a German shepherd dog. Histologic examination of the biopsied material from the left tibia revealed septate, irregularly branched hyphae, swollen cells, and ovate-to-spherical cells divided by a transverse septum. The majority of the fungal elements were hyaline, but a few had lightly pigmented cell walls that had a greenish yellow tint. The presence of melanin in the cell walls of the hyphae and especially in their septa was verified by the use of the Fontana-Masson silver stain. P. obovatum formed moist, off-white-to-ochraceous, spreading colonies with a characteristic green pigment on their reverse side. The pigment was more prominent in cultures grown at 37 degrees C than in those grown at 25 degrees C. The isolate also grew at 40 degrees C. The dog isolate produced characteristic adelophialides without conspicuous collarettes and also basal septa from the creeping vegetative hyphae growing on the surface of the medium. The numerous obovate phialoconidia were smooth and one-celled.

Animals↗

Evidence for oligoclonal B cell expansion in the peripheral blood of patients with rheumatoid arthritis.

Peripheral blood lymphocytes from patients with rheumatoid arthritis and osteoarthritis were examined for evidence of oligoclonal B cell expansion using the computer assisted flow cytometric technique of kappa-lambda (kappa-lambda) analysis. Eleven of 29 patients with rheumatoid arthritis but only one of 16 with osteoarthritis gave abnormal results (p less than 0.025). Abnormal kappa-lambda determinations did not correlate with age, duration of disease, presence of rheumatoid factor, or other clinical and laboratory parameters. Therapy with oral or intramuscular gold compounds appeared to diminish the incidence of kappa-lambda abnormality. These findings may indicate defective control of clonal B cell proliferation in rheumatoid arthritis.

Adult↗

Aortic arch development.

Stereomicroradiographic images of timed-gestation mouse embryos clarify aortic development and help one to understand human vascular anomalies.

Angiography↗

HTLV-III infection after bone marrow transplantation.

We prospectively documented the development of a fatal, secondarily acquired severe immunodeficiency in a 19-year-old man who underwent uncomplicated bone marrow transplantation. He had no graft v host disease (GVHD) and had normal recovery of his immune system as determined by lymphocyte phenotyping, mitogenic responses of his peripheral blood lymphocytes, and his ability to secrete immunoglobulin. This alteration in immunity was associated with the acquisition of antibody to HTLV-III. His only risk factor for the development of HTLV-III infection was the transfusions he had received during the transplant and recovery period. Two of his 54 transfusions were from an asymptomatic individual at high risk for acquired immunodeficiency syndrome (AIDS), who was subsequently found to be seropositive for anti-HTLV-III and from whom HTLV-III was isolated. The loss of immunocompetence in patients without chronic GVHD disease is unusual, and our data support the view that this patient's immunodeficiency was due to HTLV-III. When bone marrow transplant recipients without chronic GVHD develop late opportunistic infections, consideration should be given to transfusion-associated AIDS.

Acquired Immunodeficiency Syndrome↗

Phenotype of recovering lymphoid cell populations after marrow transplantation.

Four patients who received bone marrow transplants were studied sequentially during the posttransplant period to define the pattern of recovering lymphoid cell types. Three patients received T cell-depleted, HLA-matched marrow, and one received untreated marrow from an identical twin. Blood lymphoid cells were labeled with 25 different pairs of monoclonal antibodies. In each sample, one antibody was conjugated to fluorescein and one to phycoerythrin, thus allowing simultaneous assessment of the expression of the two markers using the fluorescence activated cell sorter. A total of 14 antibodies were used, routinely including HLE, Leu-M3, Leu-4, Leu-1, Leu-5, Leu-9, Leu-6, Leu-2, Leu-3, HLA-DR, Leu-7, Leu-11, Leu-15, and Leu-12. Other antibodies were used to further define some populations. This study has allowed us to define six distinct cell types that have appeared in all four patients by day 90 posttransplantation, and which account for 90-100% of all circulating lymphoid cells. These cell types are (a) T helper cells expressing Leu-1, Leu-4, Leu-9, Leu-5, Leu-3, and variable amounts of HLA-DR; (b) T suppressor cells expressing Leu-1, Leu-4, Leu-9, Leu-5, Leu-2, and variable amounts of HLA-DR; (c) B cells expressing Leu-12, B1, HLA-DR, IgD, and IgM, but none of the T cell antigens; (d) an unusual B cell phenotype (Leu-1 B) expressing all of the B cell markers, and also having low amounts of Leu-1, but none of the other T cell antigens; (e) natural killer (NK) cells expressing Leu-11, Leu-15, Leu-5 but none of the other T cell or B cell markers; (f) NK cells expressing Leu-11, Leu-15, Leu-5, and low levels of Leu-2. Both NK types also express Leu-7 on some, but not all cells. The relative frequencies of these cell types varied among the patients and with time, but the striking findings were the presence of relatively few mature T cells, large numbers of NK cells, and the preponderance of the unusual Leu-1 B cell over conventional B cells in all three patients who developed B cells. Sorting experiments confirmed the NK activity of the major NK cell phenotypes, and DNA analysis confirmed that all of the cells studied were of donor origin. In addition, analysis of Ig genes in one patient showed that the Leu-1 B cells were not clonally rearranged.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

A time-dependent biphasic effect of an acute ethanol injection on 3-methoxy 4-hydroxyphenylethylene glycol sulfate in rat brain.

The present experiment demonstrated that acute administration of ethanol appeared to have a biphasic effect on the accumulation of 3-methoxy-4-hydroxyphenylethylene glycol sulfate (MHPG-SO4) in rat brain. The magnitude of these alterations in MHPG-SO4 levels was also observed to be highly correlated with peripheral blood ethanol levels. Since levels of MHPG-SO4 are considered to be an index of noradrenergic activity, the findings suggest that ethanol may affect norepinephrine activity in a specific dose- and time-dependent manner. These results are discussed in reference to previous reports describing apparent divergent effects on norepinephrine. Possible mechanisms for the biphasic actions are also suggested.

Animals↗

Treatment of the blastic transformation of chronic granulocytic leukemia using high dose BCNU chemotherapy and cryopreserved autologous peripheral blood stem cells.

Seven nonsplenectomized patients with blastic CGL have received high dose BCNU chemotherapy followed by cryopreserved peripheral blood stem cells (PBSC). The PBSC obtained at diagnosis were stored in the vapor phase of liquid nitrogen in 10% dimethyl sulfoxide for 11-46 months prior to use. Patients received 2.9 X 10(8) (1.9-7.8) thawed washed mononuclear cells/kg over 30 minutes with minimal morbidity. One patient was not rendered pancytopenic and died with blastic leukemia at 4 months. One patient, previously treated with daily busulfan, died of progressive hepatic failure 2 months after high dose BCNU. Restoration of the chronic phase of CGL was observed in the remaining five patients. Peripheral blood counts returned to normal ranges after a median of 19 days. Median survival for all patients is 11 months. Cytogenetic studies revealed elimination of acquired aneuploid cell lines in four of seven patients with persistence of Ph1. We conclude that: 1) frozen PBSC retain their viability for up to 4 years after cryopreservation and 2) the use of autologous PBSC following ablative chemotherapy may be associated with both symptomatic and karyotypic improvement in patients with blastic CGL.

Adolescent↗

The role of gamma-aminobutyric acid (GABA) in the regulation of ethanol and acetaldehyde self-administration.

Laboratory rats were presented with ethanol and water in a free-choice paradigm to determine each animal's preference for ethanol. Following a three week ethanol free period, it was observed that the duration of gamma-butyrolactone induced loss of righting reflex was negatively correlated to voluntary ethanol intake. It was also observed that the rate of intracerebroventricular self-administration of acetaldehyde was positively correlated with the latency to gamma-butyrolactone induced loss of righting reflex. These findings indicate that high ethanol drinking rats and high acetaldehyde self-administrating rats are less sensitive to the sedative action of gamma-butyrolactone.

4-Butyrolactone↗

Gram-negative bacillary meningitis.

The incidence of gram-negative bacillary meningitis has increased significantly in the past two decades. Approximately two thirds of all reported cases have occurred after neurosurgical procedures. With the development of the newer cephalosporins, the overall mortality rate has decreased from 40 to 80 per cent to 10 to 20 per cent.

Aminoglycosides↗

IgG-mediated haemolysis masquerading as cold agglutinin-induced anaemia complicating severe infection with mycoplasma pneumoniae.

Haemolytic anaemia complicating Mycoplasma infection has usually been attributed to IgM cold agglutinins. This report describes a patient with pneumonia due to Mycoplasma pneumoniae in whom severe haemolysis persisted despite declining thermal amplitude and titre of cold agglutinins as the infection resolved. Class-specific anti-globulin (Coombs) testing defined an IgG warm agglutinin coating the patient's erythrocytes that was distinct from the IgM cold agglutinin identified by Sephadex G-200 gel filtration and dithiothreitol inactivation. Monoclonal IgM(gamma) and IgK(k) circulating proteins were identified and immuno-electrophoresis of the cold agglutinin-containing cryoglobulin fraction identified the cold agglutinin as an IgM(gamma). In this patient initially presumed to have cold agglutinin induced haemolysis secondary to Mycoplasma infection, an IgG warm agglutinin was identified as the aetiology for the patient's haemolysis, underscoring the clinical relevance of careful evaluation of the mechanism of haemolysis accompanying Mycoplasma pneumonia.

Agglutinins↗

Comparative in vitro evaluation of cefpimizole (U-63196E), a new antipseudomonal cephalosporin.

The activity of cefpimizole (formerly U-63196E) was compared with that of other broad-spectrum cephalosporins and penicillins. Overall, cefpimizole exhibited limited activity against gram-positive cocci and members of the family Enterobacteriaceae as compared with the other cephalosporins tested. The activity of cefpimizole against Pseudomonas aeruginosa was similar to that of cefoperazone and mezlocillin (90% MIC, 32 micrograms/ml) but poorer than that of ceftazidime (90% MIC, 8 micrograms/ml). Cefpimizole appears to have no in vitro advantage over the cephalosporins with which it was compared.

Cephalosporins↗