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Biomedical subjects

J M Andrews

Publications and source records attributed to J M Andrews.

At least 19 recordsLinked to original sources
PubMed1992

Cytomegalovirus infection, fetal liver disease, and neonatal hemochromatosis.

Neonatal hemochromatosis is an uncommon disorder, clinicopathologically defined by severe and generally fatal liver disease of intrauterine onset associated with extrahepatic siderosis that spares reticuloendothelial elements (hemochromatotic siderosis). The agent or agents of liver disease in neonatal hemochromatosis are not known. It also is not known if intrauterine liver disease of defined infective etiology can lead to hemochromatotic siderosis. We present two patients with fetal liver disease and hemochromatotic siderosis whose cases help address these points. In the first patient rare hepatobiliary and numerous renal tubular cytomegalovirus (CMV) inclusions were found; CMV infection was confirmed by the polymerase chain reaction. Studies of the mother of the second patient 1, 5, and 9 weeks post-partum showed recent seroconversion against CMV; seroconversion against other infectious agents (toxoplasma, rubella, herpes, parvovirus B19, hepatitis A/B/C) was not present. Histologic, immunohistochemical, in situ hybridization, or polymerase chain reaction evidence of CMV infection was not present in infant tissues, even though peripartum maternal seroconversion against CMV was observed. We conclude that hemochromatotic siderosis may accompany chronic fetal liver disease of defined infective etiology (patient no. 1) and that recent maternal seroconversion against CMV in the presence of severe fetal liver disease does not necessarily mean that transplacentally acquired CMV infection caused the fetal liver disease (patient no. 2). Polymerase chain reaction documentation of infective-agent genomic sequences in fetal or infant tissues permits more accurate interpretation of maternal serologic data.

Adolescent↗
PubMed1992

In-vitro activity of PD 131628, a new quinolone antimicrobial agent.

The in-vitro activity of PD 131628, the active metabolite of the prodrug PD 131112, was compared with that of ciprofloxacin and members of other groups of antimicrobial agents against 701 recent clinical isolates and strains with known mechanisms of resistance. The MIC90s of PD 131628 against the Enterobacteriaceae were between 0.008 and 0.5 mg/L; PD 131628 was one- to four-fold more active than ciprofloxacin against these strains and was four-fold more active than ciprofloxacin against Pseudomonas aeruginosa. Against the Gram-positive species tested, PD 131628 was two- to four-fold more active than ciprofloxacin, inhibiting all strains of Staphylococcus aureus and Streptococcus pneumoniae with 0.5 mg/L or less. PD 131628 was very active against Neisseria spp., Haemophilus influenzae and Moraxella catarrhalis, with MIC90s ranging from 0.004 to 0.008 mg/L. Organisms with decreased susceptibility to other quinolones had decreased susceptibility to PD 131628, but there was no cross-resistance between this class of antimicrobial and other classes. The protein binding of PD 131628 was at most 25% across a broad range of concentrations. The addition of 70% human serum had little effect on the MICs, but caused a two- to eight-fold increase in MBCs.

Anti-Infective Agents↗
PubMed1992

The in-vitro activity of two new quinolones: rufloxacin and MF 961.

The in-vitro activity of two new quinolone antimicrobials, rufloxacin and MF 961, together with the desmethylated metabolite of rufloxacin (MF 922) were compared with other orally administered agents against 622 bacterial strains. Against Enterobacteriaceae and Pseudomonas aeruginosa rufloxacin was generally active (MIC90 1-8 mg/L) with the exception of Klebsiella and Serratia spp. (MIC90 32 mg/L and Enterobacter spp. (MIC90) 64 mg/L. The respiratory pathogens Haemophilus influenzae and Moraxella catarrhalis were susceptible to rufloxacin (MIC90 0.5 and 1 mg/L respectively) but Streptococcus pneumoniae was less susceptible (MIC90 32 mg/L). Staphylococcus aureus were susceptible to rufloxacin (MIC90 2 mg/L). The rufloxacin metabolite MF 922 was generally as active as its parent. MF 961 was usually two-fold more active than rufloxacin. All three compounds were four to 16 times less active than norfloxacin, but rufloxacin was as active or somewhat more active than norfloxacin against Staphylococcus spp. Any strains showing decreased susceptibility to other quinolones exhibited cross resistance to these new agents. The MBC of rufloxacin and MF 922 was within one dilution of the MIC and human serum had little effect upon the activity of both agents. The protein binding of rufloxacin and MF 922 at 1 and 10 mg/L were 55% and 63.8% and 30.3% and 32.6% respectively. The activity of rufloxacin against four strains of Chlamydia trachomatis and one strain of Chlamydia pneumoniae was determined. The MICs for C. trachomatis were 4-8 mg/L and 4 mg/L for C. pneumoniae.

Anti-Infective Agents↗
PubMed1992

Pharmacokinetics and inflammatory fluid penetration of sparfloxacin.

A single 400-mg oral dose of sparfloxacin was given to each of six healthy male volunteers, and the concentrations of the drug were measured in plasma, cantharides-induced inflammatory fluid, and urine over the subsequent 52 h. The mean peak concentration in plasma of 1.6 micrograms/ml was attained at a mean time of 2.7 h postdose. The mean peak concentration in inflammatory fluid of 1.3 micrograms/ml was attained at a mean time of 5 h postdose. The mean elimination half-life in plasma was 17.6 h, and that in inflammatory fluid was 19.7 h. The overall penetration into inflammatory fluid was 117%. Urinary recovery within the first 52 h postdose was 8.8% of the administered dose. Our results indicate that a once-daily dosage of sparfloxacin should be adequate to treat systemic infections caused by most common bacterial pathogens.

Administration, Oral↗
PubMed1992

Pharmacokinetics and tissue penetration of ampicillin and brobactam following oral administration of 2085P.

Eight healthy volunteers received a 1,000-mg single oral dose of 2085P which consisted of 800 mg of pivampicillin and 200 mg of brobactam. Concentrations of ampicillin and brobactam in plasma, inflammatory fluid, and urine were measured over the subsequent 24 h. Pivampicillin and brobactam were moderately rapidly absorbed. The mean (standard deviation) maximum concentration in plasma (Cmax) of ampicillin was 8.2 (1.9) micrograms/ml, and that of brobactam was 2.1 (2.0) micrograms/ml at mean times of 1.9 (0.5) and 2.3 (0.8) h, respectively. The elimination half-lives in plasma were 1.8 (0.5) and 1.6 (2.0) h, respectively. Both agents penetrated the experimentally induced inflammatory fluid, reaching a mean maximum at 3 h. The Cmax of ampicillin was 6.8 (2.3) micrograms/ml, and that of brobactam was 1.0 (0.4) micrograms/ml. The penetration (derived by comparing the area under the concentration-time curve from 0 h to infinity for inflammatory fluid with that for plasma) was 97.3% (26.0%) for ampicillin and 81% (22.3%) for brobactam. The 24-h urinary recovery was 54.2% (16.6%) of the administered dose for ampicillin and 40.2% (11.4%) for brobactam. These data suggest that this combination of beta-lactam and inhibitor should be efficacious in treating infections caused by ampicillin-resistant pathogens.

Administration, Oral↗
PubMed1992

The distribution of temafloxacin in bronchial epithelial lining fluid, alveolar macrophages and bronchial mucosa.

The concentrations of temafloxacin, a new fluoroquinolone antimicrobial, in the potential sites of pulmonary infection were assessed by fibreoptic bronchoscopy with bronchoalveolar lavage. Fourteen patients received a course of temafloxacin, 600 mg twice daily, for three days prior to sampling. The mean serum concentration was 9.6 (SEM 1.2) mg.l-1, compared with 14.9(SEM 1.8) mg.kg-1 for bronchial mucosa, 26.5 (SEM 3.6) mg.l-1 for epithelial lining fluid and 83.0 (SEM 11.5) mg.l-1 for alveolar macrophage. In the ten patients who completed the protocol, site concentrations correlated well with serum concentrations. Temafloxacin was concentrated in each of the potential sites of infection examined and is, therefore, a promising new agent for the treatment of respiratory tract infection.

Anti-Infective Agents↗
PubMed1979

Mezlocillin and azlocillin: an evaluation of two new beta-lactam antibiotics.

Mezlocillin and azlocillin are broad spectrum penicillins for parenteral administration. In this study it was shown that they were very active against a wide range of pathogenic bacteria. Thirty-five patients were treated with mezlocillin, and 5 patients were treated with azlocillin (in combination with cefoxitin in 3 cases). The serum, bile and CSF levels of the drugs were measured. Both antibiotics would appear to be safe and efficacious in treating serious infections by sensitive pathogens. Infections caused by unknown pathogens could be treated by one of these agents in combination with a broad spectrum beta-lactamase stable cephalosporin or cephamycin.

Adolescent↗
PubMed1979

A pharmacological and in vitro comparison of three oral cephalosporins.

The pharmacology of cephradine, cephalexin and a new oral cephalosporin, cefaclor, has been compared in six volunteers. Cefaclor was absorbed rapidly and was cleared from the serum more rapidly than the other two agents. This was probably partially due to its instability in serum at body temperature, which was investigated. Against a wide range of common pathogens cefaclor was the more active oral cephalosporin. In particular the activity against Neisseria gonorrhoeae and Haemophilus influenzae was of interest.

Administration, Oral↗
PubMed1979

LY127935, a novel oxa-beta-lactam: an in vitro comparison with other beta-lactam antibiotics.

The in vitro activities of LY127935 (LY) were compared with those of other beta-lactam antibiotics. LY was highly active (minimal inhibitory concentration [MIC] range 0.06 to 0.25 micrograms/ml) against the common Enterobacteriaceae (including Providencia stuartiia, Enterobacter, and Serrati marcescens), 8 to 16 times more active than cefoxitin, cefuroxime, or cefazolin, and from one-half to one-eighth as active as cefotaxime (HR756). The activity of LY against Pseudomonas aeruginosa (with MICs of 4 and 64 micrograms/ml for 50 and 90% of test strains, respectively) was essentially similar to that of cefotaxime, but was only one-half as active as CGP 7174/E. LY, cefoxitin, and cefotaxime were essentially equally active against Bacteroides fragilis--each was more active than cefuroxime and cefazolin. Against Staphylococcus aureus, LY (50% MIC and 90% MIC of 4 and 16 micrograms/ml, respectively) was less active than cefotaxime, cefoxitin, or cefuroxime and one-eighth as active as cefazolin. The composition and pH of the culture medium had little effect on the activity of LY, although 7.2 appeared to be the optimum pH.

Anti-Bacterial Agents↗
PubMed1979

Comparative in vitro microbiological activity and stability of cefaclor.

The in vitro activity of cefaclor was compared with that of cephalexin and cephradine. This new antibiotic was the most active of the oral agents against Haemophilus influenzae (especially non-beta-lactamase producing strains). It was also significantly more active against N. gonorrhoeae and the Enterobacteriaceae. The instability in agar raises some issues that need further study.

Bacteria↗
PubMed1979

The enzymatic nature of human c1r: a subcomponent of the first component of complement.

The esterase activity of the C1r subcomponent of the first component of complement has been investigated. C1r was found to hydrolyze two amino acid methyl esters; N-acetyl-L-arginine methyl ester and N-acetyl-glycyl-L-lysine methyl ester, and two amino acid p-nitrophenyl esters, N-carbobenzyloxy-L-tyrosine-p-nitrophenyl ester and N alpha-carbobenzyloxy-L-lysine-p-nitrophenyl ester. A detailed kinetic analysis of the hydrolysis of N-Z-L-Tyr-ONp by C1r revealed that the enzymatic activity per microgram of protein decreased as the C1r concentration was increased. The loss of activity suggested that above 0.5 micron C1r was undergoing aggregation with a loss of active sites. Similarly, when C1r was titrated with the active site titrant p-nitrophenyl-P'-guanidinobenzoate the number of titratable sites per milligram of protein decreased with increasing protein concentration. The hydrolysis of N-Z-L-Tyr-ONp by C1r was inhibited by several synthetic inhibitors including phenylmethanesulfonylfluoride, p-amidinophenylmethanesulfonylfluoride, diisopropylfluorophosphate, and p-tosyl-L-lysine-chloromethyl ketone. However, the peptide esterase inhibitors Trasylol, hirudin, leupeptin, and C1 esterase inhibitor had no effect on the esterase activity of C1r.

Chemical Phenomena↗
PubMed1978

Decreased spinal cord cGMP in murine (wobbler) spontaneous lower motor neuron degeneration.

Of the secondary messengers, cyclic quanosine monophosphate, but not cyclic adenosine monophosphate, was reduced by 80% in the cervical spinal cord and by 56% in the cerebellum of clinically affected homozygote "wobbler" mice compared to sex- and age-matched litter-mate clinically unaffected control mice. A neurotransmitter, gamma aminobutyric acid, and high-energy intermediates, adenosine triphosphate and phosphocreatine, were not significantly different in affected or unaffected mice.

Animals↗
PubMed1978

Inhibition of four human serine proteases by substituted benzamidines.

A series of substituted benzamidines has been examined for their inhibitory activity against the human serine proteases--trypsin, thrombin, plasmin, and C1s, a subunit of the first component of complement. The inhibition constants obtained for each enzyme were correlated with physical-chemical properties of the substituent group using the quantitative structure-activity relationship approach. This analysis indicated that plasmin and C1s are very similar in their interactions with substituted benzamidines. The binding of benzamidines in both enzymes was affected by electron donation from the substituent and its hydrophobicity. Thrombin-benzamidine interaction was affected only by the hydrophobicity of the substituent. Trypsin displayed a complex interaction with substituted benzamidines, and interaction was dependent on molar refractivity and molecular weight. Certain substituents deviated significantly from the interactions predicted by the analysis. These compounds, the (m- and p-amidinophenyl)pyruvic acids, when analyzed by computer modeling, suggested that direct interaction between the substituent and the enzyme surface is important in assessing the effect of substituent groups on inhibitory activity.

Amidines↗