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Biomedical subjects

H Mattie

Publications and source records attributed to H Mattie.

At least 109 records · Page 6Linked to original sources
PubMed1984

Role of granulocytes in the prevention and therapy of experimental Streptococcus sanguis endocarditis in rabbits.

The contributions of granulocytes to the prevention and therapy of Streptococcus sanguis endocarditis with procaine benzylpenicillin (PBP) was investigated in rabbits. Depletion of granulocytes by treatment with mechlorethamine appeared to have no significant effect on either the prophylactic or therapeutic activities of PBP. Administration of 3,000 IU of PBP before inoculation with S. sanguis retarded the course of the endocarditis for only 24 h whether granulocytes were normal or depressed in numbers. Prophylaxis with either 15,000 or 30,000 IU of PBP was equally effective in non-granulocytopenic and granulocytopenic rabbits. Treatment of established infections with PBP at doses of 3,000 to 300,000 IU of PBP at 12-h intervals for 48 h was equally effective in rabbits with normal and depressed numbers of granulocytes. The effect of 3,000 IU of PBP was equivalent, however, to that of granulocytes alone, as shown by the fact that the numbers of CFU per gram of vegetation in the granulocytopenic rabbits treated with this dose of PBP and in the non-PBP-treated control rabbits were not significantly different.

Agranulocytosis↗
PubMed1983

The antibacterial activity of combinations of mecillinam and ampicillin in vitro and in normal and granulopenic mice.

The antibacterial activity of mecillinam and ampicillin, alone and in combination, against Escherichia coli was quantitated and compared in vitro and in vivo. Minimum inhibitory concentrations (MICs) were determined for both antibiotics individually and combined. Two-hour growth curves were established in vitro. A quadratic fit to these growth curves provided quantitative concentration-dependent growth characteristics. The antibacterial activity in vivo was determined by applying a short-term thigh muscle infection model to normal and irradiated granulopenic mice. The effects in vivo were also quantitated as dose-dependent or concentration-dependent parameters. Mecillinam showed activity in vitro, but none in vivo. Combinations of mecillinam with ampicillin showed a strong potentiation, as judged from MICs and from short-term experiments in vitro and in the normal and irradiated granulopenic mice. The potentiating activity in vivo was not influenced by host factors (i.e. granulocytes). However, the degree of potentiation indicated by the MICs led to strong overestimation of the effect of the combination of the two antibiotics on short-term in vitro growth. Furthermore, the combined activity in vitro overestimated the potentiating effect of the two antibiotics in vivo.

Amdinocillin↗
PubMed1983

Comparison of in vitro and in vivo ampicillin susceptibility of Escherichia coli pretreated with low concentrations of mecillinam and ampicillin.

The ampicillin susceptibility of Escherichia coli showing morphological changes after pretreatment with low concentrations of mecillinam (spherical forms) or ampicillin (filaments) was compared in vitro and in vivo in short term experiments. Normal non-pretreated bacteria and mecillinam- or ampicillin-pretreated bacteria were cultured in vitro in the presence and absence of ampicillin. The growth curves were mathematically described as quadratic functions of time and these functions provided parameters characterizing the growth kinetics. The mecillinam pretreatment did not affect the growth rate relative to that of normal non-pretreated bacteria. The ampicillin susceptibility of these mecillinam-pretreated forms was, however, strongly increased. The ampicillin pretreatment resulted in an increased initial growth rate of the bacteria which normalized after about 1 1/2 h. The ampicillin susceptibility of these bacteria was unchanged. The growth and the ampicillin susceptibility of these ampicillin- or mecillinam-pretreated bacteria in an intramuscular infection in irradiated granulopenic mice were comparable with those seen in vitro. This outcome in vivo was influenced by the granulocytes when growth and ampicillin susceptibility were determined in non-irradiated mice. The mecillinam-pretreated bacteria were slightly more affected by both granulocytes and ampicillin than normal bacteria were. The ampicillin-pretreated bacteria were affected by both these factors to the same extent as normal bacteria.

Amdinocillin↗
PubMed1983

A quantitative evaluation of pulmonary macrophage kinetics.

A new mathematical approach to the calculation of the kinetics of macrophages in a tissue compartment is presented. This approach, which takes into account the influx of monocytes into the compartment, the local division of mononuclear phagocytes, and the efflux of macrophages from the compartment, was applied to data on the pulmonary macrophages of mice in the normal steady state. The results show that at least 70% of the pulmonary macrophage population is supplied by monocyte influx and at most 30% by local division of immature mononuclear phagocytes originating from the bone marrow. The calculated turnover time of pulmonary macrophages is about 6 days, and the turnover amounts to 14.6 X 10(3) macrophages/hr.

Animals↗
PubMed1982

Role of granulocytes in experimental Streptococcus sanguis endocarditis.

We investigated the role of granulocytes during the induction and course of experimental Streptococcus sanguis endocarditis in rabbits by depleting blood granulocytes with nitrogen mustard. The induction of the endocarditis was not influenced by granulocytopenia: the 50% infectious dose was 5.4 X 10(4) colony-forming units in normal and granulocytopenic rabbits. However, granulocytopenia influenced the curse of the endocarditis, as shown by a significant increase in the number of colony-forming units per gram of vegetation (P less than 0.02) from 24 to 72 h after the injection of 10(5) colony-forming units of S. sanguis. This rise did not occur in the control rabbits. Furthermore, bacteremia was significantly higher in the granulocytopenic rabbits (P less than 0.05) during the first 48 h compared with the control rabbits. This was not because of altered clearance of the streptococcus inoculum or seeding of streptococci from extracardiac bacterial foci. We concluded that granulocytes have no measurable effect on the induction of S. sanguis endocarditis, but during the course of the endocarditis, granulocytes keep the endocardial infection in check.

Agranulocytosis↗
PubMed1981

The effect of co-trimoxazole on serum creatinine.

1 Co-trimoxazole induces a highly significant and reversible elevation of the serum creatinine level. 2 In renal-allograft patients the degree of this elevation is significantly correlated with the concentration of serum creatinine before administration of co-trimoxazole and with the concentration of non-protein-bound trimethoprim.

Anti-Infective Agents↗
PubMed1981

The relative potency of amoxycillin and ampicillin in vitro and in vivo.

The relative antibacterial efficacy of amoxycillin ampicillin was compared in vitro and in vivo against a strain of Escherichia coli in short-term experiments (hours). The quadratic fit to the growth curves in vitro in the presence of the antibiotic gave concentration dependent parameters. The concentration effect curves for both antibiotics showed that amoxycillin varied between equipotent (at 2 mg/l) and twice as potent (at higher concentrations) as ampicillin. The relative efficacy in vivo was determined in a thigh muscle infection in irradiated as well as normal mice. Numbers of colony forming units 3 h after infection were dose (or concentration) dependent, the slopes for amoxycillin and ampicillin being parallel. Slopes in irradiated and non-irradiated mice differed significantly. In both kinds of animals the average potency ratio was 1.5 in favour of amoxycillin. Thus, no difference was found between the in vitro and in vivo situation regarding relative efficacy.

Amoxicillin↗
PubMed1981

Comparative study on the circulatory and respiratory effects of buprenorphine and methadone.

A comparative study on the effects on circulation and respiration of buprenorphine and methadone was performed on a group of four healthy volunteers in a double blind way. Both drugs were given by continuous slow i.v. infusion. Before and after administration of the drugs, the subjects breathed in an open, resp. closed system, gas mixtures of 50% O2 / 50% N2 resp. 50% O2 / 43% N2 / 7% CO2. After each breathing/rebreathing period pupil diameters were measured photographically. The effects on respiration were calculated as shifts in vol. % CO2 necessary to obtain a standard respiratory minute volume. Analysis of variance showed a dose-independent inhibition of respiration of buprenorphine and a dose-dependent inhibition of methadone. Both drugs caused a weakly dose-dependent miosis. There were no significant dose-dependent effects on circulation and both drugs caused a similar side effect profile.

Adult↗
PubMed1979

Rectal bioavailability of lidocaine in man: partial avoidance of "first-pass" metabolism.

It is often speculated that after rectal administration drugs will enter the systemic circulation without first passing through the liver, because at least the lower hemorrhoidal veins are not connected to the portal system. To test this hypothesis, the systemic availability of the high-clearance drug lidocaine was investigated in 6 healthy subjects following administration of 200 mg intravenous, 300 mg oral, and 300 mg rectal lidocaine in a balanced crossover design. Plasma and whole blood concentrations of lidocaine were measured by capillary gas chromatography. The mean rectal systemic availability was higher than the oral: 63% vs 31% (whole blood) and 71% vs 34% (plasma). The elimination half-lifes (t1/2els) lidocaine were about the same intravenously and orally, whereas these were slightly longer after rectal administration. The oral and rectal investigations were repeated in the same panel of volunteers about 6 mo later. The mean rectal systemic availability, based on plasma concentrations, was then 67% vs 27% orally. Intraindividual variability was rather small, indicating that oral and rectal bioavailability of lidocaine is reproducible in individuals. An equation was derived for the calculation of the fraction of the dose given rectally that bypasses the liver after absorption which is slightly more than half the dose, assuming that dose is 100% absorbed. This investigation indicates that in principle it is possible to avoid, at least partly, drug loss caused by "first-pass" metabolism by giving the drug rectally.

Administration, Oral↗
PubMed1979

Antibacterial efficacy of cefazolin and cephradine in neutropenic mice.

The activity of cefazolin (CEZ) and cephradine (CED) was studied in experimentally infected neutropenic mice. Neutropenia was induced by 600 rad whole-body irradiation; an infection was induced by the injection of 5 X 10(6) Escherichia coli into the thigh on Day 5 after irradiation. Antibiotics were administered 1 h later, and antibacterial activity was estimated from bacteria counts made in the homogenized individual thighs 3 h after infection. The effect of a low dose of each of the cephalosporins on the infection was significantly lower in the absence of granulocytes than in animals with intact host defence; at higher dosages the effect of both antibiotics on the infection was the same in neutropenic and unirradiated mice. In the neutropenic mice, CEZ was 2.95 times more active than CED against E. coli in vivo, this difference in activity being similar to that found earlier in normal mice.

Agranulocytosis↗
PubMed1979

Influence of aminopenicillins on bacterial growth kinetics in vitro in comparison with the antibacterial effect in vivo.

To quantify the relative antibacterial efficacy of beta-lactam antibiotics in vitro, a mathematical description of bacterial growth was developed. Curves of growth in the presence of the antibiotic are expressed as quadratic functions of time, with initial growth rate (ko) and rate of change of growth (a) as concentration dependant variables. For these variables the concentration-effect slopes were not parallel; therefore the potency ratio varied between 1 (at about 2 mg/l) and 2 (at higher concentrations). The relative efficacy in vivo was expressed as a potency ratio with regard to the number of bacteria in an infected thigh muscle in mice. The potency ratio was 1.5, which is between the limits of the in vitro results.

Amoxicillin↗
PubMed1979

Clinical pharmacological evaluation of aminopenicillins.

To establish the clinical value of antibiotics, clinical trials are necessary. Both bacteriological and clinical-pharmacological data are helpful when designing a proper clinical trial. The difference between amoxicillin and ampicillin preparations cannot be defined on pharmacokinetic grounds alone. The difference in absorption between ampicillin and either pivampicillin or bacampicillin shows the latter two to be superior.

Amoxicillin↗