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Biomedical subjects

G Laber

Publications and source records attributed to G Laber.

At least 19 recordsLinked to original sources

Bronchoalveolar lavage in dogs; analysis of proteins and respiratory cells.

In an attempt to establish the normal values, bronchial alveolar lavage (BAL) of portions of the right upper lobe was done during fiberoptic bronchoscopy in 18 Beagle dogs of various ages. Albumin, IgA and IgG were identified in BAL fluids. The respiratory cells obtained were, in the order of decreasing occurrences, alveolar macrophages, lymphocytes, epithelial cells and neutrophils. No age-related changes were found in the content of immunoglobulins or in the differential cell counts of respiratory cells. Bacterial cultures of BAL were invariably contaminated with resident flora of the upper respiratory tract. Therefore, in determining the etiology of pulmonary infections, the results of such cultures should be interpreted with caution. As an aid to diagnosis of pulmonary diseases in dogs, the analysis of BAL fluid components could be helpful when compared with findings in healthy animals.

Albumins↗

Epizootiological examination of a respiratory disease associated with mycoplasma infection in horse.

The authors examined 585 samples from 92 mares of 2 studs and 346 nasal swabs taken from their foals for the presence of mycoplasmas. The positive rates of mares and foals were 81.5% and 71.7%, respectively, with positivity of samples being variable. Clinical symptoms developed in 2-4 waves and lasted 3-7 days, with intervals of 7-12 days. The disease started in April among foals born in February, at an average age of 88 days. Later on, the average age of the affected foals decreased. There was a correlation between presence of mycoplasmas in nasal cavity and disease of foals.

Animals↗

Investigation of pharmacokinetic parameters of tiamulin after intramuscular and subcutaneous administration in normal dogs.

Kinetic variables for tiamulin in the normal dog have been determined. Serum concentrations of tiamulin were compared after intramuscular (i.m.) and subcutaneous (s.c.) administration of a single dose of tiamulin. Following a single i.m. dose of 10 mg/kg body weight, the compound was calculated to have a Cmax = 0.61 +/- 0.15 micrograms/ml, a Tmax = 6 h and a t1/2 = 4.7 +/- 1.4 h. Tiamulin showed dose-dependent pharmacokinetics when given as a single s.c. dose of either 10 mg or 25 mg/kg body weight. For the lower dose, the values Cmax = 1.55 +/- 0.11 micrograms/ml, Tmax = 8 h and t1/2 = 4.28 +/- 0.18 h were obtained. For the higher dose Cmax = 3.14 +/- 0.04 micrograms/ml, Tmax = 8 h and t1/2 = 12.4 +/- 3.4 h were calculated. When tiamulin was administered subcutaneously at a dose rate of 10 mg/kg body weight, higher and better maintained serum levels were achieved than those following i.m. administration. After repeated s.c. doses no significant accumulation of tiamulin occurred. Assuming that a continuous effective serum concentration is necessary throughout the course of therapy, these data would indicate that tiamulin should be given every 24 h.

Animals↗

[Nitroblue tetrazolium (NBT) test as a potential diagnostic aid in the preoperative detection of patients at risk for infection].

The clinical application of a simple quantitative NBT-test to investigate the "killing function" of granulocytes in surgical patients with various underlying diseases is described. In this test preoperative patients showing a decreased NBT-reduction in their leucocytes always developed infectious complications after surgery. Taken together, these results indicate that the NBT-test could be used as a "simple indicator" of the granulocyte function in respect to the predictability for patients with high risk of infection.

Aged↗

Tiamulin, a new antibiotic for eliminating mycoplasmas from bovine serum 1. Investigations on Spermatozoal Toxicity.

Tiamulin, a new diterpene antibiotic, was investigated for toxicity to spermatozoa. The compound was added to ejaculates via semen extender at a concentration of 50 to 90 mg per 100 ml of total liquid. Motility and the proportion of non-viable spermatozoa were used as criteria of the drug's effect. Tiamulin proved to be safe up to doses of 70 mg per 100 ml of semen extender.

Journal Article↗

A comparison of the effect of tiamulin hydrogen fumarate and tylosin tartrate on mycoplasmas of ruminants and some animal ureaplasmas.

The in vitro efficacy of tiamulin was compared to that of tylosin against 7 bovine, 7 ovine and 3 caprine mycoplasma strains isolated from various organs and belonging to different species, as well as 7 ureaplasma strains cultured from cattle, sheep, swine, chickens and turkeys. The minimal mycoplasmacidal concentrations of tiamulin varied between 0.01 and 10.0 micrograms ml-1, while tylosin proved to be active in concentrations of 0.5 and 100.0 micrograms ml-1. Five of 17 mycoplasma strains showed identical sensitivities to both antibiotics while all other strains, including the ureaplasmas, were sensitive to tiamulin at concentrations 5-5000-times lower than tylosin.

Animals↗

Therapeutic relevance of penicillin-induced hypersensitivity of Staphylococcus aureus to killing by polymorphonuclear leukocytes.

There is an overwhelming body of evidence that certain Staphylococcus aureus strains become more sensitive to killing by polymorphonuclear leukocytes after their growth in media containing subinhibitory concentrations of penicillin. However, it is not clear to what extent this phenomenon contributes to the curative effect of penicillin in vivo. To explore its therapeutic relevance, we evaluated the interaction of staphylococci pretreated with penicillin in vitro with leukocytes in cell-proof diffusion chambers (porosity, 0.22 micron) implanted subcutaneously in rabbits. Under this in vivo environment, staphylococci pretreated with penicillin remained hypersensitive to leukocyte killing as under in vitro conditions. Furthermore, when the staphylococci were mixed with the leukocytes in chambers implanted intraperitoneally in mice which subsequently received intravenously a suboptimal dose of penicillin, they also became hypersensitive to leukocytic killing. However, because the staphylococcal growth rate was considerably reduced in vivo, the degree of penicillin-induced sensitivity to leukocytic killing was smaller than that obtained in test tube cultures; nevertheless, the enhanced killing was significant. Additional support that the curative effect of penicillin partly depends on its synergistic action with the leukocytes was provided by the relative decrease in virulence of staphylococci pretreated with penicillin in mice in which the cellular host defenses were already recruited at the focus of inoculation. These observations indicate that penicillin-induced hypersensitivity of staphylococci to leukocytic killing is not only an in vitro phenomenon, but an effect which has therapeutic relevance.

Animals↗

Sensitivity of various spiroplasma strains against ethanol, formalin, glutaraldehyde, and phenol.

The efficacy of four different disinfectants on spiroplasmas pathogenic for plants, insects and vertebrates was determined using a microtiter technique. The results of the sensitivity testing indicate that spiroplasmas display a considerable resistance in comparison to cell wall bearing organisms. Particularly honey bee spiroplasmas proved to be less sensitive to the disinfectants tested, whereas Spiroplasma citri and the tick spiroplasmas showed a susceptibility comparable to E. coli and Staph. aureus. The findings are discussed in relation to the technique used and in respect of the implications for laboratory work.

Disinfectants↗

[Prerequisites for enhancement of the efficacy of fosfomycin by glucose-6-phosphate in treatment of experimentally infected animals (author's transl)].

In chemotherapy of otherwise fatally infected mice (intraperitoneally) the effective dose50 (ED50) of fosfomycin (2 single doses, subcutaneous application 1 and 6 h post infect.) was decreased significantly by supplementing the antibiotic solution with 100 mg glucose-6-phosphate (G-6-P) per kg animal and per injection if also the MIC of the infecting strain (Klebsiella oxytoca and K. aerogenes II) was lowered by addition of G-6-P (25 mg/l) to the nutrient medium (Table 1 and 2). With strains not exhibiting any influence on the MIC no such effect was observed (Table 1). From this it is concluded that the enhancement of antimicrobial activity of fosfomycin in vivo is based on the same mechanism as in vitro. This mechanism is the initiation of a second route of transportation into the bacterial cell (7), the hexose-6-phosphate transport system that apparently is inducible not only in vitro but also in vivo. Blood levels of G-6-P sufficient or above to induce this system in vitro (5 mg/l) were being held with doses of 100 mg/kg body weight in dogs during 70 to 120 min (Fig. 3) and 45 to 70 min (Fig. 4) when applied subcutaneously or intravenously respectively. These periods of contact area adequate to induce a considerable decrease of the MIC. With the strain used (K. oxytoca) the MIC of 128 mg/l was lowered by contact with G-6-P during 60 or 120 min to 16 or 8 mg/l respectively (Fig. 5). For full induction of the hexose-6-phosphate system resulting in a MIC of 2 mg/l however, 8 h were necessary. From the above findings it is concluded that clinical studies are necessary. As G-6-P is a (short-lived) physiological product of cell metabolism and nontoxic such studies are justifiable in cases where therapeutic use of fosfomycin can be regarded as an indication.

Animals↗

Composition of fluids from diffusion chambers implanted in the soft tissue and kidneys of rabbits.

The fluids from diffusion chambers implanted in soft tissue and kidneys of rabbits were analysed for total protein, albumin, enzymes, ions, glucose, creatinine, urea, uric acid, bilirubin and cholesterol. These date were compared with the corresponding values in plasma. Our data for chamber fluid are in good agreement with data reported for interstitial fluids. The composition of the kidney chamber fluid is nearly constant from three to ten weeks after implantation. The low urea, uric acid and creatinine concentrations indicate that the chamber is not located in the urine collecting area of the kidney. Three days after subcutaneous implantation of chambers, the fluid contains less protein than plasma but has an equal concentration of ions, thus meeting the principal requirements for interstitial fluid. There are indications that the healing process lasts up to ten days after the surgical implantation. In order to examine the permeability of the diffusion chambers, the equilibration half-life times of antibiotics and substances of high and low molecular weights were determined in vitro.

Animals↗

A diffusion chamber technique for measuring concentrations of antibiotics in interstitial fluid.

A method for collecting soft tissue interstitial fluid in experimental animals for the measurement of antibiotic concentrations is described. Diffusion chambers with permeable membranes of 0.45 micron porosity were implanted subcutaneously for four days in order to determine simultaneous concentrations of ampicillin and clindamycin in serum and chamber fluid after perioral administration in rabbits and of oxytetracycline after intravenous injection in dogs. The results are discussed in view of findings from other investigators using different types of tissue cages.

Ampicillin↗

Measurements of antimicrobial drug concentrations in renal interstitial fluid using the diffusion chamber technique.

A technique is described to obtain renal interstitial fluid (RIF) from rabbits after implantation of diffusion chambers with permeable membranes of 0.45 mu porosity in both kidneys. Pharmacokinetic studies were conducted two to three weeks after implantation. No difference in gentamicin concentrations, as measured microbiologically, was seen between RIF withdrawn from the left and right kidney chambers at the same points in time. Simultaneous drug concentrations were determined in RIF and serum of rabbits after oral administration of ampicillin or nalidixic acid and after intramuscular injection of gentamicin. Ampicillin concentrations in RIF peaked at two hours with about one fourth of the peak concentration measured in serum at one hour. These curves crossed at 3.45 hours. In RIF, the maximum concentration of gentamicin found at two hours was again approximately one fourth of the serum peak level determined at half an hour. The gentamicin curves crossed at 3.15 hours. No levels of nalidixic acid could be detected microbiologically in serum and RIF. In collected urine, however, concentrations of this drug could be measured for several sampling periods. Our results show that this diffusion chamber technique can be useful in the pharmacokinetic examination of drugs, also with respect to their distribution in the kidneys.

Ampicillin↗

Experience with testing for mycoplasma with five different methods.

Five methods for mycoplasma-content detection in cell-cultures are established in this laboratory. Results with about 20 different cell lines continuously grown in this laboratory in some determinations indicate that four methods give good correspondence. A microbiological method gave contrary results in many cases. It is possible that new infections will grow on mycoplasma broth but the older infections are adapted to cell-culture and give negative results on artificial medium. New low-level infections cannot be detected by the other methods which do not include any efficient enrichment step. The most convenient method in our opinion is a DNA-staining method according to Chen because this is a very quick, inexpensive and easily performable process. In practice it seems necessary to check cell cultures in two ways, firstly with a quick method and additionally with the microbiological test to ensure the detection of new low-level infections.

Animals↗

In vitro activity of tiamulin (81.723 HFU), a new pleuromulin derivative, against clinically significant anaerobes.

The susceptibility of more than 40 strains of Gram-negative and Gram-positive anaerobes to tiamulin (Sandoz 81.723 hfu), a new pleuromulin (pleuromutilin) derivative, was determined by broth dilution and agar dilution tests. The influences of density of the inoculum upon MICs was studied by a specially designed pour plate-technique. Bacteroides fragilis, B. vulgatus, B. splanchnicus, B. oralis, B. asaccharolyticus, B. melaninogenicus, Fusobacterium fusiforme (F. nucleatum), Sphaerophorus necrophorus, Clostridium perfringens, C. fallax, Propionibacterium acnes and several species of Peptococcaceae showed broth dilution MICs of 0.03 similar to 1 microgram/ml. Members of B. thetaiotaomicron, B. distasonis and S. freundii (F. mortiferum) were inhibited by 8 similar to 32 microgram/ml and 2 strains of S. varius had a broth dilution MIC of 256 microgram/ml. With most strains, the agar dilution MICs were 2 similar to 4 similar to 8 times the broth dilution MICs. In pour plate-tests, the MICs were not considerably influenced influenced by varying initial concentrations of viable cells. With most anaerobes, the MBCs of tiamulin were more than 100-fold higher than the MICs. The results obtained indicated that, apart from S. varius, B. thetaiotaomicron, B. distasonis and S. freundii (F. mortiferum), members of 16 other anaerobic species including B. fragilis were without exception sensitive to tiamulin.

Anti-Bacterial Agents↗