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Biomedical subjects

C R Clarke

Publications and source records attributed to C R Clarke.

At least 55 records · Page 3Linked to original sources
PubMed1989

Characterization of a soft-tissue infection model in the horse and its response to intravenous cephapirin administration.

A soft-tissue infection model was created in eight horses by infecting subcutaneous tissue chambers with Streptococcus zooepidemicus organisms. Responses of the horses to the infections were determined by monitoring changes in the complete blood count and body temperature and by following changes in the cytology and protein content of the tissue chambers. Systemic reactions to the infections included a mild neutrophilia, mild pyrexia and mild anemia. There was a marked influx of neutrophils and protein into the chambers after they were seeded with bacteria and chamber neutrophil viability decreased markedly at the height of the infection. Subsequent to establishing tissue chamber infections four of the horses were treated with intravenous cephapirin t.d. at a dosage of 20 mg/kg for 5 days. Quantitative culturing of tissue chamber fluid was performed to analyze the efficacy of cephapirin therapy. Cephapirin therapy was accompanied by decreases in the systemic neutrophilia, pyrexia, anemia, and chamber bacterial counts. However, cephapirin did not eliminate the infection in any of the chambers. Chamber neutrophil viability was markedly increased during the cephapirin therapy period.

Animals↗
PubMed1989

Subcutaneously implanted tissue chambers--a pharmacokinetic study.

The purpose of this study was to characterize the pharmacokinetics of a subcutaneously implanted tissue-chamber model. Thermoplastic tissue chambers were implanted in the paralumbar fossae of six steers. Starting 30 days after implantation, the distribution of intravenously administered antipyrine and phenylbutazone into the tissue chambers was studied. These pharmacokinetic experiments were repeated 10 days later to determine the effect of time after implantation on tissue-chamber distribution. Fifty days after implantation, tissue chambers were drained of transudate, refilled with sterile saline and the rate of influx of endogenous urea, creatinine and albumin was measured. Delayed diffusion of antipyrine and phenylbutazone into tissue chambers was well described using a compartmental model in which tissue-chamber fluid represented the third of three compartments arranged in series. The distribution of antipyrine into tissue chambers was greater than that of phenylbutazone; an observation which is well correlated with the high degree of protein binding of phenylbutazone. There was no effect of time on the penetration of the two agents. Rapid diffusion of urea and creatinine and extremely slow influx of albumin into chambers showed that these chambers formed true interstitial compartments.

Animals↗
PubMed1989

Subarachnoid haemorrhage--can we do better?

Patients with subarachnoid haemorrhage often have warning symptoms which are unrecognized. Specific neurological signs such as cranial nerve palsies due to aneurysm expansion may occur. Sudden and severe 'out-of-the-blue' headache following minor haemorrhage may be misinterpreted as migraine. Focal neurological signs from secondary ischaemia may be misinterpreted as thromboembolic events. Computed tomography (CT) head scans can be misleading especially if performed too late.

Adult↗
PubMed1989

Subcutaneously implanted tissue chambers: a pathophysiological study.

Tissue and fluid changes occurring within tissue chambers were characterised as a function of time after subcutaneous implantation in cattle. Cytological and chemical investigation revealed that the composition of fluid within chambers approached the theoretical composition of true interstitial fluid as time after implantation progressed. Erythrocyte and leucocyte numbers decreased sharply immediately after implantation and had reached stable numbers by 40 days after implantation. At this stage, chamber fluid samples had lower total protein and albumin concentrations, higher K+ and Cl- concentrations and lower pH than corresponding blood samples. Despite an ongoing low-grade chronic inflammatory reaction resulting in fibrous encapsulation of chambers, the vascularity of chamber tissue did not diminish with time after implantation. By 40 days after implantation, the cellular and chemical constituents had stabilised enough to allow use of the model to study drug distribution.

Albumins↗
PubMed1989

Effect of Pasteurella haemolytica infection on the distribution of sulfadiazine and trimethoprim into tissue chambers implanted subcutaneously in cattle.

A study was designed to determine the effect of Pasteurella haemolytica infection on the rate and extent of penetration of sulfadiazine and trimethoprim into tissue chambers implanted SC in cattle. Thermoplastic tissue chambers were implanted SC in 6 calves. At 35 days after implantation, sulfadiazine (25 mg/kg of body weight) and trimethoprim (5 mg/kg) were administered IV to 5 of the calves. Chamber fluid and blood samples were collected from each animal at various time intervals for 24 hours after administration. Ten days later, all chambers were inoculated with P haemolytica serotype 1. At 36 hours after inoculation, a second pharmacokinetic study was conducted, using sulfadiazine and trimethoprim. Drug doses and sampling schedules were identical to those used prior to inoculation. A histologic study of infected chamber tissue was conducted, using the calf not included in the pharmacokinetic studies. Disposition curves of antimicrobials in serum and chamber fluid were well described by 2-compartment and 1-compartment pharmacokinetic models, respectively. Inoculation of P haemolytica into tissue chambers was accompanied by marked changes in the composition of chamber fluid. Increased total protein and albumin concentrations, decreased pH, and disruption of chamber tissue vasculature were associated with a significant increase in the penetration of sulfadiazine and trimethoprim into infected tissue chambers, compared with that in noninfected chambers. This increased penetration was accompanied by increases in the apparent volume of distribution for sulfadiazine and trimethoprim.

Animals↗
PubMed1989

Interaction between Pasteurella haemolytica, sulfadiazine/trimethoprim, and bovine viral diarrhea virus.

A study was designed to develop and define a sc tissue chamber as a suitable device for establishing a soft-tissue infection model in cattle and to use this model to study the interaction between Pasteurella haemolytica, sulfadiazine/trimethoprim, and bovine viral diarrhea virus (BVDV). Thermoplastic tissue chambers were implanted in the paralumbar fossae of 20 calves. At 35 days after implantation, calves were allotted to 4 groups of equal size and the calves in 2 groups were inoculated intratracheally with a New York-1 strain of BVDV. At 45 days after implantation, all chambers were inoculated with a 6-hour culture of P haemolytica serotype 1. Starting 36 hours after bacterial inoculation, sulfadiazine/trimethoprim was administered IV once a day to half of the virus-inoculated calves and to half of those calves that had not been exposed to virus. Inoculation of P haemolytica into tissue chambers resulted in the establishment of a localized soft-tissue infection, characteristic of pneumonic pasteurellosis. Despite the maintenance of chamber antimicrobial concentrations that exceeded minimal bactericidal concentrations established in vitro, the infections were not sterilized. This lack of efficacy was associated with decreased pH and increased protein concentrations in chamber fluids after inoculation. Infection with BVDV, which is thought to depress host defenses, had no effect on the response of P haemolytica to sulfadiazine/trimethoprim administration. Observation of responsive antibody titers, bacterial phagocytosis, and high leukocyte viability within P haemolytica-infected chambers documented functional host defenses within tissue chambers.

Animals↗
PubMed1988

Plasma exchange in dermatomyositis/polymyositis: beneficial effects in three cases.

We describe ameliorative effects of plasmapheresis in three patients with dermatomyositis-polymyositis resistant to other therapy, particularly prednisolone. Serologically, the cases were marked, respectively, by a weakly-reactive speckled-type ANA; a strongly reactive speckled-type ANA and an unidentifiable precipitin line by CIEP; and an antibody to cytoplasm and to Jo1. The remission induced by plasmapheresis was temporary in one case and lasting, with low doses of prednisolone, in two. The nuclear autoantibody in case two became undemonstrable after plasmapheresis but recurred during a subsequent relapse. This experience with plasmapheresis in myositis supplements a substantial reported experience of benefit from this therapy.

Adult↗
PubMed1987

Distribution of cephapirin into a tissue chamber implanted subcutaneously in horses.

The pharmacokinetics of cephapirin sodium and its distribution into a tissue chamber implanted subcutaneously in the neck of mature horses are described. Cephapirin was administered as an intravenous bolus dose of 20 mg/kg. The serum concentration vs time curve was best described by a two-compartment open model. Cephapirin disappeared from serum rapidly (t1/2 beta = 18.8 min), and had only a modest volume of distribution (Vd(area) approximately equal to 346 mg/kg, Vd(ss) approximately equal to 204 ml/kg). Total clearance was also rapid (approximately equal to 13 ml/min.kg). Concentrations of the antibiotic in tissue chamber fluid, however, were quite constant from 30 min to 3 h post-injection, and did not decay in parallel with either the concentration of the drug in serum or the estimated concentration of drug in the peripheral compartment. The ratio of area under the curve (AUC0-3 h) for serum: chamber fluid was 13.8 : 1, while that for peripheral compartment : chamber fluid was 11 : 1. The slow rate of cephapirin transport into, and out of, the chamber may be related to its hydrophilic nature. The lack of parallelism between the chamber fluid decay curve and that of serum is characteristic of drugs with a very short half-life.

Animals↗
PubMed1986

Hyperbaric oxygen in multiple sclerosis: a double blind trial.

Eighty four patients with multiple sclerosis were treated in monoplace chambers with either hyperbaric oxygen at 2 atmospheres absolute or placebo. Comprehensive double blind assessment was carried out before, immediately after, and one month after treatment. There was no clinically important or significant benefit in any of the four major criteria of outcome--namely, the patient's subjective opinion, the examiner's opinion, the score on the Kurtzke disability status scale, or the time taken to walk 50 m. Out of 40 other clinical variables assessed, two (the sensory scale and timed writing with the left hand) showed a significant improvement without any subjective clinical correlate or change in any of seven other tests of left hand function. No group of symptoms was perceived by the patients as having improved more after treatment with hyperbaric oxygen than placebo. It is concluded that there is no basis for recommending hyperbaric oxygen in the treatment of multiple sclerosis.

Adult↗
PubMed1986

The lack of effect of inoculation with equine influenza vaccine on theophylline pharmacokinetics in the horse.

Several studies conducted during the past few years have shown that the pharmacokinetics of a variety of drugs may be altered following viral infection or vaccination. The elimination of drugs which are extensively metabolized, such as theophylline, may be prolonged, especially following exposure to RNA viruses such as Type A influenza or similar orthomyxoviruses. The purpose of this study was to determine whether vaccination of horses with equine influenza virus affected pharmacokinetic parameters describing the distribution and elimination of intravenously administered theophylline. Three thoroughbred horses and three ponies were vaccinated with a trivalent vaccine containing inactivated strains of A/Equi 1 (Prague), A/Equi 2 (Miami) and A/Equi 2 (Kentucky 81). Antibody titre, serum interferon concentrations, and the pharmacokinetic parameters t1/2 beta, Vc, Vd(ss), Vd(area) and ClB were measured at various intervals after vaccination. Antibody titre increased substantially in only two animals, while plasma interferon was detectable in low concentrations in four subjects. There was no significant change in any parameter describing the pharmacokinetics of theophylline when measured 2, 6, or 12 days after vaccination. It is suggested that the failure of vaccination to substantially increase plasma interferon concentrations, and thereby alter theophylline elimination, was related to the use of an inactivated viral vaccine, the only type available for vaccination of horses against infection with equine influenza. Regular use of such vaccines, as is required by most Racing Authorities, is therefore unlikely to affect drug withdrawal times.

Animals↗
PubMed1985

Pharmacokinetics of gentamicin in the calf: developmental changes.

The purpose of this study was to determine the pharmacokinetic values for gentamicin in neonatal calves and to compare these values with those in adult cattle (cows). Gentamicin (4 mg/kg of body weight) was administered IV to 7 Holstein bull calves on days 1 (between 12 and 24 hours of age), 5, 10, and 15 after birth, and was administered once IV to 7 Holstein cows. Serum was collected from each animal before administration and at 22 different time intervals from 2 to 400 minutes after injection. Sera were analyzed for gentamicin concentrations. Decay of serum gentamicin concentrations was best described by a 2-compartment pharmacokinetic model. Elimination half-life (t1/2 (beta)) of gentamicin decreased from day 1 (149 minutes) to day 5 (119 minutes), but did not change between days 5 and 15 (111 minutes). Compared with the t1/2(beta) in 1- and 15-day-old calves, the t 1/2 (beta) in cows was shorter (76 minutes). In the calves, apparent volume of distribution (based on total area under the disposition curve) did not change between 1 (393 ml/kg) and 5 (413 ml/kg) days of age, decreased on day 10 (341 ml/kg) and cows day 15 (334 ml/kg), and was markedly smaller than that in cows (140 ml/kg). Total body clearance of gentamicin in cows (1.29 ml/min X kg) was lower than that seen in calves on day 1 (1.92 ml/min X kg) and on day 15 (2.10 ml/min X kg). The decrease in apparent volume of distribution of gentamicin was mirrored by a large decrease in the extracellular fluid volume, as measured by inulin space.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1983

Renin-aldosterone and angiotensin-converting enzyme during prolonged altitude exposure.

The effect of 7 wk altitude exposure on plasma renin activity (PRA), plasma aldosterone concentration (PAC), and angiotensin-converting enzyme (ACE) activity was studied in 10 male subjects at 4,500 m. There was an initial increase in PRA and a reduction in PAC and ACE. The reduction in ACE was significantly greater in the four subjects who had frequently been exposed to extreme altitudes than in the other six subjects. These changes had returned to control values between 12 and 20 days. Exercise caused a marked elevation of PRA and PAC, but the PAC response to PRA was blunted compared with that at sea level. The ratio PAC/PRA at rest was reduced initially but returned to control values with a similar time course to that of ACE activity. The results are compatible with the hypothesis that ACE activity governs the adrenal response to PRA.

Adult↗
PubMed1983

Cardiorespiratory response to exercise in men repeatedly exposed to extreme altitude.

The ventilatory and heart rate responses to exercise were studied in four experienced high-altitude climbers at sea level and during a 6-wk period above 4,500 m to discover whether their responses to hypoxia were similar to those of high-altitude natives. Comparison was made with results from four scientists who lacked their frequent exposure to extreme altitude. The climbers had greater Vo2max at sea level and altitude but similar ventilatory responses to increasing exercise. On acute hypoxia at sea level their ventilatory response was less than that of scientists. Their heart rate response did not differ from that of scientists at sea level, but with acclimatization the reduction in response was significantly greater. Alveolar gas concentrations were similar after acclimatization, but climbers achieved these changes more rapidly. The increase in hematocrit was similar in the two groups. It is concluded that these climbers, unlike high-altitude residents, have cardiorespiratory responses to exercise similar to those of other lowlanders except that their ventilatory response was lower and the reduction in their heart rate response was greater.

Adult↗