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Biomedical subjects

J D Powers

Publications and source records attributed to J D Powers.

At least 37 records · Page 2Linked to original sources

Pharmacokinetics and the dosage regimen of antimicrobial agents.

Some consider antimicrobial therapy an art rather than a science. The drug concentration at the site of infection is often assumed to be a major factor in predicting efficacy and high serum concentrations are assumed to have an advantage by increasing the amount of drug that diffuses into the various body tissues and fluids. Pharmacokinetic studies, along with pharmacodynamic studies, remain to be an important and essential portion of the data base needed for the determination of a proper dosage regimen for antimicrobial agents prior to clinical trials. Additional studies are needed to define the influence of the post antibiotic effect and post antibiotic leukocyte enhancement, as well as the subminimal and supraminimal inhibitory concentrations, on establishing the proper dosage regimen. It is recommended that the insert for a prescription antimicrobial agent should contain pharmacokinetic parameters, such as volume of distribution, t1/2 and body clearances.

Animals↗

Clinicopathologic findings in dogs with renal amyloidosis: 59 cases (1976-1986).

The medical records of 59 dogs with renal amyloidosis were reviewed. Most dogs with amyloidosis were greater than 6 years old, and females were affected more often than males. Beagles, Collies, and Walker Hounds were at increased risk, whereas German Shepherd Dogs and mixed-breed dogs were at decreased risk. Common historical findings were anorexia, polyuria, polydipsia, lethargy, vomiting, and weight loss. Common laboratory findings were leukocytosis, lymphopenia, nonregenerative anemia, hypercholesterolemia, azotemia, hyperphosphatemia, metabolic acidosis, isosthenuria, cylindruria, and proteinuria. Proteinuria was moderate to severe in most dogs, as assessed by qualitative determination of urine protein concentration, urine protein/urine creatinine ratio, and 24-hour urine protein excretion. Conservative medical management was of little value, and survival ranged from 3 to 20 months in 12 dogs for which this information was available. Moderate to severe diffuse global glomerular amyloidosis was detected in all dogs. Medullary amyloid deposition was multifocal and less severe, but was evident in most dogs. Secondary tubulointerstitial and glomerular lesions were mild or absent in most dogs. Thromboembolism was identified in approximately 14% of affected dogs, underlying inflammatory disease in 37%, and neoplasia in 20%. Laboratory indicators of renal function correlated poorly with histologic lesions, with the exception of glomerular amyloid deposition and "chronic renal disease" index with endogenous creatinine clearance.

Age Factors↗

Single- and repeat-dose pharmacokinetic studies of chloramphenicol in horses: values and limitations of pharmacokinetic studies in predicting dosage regimens.

A single-dose pharmacokinetic study of chloramphenicol in propylene glycol was done in 6 horses after 22 mg/kg was administered IV. Serum drug concentrations obtained at various predetermined intervals were determined by an electroncapture gas-chromatographic technique. The time-concentration data were described by a 2-compartment open model, and various pharmacokinetic variables were estimated. The median elimination rate constant was estimated to be -0.0185 minute-1 (-0.0225 to -0.0148 minute-1), and the median half-life was 37.36 minutes (30.74 to 46.90 minutes). The median apparent volume of distribution and total body clearance were 1.46 L/kg (1.13 to 1.60 L/kg) and 25.56 ml/kg/min (23.66 to 32.21 ml/kg/min), respectively. On the basis of these data, single- and repeat-dose kinetic studies were done in another group of 6 animals. The drug was administered at a dosage of 22 mg/kg every 4 hours for 3 days. Blood samples were obtained for pharmacokinetic studies after the first and the last doses were given. The half-life, volume of distribution, and total body clearance did not change significantly (Wilcoxon signed rank test) after 3 days of therapy with chloramphenicol. The IV dose schedule for treating bacterial infections with organisms of different sensitivities has been determined from the estimates of the pharmacokinetic variables. The limitations of calculating the dose schedules for chloramphenicol on the basis of pharmacokinetic variables in horses are discussed.

Animals↗

Pharmacokinetics of florfenicol in veal calves.

The pharmacokinetic disposition of florfenicol was described in veal calves after administration of a single 22-mg/kg dose intravenously, orally after a 12-h fast and orally 5 min post feeding. Both serum concentrations and urinary excretion were studied. After intravenous administration the median elimination half-life was 171.9 min while the half-life of the distribution phase was 5.9 min. The median body clearance (Cl) and apparent volume of distribution (Vz) were 2.85 ml/kg/min and 0.78 l/kg, respectively. Following oral administration the median bio-availability (f) was 0.88 for calves dosed after a 12-h fast and 0.65 for calves dosed 5 min post feeding. Calves given the oral doses had a complex absorption pattern with delayed absorption. Slightly more than 50% of the administered dose both orally and intravenously was recovered as unchanged florfenicol in the urine by 30 h.

Administration, Oral↗

Pedigree analysis of Abyssinian cats with familial amyloidosis.

Pedigrees of 62 Abyssinian cats with familial amyloidosis were compared with those of 100 Abyssinian cats registered with the Cat Fanciers Association. The inbreeding coefficients of the 2 samples of cats were not significantly different. Analysis of the pedigrees with respect to specific ancestors, however, showed that certain cats were significantly more common in the pedigrees of affected cats than in those of cats in the randomly selected sample. These data support a genetic basis for this disease, but do not allow determination of the mode of inheritance.

Amyloidosis↗

Municipal sewage sludge application on Ohio farms: tissue metal residues and infections.

Transmission of infectious agents and translocation of Cd, Cu, Pb, and Zn from anaerobically digested sludge to the tissues of farm animals grazing on pastures to which sludge was applied (2-10 metric tons per hectare) were studied on eight farms. No significant health risk associated with the possible presence in sludge of Salmonella spp., or of common animal parasites including Nematodirus spp., Strongylus spp., Strongyloides spp., Trichuris spp., Eimeria spp., Ascaris spp., and Ancylostomum spp. was noted. Caudal fold as well as cervical tuberculin testing indicated no conversions from negative to positive following exposure of cattle to sludge. Significantly higher fecal Cd concentrations were detected in samples collected from cattle soon after being placed on sludge-treated pastures compared to preexposure values in the same animals. Significant Cd and Pb accumulations were found in the kidneys of calves grazing sludge-treated pastures compared to control calves. Although older cows grazing sludge-treated pastures had significantly higher blood Pb levels, no metal accumulation was observed in other tissues. Statistically significant accumulations of Cd and Pb in the kidney of calves grazing these pastures for a relatively short period suggest that caution should be exercised to avoid prolonged grazing of cattle on pastures receiving heavy sludge applications, especially with sludges containing high concentrations of heavy metals.

Agriculture↗

Clearance of penicillin G in the newborn calf.

Sodium penicillin G was administered intravenously (4545 IU/kg) to calves on the day of birth (12-24 h old) and at 5, 10, and 15 days of age. Serum was collected at varying intervals for 120 min after injection and analysed for penicillin G. The mean total body clearance (ClB) of penicillin G on the day of birth was 2.98 ml/min/kg compared to 4.83 ml/min/kg at 5 days, 3.11 ml/min/kg at 10 days and 4.65 ml/min/kg at 15 days of age. Clearances at 5 and 15 days were significantly (P less than or equal to 0.05) higher than on the day of birth. The half-life (t1/2 beta), however, did not change significantly over the 15-day period of the study. These results indicate that the newborn calf has an appreciable ability to excrete penicillin G before it is 24 h old, and that total body clearance of the antibiotic increases rapidly in the immediate postnatal period.

Aging↗

Standardization of an experimental disease model of Streptococcus zooepidemicus in the equine.

A reproducible experimental disease model in horses using Streptococcus zooepidemicus was developed. An intravenous challenge dose of 1 X 10(10) colony-forming units (CFU), followed 24 h later with another challenge of 1 X 10(8) CFU of Strep. zooepidemicus produced the desired disease model. The disease was characterized by depression, pyrexia, anorexia, abnormal lung sounds, inflammation of joints, moderate to severe lameness, gradual loss of condition and emaciation. The effects of the disease on hematology, serum chemical profile and different protein fractions were studied. The disease state had no effect on serum glucose, sodium, potassium, chloride, urea nitrogen, creatinine, uric acid, calcium, phosphorus and enzymes SGOT or SGPT. However, the alkaline phosphatase showed a gradual decline. The serum iron levels dropped markedly and remained low to the last day of observations (post-infection day, PID 13). On serum protein electrophoresis, the albumin showed a gradual decrease; whereas, alpha II, beta and gamma globulin levels rose suggesting an immune response. The elevation of rectal temperatures and white blood cell counts related well with clinical observations. The serum iron levels proved very helpful in predicting the severity of clinical signs and often dropped before the onset of clinical signs and pyrexia.

Animals↗

A health index to evaluate clinically a beta-hemolytic streptococcal infectious disease model in the horse.

Quantification of the clinical manifestations of a disease has been a serious problem particularly as related to clinical trials or drug efficacy studies. Historically, this quantification has been limited to categorizing each patient into one of three or four groups, e.g. worse, no improvement, improved. This problem becomes serious when an investigation utilizes an experimentally induced animal disease model. A health index, which quantifies the clinical state of horses which have an experimentally induced beta-hemolytic streptococcal infection, is described. Aspects of experimental design and statistical analysis are also discussed in relationship to the use of the index for drug efficacy studies.

Animals↗

Experimental Pseudomonas aeruginosa ulcerative keratitis model in the dog.

Primary Pseudomonas aeruginosa ulcerative keratitis and accompanying secondary ocular disease were induced bilaterally in 12 of 12 dogs subjected to corneal trephination and intrastromal inoculation. Successful experimental infection was based on recovery of viable Pseudomonas organisms from the lesions, as well as gross and biomicroscopic appearance of the corneas.

Animals↗

Further improvement of the enzyme-linked antiglobulin test (ELAT) for erythrocyte antibodies.

The enzyme-linked antiglobulin test (ELAT) was found to be nine times more sensitive than the direct antiglobulin test (DAT) in detecting erythrocytes sensitized by IgG antibody in vitro. The release of hemoglobin and other interfering substances from the erythrocytes gave falsely high absorbance values which were corrected by the use of a hemolysis bland with each test. ELAT results showed good precision. With the use of the hemolysis blank, the ELAT should prove to be a useful tool for hospital blood blanks in the detection of weakly reactive allo- and autoantibodies.

Antibodies↗

A study on renal function in the Indian buffalo (Bubalus bubalis).

Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) in buffalo species (Bubalus bubalis) were estimated using a single injection technique. The total body clearances of inulin and para-aminohippuric acid (PAH) served as estimates of GFR and ERPF, respectively. Inulin and PAH were administered to animals as a single i.v. bolus. The time-concentration curves were determined for each compound. Three mathematical models were applied to the data. The two compartment model gave the best fit to the data. The single compartment model gave slightly higher values, but could be used in clinical and certain research situations to estimate renal functions when it is not practical to take large number of samples.

Animals↗

Statistical considerations in clinical field evaluation of drugs.

Statistical problems associated with clinical field evaluation of drugs are many. The Food and Drug Administration requires that the safety and efficacy of a drug must be shown in adequate and well-controlled clinical investigations. From a statistical point of view, safety and efficacy must be precisely defined, and a quantitative method must be developed to measure these properties. It is proposed that efficacy be defined in both the therapeutic and pharmacologic aspects. Further, to measure therapeutic efficacy, it is suggested that an appropriate health index be used. This index would provide information regarding degree of improvement and also the time course of improvement. To measure or evaluate pharmacologic efficacy, it is suggested that kinetic studies be done to compare half-lives, volumes of distribution, and any other relevant kinetic parameter(s).

Animals↗