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Biomedical subjects

C Brownie

Publications and source records attributed to C Brownie.

16 recordsLinked to original sources

Fractional excretion of electrolytes in lactating dairy cows.

Samples of serum and urine were obtained simultaneously from 56 healthy lactating cows to determine ranges of fractional excretion (FE) of calcium (Ca), phosphate (PO4), magnesium (Mg), sodium (Na), potassium (K), and chloride (Cl). Samples were obtained at 3 stages of lactation: period 1 = 1 to 7 days, 2 = 83 to 112 days, and 3 = 175 to 197 days. The FE of electrolytes were significantly different among periods 1, 2, and 3 for Ca (P less than 0.001), PO4 (P less than 0.025) and Mg (P less than 0.025), but were not significantly different for Na, K, and Cl. Least squares mean FE of Ca was lowest in period 1 and not significantly different for periods 2 and 3, whereas mean FE values for PO4 and Mg were highest in period 2 and not significantly different for periods 1 and 3. The mean FE values of Na, K, and Cl did not change with stage of lactation. Age and category of milk production (high, medium, and low) did not influence the FE values of the electrolytes.

Animals

A rank-based mixed model approach to multisite clinical trials.

New rank-based methods for analyzing data from multisite clinical trials are presented in the context of "mixed" linear models. In contrast to current rank methods, the new procedures test for a drug main effect in the presence of a random drug by site interaction (or drug by investigator interaction when there is only one investigator per site). Analogous procedures are also provided for the "fixed-effects" situation, and comparisons are made with current methods. The rationale for an analysis that assumes random investigator effects is described.

Analysis of Variance

Clinical and metabolic findings in dogs with chronic renal failure fed two diets.

Exogenous creatinine clearance, urinary electrolyte excretions, calcium and phosphorus balance, serum cholesterol concentration, arterial blood pressure, and body weight were evaluated in dogs with chronic renal failure that were fed 2 commercial diets. Nine dogs ranging in age from 1 to 15 years were identified as having mild to moderate chronic renal failure (CRF, exogenous creatinine clearance = 0.5 to 2.13 ml/kg of body weight/min). These dogs and a group of 10 clinically normal controls were fed a diet containing 31% protein for 8 weeks at which time hematologic and biochemical evaluations and clearance studies were performed. All dogs then were fed a phosphorus-restricted diet containing 16% protein and then reevaluated after 8 weeks. The dogs in this study had hematologic and biochemical abnormalities typical of CRF. Urine absolute and fractional excretion of electrolytes was higher in dogs with CRF than in controls and was affected by diet. Serum cholesterol concentration was higher in dogs with CRF and increased in those dogs after feeding the low protein diet. Changes in dietary sodium intake did not affect arterial blood pressure. The phosphorus-restricted diet did not affect serum amino terminal parathyroid hormone concentration in either group. Control dogs lost body weight, whereas dogs with CRF gained weight when fed the low protein diet. We concluded that dogs with mild to moderately severe CRF have the same biochemical abnormalities and response to dietary restriction of protein and phosphorus as has been previously reported in dogs with experimentally induced CRF. Restriction of dietary sodium may not decrease arterial blood pressure in some dogs with CRF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed

Amino acid profiles in dogs with chronic renal failure fed two diets.

Amino acid profiles and serum albumin and serum total protein concentrations were evaluated in dogs with renal disease. Nine dogs ranging in age from 1 to 15 years were identified as having mild to moderate chronic renal failure (CRF; exogenous creatinine clearance, 0.5 to 2.13 ml/kg of body weight/min). These dogs and a group of 10 clinically normal control dogs were fed a diet containing 31% protein for 8 weeks, at which time serum and urine amino acid assays and clearance studies were performed. All dogs then were fed a diet containing 16% protein for 8 weeks and then reevaluated. Chronic renal failure was associated with mild abnormalities in serum concentrations of amino acids. When fed the higher protein diet, dogs with CRF had lower serum concentrations of glutamine, leucine, proline, and serine and higher serum concentrations of cystathionine and 3-methylhistidine than clinically normal control dogs. When fed the low protein diet, dogs with CRF had lower serum serine concentrations and higher serum concentrations of cystathionine, phenylalanine, and 3-methylhistidine. Urine excretion of amino acids in all dogs on both diets was low, and dogs with CRF had lower renal clearances of 3-methylhistidine than control dogs. There were no significant differences in concentrations of serum albumin and total solids between either group, regardless of diet. We concluded that dogs with mild to moderately severe CRF have mild abnormalities of serum free amino acid concentrations, but renal conservation of essential amino acids is not impaired.

Amino Acids

Impact of menstrual periodicity on serum lipid levels and estimates of dietary intakes.

Nine eumenorrheic women were studied at five separate times each month for a minimum of 2 months. Fasting bloods and 1-day food records were obtained from all women at these times to describe the pattern and magnitude of within-person variation in selected nutrient and lipid indicators attributable to menstrual cyclicity. Serum cholesterol, beta-carotene, 17 beta-estradiol (E2), and dietary selenium intakes exhibited significant periodic regressions against time. For the group as a whole, however, only serum cholesterol and E2 measures exhibited significantly strong consistent periodicities. Future studies with a larger sample of women are warranted to confirm these findings. Unless strict blood sampling protocols are followed, variation attributable to menstrual cyclicity may mitigate the reliability of the serum cholesterol screenings advocated in the past few years.

Adult

Mixture models for continuous data in dose-response studies when some animals are unaffected by treatment.

A mixture model is described for dose-response studies where measurements on a continuous variable suggest that some animals are not affected by treatment. The model combines a logistic regression on dose for the probability an animal will "respond" to treatment with a linear regression on dose for the mean of the responders. Maximum likelihood estimation via the EM algorithm is described and likelihood ratio tests are used to distinguish between the full model and meaningful reduced-parameter versions. Use of the model is illustrated with three real-data examples.

Algorithms

Preliminary study on serum enzyme changes in Long Evans rats given parenteral ochratoxin A, aflatoxin B1 and their combination.

Long Evans rats of both sexes were each administered a total of 250 micrograms aflatoxin B1 (AFB1), ochratoxin-A (OCH-A) or 500 micrograms AFB1 + OCH-A (1:1 ratio) in corn oil over 5 equal daily intraperitoneal (IP) injections of 50 micrograms/rat/day. Control rats were given a total of 1.25 ml corn oil over 5 equal daily IP injections of 0.25 ml/rat. All rats were observed daily for clinical signs of toxicity. Twenty-four hr following the last injection all rats were weighed, killed, examined for gross pathologic lesions and blood samples collected for routine hematologic and serum chemistry evaluation. All rats gained weight over the treatment period. Though not significantly different among the treatment groups, weight gain was significantly greater for males (54.0 g) than females (33.8 g). Routine hematology showed no difference among treatment groups. Serum enzyme aspartate aminotransferase (AST = SGOT) activities were indicative of hepatoxicity. Lactate dehydrogenase (LDH) activity was significantly increased in the AFB1 and AFB1 + OCH-A treatment groups, signifying a possible interaction between these 2 mycotoxins. LDH isoenzyme fractionation studies would be helpful in delineating the organ system(s) involved and the possible diagnostic value of this interaction.

Aflatoxin B1

Teratogenic effect of calcium edetate (CaEDTA) in rats and the protective effect of zinc.

The calcium chelate of EDTA (CaEDTA) currently is the drug of choice in the treatment of lead intoxication. This study investigated the teratogenic potential of CaEDTA, administered parenterally during periods of organogenesis and determined if incorporating zinc into EDTA would protect against teratogenic effects. Four doses (2, 4, 6, and 8 mmol/m2/day) of CaEDTA, two concentrations (8 and 20 mmol/m2/day) of ZnEDTA and ZnCaEDTA (molar ratio 0.5:0.5:1) were used, and a saline control (0.9% NaCl). Timed-pregnant Long-Evans rats were assigned at random to the treatment groups, 20 per dose for each chelate and 30 to the saline control. Rats were injected with the chelate or saline solution sc, twice daily during the 11th through 15th days of gestation. Pups removed by cesarean section on the 21st day were processed for osseous and visceral examination. Additional animals per treatment group were used for maternal plasma and liver and fetal zinc determinations. Results showed increases in several abnormalities (submucous cleft, cleft palate, adactyly-syndactyly, curly tail, abnormal rib and vertebrae) with increasing amounts of CaEDTA. No malformations were seen with ZnEDTA at either dose or with ZnCaEDTA at 8 mmol/m2/day. However, submucous cleft was seen in 6 of 20 litters from the dams receiving the higher dose of ZnCaEDTA. It was concluded that CaEDTA is teratogenic in rats at concentrations which, except for decreased weight gain, produce no discernible toxicity to the dam, and which are comparable to the recommended therapeutic dosage in humans (1500 mg/m2/day corresponding to 4 mmol/m2/day). Protection is afforded by incorporating zinc in the chelate.

Abnormalities, Drug-Induced

The effects of exposure misclassification on estimates of relative risk.

In epidemiologic studies, individuals may be misclassified with respect to exposure to a risk factor for disease. Such misclassification causes the relative risk of disease associated with the exposure in the population to be biased toward the null value. Here, a formula is derived for the apparent relative risk under misclassification (R) as a function of the sensitivity (U) and specificity (V) of the test for exposure and of the true relative risk (R) and true prevalence of exposure (P(E] in the population. The relative influence of U and V on the bias in R depends both on R and on P(E), with U tending to be more influential at higher values of P(E). When there is misclassification of exposure, variation in P(E) may bias comparisons of relative risk between groups or exposures, either by producing spurious differences or by masking true differences, and may generate spurious trends associated with a third variable such as age. Because the possible effects of misclassification of exposure on relative risk are complex and not easily generalized, the potential degree of bias should be evaluated individually in each situation.

Diagnostic Errors

Comparing indicators of health or nutritional status.

The performance of an indicator of health or nutritional status depends on its sensitivity and specificity properties over a range of cut-offs. Frequently, it is of interest to compare indicators to pick the best for a given purpose, such as screening for disease or monitoring to detect changes in prevalence of inadequate nutriture. Relative operating characteristic (ROC) analysis provides an objective method for making this comparison, but the application of this methodology as described for epidemiologists in this Journal is now outdated for most indicators. Recent developments are noted and an alternative analysis for use with continuous Gaussian data is presented here. The estimators and statistical test procedures proposed here are compared with the previously described methods, by means of a computer simulation study. The new procedures are found to be superior for continuous Gaussian data, and have the practical advantage that they do not require use of a specialized computer program. The implications of these results for comparing indicators to be used to monitor population prevalences are discussed.

Computers

Constant-parameter capture-recapture models.

Jolly (1982, Biometrics 38, 301-321) presented modifications of the Jolly-Seber model for capture-recapture data, which assume constant survival and/or capture rates. Where appropriate, because of the reduced number of parameters, these models lead to more efficient estimators than the Jolly-Seber model. The tests to compare models given by Jolly do not make complete use of the data, and we present here the appropriate modifications, and also indicate how to carry out goodness-of-fit tests which utilize individual capture history information. We also describe analogous models for the case where young and adult animals are tagged. The availability of computer programs to perform the analysis is noted, and examples are given using output from these programs.

Aging

Testing for a treatment effect in the presence of nonresponders.

Good (1979, Biometrics 35, 483-489) introduced a new randomization test for the two-sample problem where a proportion 1 - p of the treatment group does not respond to the treatment, and suggested that the Wilcoxon test is not effective for this situation. We show to the contrary that the Wilcoxon test is quite useful when p greater than or equal to .6 and point out an error in his definition of a one-tailed randomization test.

Animals

Models allowing for age-dependent survival rates for band-return data.

Seber [1970] and Robson and Youngs [1971] developed a statistical model for a tag-recapture experiment on an exploited animal population in which banded or tagged individuals are released into a population each year, and the bands from harvested individuals are returned by hunters or fishermen in following years. Consideration of certain biological and ecologicw models for an experimental situation where data are recorded separately for birds released as adults and as young-of-the-year. In particular, the effect of different survival rates of young birds, and the effect of migration on reporting rates, are taken into account in the models presented in this study. Maximum likelihood estimators of parameters are derived under the different models, and procedures are developed to discriminate between alternative models as well as provide non-discriminant goodness-of-fit tests.

Age Factors

Experimental infection of turkeys with Mycoplasma gallisepticum of low virulence, transmissibility, and immunogenicity.

Three-week-old turkeys were inoculated intranasally with approximately 10(6) colony-forming units (CFU) of putative variant Mycoplasma gallisepticum (MG) strains M876, M35, or the virulent S6 reference strain. Uninoculated turkeys in each group served as contact sentinels. The hemagglutination-inhibition (HI) test and enzyme-linked immunosorbent assay (ELISA) were used to determine serologic responses. MG was isolated from 100% and 92% of S6- and M876-inoculated turkeys, respectively, on day 7 PI. However, culture-positive rates among M876-inoculated turkeys declined more rapidly, transmission to contact sentinels took longer and occurred at lower rates, and serologic responses measured by HI and ELISA were lower than in S6-infected turkeys. Testing sera from inoculated turkeys for antibodies to MG in homologous and heterologous ELISA systems indicated that strain M876 was significantly (P less than 0.05) less immunogenic than S6 (days 62 and 95 PI), and that the homologous ELISA was more sensitive (P less than 0.005). MG strain M35 failed to infect turkeys in three attempts, even though the inocula used were viable on culture media.

Animals