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Biomedical subjects

K R Refsal

Publications and source records attributed to K R Refsal.

At least 37 records · Page 2Linked to original sources

Thyroid function in dogs with spontaneous and induced congestive heart failure.

The effects of spontaneous and experimentally induced congestive heart failure on serum thyroxine (T4), 3,5,3'-triiodothyronine (T3), 3,3'5'-triiodothyronine (reverse T3), free T4, free T3 concentrations, and the serum T4 and T3 concentrations in response to administration of thyrotropin were studied. Serum thyroid hormone concentrations were not different between eight dogs with spontaneous congestive heart failure and normal age matched control dogs. Seven dogs with experimental heart failure were tested before and after induction of congestive heart failure by rapid ventricular pacing. Mean serum T4 and free T3 concentrations were decreased and mean serum reverse T3 concentration was increased following induction of heart failure. The serum T4 and T3 responses to thyrotropin were not altered. Thyroid gland morphology appeared normal in dogs with experimental heart failure. Experimental congestive heart failure, similar to some other nonthyroidal illnesses, alters thyroid hormone secretion and metabolism in dogs.

Animals↗

Pharmacokinetics of L-thyroxine after its oral administration in dogs.

Twelve mature (5 sexually intact males, 4 castrated males, and 3 females) mixed-breed dogs were surgically thyroidectomized and used in a Latin-square design pharmacokinetic study of orally administered L-thyroxine. The dogs were treated with 44, 22, and 11 micrograms of L-thyroxine/kg as a single morning dose or in divided doses, morning and evening. Serum concentration of thyroxine (T4) was evaluated to determine a number of pharmacokinetic variables for comparison. Mean steady-state concentrations (Css) were determined from the area under the curve. Variables were analyzed for comparisons between dosages by use of ANOVA. Concentration at steady state was highest for dogs of the 44-micrograms/kg of body weight once-daily group and was lowest for dogs of the group given 11 micrograms/kg in 2 daily doses. Single daily administration resulted in higher Css, except at the 22-micrograms/kg/d dosage. Clearance was faster for the 22- and 44-micrograms/kg/d dosages than for the 11-micrograms/kg/d dosage. The half-life (t1/2) and mean residence time (MRT) also were shorter for the 44-micrograms/kg/d dosage, possibly indicating more rapid elimination of the drug at higher doses and dose-dependent kinetics. Perhaps, as the dogs' metabolism increased with higher iodothyronine concentrations, hormone degradation was accelerated. Interval (divided vs single dose) caused some expected changes: maximal concentration was higher and minimal concentration was lower when single administration was used. These undulations resulted in iodothyronine concentrations above the physiologic range for a number of hours, whereas concentration closer to physiologic ranges was achieved by use of divided doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Radioimmunoassay monitoring of thyroid hormone concentrations in dogs on thyroid replacement therapy: 2,674 cases (1985-1987).

Serum iodothyronine concentrations from 4,064 samples submitted for monitoring of thyroid replacement therapy were evaluated in a retrospective study. After exclusion of samples because of the presence of 3,5,3' triiodothyronine (T3) autoantibodies, insufficient numbers of dogs on some commercial preparations or medication with corticosteroids or synthetic T3 preparations, data from 2,674 dogs remained. Data were analyzed by using information on dose, time after dosing, commercial product, and once-a-day or twice-a-day dosing regimens. Serum total thyroxine (T4) and total T3 and estimates of free T4 and free T3 were significantly high in serum from dogs given higher doses of synthetic L-thyroxine orally. Doubling the oral dosage did not double the serum iodothyronine concentrations, perhaps because of poor absorption or more rapid catabolism of the hormones at higher L-thyroxine doses. Wide variation in the therapeutic hormone concentrations was found. Some dogs given low dosages of L-thyroxine had normal iodothyronine concentrations whereas some others given higher dosages had low normal to low concentrations. Monitoring the serum concentrations is an objective way to ensure adequate concentrations for successful therapy. When a therapeutic trial is used as a diagnostic procedure, one should not rule out hypothyroidism unless a therapeutic monitoring sample has indicated that replacement dose and absorption of the exogenous iodothyronine has been adequate. Thyroid hormone concentrations peaked at 4 to 6 hours after oral administration of L-thyroxine for once-a-day and twice-a-day dosage regimens. Higher concentrations were achieved with once-a-day than with twice-a-day regimens at the same total daily dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Prevalence of autoantibodies to thyroglobulin, thyroxine, or triiodothyronine and relationship of autoantibodies and serum concentrations of iodothyronines in dogs.

Assays were developed to detect and measure autoantibodies (AA) to thyroglobulin (Tg) and to the thyroid hormones, thyroxine (T4) and triiodothyronine (T3). An ELISA to detect AA to Tg was developed, using purified canine Tg as the antigen and goat anti-canine IgG conjugated with alkaline phosphatase as the second antibody. A highly charged agarose electrophoresis assay was used for determination of AA to T4 and T3. Sera from dogs (n = 119) with clinical signs consistent with hypothyroidism were tested for AA to Tg, T4, and T3. Autoantibodies to at least 1 of the 3 thyroid antigens were detected in 58 of the 119 (48.7%) sera tested. Autoantibodies to Tg were detected more frequently in samples with low serum concentrations of thyroid hormones than in samples with normal concentrations. The presence of AA to T4, T3, or both was not significantly associated with low thyroid hormone concentrations, but this lack of association may have been attributable to binding of AA in the measurement of thyroid hormones by radioimmunoassay.

Animals↗

Use of the triiodothyronine suppression test for diagnosis of hyperthyroidism in ill cats that have serum concentration of iodothyronines within normal range.

Administration of triiodothyronine (liothyronine, 15 micrograms, q 8 h, for 6 treatments) caused marked decrease in serum concentration of thyroxine (T4) and estimates of free T4 (fT4) concentration in clinically normal cats. A prospective clinical study was done to evaluate the use of this suppression test for diagnosis of hyperthyroidism in cats with clinical signs suggestive of the disease, but lacking high serum concentration of iodothyronines. Twenty-three cats were confirmed as hyperthyroid on the basis of histologic changes in the thyroid gland or clinical improvement in response to administration of methimazole. Mean +/- SD serum concentration of T4 (34.3 +/- 12.7 to 31.3 +/- 11.5 nmol/L) and estimate of fT4 concentration (26.6 +/- 6.4 to 25.6 +/- 6.9 pmol/L) did not change after administration of liothyronine to these cats. Twenty-three cats were classified as nonhyperthyroid by histologic confirmation of other disease, abnormal results of other diagnostic tests that strongly supported primary disease other than hyperthyroidism, or spontaneous remission of weight loss without treatment. Mean +/- SD serum concentration of T4 (27.9 +/- 10.3 to 11.7 +/- 6.4 nmol/L) and estimate of fT4 concentration (21.7 +/- 5.4 to 10.4 +/- 4.4 pmol/L) decreased significantly (P less than 0.001) in response to administration of liothyronine. Discriminant analysis was used to identify variables from iodothyronine assays (eg, absolute concentration of T4 or absolute estimate of fT4 concentration, or changes of T4 or fT4 concentration) that provided the best diagnostic sensitivity and specificity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Concentrations of estrone sulfate in peripheral serum of pregnant goats: Relationships with gestation length, fetal number and the occurrence of fetal death in utero.

Blood sampling was initiated shortly after breeding and continued weekly through 60 to 72 days post breeding in 20 pregnant and 5 nonpregnant dairy goat does. In does not showing a return to estrus by 72 days, collection of blood was continued at 10- to 14-day intervals until 135 days post breeding. At parturition, the numbers of does delivering one, two, three, four or five kids was four, ten, three, two and one, respectively. Immunoreactive estrone sulfate (ES) was measured in serum by radioimmunoassay (RIA). In nonpregnant does, the mean+/-SD concentration of ES was 0.1+/-0.1 nmol/l (n=36 samples). At 40 to 50 days post breeding, ES concentrations increased dramatically in pregnant does. Statistically, does were classified as pregnant when serum ES increased and remained above 1.1 nmol/l (P<0.05). Serum ES in pregnant does peaked at 65 to 75 days of gestation, remained at a relative plateau through 120 days and then gradually increased for the remainder of the sampling schedule. There were positive correlations between serum ES and the number of kids born in sampling periods of 50 to 55 days and after 90 days of gestation (P<0.05). Fetal loss was documented in two does that were not included in the survey data. One doe delivered two normal kids and two mummified fetuses. Time-trend changes in ES were typical of a normal pregnancy. Another doe had a marked decrease in ES (below 0.8 nmol/l) in samples drawn on Days 94 and 108 of gestation while luteal concentrations of progesterone were maintained. This doe delivered one weak, depressed kid, one stillborn kid and a decomposed fetus at the expected time for parturition.

Journal Article↗

Changes in adrenal cortisol secretion as reflected in the urinary cortisol/creatinine ratio in dogs.

In Experiment 1, voided urine samples were collected from 12 adult dogs at 0500, 1400, and 2200 hr for 4 days. Cortisol was measured in unextracted urine by radioimmunoassay, creatinine by spectrophotometry, and the cortisol/creatinine ratio (UCCR) was calculated for each sample. There was considerable variation both within and among dogs in UCCR but there was no consistent time of day fluctuation in UCCR. In Experiment 2, these dogs were randomly assigned to 1 of 4 groups. The groups received each of 4 treatments (saline, dexamethasone, ACTH gel, and aqueous ACTH) at 7 day intervals in Latin square design. All urine was collected from 0 through 8 hr. Blood samples were collected at 20 minute intervals from 0 through 8 hr. Plasma cortisol exposure was determined by quantifying area under the curve (AUC). UCCR measurement was shown to differentiate basal from elevated, but not lowered, cortisol secretion. A positive linear relationship between UCCR and AUC was seen for all treatments except dexamethasone. These results indicate that changes in cortisol secretion are reflected in changes in UCCR, but measurement of UCCR may lack sensitivity to differentiate basal from reduced states of cortisol secretion. In Experiment 3, urine was collected daily before and during induction therapy with o,p'-DDD from dogs with pituitary-dependent hyperadrenocorticism. Successful suppression of the adrenal glands was accompanied by a progressive decrease in UCCR. There was considerable variation in the rate of adrenal suppression.

Adrenal Cortex↗

Effects of dietary acidification and potassium depletion on acid-base balance, mineral metabolism and renal function in adult cats.

Effects of dietary potassium restriction, with or without dietary acidification, on acid-base balance, mineral metabolism and renal function were evaluated in 12 adult cats. Six cats were fed a potassium-restricted diet (0.2% potassium) for 8 wk, and six cats were fed the same potassium-restricted diet plus a dietary acidifier (0.8% NH4Cl) for 8 wk. Both groups of cats were then fed the same diet supplemented with potassium gluconate (0.7% dietary potassium) for an additional 4 wk. Renal function was evaluated before treatment and again at 8 and 12 wk. Serum potassium concentration declined in all cats by wk 1 and was also lower in NH4Cl-treated cats at 2, 3, 6 and 8 wk than in control cats. Metabolic acidosis developed in both groups of cats. Dietary balance studies indicated negative potassium balance in NH4Cl-treated cats. Glomerular filtration rate declined significantly in NH4Cl-treated cats after 8 wk but was unchanged in control cats. From the results of this study, we conclude that adding a dietary acidifier to a potassium-restricted diet worsens hypokalemia, possibly by affecting gastrointestinal potassium handling, and induces severe metabolic acidosis and renal dysfunction in adult cats.

Acidosis, Renal Tubular↗

Thyroid function tests in euthyroid dogs treated with L-thyroxine.

The effects of treatment with L-thyroxine (1 mg/m2 of body surface/d, PO, for 8 weeks) on the thyroxine (T4) and triiodothyronine (T3) responses to thyrotropin (TSH) and thyrotropin-releasing hormone (TRH) administration were determined in 10 euthyroid Beagles; 4 other dogs acted as controls. The TSH response test was performed before treatment and at weeks 2, 4, and 8 of treatment in all dogs and at 2 and 4 weeks after cessation of treatment in 6 dogs. The TRH response test was performed before treatment and at week 6 of treatment in all dogs and at 5 weeks after cessation of treatment in 6 dogs. Suppression of the T3 response to TSH was evident at treatment week 2, whereas the T4 response was suppressed at week 4 and remained suppressed for the duration of the study. Four weeks after stopping treatment, T4 and T3 responses to TSH in 2 dogs were within the hypothyroid range. The T4 response to TRH was completely suppressed after 6 weeks of thyroxine treatment, but returned to pretreatment values by 5 weeks after cessation of treatment. Suppression of thyroid and pituitary function is evident after administration of a replacement dose of L-thyroxine to euthyroid dogs.

Animals↗

Caprine beta-mannosidosis. Abnormal thyroid structure and function in a lysosomal storage disease.

Deficient activity of the lysosomal enzyme beta-mannosidase leads to widespread tissue accumulation of oligosaccharides in caprine beta-mannosidosis, an autosomal recessive neurovisceral storage disease. Severe thyroid morphologic abnormalities found in a previous light microscopic survey of tissues from neonatal affected goats suggested the possibility of impairment of function. Since considerable evidence indicates that thyroid hormone plays an important role in regulation of myelination, thyroid hormone deficiency, if present during central nervous system development, could be a factor in the hypomyelination seen in affected animals. Thus, this study was designed to characterize thyroid structure and function in beta-mannosidosis. To investigate developmental aspects of structural abnormalities, thyroids from six pairs of affected and control animals ranging in age from 96/150 days gestation to 3 days postnatal were analyzed by light and electron microscopy. Major findings in thyroids from affected animals, as early as 96/150 days gestation, included follicle irregularities and pronounced presence of lysosomal storage vacuoles in all cell types, particularly in follicular cells. The degree of cytoplasmic vacuolation increased with advancing age. To assess thyroid function, thyroid hormone concentrations were determined in six age-matched, neonatal pairs of affected and control goats. Significantly decreased thyroid hormone concentrations were present in affected animals. It is hypothesized that thyroid hormone deficiency plays a role in the pathogenesis of hypomyelination in affected animals. This study comprises, to our knowledge, both the most complete description of developmental abnormalities and the first report of abnormal function in an endocrine organ in a lysosomal storage disease. Further, this report suggests that systemic perturbations induced by a genetically determined deficiency of a lysosomal hydrolase could be a factor in the pathogenesis of central nervous system lesions.

Aging↗

Pulmonary excretion of H2 in calves with Cryptosporidium-induced malabsorption.

Pulmonary hydrogen gas (H2) concentrations were used to assess the malabsorption of dietary nutrients in preruminating calves inoculated with Cryptosporidium sp. Normal values were established in five control calves and seven calves (principals) were inoculated with 1.0 x 10(8) Cryptosporidium sp. oocysts. Hydrogen concentrations and wet fecal weights were measured at three stages: before Cryptosporidium sp. inoculation (stage 1), three days after the onset of diarrhea (stage 2), and after the resolution of diarrhea (stage 3). Mean end-breath and total-breath H2 concentrations in the principal calves were higher (P less than 0.025 and P less than 0.05) for stage 2, when compared to control values. Both end-breath and total-breath H2 concentrations were increased (P less than 0.001 and P less than 0.025, respectively) in the principal calves during stage 2 when compared to values obtained for stages 1 and 3. Concurrently, Cryptosporidium sp. infection was associated with increased (P = 0.06) fecal output during stage 2, only. The increased H2 concentrations and cumulative fecal output show that Cryptosporidium sp. caused malabsorption of fermentable nutrients.

Animals↗

Adrenal function in 15 dogs with insulin-dependent diabetes mellitus.

Pituitary-adrenal function was assessed by a combined dexamethasone suppression-ACTH stimulation test in 15 diabetic and 9 healthy dogs. In both groups, plasma cortisol concentrations decreased (P less than 0.001) after dexamethasone administration and increased (P less than 0.001) after ACTH administration. Differences between groups (P greater than 0.05) and group-by-time interactions were not significant (P greater than 0.05). Seemingly, adrenal function was not altered in well-regulated diabetic dogs.

Animals↗

Basal and estradiol-induced release of gonadotropins in dairy cows with naturally occurring ovarian cysts.

A study was conducted to identify relationships between serum sex steroid concentrations and release of gonadotropins in dairy cows with ovarian cysts. Cows with ovarian cysts were grouped according to sex steroid profiles as being under estrogenic (n = 6) or low steroid (n = 6) influence. All cows were submitted to a sampling and treatment protocol to 1) record basal pulsatile release of gonadotropins and 2) determine whether luteinizing hormone (LH) or follicle stimulating hormone (FSH) was released after sequential administration of exogenous estradiol and gonadotropin releasing hormone (GnRH) treatments were given 30 h apart. Basal LH was higher in the estrogen-influence group (P < 0.05). There were no differences between groups in basal FSH concentrations or frequency and amplitude of pulsatile LH or FSH release. Only one of the twelve cows, an individual from the low steroid group, had a preovulatory-like surge of gonadotropins after exogenous estradiol. All cows released LH and FSH in response to GnRH treatment, with no differences between groups. These results show that 1) there is considerable variation in pulsatile release of gonadotropins in cows with ovarian cysts, even among individuals with similar sex steroid profiles, and 2) suggest that a factor in the persistence, and perhaps initiation, of the cystic condition is refractoriness to the positive feedback effect of estradiol on gonadotropin release.

Journal Article↗

The relationship between composition of gain and circulating hormones in growing beef bulls fed three dietary crude protein levels.

Twenty-one Simmental crossbred bulls (311 +/- 11 kg, 9 mo of age) were used to determine the effect of feeding 10, 12 or 14% CP on concentration of hormones in blood and the relationship of these hormones to composition of gain. Six bulls were slaughtered on d 0 to provide an estimate of initial carcass composition (9-11 rib section). Remaining bulls were assigned to dietary treatments. Blood samples were collected every 30 min from 0800 to 2000 on d 0, 66, 136 and 202 of treatment; bulls were slaughtered on d 203. Across all treatments, growth hormone (GH) declined (P less than .05) from d 0 to d 202. Free insulin-like growth factor I (IGF-I) was lowest (P less than .05) on d 0. In four randomly selected bulls, IGF-I fluctuated during the 12-h sampling periods. Within each treatment group, insulin was greatest on d 202 (P less than .05). Testosterone (T) increased from d 0 to d 66, then declined. Cortisol (C) was lowest on d 66. Thyroid hormones increased (P less than .05) after d 0. Growth hormone and IGF-I were correlated negatively with carcass fat percentage, fat accretion rate and fat thickness. IGF-I concentrations were correlated positively with percentage of carcass protein. Testosterone:cortisol ratio was not related to composition, but high T coupled with low C may be related to carcass leanness (mean carcass fat = 24.4%). These data suggest that GH and IGF-I are the hormones most related to composition of gain in growing beef bulls.

Animals↗

Effect of nonadrenal illness on adrenal function in the cat.

Adrenal function was assessed by a combined dexamethasone suppression-ACTH stimulation test in 18 healthy cats, 17 diabetic cats, and 19 sick nondiabetic cats. In all groups, plasma cortisol concentrations decreased after dexamethasone was administered and increased after ACTH was administered. There were no significant (P greater than 0.05) differences among groups in time trend changes in cortisol concentration. There was considerable variation in adrenal response between cats in each group. Diabetic cats had more variation in base-line and postdexamethasone plasma cortisol concentrations (P less than 0.05) than did other groups. In sick, nondiabetic cats, cortisol concentrations tended to be higher in cats with hyperthyroidism (P = 0.06) than in cats with other diseases.

Adrenal Cortex Function Tests↗

Breath hydrogen concentration and small intestinal malabsorption in calves.

Breath hydrogen concentrations were measured to assess intestinal carbohydrate malabsorption in preruminating calves. Oral administration of 1.25 g of lactulose (a nonabsorbable carbohydrate)/kg to calves produced breath hydrogen concentrations significantly (P less than 0.001) higher than values determined after calves were fed milk and before the treatment was given. This indicates that, in the calf, fermentation of nonabsorbed carbohydrates results in increased breath hydrogen values. To induce small intestinal malabsorption, chloramphenicol was administered orally at 50 mg/kg, 2 times a day, to 5 calves for 3 days. Before therapy was started, each calf was fitted with a duodenal cannula to facilitate collection of intestinal mucosal biopsy samples during treatment. Chloramphenicol therapy significantly (P less than 0.001) increased breath hydrogen concentrations from those values measured after calves were fed milk alone. Concurrently, chloramphenicol administration significantly decreased intestinal villous length (P less than 0.001) and D-xylose absorption (P less than 0.05), compared with those values before treatment was given. These results demonstrate that decreased intestinal absorptive capacity is associated with an increase in breath hydrogen concentrations and that breath hydrogen may be useful in evaluating malabsorption in calves with naturally occurring enteric disease.

Animals↗

Testicular degeneration in a male goat. A case report.

Semen samples from an 18-month-old infertile Lamancha buck contained less than 10% motile spermatozoa and a high incidence of morphological abnormalities. Degenerate detached heads, tightly coiled tails, and thickened midpieces were the prominent morphological defects, affecting 46%, 30%, and 15% of ejaculated spermatozoa, respectively. At necropsy, the diagnosis of testicular degeneration was made, characterized by focal, noninflammatory seminiferous tubule occlusion and mineralization, with a more generalized sloughing of tubular germinal epithelium. When examining spermatozoa morphology from various sites of the excurrent ducts, detached heads were readily seen in efferent duct fluid (> 30% incidence) and the coiled tails and other midpiece defects became prominent with passage through the caput epididymis.

Journal Article↗

Effect of binding and pinealectomy on photoperiod and seasonal variations in secretion of prolactin in cattle.

The role of the eyes and pineal gland on photoperiod- and season-induced changes in secretion of prolactin were studied in male cattle. Increasing exposure to light from 8 to 16 hr each day increased basal and thyrotropin-releasing-hormone-induced secretion of prolactin 3.7- and 4.1-fold in three sham-pinealectomized steers. In contrast, basal and thyrotropin-releasing-hormone-induced increases in secretion of prolactin did not change in four blind bulls and were markedly suppressed in three pinealectomized steers when exposure to light was increased from 8 to 16 hr/day. There was no diurnal variation in secretion of prolactin regardless of photoperiod or surgical treatment. However, seasonal changes (averaged 46 ng/ml in June-Aug vs 7 ng/ml in Dec-Feb) in secretion of prolactin persisted in blind and pinealectomized steers previously shown to be nonresponsive to changing photoperiods. Ambient temperature and photoperiod account for most, but not all, of the seasonal variation in secretion of prolactin. We hypothesize there is an endogenous annual rhythm in the secretion of prolactin in cattle.

Analysis of Variance↗