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Biomedical subjects

K R Refsal

Publications and source records attributed to K R Refsal.

At least 19 recordsLinked to original sources

Adult-onset hair loss in Chesapeake Bay retrievers: a clinical and histological study.

Ten Chesapeake Bay retriever (CBRS) dogs with hair loss were recruited in collaboration with the American Chesapeake Club. All dogs had nonpruritic, noninflammatory, regionalized hair loss affecting the same areas of the body in male and female dogs. Hormonal investigations showed increased adrenal and sex steroid concentration in seven cases. Histopathology revealed follicular hyperkeratosis and plugging, follicular atrophy, and occasional melanin clumping with malformed hair shafts. This study suggests that hair loss in CBRS is a breed syndrome in which young adult dogs have hair loss characterized by unusual histological features and abnormal steroid production. A familial predisposition seems likely and selective breeding might reduce the occurrence of this condition.

Alopecia↗

Effects of propylthiouracil and bromocryptine on serum concentrations of thyrotrophin and thyroid hormones in normal female horses.

REASONS FOR PERFORMING STUDY: There exists a need for better diagnostic tests to characterise thyroid disease in horses. Currently available diagnostic tests fail to differentiate between thyroid gland disorders and thyroid abnormalities resulting from pituitary or hypothalamic problems. OBJECTIVES: To evaluate the effects of treatment with propylthiouracil (PTU) and bromocryptine (BROM) on serum concentrations of triiodothyronine (T3), thyroxine (T4), reverse T3 (rT3) and equine thyroid-stimulating hormone (e-TSH, thyrotrophin) in mature horses. METHODS: Healthy mature horses were treated using either PTU or BROM for 28 days. The effect of treatment on the thyroid axis was assessed by measuring T3, T4, rT3 and e-TSH before and at +14 and +28 days. The effect of PTU and BROM on the response of T3, T4, rT3 and e-TSH to thyrotrophin-release hormone (TRH) administration was also assessed before and at +14 and +28 days of treatment. RESULTS: Treatment with PTU led to a significant reduction in serum concentrations of T3, T4 and rT3 on Day 28 and increase of e-TSH on Day 28 (P < 0.05). Treatment with BROM did not cause any measurable effect on serum concentrations of T3, T4, rT3 or e-TSH. The percentage increment by which serum concentration of T4, T3 and e-TSH increased following stimulation with TRH was decreased by treatment with PTU for 28 days (P < 0.05) but were not affected by treatment with BROM for 28 days. CONCLUSIONS: These results suggest that 1) treatment with PTU may be used in horses as a model of primary hypothyroidism; 2) the use of BROM as a model of secondary hypothyroidism in horses is not supported; and 3) e-TSH assay deserves further investigation for the clinical diagnosis of thyroid axis dysfunction in horses. POTENTIAL RELEVANCE: Propylthiouracil effectively causes primary hypothyroidism. There is substantial variability between horses with respect to their sensitivity to this substance when administered orally. Further studies pertaining to the characterisation of equine thyroid disorders are warranted and the use of both PTU for the experimental induction of primary hypothyroidism and e-TSH for the diagnostic characterisation of thyroid disorders in horses should be considered.

Animals↗

Heparinised blood ionised calcium concentrations in horses with colic or diarrhoea compared to normal subjects.

Our objectives were to 1) establish ionised calcium (ICa), C-terminal PTH and biologically active PTH (intact molecule) concentrations in blood from normal horses, 2) examine the stability of ionised calcium and acid-base values in stored equine heparinised blood and serum and 3) check the applicability of the formulas based on these parameters in certain disease states. Mean +/- s.d. % ionised calcium in heparinised blood of normal Warmbloods was 51 +/- 2.7 (n = 20) of total calcium, range 1.45-1.75 mmol/l (n = 15) at Michigan State University and 1.43-1.69 mmol/l (n = 20) at Utrecht University. Mean +/- s.d. EDTA plasma concentration for intact +/PTH in normal horses measured 0.6 +/- 0.3 pmol/l (n = 11). Both mean serum and the heparinised blood ionised calcium concentrations changed (not significantly) after 102 h storage at room temperature. Six cycles of freezing and thawing did not affect serum ionised calcium concentration significantly. Ionised calcium concentration and pH in heparinised blood of 20 normal Warmbloods were used to calculate the regression equation for the prediction of the adjusted ionised calcium concentration to a pH of 7.4. The linear regression equation found was: adjusted plasma ICa at pH 7.4 mmol/l = -6.4570 + 0.8739 x (measured pH) + 0.9944 x (measured ICa mmol/l). By means of this formula, mean adjusted ionised calcium concentration in heparinised blood calculated was 100% of the actual value given by the analyser in the normal horses. When using this formula in horses with colic or diarrhoea, mean adjusted ionised calcium concentration was underestimated by 0.2 and 0.3%, respectively. Furthermore, to adjust the measured ionised calcium concentration in heparinised blood to a pH of 7.4 in healthy as well as in 2 groups of diseased horses 2 formulas with a good prediction are now available.

Algorithms↗

Lymphocytic thyroiditis.

Lymphocytic thyroiditis is a common canine condition that can lead to functional hypothyroidism. It is associated with more than 50% of cases of canine hypothyroidism. Evidence in human beings and experimental situations suggests that it is a disease of defective immunoregulation, but specific investigation of the molecular pathogenesis of the naturally occurring disease in dogs has not yet been carried out. The condition is heritable in those breeds that have been studied, and progression to hypothyroidism, if it occurs, can be slow. Factors that influence the progression from subclinical thyroiditis to hypothyroidism in dogs are still to be identified, but excessive iodine intake is an important factor in other species.

Animals↗

Update on the diagnosis and treatment of disorders of calcium regulation.

The availability of PTH, iCa, PTHrP, and 25OHD assays for evaluation of calcium abnormalities in companion animals has been well received [table: see text] by clinicians and diagnosticians. Use of these assays has heightened awareness that some of these disorders are more common than originally thought. Also, there is added insight of alterations of calcium homeostasis as a consequence of other illness or environmental factors such as diet. Animal counterparts of other disorders of calcium metabolism in people are likely to be identified, and use of these assays should play a significant role. As already emphasized, the foundation of using [table: see text] these assays is first assessing whether the calcium abnormality is of a parathyroid-dependent or parathyroid-independent classification.

Animals↗

The postmortem diagnosis of cholecalciferol toxicosis: a novel approach and differentiation from ethylene glycol toxicosis.

The objectives of this study were to develop a novel approach to postmortem diagnosis of cholecalciferol (CCF) toxicosis in dogs using kidney, bile, and urine samples, and to differentiate CCF from ethylene glycol (EG) toxicosis. To achieve these objectives, specimens collected from 2 previous laboratory studies in which dogs were given a single oral toxic dose of CCF (8.0 mg/kg) were used. For EG toxicosis, historical data from the previous 13 years (1985-1998) were reviewed and confirmed cases of EG toxicosis were selected. The historical data were used to compare trace mineral concentrations, specifically of calcium and phosphorus to differentiate between intoxications caused by CCF from that caused by EG in dogs. Kidneys, bile, and urine from dogs that died of CCF toxicosis were analyzed for 25 monohydroxy vitamin D3 (25(OH)D3) and 1,25 dihydroxy vitamin D3 (1,25(OH)2D3) and compared to known control unexposed dogs. Results of this study show that biliary and renal 25(OH)D3 concentrations and renal calcium to phosphorus ratio are of diagnostic value in dogs exposed to toxic concentrations of CCF. The renal calcium to phosphorus ratio was <0.1 in normal dogs, 0.4-0.9 in dogs that died of CCF toxicosis, and >2.5 in dogs that died of EG toxicosis.

Animals↗

Effects of electrolyte and glycerol supplementation on recovery from endurance exercise.

Incomplete recovery from endurance exercise after an overnight rest period is reflected by persisting weight loss and an elevated plasma aldosterone concentration, even in successful competitors. To determine whether supplementation with high doses of electrolytes, with or without glycerol, enhances recovery, the following were measured in 6 Arabian horses before and after completion of a 60 km treadmill exercise test simulating an endurance ride and after 12, 24, 48, and 72 h of recovery: bodyweight; plasma osmolality; plasma concentrations of protein, electrolytes, aldosterone and cortisol; and urine and faecal electrolyte concentrations. Before and during the exercise test, horses were supplemented with a total of 2.4 ml/kg bwt of water (W); 0.2 g/kg bwt KCl and 0.4 g/kg bwt NaCl in 2.4 ml/kg bwt of water (E); or 0.2 g/kg bwt KCl and 0.4 g/kg bwt NaCl in 2.4 ml/kg bwt (3 g/kg bwt) of glycerol (GE). Although weight loss after completion of the simulated ride was greater (P < 0.01) for W (3.2%) than for E and GE (1.0 and 0.9%, respectively), horses supplemented with E or GE experienced further weight loss by 24 h after the simulated ride (2.2 and 2.1% for E and GE, respectively) while bodyweight with W remained unchanged (3.0%) from the finish value. After 48 h of recovery, bodyweight was not different from the starting values with E and GE but remained decreased (P < 0.01) with W throughout the recovery period (2.2% persisting weight loss after 72 h of recovery). Plasma osmolality and plasma Na+ and Cl- concentrations increased (P < 0.01) and plasma protein concentration decreased (P < 0.01) after the exercise test with E and GE but were unchanged with W. Plasma osmolality and protein and electrolyte concentrations returned to pre-exercise values within 12 h of recovery with the exception of a persistent increase in plasma Na+ concentration with GE. The greatest plasma aldosterone concentration was measured after 12 h of recovery with W (1357 pmol/l) and was greater (P < 0.02) than that with E and GE (24 and 304 pmol/l, respectively). Urine production during the simulated ride increased (P < 0.01) with GE and resulted in loss of approximately 20% and essentially 100% of supplemented Na+ and K+, respectively. In contrast, electrolyte losses in faeces were unaffected by electrolyte or glycerol supplementation. In conclusion, supplementation with high doses of electrolytes as hypertonic oral pastes attenuated weight loss during a simulated endurance ride (by enhancing voluntary water intake); however, it did not prevent development of significant weight loss during the initial 24 h of recovery. Glycerol administration resulted in no benefits, and actually increased urine electrolyte losses, in comparison to supplementation with electrolytes alone.

Animal Feed↗

Short-term influence of prednisone and phenobarbital on thyroid function in euthyroid dogs.

The short-term effects of prednisone and phenobarbital on serum total thyroxine (tT4), free thyroxine (fT4), and thyroid stimulating hormone (TSH) were evaluated in euthyroid dogs. Twenty-six beagles were randomly divided into 3 groups receiving, respectively, a placebo, prednisone (1.2 to 2 mg/kg body weight, per os, every 12 hours for 3 weeks), or phenobarbital (1.8 to 3 mg/kg body weight for 1 week, then 2.7 to 4.5 mg/kg body weight, per os, every 12 hours for 2 weeks). Blood samples taken over a 6-week period were assayed for serum tT4, fT4, and TSH. Phenobarbital therapy in our study did not affect serum tT4, fT4, or TSH concentrations. Prednisone therapy, however, significantly decreased serum tT4 and fT4, but did not affect serum TSH concentrations.

Animals↗

Prevalence of autoantibodies to thyroglobulin in dogs with nonthyroidal illness.

OBJECTIVE: To evaluate a thyroglobulin autoantibody (TgAA) assay and determine a diagnostic threshold. SAMPLE POPULATION: Serum samples from dogs with various endocrine abnormalities and from 30 obese adult female Beagles. PROCEDURE: TgAA were determined by use of the ELISA. Six experiments were done: 1, definition of positive results for TgAA using samples from normal and T3 autoantibody (T3AA) positive dogs; 2, establishment of prevalence of positive results in 91 clinically normal dogs; 3, evaluation of positive results for sera from dogs with nonthyroidal illnesses; 4, testing of samples from dogs with primary hypothyroidism but absence of T4AA or T3AA, or both; 5, determination of prevalence of false-negative results in dogs that are T4AA and/or T3AA positive, which were (18 dogs) or were not (22 dogs) receiving L-thyroxine replacement therapy; and 6, examination of thyroid biopsy specimens from 18 dogs (8 TgAA positive and 10 TgAA negative). RESULTS: Positive results were defined as at least twice (200%) the optical density of the negative-control sample. False-positive results were obtained for only 3.4% of 146 dogs with nonthyroidal illness. Thirty-seven percent of dogs with primary hypothyroidism, but no evidence of T4AA or T3AA, or both, were TgAA positive. False-negative results were found in 1 of 22 and 2 of 18 T3AA-positive dogs with and without thyroid replacement therapy, respectively. Thyroid biopsy specimens from 8 TgAA-positive dogs had evidence of lymphocytic thyroiditis, whereas those from 10 TgAA-negative dogs did not. CONCLUSION AND CLINICAL RELEVANCE: The assay is sensitive and specific for identification of lymphocytic autoimmune thyroiditis in dogs, and has potential for aiding early diagnosis of thyroiditis in dogs and identifying dogs likely to perpetuate hypothyroidism in breeding programs.

Animals↗

Ovarian steroid cell tumor resembling luteoma associated with hyperadrenocorticism (Cushing's disease) in a dog.

An ovarian steroid cell tumor was diagnosed in a 6.5-year-old female Rottweiler. The animal was polydipsic and polyuric, with an enlarged, pot-bellied abdomen. Radiographs and ultrasound examinations revealed an approximately 13-cm-diameter cystic mass below the right kidney. A low-dose dexamethasone suppression test was consistent with hyperadrenocorticism. Surgical exploration revealed an enlarged, lobulated left ovary approximately 10 cm in diameter, weighing 550 gs. Histologically, the ovarian tumor consisted of dense sheets and nests of round to polyhedral cells with abundant, finely vesiculated cytoplasm. The overall features were most consistent with ovarian steroid cells tumor resembling luteoma and associated with hyperadrenocorticism.

Animals↗

Hypercalcemia and renal failure. Etiology, pathophysiology, diagnosis, and treatment.

Hypercalcemia is a frequent disorder of calcium metabolism in dogs and cats. Hypercalcemia-induced alterations in renal function and morphology are linked to many of the clinical manifestations observed in hypercalcemic patients. Since many renal effects induced by hypercalcemia are potentially reversible, early recognition and characterization of the problem facilitates rapid therapeutic intervention.

Animals↗

Effects of sample handling temperatures on bovine skim milk progesterone concentrations.

The effects of incubation of whole milk at various temperatures and times on the concentration of progesterone in the skim milk fraction was determined. For the study, milk samples were collected from 10 pregnant Holstein cows. The milk from each cow was transferred to culture tubes to provide 32 replicates of 3 ml volume. To begin the incubation study, all samples were placed in a 37 degrees C water bath for 4 h. The end of this incubation was designated as time 0 and a sample from each cow was centrifuged to harvest skim milk. At time 0, samples from each cow were divided among incubation temperatures of 0 degrees, 4 degrees, 20 degrees and 37 degrees C. Samples were removed from each incubation group at 30, 60, 90 and 120 min. After 120 min, all remaining samples were returned to the 37 degrees C incubation and skim milk was collected at 30, 60 and 90 min. Progesterone was measured in skim milk by radioimmunoassay. The mean +/- SE concentration of progesterone in skim milk at time 0 was 10.9 +/- 1.1 nmol/L. The mean concentration of progesterone in skim milk was higher (P < 0.05) in all samples incubated at 0 degrees and 4 degrees C, with incremental increases ranging from 34% to 67% above time 0. Progesterone in skim milk returned to time 0 concentrations in milk samples transferred from 0 degrees or 4 degrees C to 37 degrees C. There was no change in skim milk progesterone in whole milk samples incubated at 20 degrees or 37 degrees C. From this study, it can be concluded that the concentration of progesterone in skim milk is temperature dependent. Inconsistency in handling whole milk samples can have a profound effect in the concentration of progesterone on skim milk. The temperature-dependent effect was reversible and may be related to solubility of progesterone in milk fat.

Journal Article↗

Effects of sample handling temperatures on bovine skim milk progesterone concentrations.

The effect of incubation of whole milk at various temperatures and times on the amount of progesterone (nmol/l) in the skim milk fraction was determined. For this study, milk samples were obtained from 10 pregnant Holstein cows. The whole milk samples were incubated at 37 degrees C (near normal body temperature of the cow) for 4 h and the initial skim milk progesterone concentration was determined. After that, the experiment was carried out in two main steps: (I) The test tubes containing the whole milk were divided into 4 groups and incubated at different temperatures (0, 4, 20 and 37 degrees C). Samples were removed at 30, 60, 90 and 120 min. (II) After 120 min of incubation at different temperatures, the remaining test tubes were returned to the water bath at 37 degrees C for another 30, 60 and 90 min. The initial average of skim milk progesterone concentrations after incubating the whole milk at 37 degrees C for 4 h was 11.0 +/- 4.4 nmol/l. When the whole milk was incubated at 0 degrees C, the skim milk progesterone concentration increased (P < 0.05) to 14.6 nmol/l at 30 min and reached 16.2 nmol/l at 60 min of incubation. At 4 degrees C incubation temperature, skim milk progesterone increased significantly (P < 0.05) to 15.3 nmol/l and reached 16.9 nmol/l after 90 min. When the whole milk was left at 20 degrees C, the initial skim milk progesterone values decreased to 9.5 nmol/l after 30 min incubation and no further decreases were found even if the whole milk was returned to 37 degrees C for 90 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of food deprivation on baseline iodothyronine and cortisol concentrations in healthy, adult horses.

Six healthy, adult horses, with normal (mean +/- SEM) baseline serum concentrations of total triiodothyronine (T3, 1.02 +/- 0.16 nmol/L), free T3 (FT3, 2.05 +/- 0.33 pmol/L), total thyroxine (T4, 19.87 +/- 1.74 nmol/L), free T4 (FT4, 11.55 +/- 0.70 pmol/L), total reverse T3 (rT3, 0.68 +/- 0.06 nmol/L), and cortisol (152.75 +/- 17.50 nmol/L), were judged to be euthyroid on the basis of response to a standardized thyroid-stimulating hormone response test. Serum concentrations of T3, FT3, T4, FT4, rT3, and cortisol were determined immediately before and every 24 hours during a 4-day period of food deprivation, when water was available ad libitum. Similar variables were measured 72 hours after refeeding. Decreases (to percentage of baseline, prefood deprivation value) in circulating T3 (42%), T4 (38%), FT3 (30%), and FT4 (24%) concentrations were maximal after 2, 4, 2, and 4 days of food deprivation, respectively (P < 0.05). Increases (compared with baseline, prefood deprivation value) in rT3 (31%) and cortisol (41%) concentrations were maximal after 1 and 2 days of food deprivation, respectively (P < 0.05). Refeeding resulted in increase in serum T4 and FT4, and decrease in rT3 and cortisol concentrations toward baseline values, after 72 hours (P < 0.05). Refeeding did not effect a return of T3 or FT3 concentration to baseline values after 72 hours (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Isolation of thyroid peroxidase and lack of autoantibodies to the enzyme in dogs with autoimmune thyroid disease.

Fifty serum samples from dogs with clinical signs of hypothyroidism and autoantibodies (AA) to thyroglobulin (Tg), thyroxine, or triiodothyronine were screened for AA to thyroid peroxidase (TPO). Thyroid peroxidase is the antigen against which microsomal AA are formed in human beings with lymphocytic thyroiditis. The TPO was isolated from canine thyroid tissue, using a modification of the procedure for purifying porcine TPO. The enzyme was solubilized from the membrane, using a deoxycholate-trypsin solution, followed by ammonium sulfate precipitation and diethylaminoethyl Sephadex chromatography. Activity of TPO was determined, using an iodide oxidation assay and a guaiacol assay. A monoclonal antibody to canine Tg, coupled to an immunoaffinity column, was used to eliminate the contaminating Tg from the TPO preparation. Using the TPO preparation as an antigen, an ELISA was performed on 10 serum samples and immunoblot assays were performed on 50 canine sera. Autoantibodies to TPO were not found in any of the sera. Assays also were performed, using purified porcine and human TPO and evidence of cross-reactivity with canine TPO was not identified. The absence of AA to TPO in dogs suggests a different pathogenesis for autoimmune thyroid disease in dogs than that hypothesized for lymphocytic thyroiditis in human beings.

Animals↗

Skim milk progesterone in pregnant cows from insemination throughout lactation.

The skim milk progesterone profile was assessed by radioimmunoassay, without extraction, from the day of insemination (day 0) until the cows were dried off on day 225 of gestation. A total of 418 samples were collected from 154 pregnant Holstein cows. The daily variation in skim milk progesterone was recorded from day 1 until day 45 of pregnancy to detect the commencement of progesterone secretion from the corpus luteum after insemination. Subsequent determinations were made every 2 weeks from day 46 until lactation ceased. On the day of artificial insemination and for the first 2 days after insemination, all the cows had a basal progesterone concentration < 0.1 ng/ml. A rise in progesterone (0.2 +/- 0.1 ng/ml) was first detected on the third day after insemination. The progesterone values then increased significantly (p < 0.001) until day 15. The values then remained nearly constant (2.5-3.5 ng/ml) until day 106 of pregnancy, when they began to decline. Between days 120 and 180 of gestation, progesterone was significantly decreased (2.2-2.9 ng/ml) before it rose again to the previous plateau (3.5-3.9 ng/ml) around day 180. The progesterone concentration then remained at the higher level until the animals were dried off.

Animals↗