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Biomedical subjects

R W Nelson

Publications and source records attributed to R W Nelson.

At least 19 recordsLinked to original sources
PubMed1992

Pituitary tumor size, neurologic signs, and relation to endocrine test results in dogs with pituitary-dependent hyperadrenocorticism: 43 cases (1980-1990).

Pituitary neoplasm was identified in 43 dogs with pituitary-dependent hyperadrenocorticism via necropsy (n = 33), diagnostic imaging with computerized tomography or magnetic resonance imaging (n = 5), or diagnostic imaging and necropsy (n = 5). All dogs had clinical signs and clinicopathologic test results typical of hyperadrenocorticism. Thirty-seven dogs had grossly visible pituitary tumors, and 6 dogs had microscopic pituitary tumors. Fifteen dogs had developed neurologic signs typical of those resulting from an enlarging pituitary mass. Twenty-three dogs had pituitary tumors greater than or equal to 1 cm in diameter. Provocative testing of the pituitary-adrenocortical axis was performed on all dogs. Dogs with grossly visible pituitary tumors and dogs with neurologic signs had significantly (P less than 0.05) higher mean plasma endogenous ACTH concentrations, compared with values from dogs with microscopic tumors and dogs without neurologic signs, respectively. Dogs with grossly visible pituitary tumors and dogs with tumors greater than or equal to 1 cm in diameter had significantly (P less than 0.05) lower adrenocortical responsiveness to exogenous ACTH, compared with dogs with microscopic pituitary tumors and dogs with tumors less than 1 cm in diameter, respectively. Despite these differences, there was overlap between test results among dogs. On the basis of endocrine test results, it would appear difficult to distinguish dogs with pituitary-dependent hyperadrenocorticism and large pituitary tumors from those with pituitary-dependent hyperadrenocorticism and microscopic pituitary tumors prior to onset of neurologic signs.

Adrenocorticotropic Hormone↗
PubMed1992

Synthetic metal-binding protein surface domains for metal ion-dependent interaction chromatography. I. Analysis of bound metal ions by matrix-assisted UV laser desorption time-of-flight mass spectrometry.

To extend the analytical capabilities of immobilized metal ion affinity chromatography (IMAC) for evaluation of biologically relevant peptide-metal ion interactions, we have prepared synthetic peptides representing metal-binding protein surface domains from the human plasma metal transport protein known as histidine-rich glycoprotein (HRG). Three synthetic peptides, representing multiples of a 5-residue repeat sequence (Gly-His-His-Pro-His) from within the histidine- and proline-rich region of the C-terminal domain were prepared. Prior to immobilization, the synthetic peptides were evaluated for identity and sample homogeneity by matrix-assisted UV laser desorption time-of-flight mass spectrometry (LDTOF-MS), a method developed recently for the mass determination of high-molecular-mass biopolymers. 2,5-Dihydroxybenzoic acid was evaluated as a matrix to facilitate the laser desorption and ionization of intact peptides and was found to be ideally suited for determinations of mass within the low-mass region of interest (641.7 to 1772.8 dalton). We observed minimal chemical noise from photochemically generated peptide-matrix adduct signals, clustering, and multiply-charged peptide species. Peptides with bound sodium and potassium ions were observed; however, these signal intensities were reduced by immersion of the sample probe tip in water. Mixtures of the three different synthetic peptides were also evaluated by LDTOF-MS after their elution through a special immobilized peptide-metal ion column designed to investigate metal ion transfer. We found LDTOF-MS to be a useful new method to verify the presence of peptide-bound metal ions.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1992

Comparison of mitotane treatment for adrenal tumor versus pituitary-dependent hyperadrenocorticism in dogs.

The purpose of this study was to determine the sensitivity of dogs with hyperadrenocorticism to treatment with the adrenocorticolytic agent mitotane. Specifically, we looked for differences in response to treatment using this drug in dogs with adrenocortical tumors (adrenal tumor hyperadrenocorticism, ATH) vs those with pituitary-dependent hyperadrenocorticism (PDH). For inclusion in this study, each dog must have had clinical signs, data base laboratory abnormalities, and endocrine screening test results consistent with the diagnosis of hyperadrenocorticism. Further, each dog had to have been treated for at least 6 months with mitotane and have histologic evidence for adrenocortical or pituitary neoplasia (all dogs were necropsied). Thirteen dogs with ATH (8 carcinomas, 5 adenomas) were identified. The ages and body weights of these 13 dogs were computer-matched to 13 dogs with PDH. All dogs were initially treated with approximately 50 mg of mitotane/kg/d of body weight. Reexaminations were performed after 7, 30, 90, and 180 days of treatment. Individual dosages varied widely after the initial 5 to 12 days of treatment. The mean (+/- SD) dose of mitotane (mg/kg/d) for the first 7 days of treatment was 47.5 +/- 9.4 for dogs with ATH vs 45.7 +/- 11.9 for dogs with PDH. The mean plasma cortisol concentrations 1 hour after ACTH administration at the 7-day recheck were significantly higher in dogs with ATH (502 +/- 386 nmol/L) than in dogs with PDH (88 +/- 94 nmol/L).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1992

Treatment of pyometra in cats, using prostaglandin F2 alpha: 21 cases (1982-1990).

Treatment with prostaglandin F2 alpha (PGF2 alpha) was evaluated in 21 queens with open-cervix pyometra. The PGF2 alpha was administered (0.1 or 0.25 mg/kg of body weight, sc, q 12 to 24 h) for 3 or 5 days. Transient postinjection reactions caused by PGF2 alpha administration included vocalization, panting, restlessness, grooming, tenesmus, salivation, diarrhea, kneading, mydriasis, emesis, urination, and lordosis. Reactions began as quickly as 30 seconds after PGF2 alpha administration and lasted as long as 60 minutes. All queens improved clinically after PGF2 alpha treatment. One month after completion of the initial series, 1 queen required a second series of PGF2 alpha injections before pyometra resolved. Of 21 queens, 20 (95%) resumed normal estrous cycles without further treatment and 17 (81%) delivered normal litter(s). Use of PGF2 alpha is an acceptable treatment for open-cervix pyometra in queens.

Animals↗
PubMed1992

Recognition of transition metal ions by peptides. Identification of specific metal-binding peptides in proteolytic digest maps by UV laser desorption time-of-flight mass spectrometry.

Metal-binding peptides in proteolytic digest maps have been identified by matrix-assisted UV laser desorption time-of-flight mass spectrometry (LDTOF-MS). The plasma and milk metal transport protein chosen to demonstrate this process, histidine-rich glycoprotein (HRG), was purified and then digested with trypsin; the cleavage products were analyzed by LDTOF-MS with dihydroxybenzoic acid as the matrix. The selective interaction of specific peptides with one or more Cu atoms was observed when Cu(II) ions were added to the digest mixture. At least one specific metal-binding peptide was identified by computerized sequence analysis using the molecular mass data and available cDNA sequence. These results demonstrate the first direct observation by mass spectrometry of differential peptide-metal ion interactions in protein digest maps. The ability to evaluate peptide-metal ion interactions, including stoichiometry, with less than 1 pmol of sample improves significantly our ability to identify metal binding domains in metal-binding proteins.

Amino Acid Sequence↗
PubMed1992

Effect of glipizide on serum insulin and glucose concentrations in healthy cats.

With the recent identification of non-insulin-dependent diabetes mellitus (NIDDM) in cats, new possibilities arise for the use of oral hypoglycaemic agents in the treatment of feline NIDDM, similar to their use in humans. To identify the future applicability of the oral hypoglycaemic agent, glipizide, in the treatment of feline NIDDM, its effects on serum insulin and glucose concentrations in healthy cats was examined. In addition, adverse effects seen clinically or on bloodwork following short-term use of the drug were looked for. Serum insulin and glucose concentrations were evaluated after the oral administration of 2.5, 5.0 and 10.0 mg glipizide and placebo in 10 healthy cats. For each drug trial, blood was obtained five minutes before, immediately before, and 7.5, 15, 30, 45, 60, 90 and 120 minutes after glipizide or placebo administration. Mean serum insulin concentration increased after glipizide administration, with peak mean serum insulin concentration occurring 15 minutes after administration and declining to baseline by 60 minutes. There was no significant difference in peak mean serum insulin concentration, mean serum insulin concentration at 60 minutes after glipizide administration, or mean total insulin secretion between the three glipizide dosages. Mean serum glucose concentration decreased within 15 minutes of glipizide administration, with the glucose nadir occurring 60 minutes after glipizide administration. Placebo trials showed no significant change in mean serum insulin or glucose concentrations from baseline concentrations.

Administration, Oral↗
PubMed1991

Serum free thyroxine concentration in healthy dogs, dogs with hypothyroidism, and euthyroid dogs with concurrent illness.

Serum free thyroxine (fT4), thyroxine (T4), and 3,5,3'-triiodothyronine (T3) concentrations were determined in 62 healthy dogs, 51 dogs with hypothyroidism, and 59 euthyroid dogs with concurrent dermatopathy or concurrent illness for which hypothyroidism was a diagnostic consideration. Status of thyroid function was based on history, physical findings, results of thyrotropin response testing, requirement for thyroid hormone replacement therapy, and in 31 dogs, on results of histologic examination of a thyroid gland biopsy specimen. Serum fT4 concentration was determined, using a single-stage radioimmunoassay. Mean (+/- SD) serum fT4 concentration was significantly (P less than 0.05) greater in healthy dogs vs dogs with hypothyroidism (0.51 +/- 0.27 ng/dl vs 0.10 +/- 0.07 ng/dl). Significant difference in mean serum fT4 concentration was not evident between dogs with hypothyroidism and euthyroid dogs with hyperadrenocorticism (0.16 +/- 0.13 ng/dl) or peripheral neuropathy (0.19 +/- 0.10 ng/dl). Mean serum fT4 concentration in all other groups of euthyroid dogs with concurrent illness was similar to values in healthy dogs and was significantly (P less than 0.05) greater, compared with values in dogs with hypothyroidism. Similar results were found for mean serum T4 concentration. Comparison of serum fT4 vs T4 concentration revealed: sensitivity, 0.97 vs 0.98; specificity, 0.78 vs 0.73; predictive value for a positive test result, 0.79 vs 0.80; predictive value for a negative test result, 0.97 vs 0.97; and accuracy, 0.78 vs 0.86, respectively. Ten (17%) and 12 (20%) of 59 serum fT4 and T4 concentrations, respectively, were inappropriately low in euthyroid dogs with concurrent illness.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocortical Hyperfunction↗
PubMed1991

Gentamicin pharmacokinetics in diabetic dogs.

Reduction of the prolonged terminal elimination phase of gentamicin may be caused by diabetes mellitus, irrespective of the model of diabetes. To test this hypothesis, five normal dogs, three dogs with alloxan-induced diabetes mellitus, and four dogs with naturally occurring diabetes mellitus (all of which were given exogenous insulin to control hyperglycemia) were given 4.4 mg/kg gentamicin intravenously. Serum pharmacokinetics were analyzed using non-compartmental pharmacokinetics assuming a sum of exponential terms. Gentamicin pharmacokinetics during the first 8 h were the same in normal and diabetic dogs. Over 7 days, MRT in normal dogs (5830 +/- 2970 min, mean +/- SD) was longer (P less than 0.01) than in diabetic dogs (136 +/- 164 min). In diabetic dogs, Cls was greater (3.01 +/- 0.86 ml/min/kg) than in normal dogs (1.45 +/- 0.11 ml/min/kg; P less than 0.01), whereas Vd(ss) was smaller in diabetic dogs (0.405 +/- 0.508 l/kg) than in normal dogs (8.56 +/- 4.48 l/kg; P less than 0.01). Serum gentamicin concentrations were less than 0.020 microgram/ml by 2 days in all of the diabetic dogs, but were 0.048 +/- 0.018 microgram/ml at 7 days in normal dogs. Thus, diabetes mellitus, either induced by alloxan administration or naturally occurring, abolished the terminal elimination phase of gentamicin disposition in a non-rodent species.

Animals↗
PubMed1991

Effects of dietary fiber supplementation on glycemic control in dogs with alloxan-induced diabetes mellitus.

The effect of a high insoluble-fiber (IF) diet containing 15% cellulose in dry matter, high soluble-fiber (SF) diet containing 15% pectin in dry matter, and low-fiber (LF) diet on glycemic control in 6 dogs with alloxan-induced insulin-dependent diabetes mellitus was evaluated. Each diet contained greater than 50% digestible carbohydrate in dry matter. A crossover study was used with each dog randomly assigned to a predetermined diet sequence. Each dog was fed each diet for 56 days. Caloric intake was adjusted weekly as needed to maintain each dog within 1.5 kg of its body weight measured prior to induction of diabetes mellitus. All dogs were given pork lente insulin and half of their daily caloric intake at 12-hour intervals. Mean (+/- SEM) daily caloric intake was significantly (P less than 0.05) less when dogs consumed the IF diet vs the SF and LF diets (66 +/- 3 kcal/kg, 81 +/- 5 kcal/kg, and 79 +/- 4 kcal/kg, respectively). Serum alkaline phosphatase activity was significantly (P less than 0.05) higher when dogs consumed the LF diet vs the IF and SF diets (182 +/- 37 IU/L, 131 +/- 24 IU/L, and 143 +/- 24 IU/L, respectively). Mean postprandial plasma glucose concentration measured every 2 hours for 24 hours, beginning at the time of the morning insulin injection, was significantly (P less than 0.05) lower at most blood sampling times in dogs fed IF and SF diets, compared with dogs fed the LF diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗
PubMed1991

Serum glucose and insulin responses to an insulin-containing ophthalmic solution administered topically in clinically normal cats.

Serum glucose and immunoreactive insulin concentrations were monitored after topical administration of an insulin-containing ophthalmic solution in 20 clinically normal cats. Three ophthalmic surface-acting agents, benzalkonium chloride, dimethyl sulfoxide, and proparacaine hydrochloride, were evaluated individually for their effectiveness in enhancing absorption of topically applied insulin. The ophthalmic effects of insulin-containing ophthalmic preparations were assessed by complete ophthalmic examination before and at the conclusion of each test period. Withholding of food overnight (12 hours) preceded each topical application of insulin-containing ophthalmic solution (12.25 to 26.4 U/cat), either alone or in combination with surface-acting agents, after which blood samples were drawn serially from an indwelling IV catheter over a period of 8 hours. Baseline serum insulin concentration, after food was withheld for 12 hours, in nonstressed cats was 6.0 microU/ml (geometric mean), and an exponentiation of the logarithmic quantity (mean +/- SD) yielded values of 1.5 to 23.0 microU/ml. All ophthalmic solutions tested failed to significantly lower serum glucose concentration or increase serum insulin concentration. Solutions used did not induce deleterious effect on ocular structures. Results indicate that topical administration of insulin-containing ophthalmic solution, either alone at the concentrations used or in combination with surface-acting agents, did not result in effective absorption of insulin across the conjunctival and lacrimal nasal mucosa in biologically relevant quantities. Thus, this route of insulin administration, under these specific conditions, is not an effective alternative or adjunct to SC administration of insulin for treatment of cats with insulin-dependent diabetes mellitus or severe noninsulin-dependent diabetes mellitus.

Absorption↗
PubMed1990

Plasma cortisol response to ketoconazole administration in dogs with hyperadrenocorticism.

The effect of orally administered ketoconazole on plasma cortisol concentration in dogs with hyperadrenocorticism was evaluated. Every 30 minutes from 0800 hours through 1600 hours and again at 1800 hours, 2000 hours, and 0800 hours the following morning, 15 clinically normal dogs and 49 dogs with hyperadrenocorticism had plasma samples obtained and analyzed for cortisol concentration. The mean (+/- SD) plasma cortisol concentration for the initial 8-hour testing period was highest in 18 dogs with adrenocortical tumor (5.3 +/- 1.6 micrograms/dl), lowest in 15 control dogs (1.3 +/- 0.5 micrograms/dl), and intermediate in 31 dogs with pituitary-dependent hyperadrenocorticism (PDH; 3.4 +/- 1.2 micrograms/dl). Results in each of the 2 groups of dogs with hyperadrenocorticism were significantly (P less than 0.05) different from results in control dogs, but not from each other. The same cortisol secretory experiment was performed, using 8 dogs with hyperadrenocorticism (5 with PDH; 3 with adrenocortical tumor) before and after administration at 0800 hours of 15 mg of ketoconazole/kg of body weight. Significant (P less than 0.05) decrease in the 8-hour mean plasma cortisol concentration (0.9 +/- 0.2 microgram/dl) was observed, with return to baseline plasma cortisol concentration 24 hours later. Twenty dogs with hyperadrenocorticism (11 with PDH, 9 with adrenocortical tumor) were treated with ketoconazole at a dosage of 15 mg/kg given every 12 hours for a half month to 12 months. The disease in 2 dogs with PDH failed to respond to treatment, but 18 dogs had complete resolution of clinical signs of hyperadrenocorticism and significant (P less than 0.05) reduction in plasma cortisol responsiveness to exogenous adrenocorticotropin (ACTH).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1990

Primary hypoparathyroidism in a cat.

Primary hypoparathyroidism caused by lymphocytic parathyroiditis was diagnosed in a cat. Other causes of hypocalcemia (ethylene glycol toxicosis, phosphate enema administration, pancreatitis, renal insufficiency, and malabsorption) were ruled out on the basis of history, clinicopathologic data, and lack of supportive clinical signs, which in this cat included inappetence and tetanic muscle spasms. The diagnosis was confirmed by histologic examination of a surgically excised thyroparathyroid lobe that comprised lack of recognizable parathyroid tissue and a lymphocytic plasmacytic infiltrate adjacent to the cranial pole. A treatment regimen similar to that for iatrogenic postthyroidectomy hypoparathyroidism was successful in controlling clinical signs of the disease.

Animals↗
PubMed1990

Glucose tolerance and insulin response in normal-weight and obese cats.

Glucose tolerance and insulin response were evaluated in 9 normal-weight and 6 obese cats after IV administration of 0.5 g of glucose/kg of body weight. Blood samples for glucose and insulin determinations were collected immediately prior to and 2.5, 5, 7.5, 10, 15, 30, 45, 60, 90, and 120 minutes after glucose infusion. Baseline glucose concentrations were not significantly different between normal-weight and obese cats; however, mean +/- SEM glucose tolerance was significantly impaired in obese vs normal-weight cats after glucose infusion (half time for glucose disappearance in serum--77 +/- 7 vs 51 +/- 4 minutes, P less than 0.01; glucose disappearance coefficient--0.95 +/- 0.10 vs 1.44 +/- 0.10%/min, P less than 0.01; insulinogenic index--0.20 +/- 0.02 vs 0.12 +/- 0.01, P less than 0.005, respectively). Baseline serum insulin concentrations were not significantly different between obese and normal-weight cats. Insulin peak response after glucose infusion was significantly (P less than 0.005) greater in obese than in normal-weight cats. Insulin secretion during the first 60 minutes (P less than 0.02), second 60 minutes (P less than 0.001), and total 120 minutes (P less than 0.0003) after glucose infusion was also significantly greater in obese than in normal-weight cats. Most insulin was secreted during the first hour after glucose infusion in normal-weight cats and during the second hour in obese cats. The impaired glucose tolerance and altered insulin response to glucose infusion in the obese cats was believed to be attributable to deleterious effects of obesity on insulin action and beta-cell responsiveness to stimuli (ie, glucose).

Animals↗
PubMed1990

Absorption kinetics of regular insulin in dogs with alloxan-induced diabetes mellitus.

The absorption kinetics of porcine regular insulin following IV, IM, and SC administration were evaluated in 10 dogs with alloxan-induced diabetes mellitus. Plasma immunoreactive insulin (IRI) concentrations were evaluated immediately prior to and at 10, 20, 30, 45, 60, 90, 120, 180, and 240 minutes following IV administration; and immediately prior to and every 30 minutes for 2 hours and then every hour for 6 hours following IM and SC administration of 0.55 U of porcine regular insulin/kg of body weight. Model-independent pharmacokinetic analysis was performed on each data set. Plasma IRI concentration declined rapidly after IV administration of regular insulin and then returned to baseline IRI concentration by 3.2 +/- 0.8 hours. The absorption kinetics following IV administration of regular insulin were similar to those found in earlier studies in healthy dogs and human beings. The IM and SC routes of regular insulin administration resulted in a pharmacologic concentration of IRI at 30 minutes. The peak mean (+/- SD) plasma IRI concentration was significantly (P less than 0.05) greater following SC administration than it was following IM administration of regular insulin (263 +/- 185 and 151 +/- 71 I microU/ml, respectively). The time of the peak plasma IRI concentration (68 +/- 31 minutes and 60 +/- 30 minutes) and the time to return to baseline plasma IRI concentration (5.8 +/- 1.2 hours and 5.8 +/- 1.3 hours) were not significantly different following SC and IM administration of regular insulin, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Alloxan↗