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Biomedical subjects

E N Behrend

Publications and source records attributed to E N Behrend.

At least 19 recordsLinked to original sources

Use of surgery and electron beam irradiation, with or without chemotherapy, for treatment of vaccine-associated sarcomas in cats: 78 cases (1996-2000).

OBJECTIVE: To evaluate responses of cats with vaccine-associated sarcomas to treatment with surgery and radiotherapy, with or without adjunctive chemotherapy. DESIGN: Retrospective study. ANIMALS: 76 cats (78 tumors). PROCEDURE: Medical records were reviewed. Factors potentially associated with survival time, time to recurrence, and time to development of metastases were evaluated. RESULTS: Following excision, electron beam radiation, and, in some cases, chemotherapy, 32 (41%) cats experienced recurrence, and 9 (12%) cats developed metastases. One- and 2-year survival rates were 86 and 44%, respectively. Median survival time from onset of disease was 730 days (range, 30 to 2,014 days). Median disease-free interval was 405 days (range, 30 to 925 days). Cats that underwent only 1 surgery prior to radiotherapy had a lower recurrence rate than did cats that underwent > 1 surgery and had a significantly longer disease-free interval. Survival time and disease-free interval decreased as time between surgery and the start of radiotherapy increased. Cats that developed metastases had significantly shorter survival times and disease-free intervals than did cats that did not develop metastases. Castrated male cats had a significantly shorter survival time than did spayed female cats. Cats with larger tumors prior to the first surgery had shorter survival times. Twenty-six cats received chemotherapy in addition to surgery and radiotherapy. Whether cats received chemotherapy was not associated with recurrence rate, metastasis rate, or survival time. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that excision followed by electron beam irradiation may be beneficial for treatment of cats with vaccine-associated sarcomas. Extent of excision prior to radiotherapy did not seem to be associated with recurrence rate.

Animals↗

Diagnosis of canine hypothyroidism. Perspectives from a testing laboratory.

The most common sample received by our endocrine testing laboratory is submitted for the diagnosis of hypothyroidism in a dog. The current tests most frequently employed in our laboratory for thyroid evaluation in dogs are total T4, free T4 by dialysis, and canine TSH measurement. Each test has strengths and weaknesses and suffers from the possibility of both false positive and false negative results. This article provides a working description of each test and an approach to interpretation of results. Other tests that are less commonly used are also discussed. Examples of interpretation of test results in individual hypothyroid-suspect dogs are presented for illustration.

Animals↗

Diagnosis of canine hyperadrenocorticism.

Canine hyperadrenocorticism is one of the most common endocrinopathies in dogs. Diagnosis remains difficult in some cases due to factors such as the presence of non-adrenal illness and limitations in the tests. Differentiation between the pituitary and adrenal forms is important for providing accurate prognostic information and delineating treatment options and protocols. This article reviews the tests available for diagnosis (screening) and differentiation and evaluates their advantages and disadvantages. Recommendations for testing are made.

Abdomen↗

Endocrine tumors.

Because of the diverse nature of endocrine organs, and their vast range of physiologic functions, endocrine tumors encompass a wide range of origination sites and disease entities. The clinical picture of affected individuals is highly dependent on the tissue of origin, and the presence or absence of functional hormone secretions. Identification, localization, and therapeutic strategies, as well as prognosis can vary greatly. Many endocrine tumors have been described in human as well as veterinary patients. This article focuses on endocrine tumors of dogs and cats. Various tumors affecting the pancreas, thyroid, parathyroid, adrenal and pituitary glands are described, including insulinoma, gastrinoma, glucagonoma, and thyroid carcinoma, as well as parathyroid hormone- and growth hormone-secreting tumors. The syndrome of multiple endocrine neoplasia is also described.

Adrenal Gland Neoplasms↗

Regulation of Dexras1 expression by endogenous steroids.

Dexras1, a newly identified member of the Ras superfamily of proteins, was discovered in AtT-20 corticotrope cells because its expression was induced in response to glucocorticoids (dexamethasone; Dex). As yet, the function of Dexras1 is unknown, but its rapid induction in response to glucocorticoids suggests the possibility that it may be involved in negative feedback regulation of corticotropin secretion. To better understand the control of Dexras1 expression, possible effects of other steroid hormones on its expression were studied in both AtT-20 cells and in mouse pituitaries. AtT-20 cells were treated with each of 6 steroids [aldosterone, corticosterone (Cort), Dex, beta-estradiol (E(2)), progesterone and testosterone] for 2 h. Dexras1 expression was assessed using both reverse transcription polymerase chain reaction (RT-PCR) and Northern analysis. Expression of the gene was only induced in response to glucocorticoid treatment (Dex or Cort). The 6 steroids were also injected into mice, pituitaries were harvested and total RNA was obtained for RT-PCR analysis. Surprisingly, treatment with E(2), not only injection of glucocorticoids, induced Dexras1 expression in mouse pituitary. Other steroids were without effect. The results suggest that in AtT-20 corticotropes, Dexras1 expression is only induced by glucocorticoid-type steroids. In pituitary glands of mice, the gene's expression is also responsive to E(2). We conclude that either Dexras1 expression in corticotropes from normal mice is regulated differently from that in AtT-20 cells, or that Dexras1 is also expressed in other pituitary cells than corticotropes.

Animals↗

Validation of a novel high-sensitivity radioimmunoassay procedure for measurement of total thyroxine concentration in psittacine birds and snakes.

OBJECTIVE: To validate a novel high-sensitivity radioimmunoassay (RIA) procedure developed to accurately measure the relatively low serum total thyroxine (T4) concentrations of birds and reptiles and to establish initial reference ranges forT4 concentration in selected species of psittacine birds and snakes. ANIMALS: 56 healthy nonmolting adult psittacine birds representing 6 species and 42 captive snakes representing 4 species. PROCEDURE: A solid-phase RIA designed to measure free T4 concentrations in dialysates of human serum samples was used without dialysis to evaluate total T4 concentration in treated samples obtained from birds and reptiles. Serum T4 binding components were removed to allow assay of undialyzed samples. Assay validation was assessed by determining recovery of expected amounts of T4 in treated samples that were serially diluted or to which T4 was added. Intra- and interassay coefficient of variation (CV) was determined. RESULTS: Mean recovery of T4 added at 4 concentrations ranged from 84.9 to 115.0% and 95.8 to 119.4% in snakes and birds, respectively. Intra- and interassay CV was 3.8 and 11.3%, respectively. Serum total T4 concentrations for 5 species of birds ranged from 2.02 to 768 nmol/L but ranged from 3.17 to 142 nmol/L for blue-fronted Amazon parrots; concentrations ranged from 0.21 to 6.06 nmol/L for the 4 species of snakes. CONCLUSIONS AND CLINICAL RELEVANCE: This new RIA method provides a commercially available, accurate, and sensitive method for measurement of the relatively low serum T4 concentrations of birds and snakes. Initial ranges for the species evaluated were established.

Animals↗

Profound postanesthetic hypoglycemia attributable to glucocorticoid deficiency in 2 dogs.

Glucocorticoid deficiency was diagnosed as the cause of severe postanesthetic hypoglycemia in 2 dogs. Prior signs of systemic illness were not described in either dog; however, preoperative hematologic findings were consistent with glucocorticoid deficiency. Fasting hypoglycemia is a possible complication of chronic adrenal insufficiency primarily because of impaired gluconeogenesis.

Adrenocorticotropic Hormone↗

Effect of storage conditions on cortisol, total thyroxine, and free thyroxine concentrations in serum and plasma of dogs.

OBJECTIVE: To determine for dogs stability of cortisol, thyroxine (T4), and free thyroxine (fT4) in plasma and serum stored in glass or plastic tubes at -20, 4, 25, and 37 C. DESIGN: Prospective study. ANIMALS: Phase I, 7 Greyhounds; Phase II, 6 mixed-breed dogs. PROCEDURE: Phase I: blood was obtained after administration of thyroid-stimulating hormone and adrenocorticotropin. Serum and plasma samples from each dog were divided into 8 aliquots, 4 in glass and 4 in plastic tubes. A pair of aliquots, 1 in plastic and 1 in glass, were stored at -20, 4, 25, or 37 C for 5 days and then assayed for hormones. Phase II: blood was obtained without prior stimulation. For fT4 determination, serum from each dog was placed in plastic or glass tubes, assayed immediately, stored at -20 C for 5 days, and reassayed. Aliquots from each dog were also stored for 1 day at 4 or 25 C and then assayed. Samples for cortisol determination were handled as in phase I. RESULTS: Phase I: there was no effect of tube type (glass vs plastic) on cortisol. Cortisol concentrations decreased after storage in serum at 4, 25, and 37 C, and in plasma at 37 C, compared with storage at -20 C. There was no effect of sample type (serum or plasma) on T4. Thyroxine concentrations increased after storage at 37 C in glass, compared with storage at -20 C. The fT4 concentrations were lower in serum than plasma after storage at -20 C. Concentrations of fT4 increased after storage at 37 C in glass, compared with storage at -20 C. Phase II: the fT4 concentrations did not change after storage in any condition. There was no effect of tube type on cortisol concentrations. Serum cortisol concentrations decreased after storage at 37 C, compared with storage at -20 C. CLINICAL IMPLICATIONS: For cortisol, cooling of plasma is not necessary, but serum should be shipped cold. For T4 and fT4, serum is sufficient; contained within plastic tubes, samples can be shipped without cooling if assayed within 5 days.

Analysis of Variance↗

Dexamethasone rapidly induces a novel ras superfamily member-related gene in AtT-20 cells.

Differential display was used to identify a new Ras superfamily gene (Dexras1) induced by dexamethasone (Dex) in AtT-20 cells. Treatment of AtT-20 cells with Dex for 30 min resulted in increased mRNA for Dexras1; the highest concentrations appeared after 2 h of treatment. The gene was also identified in mouse heart, brain, liver, and kidney and furthermore was induced in these tissues after Dex treatment. The deduced protein shows regions of homology characteristic of members of the Ras superfamily of small GTPases. Highest homology (36% identity, 57% positives) was found with human Rap-2b, followed closely by a number of other Ras subfamily members, suggesting that Dexras1 is probably a member of the Ras subfamily of GTPases (members include Ras and Rap). Dexras1 is the first Ras superfamily member identified that is induced in response to steroids. The function of this gene is unknown; however, its wide distribution and rapid induction by Dex suggests the possibility of a role in glucocorticoid action in a variety of tissues.

Amino Acid Sequence↗

Pharmacokinetics of exogenous corticotropin in normal dogs, hospitalized dogs with non adrenal illness and adrenopathic dogs.

Corticotropin (ACTH) pharmacokinetics was assessed in 10 normal dogs receiving exogenous ACTH (0.5 U/kg, i.v.). A two-compartment open model was most appropriate for description of exogenous ACTH pharmacokinetics. The apparent distribution and elimination rate constants (alpha and beta) were 7.4 +/- 2.7 x 10(-2) min(-1) and 5.5 +/- 3.8 x 10(-3) min(-1), respectively. Area under the concentration-time curve (AUC) was 2.91 +/- 0.78 x 10(4) pg x min/mL, mean residence time (MRT) was 45.0 +/- 12.2 min, the distribution half-life (t1/2alpha) was 9.4 min (harmonic mean), and the elimination half-life (t1/2beta) was 128 min (harmonic mean). The total body clearance of ACTH (ClB) was 1.83 +/- 0.46 x 10(4) mL x min/kg and volume of distribution (Vd(area)) was 30 +/- 15 L/kg. Corticotropin pharmacokinetics was also assessed in 12 client owned dogs, six dogs with non adrenal illness (NAI) and six dogs with hyperadrenocorticism (HAC), receiving exogenous ACTH (0.5 U/kg, i.v.). For these patients, data was best fitted to a one-compartment open model. In dogs with NAI, the AUC was 6.23 +/- 0.62 x 10(5) pg x min/mL, MRT was 38.7 +/- 12 min, the apparent elimination rate constant (k(el)) was 0.26 +/- 0.0017 min(-1) elimination half-life was 26.7 min, ClB was 0.84 +/- 0.1 x 10(4) mL/min/kg, and Vd(area) was 31.9 +/- 5.7 L/kg. In dogs with HAC, AUC was 4.74 +/- 0.23 x 10(5) pg x min/mL, MRT was 20.4 min, k(el) was 0.034 +/- 0.009 min(-1), half-life was 20.4 min, CIB was 1.06 +/- 6.0 x 10(4) mL/min/kg and Vd(area) was 29.7 +/- 6.7 L/kg. Dogs with pituitary-dependent hyperadrenocorticism showed more rapid elimination and clearance of exogenous corticotropin than dogs with NAI.

Adrenal Cortex Diseases↗

Enhancement of secretagogue-induced adrenocorticotropic hormone release from cultured sheep anterior pituitary cells by recombinant ovine interleukin 1.

OBJECTIVE: To determine whether recombinant ovine interleukin (oIL)-1 or oIL-2 alters basal or hypothalamic peptide-induced secretion of ACTH from cultured sheep pituitary cells. ANIMALS: The pituitary gland was collected from castrated male sheep ranging from 0.5 to 1 year old. PROCEDURE: Cells were cultured for 3 to 5 days, then were treated with oIL for variable periods. Cells were washed and treated with the hypothalamic peptides corticotropin-releasing hormone (CRH) or arginine vasopressin (AVP) or both. Medium bathing the cells was collected and assayed for ACTH concentration. RESULTS: Ovine IL-1 alpha and oIL-1 beta, but not oIL-2, increased the amount of ACTH released in response to CRH, AVP, and CRH and AVP combined. Both oIL were effective after 3, but not 18 or 24 hours of exposure. Treatment with oIL-1 did not affect basal release of ACTH. Exposure of cells to phorbol 12-myristate 13-acetate or calphostin C before treatment with oIL-1 beta inhibited the ability of the cytokine to augment ACTH release, suggesting a role for protein kinase C in the process. CONCLUSIONS: Local concentration of oIL-1 in the sheep pituitary gland may have an important role in determining secretion of ACTH in response to CRH or AVP or both from the hypothalamus. CLINICAL RELEVANCE: The hypothalamic-pituitary-adrenocortical axis may be activated after immune challenge. The cytokine oIL-1 has been implicated as an important mediator in this process. The pituitary gland may be an important target for this effect.

Adrenocorticotropic Hormone↗

Adrenal physiology.

The adrenal glands contain elements of three distinct functional units: (1) the medulla, which secretes catecholamines; (2) the zona glomerulosa, which is responsible for mineralocorticoids (aldosterone); and (3) the zonae fasiculata and reticularis, which are the sources of glucocorticoids (cortisol). The medulla is a part of the sympathetic nervous system and releases epinephrine and norepinephrine in response to stressful stimuli. Aldosterone secretion is regulated mainly by changes in extracellular fluid-water volume and pressure, and sodium and potassium concentrations in blood. Through its actions in the kidney, aldosterone acts to retain sodium and water and enhance excretion of potassium. Glucocorticoid secretion is regulated by adrenocorticotropin from the pituitary. Cortisol has diverse actions on virtually all body tissues. One important effect of this steroid is to provide a negative feedback signal, inhibiting adrenocorticotropic hormone release.

Adrenal Cortex↗

Glucocorticoid therapy. Pharmacology, indications, and complications.

Glucocorticoids are one of the most commonly prescribed classes of medication in veterinary medicine, with numerous applications ranging from physiologic replacement therapy to immunosuppression. Due to the presence of glucocorticoid receptors in almost all cells, both the desired and undesired effects of glucocorticoid therapy are manifold. This article discusses the physiologic alterations possible with glucocorticoid therapy, glucocorticoid pharmacology, nonendocrine indications, and different therapeutic strategies. The adverse reactions potentially associated with glucocorticoid therapy also are examined.

Animals↗

Hospital-acquired acute renal failure in dogs: 29 cases (1983-1992).

OBJECTIVE: To assess factors associated with development of hospital-acquired acute renal failure (HARF) and to determine outcome of and prognostic indicators for dogs with HARF. DESIGN: Retrospective case series. ANIMALS: 29 dogs. RESULTS: The most common inciting causes for developments of HARF were exposure to a nephrotoxicant and advanced age. Mortality was 62%, and factors that contributed to mortality were age and initial urine output. Dogs > or = 7 years old and dogs that were initially oliguric had an odds ratio of mortality of 8.8 and 20, respectively. The effect of preexisting heart disease on mortality approached significance (P = 0.053). The magnitude of azotemia at the time of diagnosis was not related to the chance for survival. Dogs that died had a significantly higher initial anion gap and serum phosphorus concentration than did dogs that survived. We did not detect a relationship between cause of HARF and outcome (survived vs died or euthanatized). CLINICAL IMPLICATIONS: In most cases, HARF is associated with a poor outcome. Older dogs may be at increased risk for development of HARF, and once HARF has developed, have a greater chance of dying. Prognosis can not be determined on the magnitude of azotemia at the time of diagnosis or on the inciting cause of HARF.

Acid-Base Equilibrium↗

Effects of dietary n-3 fatty acid supplementation versus thromboxane synthetase inhibition on gentamicin-induced nephrotoxicosis in healthy male dogs.

OBJECTIVE: To evaluate the protective effects of dietary n-3 fatty acid supplementation versus treatment with a thromboxane synthetase inhibitor (TXSI) in dogs given high-dose gentamicin. DESIGN: Clinicopathologic and renal histopathologic changes induced by gentamicin (10 mg/kg of body weight, IM, q 8 h, for 8 days) were compared in dogs fed an n-3 fatty acid-supplemented diet containing a fatty acid ratio of 5.7:1 (n-6:n-3), dogs treated with CGS 12970 (a specific TXSI given at 30 mg/kg, PO, q 8 h, beginning 2 days prior to gentamicin administration), and control dogs. The TXSI-treated and control dogs were fed a diet with a fatty acid ratio of 51.5:1 (n-6:n-3). Both diets were fed beginning 42 days prior to and during the 8-day course of gentamicin administration. ANIMALS: Eighteen 6-month-old male Beagles, 6 in each group. RESULTS: After 8 days of gentamicin administration, differences existed among groups. Compared with n-3-supplemented and control dogs. TXSI-treated dogs had higher creatinine clearance. Both TXSI-treated and n-3-supplemented dogs had higher urinary prostaglandin E2 and E3 (PGE2/3) and 6-keto prostaglandin F1a (PGF1a) excretion, compared with control dogs. Urinary thromboxane B2 (TXB2) excretion was higher in n-3-supplemented and control dogs, compared with TXSI-treated dogs. Urine PGE2/3-to-TXB2 and PGF(in)-to-TXB2, ratios were increased in TXSI-treated dogs, compared with n-3-supplemented and control dogs, and these ratios were increased in n-3-supplemented dogs, compared with control dogs. In addition, TXSI-treated and n-3-supplemented dogs had lower urinary protein excretion, compared with control dogs. Proximal tubular necrosis was less severe in TXSI-treated dogs, compared with control dogs. CONCLUSION: Treatment with CGS 12970 prior to and during gentamicin administration prevented increases in urinary TXB2 excretion and reduced nephrotoxicosis. CLINICAL RELEVANCE: Increased renal production/excretion of thromboxane is important in the pathogenesis of gentamicin-induced nephrotoxicosis.

Animals↗

Effects of dietary protein conditioning on gentamicin pharmacokinetics in dogs.

Eighteen, six-month-old male Beagles with normal renal function were randomly divided into three groups of 6. Each group was fed a diet that was similar except for protein content (high = 26%, medium = 13% and low = 9%, all on an as fed basis) throughout the experimental period. After a 21 day dietary protein conditioning period (including a terminal 2 day testing period), gentamicin was administered at a dosage of 10 mg/kg q. 8 h for 8 days. The first dose on days 1 and 7 was administered i.v. and all others were given i.m. Pharmacokinetic parameters were determined using blood samples collected over an 8 h period following the i.v. dose on day 1. The elimination rate constant was calculated on days 1 and 7. The data best fit a two-compartment open model for all dogs on day 1. The volume of distribution was higher and the clearance greater in the high protein group compared to the other two groups. No difference was found in the rate of elimination between days 1 and 7 for the high protein group; however, in the medium and low protein groups the rate of elimination decreased over the 7 days of treatment. Therefore, high dietary protein prior to and during gentamicin administration induced faster gentamicin clearance and a larger volume of distribution and preserved the ability to eliminate gentamicin in dogs with normal renal function.

Animals↗

Effects of dietary protein conditioning on gentamicin-induced nephrotoxicosis in healthy male dogs.

Eighteen 6-month-old male Beagles with normal renal function were allotted at random to 3 groups of 6 dogs each. For 21 days, each group was fed a diet that was similar except for protein content (high protein, 27.3%; medium protein, 13.7%; and low protein, 9.4%). After the conditioning period, gentamicin was administered at a dosage of 10 mg/kg of body weight, IM, every 8 hours for 8 days, and the respective diet was continued. Clearance of endogenous creatinine, 24-hour urinary excretion of protein and enzymes (gamma-glutamyltransferase, and N-acetyl-beta-D-glucosaminidase, and fractional clearance of sodium and potassium (%) were determined before and after dietary protein conditioning and on days 2, 4, 6, and 8 of gentamicin administration. Additionally, trough serum gentamicin concentration was determined on days 2, 4, 6, and 8 of gentamicin administration. At the end of the study, all dogs were euthanatized; renal histologic features were graded, using a continuous ranking scale, and renal cortical gentamicin concentrations were measured. Data were ranked and analyzed, using a nonparametric equivalent of a two-way ANOVA; P < 0.05 was considered significant. After the dietary conditioning period (prior to gentamicin), dogs fed the high-protein diet had higher endogenous creatinine clearance and urinary excretion of protein, compared with dogs fed the low-protein diet. Differences existed among groups after 8 days of gentamicin administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase↗