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Biomedical subjects

C R Ward

Publications and source records attributed to C R Ward.

At least 19 recordsLinked to original sources
PubMed2001

Hyponatremia and hyperkalemia associated with peritoneal effusion in four cats.

Four cats with considerable peritoneal effusion and corresponding hyponatremia and hyperkalemia were evaluated. The Na:K ratio in all cats was < 25, which is suggestive of adrenal insufficiency. An ACTH stimulation test was performed on 3 cats for evaluation of adrenal gland function. Serum cortisol and aldosterone concentrations did not support a diagnosis of adrenal gland insufficiency. In 1 cat, histologic evaluation of the adrenal glands at necropsy also failed to support a diagnosis of hypoadrenocorticism. On the basis of these findings, and because hyponatremia and hyperkalemia could not be readily explained by another cause, the electrolyte abnormalities were presumed to be secondary to peritoneal effusion.

Adrenal Insufficiency↗
PubMed2001

Evolving collective behavior in an artificial ecology.

Collective behavior refers to coordinated group motion, common to many animals. The dynamics of a group can be seen as a distributed model, each "animal" applying the same rule set. This study investigates the use of evolved sensory controllers to produce schooling behavior. A set of artificial creatures "live" in an artificial world with hazards and food. Each creature has a simple artificial neural network brain that controls movement in different situations. A chromosome encodes the network structure and weights, which may be combined using artificial evolution with another chromosome, if a creature should choose to mate. Prey and predators coevolve without an explicit fitness function for schooling to produce sophisticated, nondeterministic, behavior. The work highlights the role of species' physiology in understanding behavior and the role of the environment in encouraging the development of sensory systems.

Animals↗
PubMed2000

Concurrent disorders in dogs with diabetes mellitus: 221 cases (1993-1998).

OBJECTIVE: To characterize concurrent disorders in dogs with diabetes mellitus (DM). DESIGN: Retrospective study. ANIMALS: 221 dogs with DM. PROCEDURE: Medical records were reviewed, and clinical signs, physical examination findings, and results of clinicopathologic testing, urinalysis, aerobic bacterial culture of urine samples, coagulation testing, endocrine testing, histologic evaluation, diagnostic imaging, and necropsy were recorded. RESULTS: For most dogs, CBC results were normal. Common serum biochemical abnormalities included hypochloremia (127 dogs, 60%) and high alanine aminotransferase (163, 78%), aspartate aminotransferase (78, 71%), and alkaline phosphatase (188, 90%) activities. Venous pH and serum ionized calcium concentration were measured in 121 and 87 dogs, respectively, and were low in 56 (46%) and 41 (47%) dogs. Lipemia was observed in 92 (42%) dogs. Urine samples from 159 (72%) dogs were submitted for aerobic bacterial culture, and 34 (21%) yielded bacterial growth. Escherichia coli was the most commonly isolated organism. Thirty-six (16%) dogs had dermatitis or otitis. Hyperadrenocorticism was diagnosed in 51 (23%) dogs on the basis of clinical signs and results of a low-dose dexamethasone suppression test (41 dogs), an adrenocorticotropic hormone stimulation test (5), both tests (4), or histologic evaluation of necropsy specimens (1). Acute pancreatitis was diagnosed in 28 (13%) dogs. Eleven (5%) dogs had tumors for which a histologic diagnosis was obtained. Eight (4%) dogs were hypothyroid. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that dogs with diabetes mellitus may have many concurrent disorders. The most commonly identified concurrent disorders included hyperadrenocorticism, urinary tract infection, dermatitis, otitis, acute pancreatitis, neoplasia, and hypothyroidism.

Animals↗
PubMed2000

Breed distribution of dogs with diabetes mellitus admitted to a tertiary care facility.

OBJECTIVE: To determine which dog breeds are at low and high risk for developing diabetes mellitus (DM). DESIGN: Cohort study. ANIMALS: Hospital population of 221 dogs with DM and 42,882 dogs without DM during 5.5 years. PROCEDURE: 165 breeds (including a mixed-breed category) were represented in the hospital population. Breed-specific expected numbers of dogs with DM were calculated by multiplying the proportion of all dogs admitted to the hospital that were determined to have DM during the study period by the breed-specific totals during the study period. Breeds or breed groups evaluated in the analysis (n = 20) were restricted to those that had a combined observed and expected count > 5 to document breeds at low and high risk for developing DM. Proportionate changes in the risk of developing DM by breed were calculated and presented using exact odds ratios, 95% confidence intervals, and P values. Mixed-breed dogs were chosen as the reference breed. RESULTS: Samoyeds, Miniature Schnauzers, Miniature Poodles, Pugs, and Toy Poodles were at high risk for developing DM. Dog breeds found to be at low risk for developing DM were German Shepherd Dog, Golden Retriever, and American Pit Bull Terrier. CONCLUSION AND CLINICAL RELEVANCE: The finding that certain dog breeds are at low or high risk for developing DM suggests that some genetic defects may predispose dogs to development of DM, whereas other genetic factors may protect dogs from development of DM.

Animals↗
PubMed2000

Effects of insoluble and soluble dietary fiber on glycemic control in dogs with naturally occurring insulin-dependent diabetes mellitus.

OBJECTIVE: To evaluate the effects of diets differing in type and quantity of fiber on glycemic control in dogs with naturally occurring insulin-dependent diabetes mellitus. DESIGN: Prospective randomized crossover controlled trial. ANIMALS: 7 dogs with well-regulated naturally occurring insulin-dependent diabetes mellitus. PROCEDURE: Dogs were fed 1 of 3 diets for 1 month each in 1 of 6 randomized diet sequences. Diets included a low-fiber diet (LF) and 2 high-fiber diets; 1 contained only insoluble fiber (HIF), and 1 contained soluble fiber in addition to insoluble fiber (HSF). Caloric intake was unchanged throughout the study. Glycemic control was assessed after each feeding trial by measuring serum fructosamine concentration and performing 5 serial measurements of blood glucose concentration every 2 hours after the morning feeding and insulin injection. RESULTS: Significant differences were not detected in body weight, required insulin dosage, or albumin concentration among dogs fed the HIF, HSF, and LF diets. Mean and maximum blood glucose concentrations and area under the blood glucose curve were significantly lower in dogs fed the HIF diet, compared with values in the same dogs fed the HSF or LF diet. Fructosamine concentration was significantly lower in dogs fed the HIF or HSF diet, compared with values in the same dogs fed the LF diet. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs with naturally occurring insulin-dependent diabetes mellitus, a dry, high insoluble-fiber diet may aid in glycemic control.

Animals↗
PubMed2000

Effect of insulin dosage on glycemic response in dogs with diabetes mellitus: 221 cases (1993-1998).

OBJECTIVE: To evaluate glycemic response to insulin treatment in dogs with diabetes mellitus. DESIGN: Retrospective study. ANIMALS: 221 dogs with diabetes mellitus. PROCEDURE: Type and dosage of insulin used, minimum and maximum blood glucose concentrations, time of blood glucose concentration nadir, and optimal duration of action of insulin were determined on the basis of data obtained prior to initial examination at the teaching hospital (127 dogs), at the time of initial examination (212 dogs), at the time a second follow-up blood glucose curve was performed (59 dogs), and at the time of clinical control of diabetes mellitus (83 dogs). RESULTS: Prior to examination, 69 of 127 dogs (54%) received 1 s.c. insulin injection daily. Thirty-one dogs (24%) received a high dose of insulin (i.e., > 1.5 U/kg [0.7 U/lb] of body weight); 27 of these dogs (87%) received 1 injection/d. Eleven of 16 dogs (69%) that were hypoglycemic (blood glucose concentration < 80 mg/dl) also received 1 injection/d. However, optimal duration of action of insulin was > 12 hours in only 5 of 83 dogs (6%) evaluated at the time diabetes mellitus was clinically controlled. At that time, only 1 dog (1%) received a high dose of insulin, and the dog received 2 injections/d. Moreover, 8 of 10 dogs (80%) with hypoglycemia received 1 injection/d. CONCLUSIONS AND CLINICAL RELEVANCE: Most dogs with diabetes mellitus are clinically regulated with 2 daily insulin injections. Administration of a high dose of insulin or development of hypoglycemia may be more common in diabetic dogs that receive insulin once daily, compared with dogs that receive insulin twice daily.

Animals↗
PubMed2000

Altered expression of G proteins in thyroid gland adenomas obtained from hyperthyroid cats.

OBJECTIVE: To determine whether expression of G proteins (G(i) and G(s)) is altered in thyroid gland adenomas obtained from hyperthyroid cats. SAMPLE POPULATION: Adenomatous thyroid glands obtained from 8 hyperthyroid cats and thyroid glands obtained from 4 age-matched euthyroid cats. PROCEDURE: Expression of G(i) and G(s) was quantified in enriched membrane preparations of thyroid gland tissue, using immunoblotting with G(i) and G(s) antibodies and toxin-catalyzed ADP-ribosylation. RESULTS: Expression of G(i) was significantly reduced in thyroid gland adenomas from hyperthyroid cats, compared with normal thyroid gland tissue from euthyroid cats. Expression of G(s) was similar between the 2 groups. CONCLUSIONS AND CLINICAL RELEVANCE: A decrease in expression of G in adenomatous thyroid glands of cats may reduce the negative inhibition of the cAMP cascade in thyroid cells, leading to autonomous growth and hypersecretion of thyroxine. Understanding the molecular mechanisms for hyperthyroidism in cats may lead to better treatment or, ultimately, prevention of the disease.

ADP-Ribosylation Factors↗
PubMed1999

The monomeric GTP binding protein, rab3a, is associated with the acrosome in mouse sperm.

Exocytosis of the sperm acrosome is an obligate precursor to successful egg penetration and subsequent fertilization. In most mammals, acrosomal exocytosis occurs at a precise time, after sperm binding to the zona pellucida of the egg, and is induced by a specific component of the zona pellucida. It may be considered an example of regulated secretion with the acrosome of the sperm analogous to a single secretory vesicle. Monomeric G proteins of the rab3 subfamily, specifically rab3a, have been shown to be important regulators of exocytosis in secretory cells, and we hypothesized that these proteins may regulate acrosomal exocytosis. Using alpha[32P] GTP binding to Immobilon blotted mouse sperm proteins, the presence of three or more monomeric GTP binding proteins was identified with Mr = 22, 24, and 26 x 10(3). Alpha[32P] GTP binding could be competed by GTP and GDP, but not GMP, ATP, or ADP. Anti-peptide antibodies specific for rab3a were used to identify the 24 kDa G protein as rab3a. Using immunocytochemistry, rab3a was localized to the head of acrosome-intact sperm and was lost during acrosomal exocytosis. It was identified in membrane and cytosolic fractions of sperm with the predominant form being membrane-bound, and its membrane association did not change upon capacitation. Immunogold labeling and electron microscopy demonstrated a subcellular localization in clusters to the periacrosomal membranes and cytoplasm. These data identify the presence of rab3a in acrosomal membranes of mouse sperm and suggest that rab3a plays a role in the regulation of zona pellucida -induced acrosomal exocytosis.

Acrosome↗
PubMed1999

Carotid sinus hypersensitivity--a modifiable risk factor for fractured neck of femur.

BACKGROUND: the potential impact on morbidity, mortality and health care economics makes it important to identify patients at risk of fracture, in particular fractured neck of femur (FNOF). Older patients with carotid sinus hypersensitivity (CSH) are more likely to have unexplained falls and to experience fractures, particularly FNOF. Our objective was to determine the prevalence of CSH in patients with FNOF. DESIGN: case-controlled prospective series. METHODS: consecutive cases were admissions over 65 years with FNOF. Controls were consecutive patients admitted for elective hip surgery, frail elderly people admitted to hospital medical wards and day-hospital patients. All patients had a clinical assessment of cognitive function, physical abilities and history of previous syncope, falls and dizziness, in addition to repeated carotid sinus massage with continuous heart rate and phasic blood pressure measurement. RESULTS: heart rate slowing and fall in systolic blood pressure was greater for patients with FNOF than those admitted for elective hip surgery (P < 0.05 and P < 0.001). CSH was present in 36% of the FNOF group, none of the elective surgery group, 13% of the acutely ill controls and 17% of the outpatients. It was more likely to be present in FNOF patients with a previous history of unexplained falls or an unexplained fall causing the index fracture. The heart rate and systolic blood pressure responses to carotid sinus stimulation were reproducible. CONCLUSION: older patients with an acute neck of femur fracture who do not give a clear history of an accidental fall or who have had previously unexplained falls are likely to have CSH. CSH may be a modifiable risk factor for older patients at risk of hip fracture.

Accidental Falls↗
PubMed1998

Association between hyperadrenocorticism and development of calcium-containing uroliths in dogs with urolithiasis.

OBJECTIVE: To determine, among dogs with urolithiasis, whether dogs that had hyperadrenocorticism would be more likely to have calcium-containing uroliths than would dogs that did not have clinical evidence of hyperadrenocorticism. DESIGN: Retrospective case-control study. ANIMALS: 20 dogs that had urolithiasis and hyperadrenocorticism and 42 breed-matched dogs that had urolithiasis but did not have clinical evidence of hyper-adrenocorticism. PROCEDURE: Signalment, urolith composition, results of bacterial culture of urine, and results of adrenal axis tests were recorded. A multivariate logistic regression model was created, including terms for age, sex, and hyperadrenocorticism. The outcome variable was presence or absence of calcium-containing uroliths. RESULTS: Among dogs with urolithiasis, those that had hyperadrenocorticism were 10 times as likely to have calcium-containing uroliths as were dogs that did not have clinical evidence of hyperadrenocorticism (odds ratio, 10.5; 95% confidence interval, 1.5 to 23.4). Neutered and sexually intact females were less likely to have calcium-containing uroliths than were neutered males (odds ratios, 0.041 [95% confidence interval, 0.0057 to 0.29] and 0.024 [95% confidence interval, 0.0012 to 0.51, respectively). CLINICAL IMPLICATIONS: Prompt diagnosis and treatment of hyperadrenocorticism may decrease prevalence of calcium-containing uroliths in dogs.

Adrenocortical Hyperfunction↗
PubMed1998

Midodrine: a role in the management of neurocardiogenic syncope.

OBJECTIVE: To determine the benefit of midodrine, an alpha agonist, on symptom frequency and haemodynamic responses during head up tilt in patients with neurocardiogenic syncope. SETTING: Cardiovascular investigation unit (a secondary and tertiary referral centre for the investigation and management of syncope). PATIENTS: 16 outpatients (mean (SD) age 56 (18) years; five men) with frequent hypotensive symptoms (more than two syncopal episodes and fewer than 20 symptom free days per month), and reproducible syncope with glyceryl trinitrate (GTN) during head up tilt. DESIGN AND INTERVENTION: Randomised double blind placebo controlled study. Patients were randomised to receive either placebo or midodrine for one month. Symptom events were recorded during each study month. At the end of each study month patients completed a quality of life scoring scale (Short Form 36) and a global assessment of therapeutic response. They received GTN with head up tilt for measurement of heart rate (electrocardiography), phasic blood pressure (digital photoplethysmography), and thoracic fluid index (transthoracic impedance plethysmography) during symptom provocation. RESULTS: Patients administered midodrine had an average of 7.3 more symptom free days than those who received placebo (95% confidence interval (CI) 4.6 to 9; p < 0.0001). Eleven patients reported a positive therapeutic response with midodrine (p = 0.002). All domains of quality of life showed improvement with midodrine, in particular physical function (8.1; 95% CI 3.7 to 12.2), energy and vitality (14.6; 95% CI 7.3 to 22.1), and change in health status (22.2; 95% CI 11 to 33.4). Fourteen patients who were given placebo had tilt induced syncope compared with six given midodrine (p = 0.01). Baseline supine systolic blood pressure was higher and heart rate lower in patients who received midodrine than in those who were given placebo (p < 0.05). A lower thoracic fluid index in patients administered midodrine indicates increased venous return when supine and during head up tilt. There were no serious adverse effects. CONCLUSIONS: Midodrine had a conspicuous beneficial effect on symptom frequency, symptoms during head up tilt, and quality of life. Midodrine is recommended for the treatment of neurocardiogenic syncope in patients with frequent symptoms.

Adrenergic alpha-Agonists↗
PubMed1995

Activation of a Gi protein in digitonin/cholate-solubilized membrane preparations of mouse sperm by the zona pellucida, an egg-specific extracellular matrix.

Mammalian sperm possess guanine nucleotide-binding regulatory proteins (G proteins) that are involved in signal transduction pathways leading to zona pellucida (ZP)-mediated acrosomal exocytosis. We have previously examined ZP-G protein dynamics in mouse sperm homogenates, as well as cell-free membrane preparations, and our data support the existence of ZP receptor-G protein complexes in sperm membranes. However, the composition of this complex has not been identified due to experimental limitations of the membrane preparations. In the present study, a detergent-solubilized preparation from mouse sperm membranes that retained the signaling properties of cell homogenates and cell-free membrane preparations was developed using buffers containing digitonin and cholate. GTP gamma S, a poorly hydrolyzable analogue of GTP, bound to these solubilized preparations in a specific and concentration-dependent fashion that reached saturation at 100 nM. Incubation of this solubilized membrane preparation with heat-solubilized ZP resulted in an increase in specific GTP gamma S binding in a concentration-dependent manner, with a maximal response at 4-6 ZP/microliters. Mastoparan (50 microM) increased GTP gamma S binding to levels similar to that seen with solubilized ZP. Mastoparan plus ZP stimulated GTP gamma S binding to the same extent as mastoparan or ZP alone. Pertussis toxin completely inhibited ZP-stimulated GTP gamma S binding and decreased mastoparan-stimulated GTP gamma S binding by 50-60%. Purified ZP3, the ZP component that possesses quantitatively all of the sperm binding and acrosomal exocytosis-inducing activities of the intact ZP, stimulated GTP gamma S binding to an extent similar to that of solubilized ZP.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrosome↗
PubMed1995

A hook-traction technique for Norplant removal.

We describe a simple technique to facilitate the removal of difficult-to-remove Norplant implants. Through a standard skin incision for Norplant removal, the fibrous capsule surrounding the implant is secured using either a dermatologic skin hook or a 25-gauge hypodermic needle fashioned into a hook with a hemostat. Traction is applied to bring the fibrous sheath into the incision site, where the implant tip is dissected free using a scalpel. The precisely localized countertraction afforded by this technique provides increased accuracy and speed for the removal of difficult-to-extract implants. Tissue trauma is minimized and the need to extend the skin incision is reduced.

Contraceptive Agents, Female↗
PubMed1994

Selective activation of Gi1 and Gi2 in mouse sperm by the zona pellucida, the egg's extracellular matrix.

Mammalian sperm acrosomal exocytosis as induced by the egg's zona pellucida (ZP) appears to be a G protein-mediated event. Previously, we demonstrated that ZP3, the acrosome reaction-inducing component of mouse ZP, activates one or more Gi subtypes in isolated sperm membranes (Ward, C. R., Storey, B. T., and Kopf, G. S. (1992) J. Biol. Chem. 267, 14061-14067). To determine the identity of the Gi subtype(s) activated in the sperm, we examined ligand-dependent decreases in pertussis toxin-catalyzed in vitro [32P]ADP-ribosylation of the different Gi alpha subtypes that were identified by immunoprecipitation using Gi alpha-specific antisera. Membranes treated with solubilized ZP or mastoparan and subsequently [32P]ADP-ribosylated using pertussis toxin displayed 35 and 56% decreases, respectively, in [32P]ADP-ribosylation when compared with controls. These changes were quantitatively similar to the percentage increases in 35S-labeled guanosine 5'-O-(thiotriphosphate) binding in membranes treated with equivalent concentrations of ZP or mastoparan (Ward et al., 1992). Immunoprecipitation with Gi alpha subtype-specific antisera and subsequent autoradiography revealed that mastoparan activated Gi1, Gi2, and Gi3 in the membranes. ZP, in contrast, selectively activated Gi1 and Gi2. These data demonstrate that the egg's extracellular matrix has the ability to activate selectively sperm membrane Gi subtypes.

Adenosine Diphosphate Ribose↗
PubMed1994

Solubilization and partial purification from mouse sperm membranes of the specific binding activity for 3-quinuclidinyl benzilate, a potent inhibitor of the zona pellucida-induced acrosome reaction.

3-Quinuclidinyl benzilate (QNB), a potent antagonist of muscarinic acetylcholine receptors, has been demonstrated to inhibit specifically the zona pellucida (ZP)-induced acrosome reaction (AR) in mouse sperm (Florman and Storey, 1982; Dev Biol 91:121-130). In this study we describe the solubilization and partial purification of the mouse sperm QNB binding activity which may represent a component of the putative receptor complex for ZP on the sperm plasma membrane. Sperm membranes were isolated from cell homogenates of washed, capacitated, epididymal mouse sperm. Scatchard plots of QNB binding to these membranes indicated a single class of binding sites with KD = 7.2 nM and Bmax = 8700 sites/cell. These binding characteristics are similar to those seen with QNB binding to whole cells (Florman and Storey, 1982, J Androl 3:157-164). Sperm membranes were solubilized using 1% digitonin/0.2% cholate, and the resultant detergent-soluble fraction possessed QNB binding activity similar to that of intact membranes. The detergent-soluble fraction maintained intact ZP receptor(s)-G protein coupling in that treatment of this fraction with either ZP or mastoparan resulted in a 35% or 65% increase in specific GTP gamma S binding, respectively. The solubilized membrane preparation was fractionated by gel permeation HPLC. A majority of specific QNB binding activity was confined to one HPLC fraction. Analysis of this fraction by SDS-PAGE revealed a complex of approximately 5 proteins unique to this fraction. The most prominent protein had a M(r) of 72 kDa, which is within the M(r) range for muscarinic receptors. A protein with M(r) = 41 kDa was also present within this fraction. Subsequent pertussis toxin (PTX)-catalyzed ADP-ribosylation of this fraction revealed this protein to be the alpha subunit of the G(i) class of G proteins. Although the QNB binding activity could not be positively identified, we propose that it is contained in one or more of the proteins unique to this fraction and that these proteins, including G(i), may act as part of a sperm receptor complex for the ZP.

Acrosome↗
PubMed1993

Antinociceptive activity of intrathecal ketorolac is blocked by the kappa-opioid receptor antagonist, nor-binaltorphimine.

Systemic and intrathecally administered ketorolac produced antinociception in the p-phenylquinone test, but not in the tail-flick or hot-plate tests. Antagonists of the subtypes of opioid receptors were used to evaluate the interaction of ketorolac with these receptors. Intrathecally administered kappa-opioid receptor antagonist nor-binaltorphimine dihydrochloride blocked the antinociceptive effects of systemic ketorolac and intrathecally administered ketorolac. Naloxone and ICI 174,864 failed to block the effects of ketorolac. Activation of nor-binaltorphimine-sensitive receptors appears to be an integral element in the mechanism of antinociception of ketorolac at the spinal level. Ketorolac did not precipitate withdrawal jumping in morphine-tolerant mice demonstrating that ketorolac does not act as a mixed agonist-antagonist at the opioid receptor. We suggest that neuraxial placement of ketorolac may prove useful in the clinical setting for the management of acute pain in humans.

Analgesics↗