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Biomedical subjects

M B Brooks

Publications and source records attributed to M B Brooks.

At least 19 recordsLinked to original sources
PubMed2001

Heritability of plasma von Willebrand factor antigen concentration in German Wirehaired pointers.

We applied quantitative genetic analyses to a population of German Wirehaired pointer dogs affected with type 2 von Willebrand disease. Plasma von Willebrand factor (vWF) protein concentration measured as vWF antigen (vWF:Ag), clinical history, and pedigree data were compiled for 331 dogs over a 5-year test period. Eight dogs had histories of abnormal bleeding and had markedly decreased plasma vWF:Ag concentrations (<1%). Four per cent of the dogs were inbred, with an average inbreeding of 2.52%. The estimated heritability of plasma vWF concentration was 0.52. We found a major gene effect on vWF concentration. Using a single gene locus model and two different prediction methods, the upper threshold value for the aa genotype was less than 1% vWF:Ag, and the optimal threshold value for discrimination between the AA and Aa genotypes was between 68% and 72% vWF:Ag. Our analyses indicate that phenotype, assigned on the basis of a single vWF:Ag determination, is heritable and can be applied for selective breeding in a von Willebrand disease test programme.

Animals↗
PubMed2001

von Willebrand disease phenotype and von Willebrand factor marker genotype in Doberman Pinschers.

OBJECTIVE: To define the relationship between clinical expression of a type-1 von Willebrand disease phenotype and genotype at 2 von Willebrand factor marker loci in Doberman Pinschers. ANIMALS: 102 client-owned Doberman Pinschers. PROCEDURES: Dogs were recruited on the basis of plasma von Willebrand factor concentration, clinical history, and pedigree. Blood samples and response to a history questionnaire were obtained for each dog. Plasma von Willebrand factor concentration was measured by use of an ELISA, and genotyping was performed via polymerase chain reaction for 1 intragenic and 1 extragenic von Willebrand factor marker. Amplification product size was determined by use of polyacrylamide gel electrophoresis (intragenic marker) or automated sequence analysis (extragenic marker). Western blots were prepared from a subset of dogs with low plasma von Willebrand factor concentration to evaluate multimer distribution. RESULTS: Strong associations were detected between plasma von Willebrand factor concentration and von Willebrand factor marker genotype. Twenty-five dogs had substantial reduction in plasma von Willebrand factor concentration and multiple hemorrhagic events. All were homozygous for a 157-base-pair intragenic marker allele and homozygous or compound heterozygous for 1 of 4 extragenic marker alleles. These marker genotypes were exclusively detected in dogs with low plasma von Willebrand factor concentration, although some dogs with these genotypes did not have abnormal bleeding. CONCLUSIONS AND CLINICAL RELEVANCE: Type-1 von Willebrand disease in Doberman Pinschers is associated with the von Willebrand factor gene locus; however, the expression pattern in this breed appears more complex than that of a simple recessive trait.

Alleles↗
PubMed2000

Effect of citrate concentration on coagulation test results in dogs.

OBJECTIVE: To determine the effect of citrate concentration (3.2 vs 3.8%) on coagulation tests in dogs. DESIGN: Original study. ANIMALS: 30 clinically healthy dogs and 12 dogs with hereditary hemostatic disorders. PROCEDURE: Blood was collected from all dogs directly into collection tubes containing 3.2 or 3.8% buffered citrate. Prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrinogen concentration were measured by use of 3 clot-detection assay systems (2 mechanical and 1 photo-optic). Factor VIII and factor IX coagulant activities (FVIII:C and FIX:C, respectively) were determined by use of a manual tilt-tube method and a mechanical clot-detection device. RESULTS: Significant differences were not detected in median PT, fibrinogen concentration, FVIII:C, or FIX:C between 3.2 and 3.8% citrate for any assay system. A significant prolongation in aPTT for 3.2% citrate, compared with 3.8% citrate, was found in 1 mechanical system. CONCLUSIONS AND CLINICAL RELEVANCE: Citrate concentration does not significantly affect results of most coagulation assays, regardless of assay system. The aPTT was mildly influenced by the citrate concentration, although this was animal-, instrument-, and reagent-dependent. The choice of 3.2 or 3.8% citrate as an anticoagulant for coagulation tests has minimal influence on assay results in healthy dogs or dogs with hereditary hemostatic disorders.

Animals↗
PubMed2000

Evidence of hypercoagulability in dogs with parvoviral enteritis.

OBJECTIVE: To determine whether dogs with naturally occurring canine parvoviral (CPV) enteritis have laboratory evidence of hypercoagulability. DESIGN: Case-control study. Animals-9 dogs with naturally occurring CPV enteritis and 9 age-matched control dogs. PROCEDURE: Blood was collected from all dogs within 24 hours of admission for thromboelastography (TEG) and determination of activated partial thromboplastin time (aP-TT), prothrombin time (PT), antithrombin III (AT) activity, and fibrinogen concentration. Fibrin-fibrinogen degradation product (FDP) concentration, D-dimer concentration, and platelet count were obtained in dogs with CPV enteritis only. Records were reviewed for evidence of thrombosis or phlebitis. RESULTS: All 9 dogs with CPV enteritis had evidence of hypercoagulability, determined on the basis of significantly increased TEG maximum amplitude and decreased AT activity. Fibrinogen concentration was significantly higher in dogs with CPV enteritis than in control dogs. The aPTT was moderately prolonged in dogs with CPV enteritis, and FDP concentration was < 5 mg/ml in 7 of 9 dogs. No dogs had a measurable D-dimer concentration. Platelet counts were within reference range. Four of 9 dogs had clinical evidence of venous thrombosis or phlebitis associated with catheters. One dog had multifocal splenic thrombosis identified at necropsy. CONCLUSIONS AND CLINICAL RELEVANCE: Dogs with CPV enteritis have a high prevalence of clinical thrombosis or phlebitis and laboratory evidence of hypercoagulability without disseminated intravascular coagulopathy. Thromboelastography may help identify hypercoagulable states in dogs.

Animals↗
PubMed2000

D-dimer concentrations in healthy dogs and dogs with disseminated intravascular coagulation.

OBJECTIVE: To determine sensitivity and specificity of assays of D-dimer concentrations in dogs with disseminated intravascular coagulation (DIC) and healthy dogs and to compare these results with those of serum and plasma fibrin-fibrinogen degradation product (FDP) assays. ANIMALS: 20 dogs with DIC and 30 healthy dogs. PROCEDURE: Semi-quantitative and quantitative D-dimer concentrations were determined by use of latex-agglutination and immunoturbidometry, respectively. Fibrin-fibrinogen degradation products were measured by use of latex-agglutination. A reference range for the immunoturbidometric D-dimer concentration assay was established; sensitivity and specificity of the assay were determined at 2 cutoff concentrations (0.30 microg/ml and 0.39 microg/ml). RESULTS: Reference range for the immunoturbidometric D-dimer concentration assay was 0.08 to 0.39 microg/ml; median concentrations were significantly higher in dogs with DIC than in healthy dogs. Latex-agglutination D-dimer and serum and plasma FDP assays had similar sensitivity (85 to 100%) and specificity (90 to 100%); the immunoturbidometric assay had lower specificity (77%) at the 0.30 microg/ml cutoff and lower sensitivity (65%) at the 0.39 microg/ml cutoff. Sensitivity or specificity of the latex-agglutination D-dimer assay was not significantly improved when interpreted in series or parallel with FDP assays. CONCLUSIONS AND CLINICAL RELEVANCE: Measurement of D-dimer concentrations by latex-agglutination appears to be a sensitive and specific ancillary test for DIC in dogs. Specificity of D-dimer concentrations in dogs with systemic disease other than DIC has not been determined, therefore FDP and D-dimer assays should be performed concurrently as supportive tests for the diagnosis of DIC in dogs.

Animals↗
PubMed1997

Complete deletion of factor IX gene and inhibition of factor IX activity in a labrador retriever with hemophilia B.

Hemophilia B is a heritable bleeding disorder caused by mutations in the gene coding for coagulation factor IX. The defect has been identified in purebred and mixed-breed dogs. Management of affected dogs requires transfusion of canine blood products supplying active factor IX. Production of inhibitors to factor IX is a complication of transfusion therapy that has been documented as affecting human patients. Risk for producing coagulation inhibitors is greatest for patients having large factor IX gene deletions. To our knowledge, this is the first report of canine factor IX inhibitor production in dogs. The affected dog had clinically severe hemophilia B caused by complete deletion of the factor IX gene and developed resistance to transfusion. Comprehensive evaluation of hemophilic dogs, including assays of specific factor activity, concentration, and factor inhibition, enhances diagnosis and management of this bleeding disorder. Characterization of the molecular defect causing hemophilia is useful for genetic counseling and identifying individuals at highest risk for producing coagulation inhibitors.

Animals↗
PubMed1997

Factor X deficiency in a cat.

Severe congenital deficiency of factor X was diagnosed in a 3-year-old castrated male domestic shorthair cat with clinical signs of generalized seizures and prolonged bleeding after venipuncture. Heritability of factor X deficiency was suspected because of a prolonged Russell's viper venom time in the dam and reductions in factor X activity in the dam and 1 sibling. To our knowledge, factor X deficiency in cats has not been reported previously. Definitive diagnosis for animals with clinical signs of coagulopathy may require repetition of coagulation screening tests using different assay methods or specific coagulation factor analyses.

Animals↗
PubMed1995

Hemophilia B (factor IX deficiency) in a family of German shepherd dogs.

Three male German Shepherd Dog pups were treated for vaccination-induced hematomas. Coagulation tests in 2 of these pups revealed markedly prolonged activated partial thromboplastin times, whereas specific coagulation factor tests revealed severe deficiency of factor IX activity. Investigation of the pedigree supported a sex-linked pattern of inheritance and a distant relationship to a pup found to have hemophilia B 7 years earlier. Dogs in the pedigree had variable manifestations of bleeding, including hematomas, deep muscle bleeding, profuse bloody diarrhea, and sudden neonatal deaths. von Willebrand's disease was concurrently detected in several dogs in the pedigree, and may have contributed to the bleeding tendency in some dogs. Medical management of 2 of the 3 pups included transfusion of fresh whole blood, canine fresh-frozen plasma, and canine plasma cryosupernatant, as indicated, and cage rest. Two pups were euthanatized because of the severity of recurrent bleeding episodes. A third dog remains alive, but requires periodic infusions of blood product to maintain hemostasis.

Animals↗
PubMed1990

Clinical and laboratory features of a severe form of von Willebrand disease in Shetland sheepdogs.

Ten clinically affected Shetland Sheepdogs were evaluated to define their severe bleeding diathesis and were determined to have von Willebrand factor antigen (vWF:Ag) values less than 0.1% by ELISA assay. The virtual absence of vWF protein by ELISA assay and on multimeric analysis was diagnostic of either homozygosity or probable double heterozygosity for the canine von Willebrand disease (vWD) gene. Clinically affected dogs have type-III vWD and are the offspring of 2 heterozygous parents carrying type-I vWD. Twenty-three percent (1,428 dogs) of the more than 6,000 Shetland Sheepdogs screened for vWD at our facility since 1982 tested within the heterozygous carrier range for the common type-I form of this inherited disorder. Veterinarians and breeders should be aware of the potential for bleeding associated with elective and medical procedures in Shetland Sheepdogs and should use caution when breeding carriers of vWD because of the risk of producing clinically affected offspring with severe type-III vWD.

Animals↗
PubMed1988

42 months of experience with the Mentor inflatable penile prosthesis.

The Mentor inflatable penile prosthesis is a hydraulic device that was introduced in May 1983 for the treatment of erectile dysfunction. Since its introduction further technical modifications and improvements have been made on the product. From the onset the reliability, function and cosmetic effect of this physiological device have been excellent. The modifications have served to improve the ease of operation and to increase further the reliability as demonstrated by our progressive decrease in the incidence of mechanical failures. From May 1983 to November 1986 we implanted 137 Mentor inflatable penile prostheses. Our over-all mechanical failure rate was 7.3 per cent. As a result of the modifications, however, the mechanical failure rate decreased to 3.1 per cent during the last 38 months of that period when 129 (94 per cent) of the prostheses were implanted, and during the last 24 months of that period when 86 (63 per cent) of the prostheses were implanted the mechanical failure rate was only 1.2 per cent.

Adolescent↗
PubMed1988

Humoral hypercalcemia of malignancy in canine lymphosarcoma.

Studies on the pathogenesis of hypercalcemia in canine lymphosarcoma have led to conflicting results. The biochemical and bone histomorphometric findings in canine lymphosarcoma were examined in 19 hypercalcemic and 17 nonhypercalcemic dogs with lymphosarcoma. Compared to the nonhypercalcemic group, the hypercalcemic dogs demonstrated an increase in fasting and 24-h calcium excretion, an increase in fractional phosphorus excretion, and a significant increase in nephrogenous AMP excretion. Plasma 1,25-dihydroxyvitamin D and immunoreactive PTH levels were equivalent in the two groups. Quantitative bone histomorphometry performed on iliac crest biopsies revealed increased parameters of bone resorption in those hypercalcemic dogs with no evidence of tumor at the biopsy site, without a compensatory increase in bone formation. Acid-urea tumor tissue extracts from eight hypercalcemic and six nonhypercalcemic dogs were examined for adenylate cyclase-stimulating activity (ACSA). All tumors from hypercalcemic dogs contained ACSA, whereas none of the tumors from nonhypercalcemic dogs had ACSA. Further purification of one tumor extract yielded an adenylate cyclase-stimulating protein which appeared to interact specifically with the PTH receptor. We conclude that in some cases, hypercalcemia in canine lymphosarcoma is mediated by a tumor-derived circulating bone-resorbing factor which is distinct from PTH. ACSA detected in tumor tissue appears to be a reliable marker for the syndrome in vivo. The role of this activity in the pathogenesis of the syndrome remains to be determined.

Adenylyl Cyclases↗
PubMed1987

Use of splenectomy in the management of lymphoma in dogs: 16 cases (1976-1985).

Sixteen dogs with lymphoma underwent splenectomy to relieve signs of massive splenomegaly including splenic rupture. The most common preoperative hematologic abnormalities, anemia and thrombocytopenia, were reversed in all dogs surviving the initial postoperative period. Within 6 weeks after surgery, 5 dogs died because of disseminated intravascular coagulation and sepsis. The remaining 11 dogs underwent chemotherapy. These 11 dogs had a complete response rate of 66% at one month after surgery; the mean and median survival times were 9.3 and 5 months, respectively. In 7 dogs evaluated until death, the mean and median survival times were 13.4 months and 14 months, respectively.

Animals↗