Search PubMed⌕ Search

Biomedical subjects

D J Weiss

Publications and source records attributed to D J Weiss.

At least 55 records · Page 3Linked to original sources

Transient alteration in intestinal permeability to technetium Tc99m diethylenetriaminopentaacetate during the prodromal stages of alimentary laminitis in ponies.

OBJECTIVES: To determine whether mucosal permeability is altered during the prodromal stages of alimentary laminitis. ANIMALS: 15 healthy adult ponies. PROCEDURES: intestinal permeability was evaluated for control ponies (n = 5) and for ponies 4 to 12 (n = 5) and 20 to 28 (n = 5) hours after administration of carbohydrate overload. Mucosal permeability was determined by measuring the percentage of orally administered technetium Tc99m diethylenetriaminopentaacetate (99mTc-DTPA) excreted in urine during an 8-hour period, then measuring blood radioactivity at hourly intervals. Plasma endotoxin-like activity was measured by use of a chromogenic Limulus amebocyte assay. RESULTS: Urinary excretion of 99mTc-DTPA was 2.45% of administered dose for control ponies, and was 16.67% of administered dose 4 to 12 hours and 3.57% of administered dose 20 to 28 hours after administration of carbohydrate. CONCLUSIONS: A marked but transient increase in intestinal permeability was observed early in the prodromal stages of alimentary laminitis. CLINICAL RELEVANCE: Absorption of substances from the intestine may be an initiating event in alimentary laminitis.

Animals↗

In situ histochemical detection of beta-galactosidase activity in lung: assessment of X-Gal reagent in distinguishing lacZ gene expression and endogenous beta-galactosidase activity.

Bacterial lacZ is one of the most commonly used reporter genes for assessing gene transfer to lung. However, lung contains endogenous beta-galactosidase (beta-Gal), which can confound estimation of exogenous lacZ expression by histochemical techniques (i.e., X-Gal) for in situ demonstration of enzyme activity. We investigated several parameters of the X-Gal reaction, including time and temperature of X-Gal exposure as well as lung tissue processing and fixation techniques, and found that none of these could be used to distinguish between endogenous and exogenous beta-Gal activities. The mammalian and bacterial beta-Gal enzymes, however, have pH optima in the acidic and neutral ranges, respectively. Exposing whole lung, lung minces, or mounted frozen sections of lung to X-Gal at mildly alkaline pH (pH 8.0-8.5), minimized detection of endogenous activity in lungs from a variety of species while preserving that resulting from bacterial enzyme activity in a transgenic mouse expressing lacZ. This technique was also useful in distinguishing endogenous activity from that resulting from adenovirus-mediated lacZ gene transfer to diploid lung fibroblasts in primary culture. An appropriate buffer that maintains the desired pH throughout the duration of X-Gal exposure must be used.

Animals↗

Cell-mediated immune responses to liver membrane protein in canine chronic hepatitis.

Peripheral blood mononuclear cells from dogs with chronic inflammatory liver disease and dogs with noninflammatory liver diseases were evaluated for proliferative responses to pokeweed mitogen and canine liver membrane protein. Dogs with chronic hepatitis were selected based on histopathological evidence of periportal lymphocytic infiltrates with or without neutrophilic infiltrates, fibrosis and necrosis. Incorporation of tritiated thymidine was assessed 72 hours after addition of liver membrane protein or pokeweed mitogen. Peripheral blood mononuclear cell proliferation in response to liver membrane protein was significantly higher in chronic hepatitis dogs compared to control dogs. Eight of 12 dogs with chronic hepatitis and 2 of 7 dogs with noninflammatory liver disease had proliferative responses to liver membrane protein greater than 2 standard deviations above the mean of the control group. These data support the hypothesis that immune-mediated processes are involved in canine chronic hepatitis, but did not determine whether this is a primary disorder or occurred secondary to liver destruction.

Animals↗

Inflammatory liver disease.

The histopathologic and clinical features of feline inflammatory liver disease are incompletely under-stood. Results of recent studies indicate that feline inflammatory liver diseases can be classified as acute (suppurative) and chronic (nonsuppurative) cholangiohepatitis and lymphocytic portal hepatitis. Histopathologic features of cholangiohepatitis include infiltration of neutrophils into walls and lumens of bile ducts and portal areas, periportal necrosis, and variable degrees of fibrosis and bile duct hyperplasia. Lymphocytic portal hepatitis is characterized by increased numbers of lymphocytes and plasma cells in portal areas, bile duct hyperplasia, and fibrosis. Liver biopsy is needed to establish a definitive diagnosis but trends in clinical laboratory test results may be helpful in establishing a tentative diagnosis. Specific treatment for cholangiohepatitis include antibiotic therapy. Corticosteroids have been recommended for treatment of lymphocytic portal hepatitis.

Animals↗

Role of tissue factor in intra-alveolar fibrin deposition and coagulopathy associated with pneumonic pasteurellosis in cattle.

OBJECTIVE: To determine the role of tissue factor (TF) in the coagulation events leading to intra-alveolar fibrin deposition and intravascular thrombosis associated with pneumonic pasteurellosis in cattle. ANIMALS: Healthy 2- to 4-week-old male Holstein calves. PROCEDURES: Blood and bronchoalveolar lavage samples were collected before and at 1, 2, 4, and 6 hours after inoculation of saline solution or Pasteurella haemolytica. Total leukocyte count, platelet count, plasma total protein concentration, prothrombin time, and partial thromboplastin time were measured in blood samples. Total nucleated cell count, total protein concentration, and procoagulant activity were measured in bronchoalveolar lavage samples. Additionally, platelet survival in blood platelet accumulation in affected lung tissue, and gross and microscopic lung lesions were determined. RESULTS: Administration of TF monoclonal antibodies (MAB) TF1-1F7 prevented the decrease in platelet survival and the increase in bronchoalveolar lavage fluid TF-dependent procoagulant activity observed in calves not treated with MAB TF1-1F7 antibody, but did not attenuate the increase in lavage fluid neutrophil numbers and total protein concentration, MAB TF1-1F7 administration reduced the percentage of lung affected by pneumonic lesions from 51.81% to 10.40% and attenuated intra-alveolar deposition of fibrin, neutrophils, and erythrocytes. CONCLUSION: Intra-alveolar fibrin deposition and activation of coagulation in cattle with pneumonic pasteurellosis is, at least in part, mediated by TF. CLINICAL RELEVANCE: Treatments that neutralize TF activity may attenuate lung injury in cattle with pneumonic pasteurellosis.

Animals↗

Evaluation of arginine-glycine-aspartate-containing peptides as inhibitors of equine platelet function.

OBJECTIVES: To determine whether synthetic peptides containing the arginine-glycine-aspartate (RGD) sequence inhibit equine platelet function. ANIMALS: For in vitro studies of blood, 3 healthy Thoroughbreds; for in vivo and ex vivo studies of administration of RGD-containing peptides, 4 young adult pony mares. PROCEDURE: Blood was incubated with and without addition of aspirin or RGD-containing peptides (RGDS, RPR 110885) and platelet aggregation responses and platelet adhesion to subendothelial collagen were determined. RPR 110885 was administered IV, and platelet function was evaluated. Platelet aggregation was determined by a turbidimetric method, and platelet adhesion was evaluated by the Baumgartner perfusion method. RPR 110885 was administered IV at dosages of 30 and 60 micrograms/kg of body weight, and bleeding time, platelet aggregation responses, and platelet count were determined at hourly intervals for 4 hours. RESULTS: Both RGDS and RPR 110885 inhibited platelet aggregation in vitro in dose-dependent manner and inhibited platelet adhesion to subendothelial collagen. The concentration of RGDS that inhibited platelet aggregation by 50% (IC50) was 100 to 142 microM for the various agonists tested, whereas the concentration of RPR 110885 that inhibited platelet aggregation by 50% was 0.03 to 0.05 microM. When administered to ponies at 30 or 60 g/kg, RPR 110885 almost completely inhibited ADP-induced platelet aggregation. CONCLUSIONS: RGDS and RPR 110885 inhibited equine platelet function; however, RPR 110885 was several thousand times more potent than RGDS. CLINICAL RELEVANCE: RGD-containing peptides may be useful for treatment of thrombotic diseases of horses.

Animals↗

Detection of activated platelets and platelet-leukocyte aggregates in horses.

OBJECTIVE: To determine the potential usefulness of tests for detection of platelet activation and platelet-leukocyte aggregates in horses. SAMPLES: Blood from 3 healthy Thoroughbreds. PROCEDURES: Microscopic and flow cytometric assays were used to evaluate spontaneous platelet aggregation, platelet activation, and platelet-leukocyte aggregates. Platelet activation was detected by evaluation of binding of anti-human fibrinogen to unactivated and ADP-, thrombin-, thrombin agonist receptor peptide-, and platelet activating factor-activated platelets. Platelet-leukocyte aggregates were evaluated microscopically and by flow cytometric determination of leukocyte fluorescence that resulted from binding of fluorescently labeled platelets to leukocytes. RESULTS: Equine platelets readily aggregated spontaneously when blood was stirred at low, medium, and high speeds. Compared with unactivated platelets, activated platelets had a marked increase in the percentage of cells with increased fluorescence intensity and in mean fluorescence intensity. Unactivated platelets formed aggregates with neutrophils and monocytes, but not with lymphocytes. Activation of platelets resulted in a calcium-dependent increase in platelet-leukocyte aggregates. CONCLUSIONS: Flow cytometric techniques can be used to detect in vitro platelet activation and platelet-leukocyte aggregates in horses. CLINICAL RELEVANCE: Flow cytometric techniques may be useful for detection of prothrombotic disorders in horses.

Adenosine Diphosphate↗

Evaluation of platelet activation and platelet-neutrophil aggregates in ponies with alimentary laminitis.

OBJECTIVES: To determine whether platelets are hyperaggregable or form platelet-neutrophil aggregates during the prodromal stages of acute laminitis of ponies. ANIMALS: Healthy adult ponies: 8 experimental and 6 control. PROCEDURES: Acute laminitis was induced by oral administration of corn starch and wood flour to 8 ponies, and indices of platelet activation were evaluated. Blood samples were collected before and at 4, 8, 12, 24, 28, and 32 hours after carbohydrate administration, and PCV, total plasma protein concentration, platelet count, activated clotting time, whole blood recalcification time, spontaneous platelet aggregation, ex vivo platelet aggregation responses, and platelet-neutrophil aggregates were determined. When lameness was first detected, ponies were euthanatized and arteriography and histologic examination of hooves were performed. RESULTS: Carbohydrate overload was associated with hyperaggregability of platelets throughout the prodromal stages of laminitis and increased numbers of platelet-neutrophil aggregates. Reduction of blood supply to affected hooves was variable, and blood clots were found in 6 of 11 laminitis-affected hooves. CONCLUSIONS: Platelets were hyperaggregable throughout the prodromal stages of carbohydrate-induced laminitis and formed platelet-neutrophil aggregates. Platelet-neutrophil aggregates may initiate or contribute to development of acute laminitis. CLINICAL RELEVANCE: Anti-platelet therapy may be useful for treatment of acute alimentary laminitis in horses.

Acute Disease↗

Relationship between inflammatory hepatic disease and inflammatory bowel disease, pancreatitis, and nephritis in cats.

OBJECTIVE: To determine whether cats with inflammatory hepatic disease had concurrent inflammatory bowel disease (IBD), pancreatitis, or chronic interstitial nephritis. DESIGN: Prospective case series. SAMPLE POPULATION: 78 tissue sections of liver, intestine, pancreas, and kidney from cats that had previous necropsy examinations at the teaching hospital. PROCEDURE: We reviewed histologic sections of liver, intestine, pancreas, and kidney from cats that had previous necropsy examinations and determined the prevalence of lymphocytic portal hepatitis, cholangiohepatitis, IBD, pancreatitis, and chronic interstitial nephritis, and the relationship among them. RESULTS: 36 cats had lymphocytic portal hepatitis, 18 had cholangiohepatitis, and 24 did not have inflammatory hepatic disease. The prevalence of IBD (10/36; 28%) and pancreatitis (5/36; 14%) in cats with lymphocytic portal hepatitis was not significantly different from cats without inflammatory hepatic disease. The prevalence of IBD (15/18; 83%) and pancreatitis (9/18; 50%) was greater (P < 0.05) for cats with cholangiohepatitis, compared with cats without inflammatory hepatic disease. Thirty-nine percent of cats (7/18) with cholangiohepatitis had IBD and pancreatitis. Evidence of IBD in association with cholangiohepatitis was characterized by infiltration of lymphocytes and plasma cells into the lamina propria; however, neutrophilic infiltrates also were found in 6 of 15 (40%) cats with cholangiohepatitis. Pancreatitis was mild in all cats. CLINICAL IMPLICATIONS: Cats with a diagnosis of cholangiohepatitis should be evaluated for IBD and pancreatitis.

Age Distribution↗

In vitro expression and inhibition of procoagulant activity produced by bovine alveolar macrophages and peripheral blood cells.

Local and systemic activation of coagulation is frequently associated with bacterial sepsis. The coagulopathy is due, at least in part, to expression of tissue factor (TF) by monocytes and macrophages. The purpose of this study was to evaluate the expression of procoagulant activity by bovine alveolar macrophages, leukocytes and platelets, and to determine the relative potency of three chemical inhibitors of TF expression (pentoxifylline, retinoic acid, and cyclosporin A). Bovine alveolar macrophages were stimulated with lipopolysaccharide (LPS) derived from Pasteurella haemolytica or recombinant bovine tumour nervous factor (TNF) and dose- and time-dependent effects on TF expression were studied. LPS and TNF induced TF expression in alveolar macrophages and LPS treatment of whole blood induced TF expression in mononuclear cells. Neutrophils and platelets also expressed procoagulant activity, but this activity was not inhibited by anti-bovine TF monoclonal antibody. Pentoxifylline (40 mumol/L), retinoic acid (0.01 mmol/L) and cyclosporin A (0.08 mumol/L) inhibited TF expression when added concurrently with LPS or TNF, but not when added 4 h after stimulation. TF mRNA was not detected in unstimulated alveolar macrophages by Northern blot analysis. In contrast, exposure to LPS or TNF for 6 h induced marked expression of TF mRNA, which was inhibited by treatment with pentoxifylline, retinoic acid and cyclosporin A. Expression of TNF by alveolar macrophages stimulated with LPS was also inhibited by these compounds. Our results indicate that procoagulant activity expressed by alveolar macrophages and monocytes is associated with expression of TF, whereas procoagulant activity expressed by neutrophils and platelets is not. The concentrations of pentoxifylline and retinoic acid necessary for inhibition of TF expression in vitro may not be achievable in vivo owing to their toxic effects. However, the in vitro concentration of cyclosporin A that inhibited TF expression did not exceed the plasma concentration observed in humans, and therefore may be useful for inhibition of TF expression in vivo.

Animals↗

Kinetics of serum antiplatelet antibodies in experimental acute canine ehrlichiosis.

The pattern of appearance of serum antiplatelet antibodies during the acute phase of experimental canine ehrlichiosis (Ehrlichia canis) was investigated in six beagles and correlated with the development of thrombocytopenia. The earliest detection of serum antiplatelet antibodies was made on Day 7 post-inoculation in one dog, on Day 13 in three out of six dogs, and on Day 17 post-inoculation in the remaining two dogs. Thrombocytopenia developed in all infected dogs. The results of this study suggest that antiplatelet antibodies play a role in the destruction of platelets in the acute phase of the disease. It is proposed that E. canis infection in dogs alters the immune system resulting in the overproduction of natural antiplatelet antibodies.

Acute Disease↗

Spinal cord injury and bladder recovery.

OBJECTIVE: To investigate whether spinothalamic tract preservation and posterior column sparing are predictors of neurogenic recovery of bladder function after spinal cord injury (SCI). DESIGNS AND PARTICIPANTS: In a retrospective review, the initial perianal pinprick sensation (S4.5 dermatomes) and position sense of the great toes were examined and correlated with bladder function at 1 year after SCI in 19 consecutive spinal cord injured patients (age 18 to 68 years), Frankel A-D, with spinal injury (level C-4-T-12). All patients were admitted to the Regional Spinal Cord Injury Center of Delaware Valley (RSCIDDV) within 72 hours of injury between July 1990 and June 1991 and were available for a 1-year follow-up evaluation. MAIN OUTCOME MEASURES: The correlation of initial perianal pinprick and great toe position sensation with bladder management approximately 1 year after SCI. RESULTS: During the initial 72 hours, 10 of the 19 patients had positive perianal pinprick sensation and 9 did not feel the pin. Eight patients had positive great toe position sense, and 11 had no proprioception. At the 1-year follow-up visit, 7 of the 10 patients with initial preserved perianal pinprick were voiding volitionally, whereas none of the 9 patients who did not have pinprick voided volitionally at 1-year after SCI. Six of the 8 with initial preserved great toe position sense were voiding volitionally at 1 year, but only 1 of the original 11 without initial toe position sense was voiding volitionally. CONCLUSIONS: Both perianal pinprick sensation and toe position sense are sensitive in predicting return of bladder function. Although both tests have positive predictive value, their negative predictive values are much more noteworthy. A patient without initial position sense of the great toes will likely not regain volitional voiding, whereas a patient without initial perianal pinprick sensation will definitely not regain volitional voiding.

Adolescent↗

Evaluation of thrombin-antithrombin complexes and fibrin fragment D in carbohydrate-induced acute laminitis.

Carbohydrate-induced laminitis has been associated with decreased platelet survival, decreased blood flow to the hoof wall and with the deposition of platelets and microthrombi within venules in the dermal laminae. To evaluate further the systemic prothrombotic events occurring in the prodromal stages of laminitis, plasma samples from control and laminitis-affected ponies and horses were tested for the presence of thrombin-antithrombin (TAT) complexes and fibrin fragment D (D-dimer). No statistically significant differences between the control and laminitis-affected animals were observed for either the D-dimer or the TAT complexes. Few of the values for individual animals exceeded the reference ranges for control animals. These data indicate that the prothrombotic events observed in carbohydrate-induced laminitis may not be associated with systemic activation of the coagulation or fibrinolytic systems.

Acute Disease↗

Histopathologic evaluation of feline inflammatory liver disease.

To better define the histopathologic features of feline inflammatory liver disease, we studied feline liver biopsies evaluated at the University of Minnesota Veterinary Teaching Hospital over a 10-year period. Of 175 liver sections examined, 45 had portal inflammatory infiltrates. Of these, 60% had infiltrates consisting of lymphocytes and plasma cells, 24% had infiltrates consisting of neutrophils, and 16% had mixed infiltrates consisting of neutrophils, lymphocytes, and plasma cells. Lymphocytic-plasmacytic portal infiltrates were characterized by various degrees of bile duct proliferation and fibrosis without evidence of bile duct infiltration or periportal necrosis. Sections with portal neutrophilic infiltrates were characterized by bile duct infiltration, bile duct epithelial degeneration, periportal necrosis, and infiltration of neutrophils into adjacent lobules. We propose that hepatitis characterized by portal lymphocyte and plasma cell infiltration be termed lymphocytic portal hepatitis and that hepatitis characterized by cholangitis and portal neutrophilic infiltrates with or without lymphocytes and plasma cells be termed cholangiohepatitis.

Animals↗

Effects of hematocrit and erythrocyte deformability on pulmonary vascular pressures in perfused pony lungs.

OBJECTIVE: To evaluate the contribution of hematocrit and RBC deformability to pulmonary vascular pressures of racehorses. DESIGN: Pony lungs were isolated and right and left lungs were perfused separately with blood. The effects of changing hematocrit and of pentoxifylline treatment were evaluated. ANIMALS: 11 healthy mixed-breed ponies. PROCEDURE: Ponies were anesthesized, blood was collected, and lungs were removed and perfused with blood at constant flow rate. RESULTS: Increasing the hematocrit from 35% to 65% resulted in increases in pulmonary arterial pressure (53%, 45%), capillary shear stress (45%, 32%), and total vascular resistance (92%, 143%) at low (352 +/- 33 ml/min) and high (1,442 +/- 48 ml/min) flow rates, respectively. Pulmonary artery pressures were lower (10%, 11%) when lungs were perfused with blood from pentoxifylline-treated ponies, compared with blood from control ponies with low hematocrit (PCV, 30%) and low-flow rate and with high hematocrit (PCV, 45%) and high flow rate, respectively. Decreases in capillary shear stress and total vascular resistance were also observed for pentoxifylline-treated blood. CONCLUSIONS: Increases in hematocrit equivalent to those occurring during competitive racing activity contribute substantially to pulmonary vascular pressures in horse lungs. Administration of pentoxifylline to ponies reduced RBC deformability and attenuated increases in pulmonary vascular pressures. CLINICAL RELEVANCE: Treatment of racehorses with pentoxifylline may reduce exercise-associated increases in pulmonary vacular pressure, thereby attenuating exercise-induced pulmonary hemorrhage.

Animals↗

Effects of furosemide on hemorheologic alterations induced by incremental treadmill exercise in thoroughbreds.

OBJECTIVE: To determine whether furosemide treatment altered the blood flow properties and serum and RBC electrolyte concentrations of Thoroughbreds during submaximal treadmill exercise. DESIGN: Thoroughbreds were subjected to submaximal treadmill exercise with and without treatment with furosemide (1 mg/kg of body weight, IV). ANIMALS: 5 healthy Throughbreds that had raced within the past year and had no history of exercise-induced pulmonary hemorrhage. PROCEDURE: Venous blood samples were obtained before exercise, at treadmill speeds of 9 and 13 m/s, and 10 minutes after exercise, and hemorheologic and electrolyte test results were determined. RESULTS: Hemorheologic changes 60 minutes after furosemide administration included increased PCV, plasma total protein concentration, whole blood viscosity, mean RBC volume, and RBC potassium concentration, and decreased serum potassium concentration, serum chloride concentration, and RBC chloride concentration. Furosemide treatment attenuated the exercise-associated changes in RBC size, serum sodium concentration, serum potassium concentration, RBC potassium and chloride concentrations, and RBC density; exacerbated exercise-associated increases in whole blood viscosity; and had no effect on RBC filterability. CONCLUSIONS: The hemorheologic effects of furosemide probably occurred secondary to total body and transmembrane fluid and electrolyte fluxes and would not improve blood flow properties. CLINICAL RELEVANCE: The beneficial effects of furosemide treatment in reducing the severity of bleeding in horses with exercise-induced pulmonary hemorrhage cannot be explained by improved blood flow properties.

Animals↗

Effects of pentoxifylline on hemorheologic alterations induced by incremental treadmill exercise in thoroughbreds.

OBJECTIVES: To determine whether pentoxifylline treatment altered hematologic, rheologic, electrolyte, or blood gas test results of Thoroughbreds during submaximal treadmill exercise. ANIMALS: 5 healthy Thoroughbreds that had raced within the past year and had no history of exercise-induced pulmonary hemorrhage. PROCEDURE: Mixed venous blood samples were obtained before exercise, at treadmill speeds of 9 and 13 m/s, and 20 minutes after exercise; hematologic, rheologic, electrolyte, and blood gas test results were determined. RESULTS: Pentoxifylline treatment resulted in a 45% reduction in RBC filtration pressures for horses at rest. The improved RBC filterability persisted during treadmill exercise. Horses treated with pentoxifylline had a greater decrease in Po2 values and a lesser increase in plasma lactate concentration during treadmill exercise. CONCLUSION: Administration of pentoxifylline improved RBC deformability of horses at rest and during treadmill exercise. CLINICAL RELEVANCE: Improved RBC deformability resulting from pentoxifylline treatment may reduce exercise-associated shear stress in pulmonary capillaries, thereby attenuating exercise-induced pulmonary hemorrhage.

Analysis of Variance↗

Demonstration of serum antiplatelet antibodies in experimental acute canine ehrlichiosis.

This report presents evidence for the presence of antiplatelet antibodies in sera of dogs experimentally infected with Ehrlichia canis, during the acute phase of the disease. Six healthy adult male beagle dogs were inoculated intravenously with blood from a longstanding infected dog with the Israel strain 611 of E. canis. Thrombocytopenia and concurrent increase in mean platelet volume were the most consistent haematological signs of the disease. The dogs developed an antibody titre to E. canis from Day 15 postinoculation. All dogs were antiplatelet antibody negative before inoculation. Twenty-four days postinoculation with E. canis, when the platelet count was at its lowest, antibodies to platelets were demonstrated, in the sera of five of the six dogs.

Acute Disease↗