Platelet GPIIb/IIIa receptor inhibition by SC-49992 prevents thrombosis and rethrombosis in the canine carotid artery

OBJECTIVE: Platelet glycoprotein IIb/IIIa (GPIIb/IIIa) receptors represent the final common pathway for aggregation. GPIIb/IIIa inhibition with antibodies or RGD peptides prevents arterial thrombosis. The present study examined the ability of SC-49992 (SC), a GPIIb/IIIa receptor antagonist, to prevent thrombosis in a canine model of carotid artery thrombosis. METHODS: Both carotid arteries of anaesthetised dogs were instrumented with Doppler probes. A 300 microA current was applied to the intimal surface of the right carotid artery via an intraluminal electrode; time to occlusive thrombus formation was noted. SC (30 and 60 micrograms/.kg-1 x min-1, intravenously) or saline was infused for 240 min. The procedure for thrombus formation was repeated after 60 min of drug infusion for the left carotid artery. RESULTS: SC did not alter heart rate or blood pressure. Frequency of occlusive thrombus formation was reduced or prevented in a dose dependent manner (control = 100%, n = 12; SC 30 micrograms = 50%, n = 6; SC 60 micrograms = 0%, n = 6; p < 0.05). SC resulted in a reduction in thrombus weight (p < 0.05) v control. Ex vivo platelet aggregation to ADP and arachidonic acid was inhibited. Platelet reactivity remained inhibited 60 min after cessation of SC infusion. In a second group of animals, a carotid artery thrombus was formed and lysed with administration of anisoylated plasminogen streptokinase activator complex (0.05 U.kg-1). SC (60 micrograms.kg-1 x min-1, intravenously, n = 6) or saline (n = 6) was infused for 240 min. In dogs receiving saline there was an 83% rate of rethrombosis; none of the SC treated animals had reocclusion after recanalisation (p < 0.05). CONCLUSIONS: SC-49992 inhibits ex vivo platelet aggregation, prevents occlusive thrombus formation in a canine model of arterial thrombosis, and prevents rethrombosis after thrombolysis. The data are consistent with results obtained with murine monoclonal antibodies directed against the platelet GPIIb/IIIa receptor.     

Disappearing subdural hematomas in children

Serum glucose and plasma C-peptide response to i.v. glucagon administration was evaluated in 24 healthy dogs, 12 dogs with untreated diabetes mellitus, 30 dogs with insulin-treated diabetes mellitus, and 8 dogs with naturally acquired hyperadrenocorticism. Serum insulin response also was evaluated in all dogs, except 20 insulin-treated diabetic dogs. Blood samples for serum glucose, serum insulin, and plasma C-peptide determinations were collected immediately before and 5, 10, 20, 30, and (for healthy dogs) 60 minutes after i.v. administration of 1 mg glucagon per dog. In healthy dogs, the patterns of glucagon-stimulated changes in plasma C-peptide and serum insulin concentrations were identical, with single peaks in plasma C-peptide and serum insulin concentrations observed approximately 15 minutes after i.v. glucagon administration. Mean plasma C-peptide and serum insulin concentrations in untreated diabetic dogs, and mean plasma C-peptide concentration in insulin-treated diabetic dogs did not increase significantly after i.v. glucagon administration. The validity of serum insulin concentration results was questionable in 10 insulin-treated diabetic dogs, possibly because of anti-insulin antibody interference with the insulin radioimmunoassay. Plasma C-peptide and serum insulin concentrations were significantly increased (P < .001) at all blood sampling times after glucagon administration in dogs with hyperadrenocorticism, compared with healthy dogs, and untreated and insulin-treated diabetic dogs. Five-minute C-peptide increment, C-peptide peak response, total C-peptide secretion, and, for untreated diabetic dogs, insulin peak response and total insulin secretion were significantly lower (P < .00l) in diabetic dogs, compared with healthy dogs, whereas these same parameters were significantly increased (P < .01) in dogs with hyperadrenocorticism, compared with healthy dogs, and untreated and insulin-treated diabetic dogs. Although not statistically significant, there was a trend for higher plasma C-peptide concentrations in untreated diabetic dogs compared with insulin-treated diabetic dogs during the glucagon stimulation test. Baseline C-peptide concentrations also were significantly higher (P < .05) in diabetic dogs treated with insulin for less than 6 months, compared with diabetic dogs treated for longer than 1 year. Finally, 7 of 42 diabetic dogs had baseline plasma C-peptide concentrations greater than 2 SD (ie, > 0.29 pmol/mL) above the normal mean plasma C-peptide concentration; values that were significantly higher, compared with the results in healthy dogs (P < .001) and with the other 35 diabetic dogs (P < .001). In summary, measurement of plasma C-peptide concentration during glucagon stimulation testing allowed differentiation among healthy dogs, dogs with impaired beta-cell function (ie, diabetes mellitus), and dogs with increased beta-cell responsiveness to glucagon (ie, insulin resistance). Plasma C-peptide concentrations during glucagon stimulation testing were variable in diabetic dogs and may represent dogs with type-1 and type-2 diabetes or, more likely, differences in severity of beta-cell loss in dogs with type-1 diabetes.     

Myotonia associated with hyperadrenocorticism in two dogs

Two dogs developed a disabling gait abnormality characterised by stiffness. The abnormality was consistent with a diagnosis of myotonia secondary to hyperadrenocorticism. The first dog had iatrogenic hyperadrenocorticism, and its signs improved substantially after corticosteroid administration was gradually withdrawn. The second had pituitary-dependent hyperadrenocorticism, but myotonic signs progressed despite effective mitotane therapy. Procainamide administration reduced the myotonic stiffness in the second case.     

Sequential pattern of non-medical drug use in the drug career of opiate dependents in Nagpur, India

OBJECTIVE: To evaluate low- and high-dose dexamethasone suppression tests for differentiating pituitary dependent hyperadrenocorticism (PDH) from adrenal tumor hyperadrenocorticism (ATH) in dogs. DESIGN: Prospective study. ANIMALS: 181 dogs with PDH and 35 dogs with ATH. PROCEDURE: Plasma cortisol concentrations from dogs with naturally developing hyperadrenocorticism were evaluated before, and 4 and 8 hours after administration of standard low- and high-doses of dexamethasone (0.01 mg/kg of body weight, i.v., and 0.1 mg/kg, i.v.; respectively). RESULTS: In response to the low-dose test, all but 3 dogs had an 8-hours post-dexamethasone plasma cortisol concentration that was consistent with a diagnosis of hyperadrenocorticism, that is, > or = 1.4 micrograms/dl. Criteria used to distinguish PDH from ATH in response to low-dose dexamethasone included a 4-hour post-dexamethasone plasma cortisol concentration < 50% of the basal value or < 1.4 micrograms/dl, or an 8-hours post-dexamethasone plasma cortisol concentration < 50% of the basal concentration. Criteria used to distinguish PDH from ATH in response to high-dose dexamethasone included 4- or 8-hour post-dexamethasone plasma cortisol concentrations < 50% of the basal concentration or < 1.4 micrograms/dl. In response to the low-dose test, 111 dogs met criteria for suppression (each had PDH). In response to the high-dose test, 137 dogs met criteria for suppression (2 had ATH, 135 had PDH). Twenty-six dogs with PDH (12%) had indications of adrenal suppression in response to high-dose but not low-dose testing. CLINICAL IMPLICATIONS: Low-dose dexamethasone test has value as a discrimination test to distinguish dogs with PDH from those with ATH. The high-dose test need only be considered in dogs with hyperadrenocorticism that do not have adrenal suppression in response to the low-dose test.     

Antithrombotic effects of MK-0852, a platelet fibrinogen receptor antagonist, in canine models of thrombosis

The antiaggregatory and antithrombotic actions of MK-0852, a cyclic heptapeptide antagonist of the platelet GP IIb/IIIa, were evaluated in a variety of canine models. In vitro, MK-0852 inhibited the aggregation of canine platelet-rich plasma induced by 10 microM ADP in the presence of 1 microM epinephrine with an IC50 value of 0.10 microM. The i.v. infusion of 1.0 and 3.0 micrograms/kg/min MK-0852 to anesthetized dogs significantly inhibited ex vivo platelet aggregation responses to ADP and collagen, with the 3.0 micrograms/kg/min infusion completely inhibiting ex vivo aggregation responses to both agonists. The i.v. administrations of 100 and 300 micrograms/kg MK-0852 suppressed platelet-dependent cyclic flow reductions in stenosed canine left circumflex (LCX) coronary artery for periods of 24 +/- 3 and 64 +/- 4 min, respectively. In a canine model of copper coil-induced femoral arterial thrombosis, i.v. MK-0852 (100 micrograms/kg + 1 microgram/kg/min), initiated 15 min before coil placement, reduced the incidence of occlusive thrombosis during the 45-min post-coil time period of continued therapy (1/5 MK-0852 vs. 7/7 saline; P < .01). MK-0852 was administered as an adjunctive therapy with tPA to evaluate its effects on thrombolysis after copper coil-induced femoral arterial thrombus formation. MK-0852 (i.v.; 100 micrograms/kg + 1 microgram/kg/min), initiated 15 min before tPA, reduced the incidence of post-thrombolysis reocclusion. During the 60-min period of continued drug infusion after the termination of tPA, 0 of 5 animals receiving MK-0852 reoccluded vs. 7/8 saline (P < .01). In a canine model of electrically induced LCX coronary artery thrombosis, i.v. MK-0852 (100 micrograms/kg + 3 micrograms/kg/min), initiated 15 min before the initiation of electrical injury, prevented occlusive thrombosis in 4 of 6 preparations despite the continued electrical stimulation of the vessel for 180 min. Thrombotic occlusion was delayed in the remaining two preparations (99 and 100 min), compared with occlusion in 4 of 4 saline-treated preparations (69.3 +/- 6.3 min). When administered as an adjunct to thrombolytic agents for lysis of electrically induced LCX coronary artery thrombi, i.v. MK-0852 (300 micrograms/kg + 3 micrograms/kg/min), initiated 15 min before tPA or streptokinase, both increased the incidence of reperfusion (tPA: 8/8 MK-0852 vs. 3/8 saline; streptokinase: 5/8 MK-0852 vs. 2/8 saline) and accelerated reperfusion. The incidence of reocclusion during continued adjunctive therapy was reduced.(ABSTRACT TRUNCATED AT 400 WORDS)     

The Fab-fragment of a PAI-1 inhibiting antibody reduces thrombus size and restores blood flow in a rat model of arterial thrombosis

The effect of PRAP-1, a Fab-fragment of a PAI-1-inhibiting polyclonal antibody, on thrombus size and arterial blood flow was studied in a rat model of arterial thrombosis. It was shown that exposure of the carotid artery to FeCl3 led to the rapid formation of an occlusive thrombus with a morphology similar to that of arterial thrombi found in humans. Tranexamic acid (50 mg/kg), an inhibitor of fibrinolysis, increased thrombus size (p = 0.014) when given intravenously (i.v.) prior to the FeCl3-exposure. Heparin (1000 U), when given i.v. after FeCl3, did not affect the thrombus size per se, but caused a reduction in the interindividual variation of the size of the thrombus (p < 0.05). Thus, heparin was included in all the subsequent experiments. An i.v. infusion of t-PA (1 mg/kg/h), starting before thrombus formation, induced a 3.3 fold increase in the perfusion rate (p = 0.006) and a 67% reduction in the thrombus size (P < 0.001). PRAP-1, an inhibitor of rat PAI-1 activity, was given i.v. as a bolus followed by an infusion. Two doses of PRAP-1 were studied (7.5 and 15 mg/kg/h), and the administration of the PAI-1 inhibitor was started 10 min before FeCl3. The lower PRAP-1 dose caused a 3.8 fold increase in perfusion rate (p = 0.036), a 1.44 fold increase in the time to occlusion (p = 0.034), and the thrombus size was decreased by 18% (p = 0.104). The corresponding effects of the high PRAP-1 dose were a 6.5 fold increase in perfusion rate (p < 0.001), a 1.6 fold increase in time to occlusion (p = 0.038) and a 32% reduction in thrombus size (p = 0.016). It is concluded that an inhibitor of PAI-1 activity, PRAP-1, caused a moderate decrease in thrombus size and partly restores blood flow in a rat model of arterial thrombus. This finding suggests a potential role for an inhibitor of PAI-1 in the treatment of arterial thrombosis.     

Value of irradiation of neck nodes metastases. Part I. Treatment of palpable nodes

The N-methyl-D-phenylalanyl-L-prolyl-arginine-aldehyde sulfate tripeptide-aldehyde (GYKI-14766) is an anticoagulant with specific thrombin inhibitor action. The molecule proved to be effective in rabbits, rats and dogs upon i.v. administration. Chromogen-substrate assay was developed for monitoring of biologically active tripeptide-inhibitor GYKI-14766 in plasma. The assay based on the inhibition of the active center of the thrombin enzyme, so it is suitable also for the assay of all those active metabolites which inhibit thrombin by a mechanism similar to the active parent compound. The chromogen substrate assay was performed in a range of 0.625-10 micrograms/ml GYKI-14766 in dog plasma. The assay was employed in pharmacokinetic study in dogs after i.v. administration. The data obtained in the chromogen-substrate assay were analyzed according to a one-compartment model. The major parameters of the plasma level studies were: D/V = 8.6 microEqv/ml t1/2 = 30.8 min AUC = 380 min microEqv/ml.     

Recombinant tissue type plasminogen activator treatment of thrombosed mitral valve prosthesis during pregnancy

PURPOSE: Prosthetic heart valve thrombosis occurring during pregnancy is a life-threatening complication. Surgical treatment requires clot removal under cardiopulmonary bypass (CPB) and carries a high mortality. We describe the successful use of thrombolytic therapy for recurrent thrombosed valve prosthesis in a pregnant patient. CLINICAL FEATURES: A 32-yr-old patient whose pregnancy was complicated by two episodes of a thrombosed St Jude mitral prosthesis is reported. The first episode occurred at 20 wk of pregnancy during the change of oral anticoagulant therapy (acenocoumarol 4 mg a day) to sc heparin. As the patient was in cardiogenic shock, the valve thrombus was treated by clot removal under CPB., with a cross clamp time of 32 min, a perfusion pressure above 70 mmHG. There was no fetal cardiac rhythm during CPB which lasted < 45 min. The second episode occurred at the 28th gestational week in a patient in cardiogenic shock and because reoperation was thought to carry too high a risk, the thrombus was successfully treated with 50 mg recombinant tissue plasminogen activators (rtPA) i.v. Following this, the course of pregnancy was uneventful and carried to term and the patient delivered vaginally. Pain relief was achieved with intravenous patient-controlled analgesia with alfentanil (bolus 100 mug; lock out = five minutes). Although rtPA has been used before, this is the first report in which pregnancy was carried to term and standard vaginal delivery performed. CONCLUSION: This case provides evidence for the efficacy and relative safety of rtPA as thrombolytic therapy in the treatment of haemodynamically compromised valve heart thrombosis in pregnancy.     

Endocrinopathies. Thyroid and adrenal disorders

This article focuses on common adrenal and thyroid diseases in the geriatric patient consisting of hypothyroidism in the dog, hyperthyroidism in the cat, and hyperadrenocorticism in the dog to include clinical signs, diagnosis, and management. A brief section on hyperadrenocorticism in the cat, thyroid tumors in the dog, and pheochromocytoma in the dog and cat are also included.     

Systemic arterial blood pressure and urine protein/creatinine ratio in dogs with hyperadrenocorticism

OBJECTIVE: To determine prevalence and severity of systemic arterial hypertension and proteinuria in dogs with naturally developing hyperadrenocorticism and to determine whether these abnormalities resolve with adequate management of the disease. DESIGN: Case series and cohort study. ANIMALS: 77 dogs with naturally developing hyper-adrenocorticism examined once; 15 dogs examined before and after treatment. RESULTS: Among dogs examined only once, hypertension was diagnosed in 21 of 26 dogs with untreated pituitary-dependent hyperadrenocorticism (PDH), 17 of 21 with inadequately controlled PDH, 8 of 16 with well-controlled PDH, 10 of 10 with an untreated adrenocortical tumor, and 0 of 4 that had undergone adrenalectomy because of an adrenocortical tumor. Untreated dogs and dogs with inadequately controlled PDH had significantly higher blood pressures than did other dogs. Proteinuria was documented in 12 of 26 dogs with untreated PDH, 5 of 16 with inadequately controlled PDH, 3 of 14 with well-controlled PDH, 5 of 8 with an untreated adrenocortical tumor, and 1 of 3 that had undergone adrenalectomy. Dogs with untreated PDH and dogs with an untreated adrenocortical tumor had higher urine protein/creatinine ratios than did dogs with well-controlled PDH. Among dogs evaluated before and after treatment, blood pressure and urine protein/creatinine ratio did not change in 8 dogs with inadequately controlled hyperadrenocorticism, but decreased in 7 dogs with well-controlled disease. CLINICAL IMPLICATIONS: Results suggest that systemic hypertension and proteinuria are common in dogs with untreated hyperadrenocorticism and that successful treatment of hyperadrenocorticism will result in resolution of these abnormalities in many, but not all, dogs.     

Acute thrombosis of the portal system. Treatment with alteplase and heparin or with heparin alone in 10 patients

OBJECTIVES: We report the efficacy of alteplase (a recombinant tissue plasminogen activator) with heparin or heparin alone in the treatment of acute thrombosis of the portal venous system. METHODS: Ten consecutive patients with acute portal venous system thrombosis were studied. Five patients were treated with alteplase and heparin, and the remaining 5 patients, who were asymptomatic or had a contraindication to alteplase, were treated with heparin alone. RESULTS: In 3 of the 5 patients treated with alteplase, ultrasonography showed total resolution of the thrombus; the remaining 2 had partial resolution of the thrombus. In 4 of the 5 patients treated with heparin alone, ultrasonography showed total resolution of the thrombus, and no change in one. No bleeding occurred. CONCLUSION: Treatment with heparin can result in complete recanalisation of acute portal venous system thrombosis. These data suggest that combined therapy with systemic alteplase does not increase the efficacy of heparin.     

Systemic hypertension and its management

The pathophysiology of hypertension in dogs and cats, the methods available to monitor blood pressure, and the signs and treatment of hypertension are reviewed. Clinical signs of hypertension are usually referable to target organ damage, most notably in ophthalmic, renal, and cardiovascular tissues, which have a rich arteriolar supply. Blood pressure should be measured in any animal with renal disease, hyperthyroidism, hyperadrenocorticism, retinal detachment or hemorrhage, hyphema, or echocardiographically determined cardiac hypertrophy. All cats with acquired cardiac murmur should also be evaluated for hypertension. Antihypertensive medication should be administered if the indirect blood pressure in cats is consistently over 170/100 mmHg, or if the indirect blood pressure in dogs is greater than 180/100 mmHg.     

Vestibulovaginal stenosis in dogs: 18 cases (1987-1995)

OBJECTIVE: To evaluate vestibulovaginal stenosis in dogs. DESIGN: Retrospective study. ANIMALS: 18 dogs with vestibulovaginal stenosis diagnosed between January 1987 and June 1995. PROCEDURE: Signalment, results of physical examination, and diagnostic testing, treatment, and outcome were analyzed. RESULTS: Mean age at initial examination was 4.6 years. Problems reported by the owners included signs of chronic urinary tract infection (6 dogs), urinary incontinence (4), failure to mate (4), signs of chronic vaginitis (2), and inappropriate urination (1). One dog did not have evidence of a clinical problem. Vestibulovaginal stenosis was detected by means of digital vaginal examination (18/18 dogs), vaginoscopy (17/17 dogs), and positive-contrast vaginography (9/10 dogs). Bacteria were isolated from the urine of 11 of 15 dogs. Twelve of 18 dogs were treated. Manual dilation (4 dogs) and T-shaped vaginoplasty (4) were less successful than vaginectomy (2) or resection of the stenotic area (3). Four of 6 dogs with signs of recurrent urinary tract infection underwent surgical correction, and none of these dogs subsequently had urinary tract infection. Three of 4 dogs with urinary incontinence responded to medical or surgical treatment for sphincter incompetence or for ectopic ureters. CLINICAL IMPLICATIONS: Surgical correction of vestibulovaginal stenosis is indicated in dogs that have mating difficulties or signs of recurrent urinary tract infection or chronic vaginitis, but stenosis is probably an incidental finding in most dogs with urinary incontinence. Vaginectomy and vaginal resection and anastomosis are the preferred surgical options.     

K-ATP-blocking diuretic PNU-37883A reduces plasma renin activity in dogs

We determined the effects of the K-adenosine triphosphate (ATP)-blocking diuretic PNU-37883A on plasma renin activity (PRA) in conscious and anesthetized dogs. In conscious dogs, oral PNU-37883A (6-60 mg/kg) was less potent than hydrochlorothiazide (0.15-1.5 mg/kg) and furosemide (FURO; 0.3-3.0 mg/kg) but exhibited high natriuretic efficacy with little kaliuresis. Unlike the standard diuretics, PNU-37883A reduced PRA by 46-76%, and its high dose minimally affected 24-h urinary aldosterone excretion. PNU-37883A, 1 mg/kg i.v., also blunted the hyperreninemia induced by 1 mg/kg i.v. FURO. In cannulated dogs, 10 mg/kg i.v. PNU-37883A maximally increased fractional Na+ clearance 140% and reduced PRA 76%, but these effects were accompanied by a mean 13 mm Hg pressor effect. In anesthetized dogs, renal artery-infused PNU-37883A (3 mg/kg/h i.r.a.) increased Na+ excretion and reduced renal venous PRA independent of hemodynamics, whereas half this dosage selectively reduced renal venous PRA and renin release, independent of hemodynamics and natriuresis. These data demonstrate that the K-ATP blocker diuretic PNU-37883A reduces PRA in dogs after oral, i.v., and i.r.a. administration and could be a useful pharmacologic agent for exploring the role of K-ATP channels in regulating renin release.     

Transcutaneous ultrasound augments lysis of arterial thrombi in vivo

BACKGROUND: External ultrasound has a synergistic effect on thrombus disruption with thrombolytic agents in vitro. We hypothesized that transcutaneous ultrasound could augment thrombolysis in vivo. METHOD AND RESULTS: Thrombus formation was induced electrically in 48 pairs of iliofemoral arteries of 24 rabbits; arterial occlusions were documented angiographically. In 17 of 24 rabbits, 25000 units/kg streptokinase was then administered intravenously. The pairs of iliofemoral arteries were randomized to receive ultrasound treatment or no ultrasound treatment. Low-frequency (26 kHz) ultrasound (continuous wave, 18 W/cm2) was applied transcutaneously over the area of occlusion. In 7 of 24 rabbits, 14 thrombotically occluded iliofemoral arteries were exposed to ultrasound alone without streptokinase. The results were evaluated through the use of angiography (TIMI grade flow) and histopathology. After 30 +/- 10 minutes of activated sonication combined with intravenous streptokinase, 10 of 17 iliofemoral arteries (59%) treated with transcutaneous ultrasound were widely patent angiographically, with TIMI grade 3 flow. Histologically, the patent arteries had only minimal focal moral thrombus. The angiographic patency rate was significantly lower in the control groups: 1 of 17 arteries (6%) treated with streptokinase alone (P = .0012) and 1 of 14 arteries (7%) treated with ultrasound alone (P = .0036). CONCLUSIONS: In vivo transcutaneous ultrasound significantly augments lysis of thrombi with streptokinase in rabbit iliofemoral arteries.     

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.     

Responses of dogs with food allergies to single-ingredient dietary provocation

OBJECTIVE: To characterize specific food ingredients causing allergic reactions in dogs and to assess cross-reactivity between proteins derived from a single animal source or from different plant products. DESIGN: Prospective study. ANIMALS: 25 dogs with histories and cutaneous signs consistent with food-allergic dermatitis. PROCEDURE: Dogs were fed a food-elimination diet until resolution of clinical signs and then challenged with their original diet. A diagnosis of food allergy was made if there was complete return of pruritus within 14 days of challenge exposure. After diagnosis, dogs were fed the food-elimination diet until signs related to dietary challenge abated. The dogs then were fed beef, chicken, chicken eggs, cows' milk, wheat, soy, and corn in single-ingredient provocation trials for 1 week. Any cutaneous reactions to these food ingredients were recorded by their owners. RESULTS: Beef and soy most often caused adverse cutaneous reactions, although all ingredients induced clinical signs in at least 1 dog. Mean number of allergens per dog was 2.4, with 80% reacting to 1 or 2 proteins and 64% reacting to 2 or more of the proteins tested. A significant difference was found between dogs reacting to beef versus cows' milk and between dogs reacting to soy versus wheat; thus, the hypothesis of cross-reactivity to ingredients derived from a single animal source or to different plant products was not supported. Similar differences between chicken meat and eggs were not identified. CLINICAL IMPLICATIONS: Long-term management of dogs with food allergies is facilitated by identification of the most commonly encountered food allergens. Because cross-reactivity cannot be verified, each protein source should be included separately in food-provocation trials.     

Differential effects of tissue plasminogen activator and streptokinase on infarct size and on rate of enzyme release: influence of early infarct related artery patency. The GUSTO Enzyme Substudy

BACKGROUND: The recent international GUSTO trial of 41,021 patients with acute myocardial infarction demonstrated improved 90-min infarct related artery patency as well as reduced mortality in patients treated with an accelerated regimen of tissue plasminogen activator, compared to patients treated with streptokinase. A regimen combining tissue plasminogen activator and streptokinase yielded intermediate results. The present study investigated the effects of treatment on infarct size and enzyme release kinetics in a subgroup of these patients. METHODS: A total of 553 patients from 15 hospitals were enrolled in the study. Four thrombolytic strategies were compared: streptokinase with subcutaneous heparin, streptokinase with intravenous (i.v.) heparin, tissue plasminogen activator with i.v. heparin, and streptokinase plus tissue plasminogen activator with i.v. heparin. The activity of alpha-hydroxybutyrate dehydrogenase (HBDH) in plasma was centrally analysed and infarct size was defined as cumulative HBDH release per litre of plasma within 72 h of the first symptoms (Q(72)). Patency of the infarct-related vessel was determined by angiography in 159 patients, 90 min after treatment. RESULTS: Infarct size was 3.72 g-eq.1(-1) in patients with adequate coronary perfusion (TIMI-3) at the 90 min angiogram and larger in patients with TIMI-2 (4.35 g-eq.1(-1) or TIMI 0-1 (5.07 g-eq.1(-1) flow (P = 0.024). In this subset of the GUSTO angiographic study, early coronary patency rates (TIMI 2 + 3) were similar in the two streptokinase groups (53 and 46%). Higher, but similar, patency rates were observed in the tissue plasminogen activator and combination therapy groups (87 and 90%). Median infarct size for the four treatment groups, expressed in gram-equivalents (g-eq) of myocardium, was 4.4, 4.5, 3.9 and 3.9 g-eq per litre of plasma (P = 0.04 for streptokinase vs tissue plasminogen activator). Six hours after the first symptoms, respectively 5.3, 6.6, 14.0 and 13.6% of total HBDH release was complete (P < 0.0001 for streptokinase vs tissue plasminogen activator). CONCLUSIONS: Rapid and complete coronary reperfusion salvages myocardial tissue, resulting in limitation of infarct size and accelerated release of proteins from the myocardium. Treatment with tissue plasminogen activator, resulting in earlier reperfusion was more effective in reducing infarct size than the streptokinase regimens, which contributes to the differences in survival between treatment groups in the GUSTO trial.     

Thrombosis, antithrombotic agents, and the antithrombotic approach in cardiac disease

To develop a rational approach to antithrombotic therapy, in cardiac disease, a sound understanding is required (1) of the hemostatic processes leading to thrombosis, (2) of the various antithrombotic agents, and (3) of the relative risks of thrombosis and thromboembolism in the various cardiac disease entities. With the understanding of pathogenesis and risk of thrombus formation, a rational approach to the use of antiplatelet and anticoagulant agents can be formulated. Those at high risk of thrombus formation should generally receive a high degree of antithrombotics and, depending on the pathophysiology of the thrombus, may benefit from the concomitant use of antiplatelet and anticoagulant agents. Those with a medium risk of thrombus formation may benefit with the use of an antiplatelet agent alone or anticoagulants alone. Patients at low risk of thrombus formation should not receive antithrombotics. Such rational approach to antithrombotic therapy serves as the basis of this article.     

Levels of tumor necrosis factor alpha, gamma interferon, and interleukins 4,6, and 10 as determined in mice infected with virulent or attenuated strains of Trypanosoma cruzi

The incidence of puerperal ovarian vein thrombosis is estimated to range between 1 in 600 and 1 in 2000 deliveries. The cardinal signs of puerperal ovarian vein thrombosis include fever, leukocytosis, and right lower quadrant abdominal pain, most often in a recently delivered female patient. These patients are classically described as failing to improve with intravenous antibiotic therapy alone; resolution of symptoms and presumptive diagnosis is made on defervescence with the addition of intravenous heparin therapy. Objective diagnostic modalities include venography, ultrasound, laparoscopy, and MRI, although CT remains the gold standard for the identification of this under-diagnosed entity. We present a case report of a 20-year-old female treated at our facility for puerperal ovarian vein thrombosis. She was transferred to our vascular surgery service after developing the classic signs of puerperal ovarian vein thrombosis and undergoing CT demonstrating ovarian vein thrombosis with extension of free-floating thrombus into her inferior vena cava (IVC). This degree of thrombosis was particularly concerning when one considers the 3 to 33 per cent rate of pulmonary embolism reported in patients with puerperal ovarian vein thrombosis. Treatment modalities for such extensive degrees of thrombosis are described in the literature and range from hysterectomy and thrombectomy to ligation of the IVC. In our case, we prophylactically placed a suprarenal IVC Greenfield filter to protect against pulmonary embolism and proceeded with the standard regimen of anticoagulation and antibiotics. This treatment approach has been reported only twice previously in the literature, to our knowledge.