Presumptive subcutaneous surgical transplantation of a urinary bladder transitional cell carcinoma in a dog.

A urinary bladder mass in a 12-year-old spayed female West Highland White Terrier was diagnosed after exploratory surgery and biopsy as a transitional cell carcinoma. Four months later the dog presented with an ulcerated plaque-like cutaneous lesion at the previous surgical incision site; concurrent inguinal lymphadenopathy and recurrence of the urinary bladder mass were identified. Transitional cell carcinoma was diagnosed at all 3 sites. Although a definitive relationship cannot be established between the initial surgery for urinary bladder mass and the resultant subcutaneous lesion, surgical implantation should be considered as a source for the neoplastic cells.

Antiinflammatory agents inhibit microvascular permeability induced by leukotrienes and by stimulated human neutrophils.

One pathologic change common to the inflammatory process is loss of microvessel membrane integrity which results in edema. Polymorphonuclear leukocytes (PMN) are primary contributors to the development of edema because they cause tissue injury which alters vascular permeability and hemodynamics. The aim of this study was to assess the influence of arachidonic acid metabolites generated by activation of human PMN on the in vivo microvascular preparation of the hamster cheek pouch. Fluorescein-labeled dextran MW: 150,000 was used to assess microvascular permeability. Human PMN were activated with arachidonic acid (AA) and the calcium ionophore A23187, and the supernatant retained for testing. Topical application of the PMN supernatant, purified LTD4 or LTB4 resulted in marked extravasation of macromolecules from post-capillary venules of control hamsters. The extravasation was reduced when hamsters were pretreated with indomethacin (5 mg/kg), imidazole (25 mg/kg), ketoconazole (10 mg/kg), 13-azaprostanoic acid (30 mg/kg), FPL 55712 (1 mg/kg) and dimethylthiourea (500 mg/kg). The interpretation of the results suggests that the increased vascular permeability induced by PMN secretions may be mediated in part by the thromboxane pathway.

Ischemia of the limb stimulates thromboxane production and myocardial depression.

Thromboxane A2 is thought to be an important mediator of cardiopulmonary dysfunction, hence stimuli that effect synthesis of this prostanoid are of major interest. In this study, the thesis that ischemia of the limb is a significant stimulus to thromboxane A2 synthesis and the generation of a circulating negative inotrope is tested. Twelve healthy volunteers, taking no medications and ranging in age from 21 to 29 years, underwent inflation of an arm cuff to either 70 or 220 millimeters of mercury for ten minutes. Immediately after deflation of the cuff from 220 millimeters of mercury, the stable degradation product of thromboxane A2, thromboxane B2, rose from a base line plasma level of 34 +/- 6 picograms per milliliter (mean +/- SEM) to 70 +/- 18 picograms per milliliter. In contrast, deflation from a cuff pressure of 70 millimeters of mercury resulted in a lower thromboxane B2 level of 26 +/- 9 picograms per milliliter (p less than 0.05). Plasma obtained before and after inflation of the cuff to 220 millimeters of mercury was used to bathe a rat papillary muscle. Developed tension fell from a base line of 2.80 +/- 0.19 to 2.44 +/- 0.17 grams (p less than 0.01). There was no significant change in developed tension induced by plasma harvested after the cuff was inflated to 70 millimeters of mercury. The base line plasma level of 6-keto-prostaglandin F1 alpha, the hydrolysis product of prostacyclin, was 46 picograms per milliliter; the plasma serotonin, 51 nanograms per milliliter; the platelet serotonin, 1.02 micrograms per 10(9) platelets; platelet count, 220,000 per cubic millimeter, and white blood count, 6,094 per cubic millimeter. These values did not change significantly with cuff inflation to either 220 or 70 millimeters of mercury. The results show that ischemia of the limb leads to thromboxane A2 production. Possible adverse cardiac effects related to this event are suggested by the bioassay demonstrating that circulating plasma with high levels of thromboxane B2 is associated with the depression of tension of an isolated rat papillary muscle.

Thromboxane mediation of cardiovascular dysfunction following aspiration.

Acid aspiration leads to an inflammatory response characterized by the activation and pulmonary entrapment of platelets and while blood cells (WBCs. We speculate that thromboxane (Tx) produced by these activated cells alters lung permeability and diminishes cardiac performance. The lungs of dogs were aspirated with 0.1N HCl (3 ml/Kg). Within 30 minutes in six untreated controls, cardiac index (CI) decreased from 121 to 104 ml/min . kg (P less than ).05), mean arterial pressure decreased from 142 to 120 mm Hg (P less than 0.05), Pao2 decreased from 91 to 73 mm Hg (P less than 0.05), and TxB2 levels increased from 70 to 130 pg/ml (P less than 0.05). Pulmonary WBC sequestration occurred after 2 hours, while at 21/2 hours edema fluid was noted in the endotracheal tube. Six dogs were treated with infusion of the imidazole derivative ketoconazole 1 hour after aspiration (2.5 mg/kg bolus followed by 10 mg/kg . hr for 2 hours). After 30 to 60 minutes of treatment, CI rose from 106 to 143 ml/min . kg (P less than 0.05), TxB2 decreased from 130 to 70 pg/ml (P less than 0.05). At 21/2 hours, plasma from treated animals used to incubate a papillary muscle led to developed tension 8% higher than that in controls (P less than 0.05). Sequestration of WBC was not observed. After 4 hours, 24 ml endotracheal edema fluid was collected in contrast to 127 ml in controls (P less than 0.05). A hamster cheek pouch used for bioassay of microvascular permeability yielded 78 leakage sites/cm2 with control edema fluid and 26/cm2 with fluid from treated animals (P less than 0.05). The importance of WBC Tx synthesis in the induction of permeability was tested by stimulation of isolated WBCs with ionophore in the presence or absence of ketoconazole (0.4 Microgram/ml). Ketoconazole reduced the number of leakage sites in the hamster cheek pouch from 196/cm2 noted in controls to 28/cm2 (P less than 0.05). These data support our hypothesis that Tx directly or indirectly lead to cardiac depression and WBC-mediated permeability.

Therapeutic benefits of 5-hydroxytryptamine inhibition following pulmonary embolism.

The smooth muscle-constricting, platelet amine, serotonin (5-hydroxytryptamine; 5-HT) is theorized to play an important role in the cardiopulmonary dysfunction that accompanies embolization. The present study was designed to examine this hypothesis. Autologous clot, 0.75 g/kg, was injected IV into 14 dogs. After 30 minutes, one half of the animals were randomly assigned to the treatment group and received a bolus infusion of 0.15 mg/kg ketanserin, a quinazoline derivative known to be a selective 5-HT receptor antagonist. Five minutes after embolization there were increases in mean pulmonary arterial pressure (MPAP) from 12 mm to 48 mmHg (p less than 0.001); pulmonary vascular resistance (PVR) from 2.2 mm to 12.2 mmHg X min/L (p less than 0.001); physiologic shunt (QS/QT) from 12% to 44% (p less than 0.01); and physiologic dead space (VD/VT), calculated from end tidal and arterial PCO2, from 8% to 39% (p less than 0.001). Within 15 minutes platelet counts decreased from 186,000/mm3 to 134,800/mm3 (p less than 0.05); 5-HT contained in circulating platelets fell from 1.71 micrograms/ to 1.44 micrograms/10(9) platelets (p less than 0.05). Five minutes after ketanserin, MPAP declined to 27 mmHg and was lower than the control value of 41 mmHg (p less than 0.05); PVR decreased to 6.2 mmHg X min/L, lower than 12 mmHg X min/L in controls (p less than 0.01); QS/QT fell to 26% in contrast to 47% in controls (p less than 0.05); and VD/VT declined moderately to 32% (p less than 0.05), although this value was not different from 38% in control animals. Cardiopulmonary function continued to improve in treated animals until termination of the experiment at four hours when pulmonary angiograms and perfusion scans demonstrated vascular recruitment compared with untreated embolized control dogs. These data demonstrate that the cardiopulmonary consequences of experimental embolization are primarily determined by the vasoconstrictive and bronchoconstrictive actions of 5-HT.

Histocytology of lymphoid tumors in the dog, cat and cow.

In a retrospective study of lymphomas in animals, tumors in 72 dogs, 81 cats and 90 cows were classified on the basis of cell size (small, medium and large), nuclear cleavage (follicular center cells), and histologic architecture (nodular or diffuse). Each subtype was classified by age of animal at death, number of metastases, breed, and sex. As in man, nodular cleaved tumors are rare in animals, the cow having the most varied tumor types. There was one cleaved-cell tumor in 72 lymphomas in dogs, 23 of 81 in cats, and 33 of 90 in cows. There were six nodular tumors of 72 in dogs, two of 81 in cats and eight of 90 in cows. Fifteen of 16 nodular lymphomas had noncleaved cells and twelve had small or predominantly small cells. Cats with nodular lymphomas were older at death than cats with diffuse lymphomas. Nodularity was not associated with greater age at death in dogs and cows. Animals with cleaved-cell lymphomas were older at death than those with noncleaved tumors; this difference was highly significant in cows. The number of metastases was greater with nodular tumors in all three species, and was equal in cleaved and noncleaved tumors. The biological behaviour of lymphoid tumors in animals is similar to those in man when the same criteria of classification are used.