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Biomedical subjects

J T Davidson

Publications and source records attributed to J T Davidson.

At least 19 recordsLinked to original sources

Recombinant leech antiplatelet protein prevents collagen-mediated platelet aggregation but not collagen graft thrombosis in baboons.

Leech antiplatelet protein (LAPP) is a specific inhibitor of collagen-induced human platelet aggregation and adhesion to collagen under static conditions. Recombinant LAPP (rLAPP) and L-366,763 (acetylated-Cys-Asn-Pro-Arg-Gly-Asp-Cys-NH2), a peptidyl fibrinogen receptor antagonist, were evaluated in an anesthetized baboon thrombosis model using a collagen-coated graft segment of an arteriovenous shunt to elicit thrombus formation. Animals were randomized to receive systemic intravenous administration of rLAPP (100 micrograms.kg-1 x min-1; n = 5), L-366,763 (8.5 micrograms.kg-1 x min-1; n = 3), or saline (n = 3). Despite complete and selective inhibition of type I collagen-induced ex vivo aggregation of platelets, rLAPP had no significant effect on the rate or the extent of 111-In-labeled platelet deposition onto the collagen graft and no effect on template bleeding time. In contrast, L-366,763 completely prevented platelet deposition, maintained blood flow, and significantly prolonged bleeding time at the dosage that inhibited ex vivo aggregation in response to all agonists studied. In this study, the absence of an antithrombotic benefit of rLAPP contrasted sharply with the efficacy of the fibrinogen receptor antagonist. These results demonstrate that specific inhibition of collagen-mediated platelet aggregation alone is not sufficient to prevent platelet-dependent thrombosis in this baboon model.

Amino Acid Sequence

Immunocytochemical localization of platelets in baboon hepatic sinusoids using monoclonal mouse anti-human platelet glycoprotein IIIa following induction of thrombocytopenia.

A commercially available mouse monoclonal antibody to human platelet glycoprotein IIIa was used to demonstrate sequestration of platelets in hepatic biopsies obtained from baboons following intravenous infusion of echistatin, a novel fibrinogen receptor antagonist derived from the venom of the snake Echis carinatus. Biopsies of liver and spleen were taken prior to administration of echistatin. The hepatic biopsies were either snap-frozen in Freon-22/liquid nitrogen or fixed in 10% neutral buffered formalin. Biopsies of spleen were snap-frozen. During infusion of echistatin (2.3 micrograms/kg/min), circulating platelet counts decreased from 331,000/mm3 to 167,000/mm3. Selective sequestration within the liver was confirmed using whole body gamma camera imaging to demonstrate 111Indium-oxine labeled platelet accumulation within the liver during the thrombocytopenic episode. Hepatic biopsies were again taken and either snap-frozen in Freon-22/liquid nitrogen or fixed in 10% neutral buffered formalin. Biopsies of spleen and inguinal lymph node were also snap-frozen. Platelet rich plasma smears, included as positive controls, dewaxed paraffin sections, and cryosections of liver, spleen, and lymph node were stained with monoclonal mouse anti-human platelet glycoprotein IIIa using an avidin biotinylated peroxidase complex (ABC) technique. Prior to infusion of echistatin, platelet staining within the liver was minimal. After echistatin infusion, hepatic cryosections showed prominent platelet staining within hepatic sinusoids. No localization was shown in lymph node, however, the spleen showed prominent platelet staining both before and after echistatin infusion. Platelet rich plasma smears were intensely positive. No prominent platelet staining was observed in formalin-fixed, paraffin-embedded material. Thus, this immunocytochemical technique may help localize platelets in cryosections of tissues from baboons and other primate species.

Animals

Selective factor Xa inhibition by recombinant antistasin prevents vascular graft thrombosis in baboons.

A baboon model of high-shear, platelet-dependent vascular graft thrombosis was used to assess the antithrombotic effect of recombinant antistasin (rATS), a 119-amino acid protein with selective, subnanomolar inhibitory potency against coagulation factor Xa. In this model, a Dacron vascular graft segment of a femoral arteriovenous (AV) shunt provided the thrombogenic stimulus. Antithrombotic efficacy of rATS was assessed by continuous monitoring of 111In-labeled platelet and 125I-labeled fibrin(ogen) deposition onto the graft surface and blood flow through the vascular shunt. Systemic intravenous administration of rATS (2 or 4 micrograms/kg.min-1) dose dependently decreased both platelet and fibrin(ogen) deposition onto the graft. Vascular graft thrombus formation was completely inhibited at a systemic dose of rATS of 4 micrograms/kg.min-1. None of the AV shunts in animals receiving rATS at either dose occluded, and blood flow was maintained at 81 +/- 4% (2 micrograms/kg.min-1 rATS) or 96 +/- 3% (4 micrograms/kg.min-1 rATS) of basal flow. Systemic fibrinopeptide A elevations in response to exposure to the Dacron graft segment were completely suppressed by both doses of rATS. The ex vivo activated partial thromboplastin times were extended to greater than 150 seconds during infusion of both doses of rATS; however, even at fully antithrombotic doses, template bleeding times were not significantly increased. Thus, in this baboon model, rATS is a potent antithrombotic agent that inhibits both platelet and fibrin(ogen) deposition onto a Dacron vascular graft segment. Furthermore, these results demonstrate that selective inhibition of coagulation factor Xa by rATS can completely prevent vascular graft thrombus formation without significantly compromising primary hemostasis as measured by template bleeding time.

Animals

Antithrombotic efficacy of recombinant tick anticoagulant peptide. A potent inhibitor of coagulation factor Xa in a primate model of arterial thrombosis.

BACKGROUND: Tick anticoagulant peptide is a specific, potent inhibitor of blood coagulation factor Xa. The effects of recombinant tick anticoagulant peptide (rTAP) and standard heparin (SH) were compared in an anesthetized baboon model of arterial thrombosis where platelet deposition onto a Dacron vascular graft segment of an arteriovenous (AV) shunt was studied. METHODS AND RESULTS: Animals were randomized to receive systemic administration of SH (10 or 100 U/kg i.v. bolus followed by 0.4 or 1.0 U/kg/min i.v. infusion, respectively) or rTAP (6.25, 12.5, or 25.0 micrograms/kg/min i.v. infusion). rTAP, but not SH, caused a significant (p less than 0.05), dose-dependent reduction of indium-111 labeled platelet and iodine-125 labeled fibrin (ogen) deposition onto the graft. Deposition was not significantly increased from baseline values during infusion of 12.5 or 25.0 micrograms/kg/min of rTAP. Blood flow was maintained at 64 +/- 9, 95 +/- 2, or 97 +/- 2% of baseline following infusion of 6.25, 12.5, or 25.0 micrograms/kg/min of rTAP, respectively. Both SH and rTAP significantly (p less than 0.05) decreased the systemic fibrinopeptide A (FPA) elevation during exposure to the Dacron graft. rTAP was fully antithrombotic at APTT values of 42.6 +/- 2.4 seconds (less than twofold basal value), while SH had no antithrombotic efficacy despite APTT values greater than 150 seconds (greater than fivefold basal value). CONCLUSIONS: The demonstrated antithrombotic effect of rTAP in the absence of alterations in primary hemostasis suggests that controlling thrombin generation through inhibition of factor Xa may be a novel and effective pharmacological approach in the prevention of high-shear arterial thrombosis.

Animals

Cancer recurrent at stapled colon incision.

Recurrence of colon cancer at a stapled colotomy site separate from the anastomosis was discovered through a rising carcinoembryonic antigen (CEA). Resection resulted in cure. Exfoliation and implantation of cancer cells is discussed.

Adenocarcinoma

Vein patch angioplasty for brachial arterial occlusion after cardiac catheterization.

Brachial artery thrombosis may be encountered after cardiac catheterization using the Sones technique. Differing opinions have been reported regarding the optimal management of this injury. During the past five years, 20 patients have had surgical repair of the brachial artery after trauma from cardiac catheterization. Satisfactory results have been obtained in the majority of cases with local arterial thrombectomy and debridement with vein patch angioplasty. Arterial resection or vein bypass was needed in unusual cases. This injury should be repaired acutely to avoid long-term functional disability in all patients who present with a pulseless upper extremity.

Acute Disease

Extradural bupivacaine and methadone for extracorporeal shock-wave lithotripsy.

Combined extradural bupivacaine and methadone analgesia was investigated in 144 patients who underwent extracorporeal shock wave lithotripsy (ESWL). Patients were assigned randomly to one of three groups: group I--extradural 0.5% bupivacaine hydrochloride 0.75 mg kg-1; group II--extradural 0.1% methadone hydrochloride 4 mg after the bupivacaine; group III--as group II, plus a continuous extradural infusion of methadone 0.3 mg h-1 after operation. In all patients, only partial motor deficit occurred. During ESWL, patients who received extradural bupivacaine and methadone had significantly less pain compared with those who had bupivacaine alone (P less than 0.025). Extradural anaesthesia and immersion in the warm water bath were accompanied by only mild fluctuations in arterial pressure. After ESWL, significantly more patients with continuous methadone infusion were pain free (P less than 0.05) and they required less systemic analgesics. The anaesthesia during and after the ESWL procedure may be carried out safely and effectively by the administration of small doses of bupivacaine combined with methadone followed by infusion of the opioid.

Analgesia, Epidural

Unusual manifestations of brachiocephalic vascular disease.

Vascular problems involving the brachiocephalic vessels may occur from atherosclerosis, trauma, vasculitis, infection, and procedures for congenital heart disease. A wide variety of symptoms and signs may result from such disorders. This study is a report of five unusual manifestations of brachiocephalic vascular diseases. Diagnosis, management, and previous surgical experience is discussed relating to each case illustrating the complexity and variability of brachiocephalic vascular pathology.

Adult

Peroneal arteriovenous fistula. A complication of Fogarty catheter thromboembolectomy.

The Fogarty catheter is an important device used by vascular surgeons to simplify the surgical treatment of thromboembolic disorders. Complications from use of the catheter are rare. This case report is about a patient who developed a peroneal arteriovenous fistula following popliteal thromboembolectomy. The literature regarding this unusual injury is reviewed.

Angiography

Open chest cardiac massage: a review.

Open-chest cardiopulmonary resuscitation (CPR) is physiologically superior to all external CPR methods studied thus far (P. Safer, Ann. Emerg. Med., 13 (1984) 856). Open-chest CPR should again be taught to physicians, and used more often after prolonged cardiac arrest. An extensive review on open cardiac massage is presented herein.

Heart Arrest

Anaesthetic considerations in facial reconstruction for Down's syndrome.

Sixty-three patients with Down's syndrome underwent facial reconstructive surgery under general anaesthesia in order to improve their acceptability and potential for functioning effectively in society. Preoperatively, one-third of the patients had respiratory illnesses, 11 (17.5%) had cardiac anomalies, and 5 (7.9%) had endocrinological abnormalities. Anaesthesia was based on spontaneous ventilation of halothane and N2O in oxygen via an endotracheal tube with appropriate monitoring. Only one patient had an intraoperative complication, an episode of ventricular dysrhythmia, but postoperatively 9 patients required nasopharyngeal airways or endotracheal intubation in order to maintain a patent upper airway. The anaesthetic considerations for facial reconstructive surgery in Down's syndrome are discussed.

Adolescent

Prolonged bradycardia and hypotension after neostigmine administration in a patient receiving atenolol.

A 78-year-old woman admitted for an elective hip operation was maintained on atenolol for control of her hypertension. She received neostigmine and atropine for reversal of muscle relaxation at the end of general anaesthesia. She then developed prolonged bradycardia and hypotension which necessitated the use of adrenaline and isoprenaline. Such an adverse reaction with atenolol has not been described previously.

Aged

Shock-wave treatment for stones in the kidney and ureter. The Jerusalem experience.

We report on our first 6 months' experience with the extracorporeal shock-wave lithotripter (ESWL). During this period, 410 treatments were given to 350 kidneys and ureters. Our series was characterized by a particularly high proportion (40%) of multiple and large calculi and included 25 complete staghorns. The latter required multiple treatments (up to five), but no adjunct percutaneous nephrolithotomies were used in this series. A percutaneous nephrostomy was inserted in 20 cases. Thirty-six ureteric calculi above the pelvic level were treated in situ, with 95% success. The presence of a ureteric catheter is useful in these cases. Posttreatment pain was graded, and 61% of the patients did not require any analgesia. High-frequency jet ventilation was used in 91% of the 172 patients receiving general anesthesia and was of great value in minimizing respiratory-stone movement. The principal complication encountered was ureteric obstruction due to impacted particles. Temperature greater than 38 C occurred in 8.5% of the cases. It is suggested that the availability of the ESWL should encourage the early treatment of both renal and ureteric calculi, as well as enable the treatment of certain patients rejected for conventional surgery.

Adolescent

Early recognition and successful management of pelvic cellulitis following hemorrhoidal banding.

Reports have focused attention on a rare but potentially serious complication following rubber band ligation of internal hemorrhoids: pelvic cellulitis with progression to shock and death. This report documents the successful treatment of pelvic cellulitis. The timely use of broad-spectrum antibiotics at an early stage is critical. Emphasis is placed on early recognition and treatment of this potentially fatal complication.

Adult