Biomedical subjects

T Dodson

Publications and source records attributed to T Dodson.

10 recordsLinked to original sources

PubMed1993

Lasting safe interruption of endarterectomy thrombosis by transiently infused antithrombin peptide D-Phe-Pro-ArgCH2Cl in baboons.

To evaluate the relative antithrombotic efficacy and hemostatic safety of antithrombin therapy for vascular thrombus formation at sites of mechanical vascular injury, we administered the potent and specific irreversible synthetic antithrombin D-PHE-PRO-ARG chloromethyl ketone (D-FPRCH2Cl) after performing carotid endarterectomies in baboons. The continuous intravenous infusion of D-FPRCH2Cl, 100 nmol/kg per minute for 1 hour, abolished acute carotid endarterectomy thrombosis for at least 48 hours. The plasma level of D-FPRCH2Cl during the infusion was maintained steady at 7.2 +/- 0.9 mumol/L, but decreased rapidly after discontinuing its infusion (T50 17 minutes). Platelet deposition, measured in real time using autologous 111In-platelet scintillation camera imaging, was 1.51 +/- 0.40 x 10(8) platelet/cm in the 14 treated animals 90 minutes postoperatively, compared with 11.7 +/- 1.16 x 10(8) platelet/cm in 14 heparin-treated controls (P < .002). The antithrombotic benefit was equivalent for treatment begun either 5 minutes before (nine animals) or 15 minutes after (five animals) reestablishing flow in the operated vessel, ie, 1.59 +/- 0.36 x 10(8) platelet/cm versus 1.35 +/- 0.51 x 10(8) platelet/min, respectively; P > .5. Endarterectomy thrombosis remained decreased for at least 48 hours postoperatively, as determined by the ratio between net 111In-platelet radioactivity at the endarterectomized site versus whole blood (ratio 0.82 +/- 0.25 in the treatment group v 3.03 +/- 0.51 in heparin controls at 90 minutes, P < .005; and 0.85 +/- 0.23 v 3.25 +/- 0.48 at 48 hours, P < .002). The marked reduction in endarterectomy thrombosis in treated animals at 48 hours was confirmed by scanning electron microscopy. Thrombin activity formed rapidly and became immediately bound to thrombus on thrombogenic segments in untreated control studies; treatment with D-FPRCH2Cl irreversibly inactivated the thrombus-bound thrombin. Hemostatic function, as measured by bleeding time (BT), activated partial thromboplastin time (APTT), and prothrombin time (PT) was impaired throughout the intravenous administration of D-FPRCH2Cl (BT > 30 minutes, APTT > 150 seconds, PT > 50 seconds); BT, APTT, and PT values were normal 30 minutes after discontinuing the infusions. As expected, blood loss into the surgical wound was substantial in nine animals receiving therapy initiated before restoring flow in the operated vessel (mean 95 mL, range 45 to 130 mL). By contrast, beginning D-FPRCH2Cl therapy in five animals 15 minutes after restoring arterial flow, a time when surgical hemostasis had been achieved, prevented excessive blood loss (mean 15 mL, range 10 to 35 mL; P < .01 compared with earlier treatment) without compromising the antithrombotic effects.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Chloromethyl Ketones↗

PubMed1993

Exteriorized chronic aorto-caval arteriovenous access shunts in the baboon (Papio cynocephalus).

A chronic arteriovenous (AV) blood access shunt has been developed in baboons. It is composed of silicone rubber tubing extensions bonded to vascular graft polytetrafluoroethylene (ePTFE) cuffs, for creating anastomoses with the distal aorta and inferior vena cava. Following surgical implantation, shunts remain patent for months (X = 9 +/- 2.5 months) and provides long-term ex vivo access to non-anticoagulated blood (Mean Blood Flow = 312 +/- 69 mL/min).

Animals↗

PubMed1992

Trigeminal somatosensory evoked potentials: a normal value study.

Normal somatosensory evoked potentials were obtained from the lower lip of 40 volunteers. Efforts were made to exclude artefact. A consistent triphasic wave form of three peaks and troughs was defined. There were greater variations in amplitude than latency between subjects. Statistically, one side of the lower lip can be used as a control for the contralateral side, but it may not be possible to have reliable normal values between subjects. Somatosensory evoked potentials may however represent an objective method of evaluating trigeminal sensory nerve function.

Adult↗

PubMed1991

Effects of angiotensin converting enzyme inhibition with cilazapril on intimal hyperplasia in injured arteries and vascular grafts in the baboon.

To determine the importance of angiotensin converting enzyme (ACE) activity in the development of arterial proliferative lesions in a primate model, the response to vascular injury was studied in five baboons treated with oral cilazapril (20 mg/kg/day) and in five untreated control animals. Each animal underwent three procedures: 1) carotid artery endarterectomy, 2) balloon catheter deendothelialization of the superficial femoral artery, and 3) surgical placement of bilateral aorto-iliac expanded polytetrafluoroethylene (Gore-Tex) vascular grafts. Cilazapril therapy was initiated 1 week preoperatively and continued throughout the study interval. At 1 and 3 weeks postoperatively, plasma ACE activity was inhibited by more than 96% versus control values. After animals were killed at 3 months, injured vessel and graft segments were evaluated morphometrically. Although the response between animals was variable, average cross-sectional areas of neointima did not differ between the cilazapril-treated and control groups at sites of carotid endarterectomy (0.26 +/- 0.12 versus 0.34 +/- 0.17 mm2, respectively; p greater than 0.5), femoral artery ballooning (0.15 +/- 0.08 versus 0.11 +/- 0.01 mm2; p greater than 0.5), or at graft anastomoses (1.86 +/- 0.50 versus 1.72 +/- 0.50 mm2; p greater than 0.5). Thus, cilazapril did not reduce intimal thickening over 3 months in these primate arterial injury models. However, a possible beneficial effect of cilazapril, which might be apparent at earlier time points or with larger animal groups, cannot be excluded.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1989

Temporomandibular joint: morphology and signal intensity characteristics of the disk at MR imaging.

Magnetic resonance (MR) imaging has been used in the temporomandibular joint (TMJ) primarily to define the disk position. This report examines altered morphology and signal intensity characteristics of the TMJ disk as they relate to the severity of internal derangement. Two hundred sixteen joints in 133 patients with a history of such derangement. were imaged with MR. Disk position, signal intensity, morphology, and the presence of osteoarthritis were determined for each joint. The normal disk was not anteriorly displaced and had a normal "bow-tie" shape. A grade 1 disk was anteriorly displaced and had a normal shape; a grade 2 disk was anteriorly displaced and had an abnormal shape. Forty (19%) joints were considered normal; none of these exhibited osteoarthritis. One hundred thirty-nine (64%) joints were grade 1; osteoarthritis was found in 17%. Thirty-seven (17%) were grade 2; osteoarthritis was found in 95%. All forty normal joints had high or intermediate signal intensity in the disk. Osteoarthritic joints had a higher percentage of disks with diminished intensity (P less than .0001). Severe or untreated osteoarthritis is known to be a complication of TMJ internal derangements; hence this grading system seems to correlate with the severity of internal derangement.

Adult↗

PubMed1987

Arteriographic assessment of patency of the inferior alveolar artery and its relevance to alveolar atrophy.

Patency of the inferior alveolar artery was investigated on 84 patients who had undergone selective external carotid angiography with digital subtraction. Patency of the artery was lost earlier in males than females, but the presence or absence of teeth did not appear to affect the outcome. The artery was visualized less well on patients with medical conditions that may predispose to early or excessive atherosclerotic disease.

Adolescent↗

PubMed1986

The effect of alloimmunization on recurrence in an experimental colon cancer model.

Primary bowel tumors were induced in Wistar/Furth (W/Fu) rats by 16 weekly injections of 1,2-dimethylhydrazine (DMH). After curative resection, 70% to 75% of control rats who receive no further treatment developed local or regional recurrence within 22 weeks. Rats immunized with three weekly subcutaneous inoculations of 1 X 10(6) irradiated (10,000 rad) Brown Norwegian (BN) X W/Fu F1 or Buffalo (Bu) tumor cells (both containing colon cancer tissue-type specific antigens [TSA] but differing from the W/Fu at Ag-B [histocompatibility] loci) developed recurrent tumor at a rate not significantly different from untreated or concurrent Ag-B antigen matched non-TSA treated controls. By 22 weeks after tumor resection, 63% of rats immunized with BN X W/Fu F1 colon adenocarcinoma and 52% of those immunized with Bu adenocarcinoma had recurred. Sixty-one percent and 44% were the respective recurrence rates for rats immunized with strain matched renal cell tissue. These data show nonspecific protection against tumor recurrence because of alloimmunization but clearly demonstrate the subordination of any beneficial colon cancer TSA immunotherapeutic effect by contained histocompatibility antigens. The problem of such nonspecific immune stimulation by alloantigen overriding an expected specific effect by TSA and possible alternative methods of immunization to prevent this phenomenon are discussed.

Animals↗

PubMed1985

Interleukin generation in experimental colon cancer of rats: effects of tumor growth and tumor therapy.

The capacity of inbred W/Fu rats bearing syngeneic colon carcinomas to generate interleukin(s) (IL) was studied during primary tumor growth, after tumor resection, and during postresection immunotherapy. During local tumor growth, there was a significant decrease in the capacity of the host's adherent mononuclear cells to generate IL-1 and of peripheral blood mononuclear cells to generate IL-2 (16.6 and 23%, respectively, when compared to control animals; P less than .01). The presence of regional metastases or large primary tumor burden resulted in a further sharp fall in IL generation (0.9 and 10% for IL-1 and IL-2, respectively, when compared to control animals; P less than .01). With the use of three different doses of tumor inoculum, inhibition of IL generation was shown to occur when tumors were barely palpable. Decrease in IL correlated with tumor growth and not with the initial number of tumor cells injected. Tumor resection resulted in a rise in IL-2 generation from 36 to 64% of control animals' levels. Postresection immunotherapy with the use of an active specific immunization protocol successfully modulated IL-2 production to normal in animals protected from tumor recurrence. Animals that developed recurrent tumors despite immunization exhibited a continued inability to generate IL (mean values of IL-2 production compared to controls: 184% in animals free of recurrence after immunotherapy, 1% in animals developing recurrent tumors after immunotherapy; P less than .01). These results suggested that alterations in IL generation may lead to immune unresponsiveness during tumor growth. Active specific immunotherapy protecting animals from recurrence after primary tumor resection may be predicated on the successful modulation of IL level generation by host immunocytes.

Adenocarcinoma↗

PubMed1984

Specific active immunotherapy with butanol-extracted, tumor-associated antigens incorporated into liposomes.

With the use of whole tumor cell vaccines in a rat colon cancer minimal residual disease model, we have recently demonstrated that although tissue type-specific tumor immunogens protect against recurrence in the absence of histocompatibility differences, these immunogens offer no predictable tumor-specific protection in the presence of such differences. We have therefore begun to test whether syngeneic and allogeneic rat colon cancer tumor-associated antigens (TAAs), when incorporated into the bilayers of liposomes, could function as effective immunogens in immunotherapy and immunoprotection models. Male Wistar/Furth (W/Fu) rats were inoculated with 5 X 10(6) DMH-W163 colon cancer cells. All nonimmunized animals died of widespread metastases within 2 weeks of complete local tumor resection. In experimental groups, four methods of immunotherapy were used after resection: (1) irradiated whole tumor cells, (2) butanol-solubilized membrane extracts containing TAA only, (3) liposomes only, and (4) liposomes containing TAA. Only animals receiving TAA incorporated into liposomes had a significant increase in survival (p = 0.026). Thirty percent remain disease-free 6 months later. In additional experiments, Buffalo rats were challenged with 1 X 10(6) Buffalo rat colon adenocarcinoma cells after immunization by irradiated whole tumor cells or liposomes and butanol-extracted colon cancer TAAs. Only animals in the group immunized with TAA incorporated into liposomes were significantly protected from subsequent tumor isograft challenge. These data provide evidence of a way to present solubilized colon cancer-associated immunogens that may be applicable in a more clinically relevant, allogeneic setting.

1-Butanol↗

PubMed1980

Vertebral arteriovenous fistulas following insertion of central monitoring catheters.

Iatrogenic vertebral arteriovenous fistulas were first reported in 1963. Since then, 20 additional cases have been reported--all following angiographic procedures. We report herein the first recognized cases of such fistulas resulting from percutaneous internal jugular and subclavian venous catheterizations performed for routine hemodynamic monitoring. The symptoms of late-occurring cervical bruit and thrill were identical to those described previously, although the ability to obliterate the thrill by pressure on the common carotid artery in one patient was inconsistent with other experience. These two patients were treated by direct ligation of the fistulous communication, after careful preoperative localization by angiography. Both patients have had complete disappearance of the symptoms and signs of the fistulas.

Adult↗