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Biomedical subjects

R Holt

Publications and source records attributed to R Holt.

At least 55 records · Page 3Linked to original sources
PubMed1990

Lysis of plasminogen activator-resistant platelet-rich coronary artery thrombus with combined bolus injection of recombinant tissue-type plasminogen activator and antiplatelet GPIIb/IIIa antibody.

Resistance of coronary occlusive thrombus to thrombolytic therapy, found in some patients with acute myocardial infarction, may be due to the presence of platelet-rich coronary clot. Reperfusion therapy in such patients may require the development and evaluation of alternative strategies in animal models. Therefore, platelet-rich coronary artery thrombus was developed by excision, eversion (inside out) and reanastomosis of a 1 cm segment of the left circumflex coronary artery in anesthetized dogs maintained on heparin antiocoagulation. Blood flow was restored in 25 of 27 dogs. Thrombotic occlusion of the everted segment graft with primarily platelet-rich thrombus or thrombus containing platelet-rich and erythrocyte-rich zones, persisting for at least 30 min, occurred within 4.5 +/- 3.5 min (mean +/- SD) in 20 of these 25 dogs. In 5 of these 20 dogs (group I, control), stable occlusion, as monitored with an ultrasound flow probe and coronary angiography, was maintained during a 2 h observation period. In group II (n = 5), intravenous bolus injections of recombinant tissue-type plasminogen activator (rt-PA) at a dose of 0.45 mg/kg body weight at four 15 min intervals did not cause reperfusion in four dogs and produced cyclic reperfusion and reocclusion in one dog. In group III (n = 5), a single intravenous bolus injection of 0.8 mg/kg of the F(ab')2 fragment of a murine monoclonal antibody (7E3) against the human platelet GPIIb/IIIa receptor [7E3-F(ab')2] produced stable reperfusion in two of the five dogs, whereas occlusion persisted in the other three. In group IV (n = 5), injection of 7E3-F(ab')2 (0.8 mg/kg) followed by rt-PA (0.45 mg/kg) caused stable reperfusion without reocclusion in all dogs (p less than 0.05 versus rt-PA alone and p less than 0.01 versus control). This study confirms that platelet-rich occlusive coronary thrombus is very resistant to lysis with intravenous rt-PA. However, this resistance may be overcome by the combined use of a reduced dose of rt-PA and the antiplatelet GPIIb/IIIa receptor antibody 7E3. The results indicate that platelet-rich thrombus resistant to thrombolytic agents may be dispersed pharmacologically without resort to mechanical recanalization. The present dog model may be useful in investigating specific strategies for the dispersion of resistant platelet-rich coronary thrombus.

Animals↗
PubMed1990

Comparative effects of aspirin, a synthetic thrombin inhibitor and a monoclonal antiplatelet glycoprotein IIb/IIIa antibody on coronary artery reperfusion, reocclusion and bleeding with recombinant tissue-type plasminogen activator in a canine preparation.

The comparative effects of intravenous aspirin, the synthetic thrombin inhibitor (2R,4R)-4-methyl-1-[N2-(3-methyl-1,2,3,4-tetrahydro-8- quinolinesulfonyl)-L-arginyl]-2-piperidinecarboxylic acid monohydrate (Argatroban) and F(ab')2 fragments of monoclonal antibody 7E3 against platelet glycoprotein IIb/IIIa (7E3-F[ab']2) on thrombolysis, reocclusion and bleeding associated with 0.45 mg/kg body weight bolus injections of recombinant tissue-type plasminogen activator (rt-PA) were studied in a canine coronary artery thrombosis model. Coronary patency was monitored for 2 h both by flow probe and by coronary angiography. Four groups were studied: Group I = pretreated with 17 mg/kg intravenous aspirin (n = 6), Group II = pretreated with 200 micrograms/kg per min intravenous Argatroban for 60 min (n = 5), Group III = pretreated with aspirin and Argatroban (n = 5) and Group IV = pretreated with 0.8 mg/kg intravenous 7E3-F(ab')2 (n = 5). In Group I, reflow occurred in four of six dogs, but did not persist; reflow was induced in Group II in four of five dogs, persisting in one; in Group III, reflow occurred in all five dogs, persisting in four; in Group IV reflow was achieved in four of five dogs, persisting in two. The frequency of persistent reflow in Group III was significantly higher than in the combined Groups I and II (p = 0.012), whereas the time to reflow was significantly shorter in the groups receiving Argatroban than in the aspirin group (median 25 versus 55 min, p = 0.04). There were no significant differences between Groups III and IV.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Pharmacodynamic study of F(ab')2 fragments of murine monoclonal antibody 7E3 directed against human platelet glycoprotein IIb/IIIa in patients with unstable angina pectoris.

The pharmacodynamics of intravenous bolus injections of 0.05, 0.10, 0.15, and 0.20 mg/kg of F(ab')2 fragments of the murine monoclonal antibody 7E3, 7E3-F(ab')2, directed against the glycoprotein IIb/IIIa (GPIIb/IIIa) receptor of human platelets, were studied in groups of four patients with unstable angina pectoris. With 0.20 mg/kg, the template bleeding time prolonged from 6.3 +/- 1.9 (mean +/- SD) to greater than 30 min; it subsequently decreased to 13 +/- 7.8 min after 12 h and to 8.3 +/- 1.5 min after 24 h. The number of unblocked GPIIb/IIIa receptors (preinfusion value, 32,000 +/- 3,000 per platelet) decreased to 13 +/- 7% of the preinfusion value 1 h after infusion, and then increased to 33 +/- 10% at 12 h, 44 +/- 8% at 24 h and 67 +/- 7% at 72 h. The logarithm of the bleeding time was inversely proportional with the residual GPIIb/IIIa receptors (r = 0.73, P less than 0.0001). ADP-induced platelet aggregation (measured by changes in light transmittance in percent) decreased from 60 +/- 5% before infusion to 1.5 +/- 3% 1 h after infusion; it then increased to 29 +/- 3% after 24 h and 39 +/- 6% after 72 h. Platelet counts decreased by 16% at 1 h and returned to control values within 24 h. Proportionally smaller effects were seen at lower doses of 7E3-F(ab')2. Antibody injection did not induce spontaneous bleeding. Angina was not observed during the first 12 h when the bleeding time was significantly prolonged, but occurred in 6 of the 16 patients within the next 3 d. 2 of the 16 patients developed low titers of IgG antibodies specific for 7E3-F(ab')2. Thus 7E3-F(ab')2 induces dose-related inhibition of platelet function; at a dose of 0.20 mg/kg, it causes profound inhibition of platelet aggregation and prolongation of the bleeding time, but no spontaneous bleeding.

Adult↗
PubMed1990

Characterization of the subgingival microbial flora around endosteal sapphire dental implants in partially edentulous patients.

The microbiota associated with oral endosteal sapphire ceramic implants was studied using cultural methods. Samples were taken from both implant and control (tooth) sites, and comparisons were made between healthy and diseased and between implant and control sites. Diseased sites harbored a microbiota with a large number and proportion of Gram-negative anaerobic rods, black-pigmented Bacteroides, and surface translocating bacteria. Healthy sites in the same patients had smaller amounts of bacteria dominated by facultative Gram-positive cocci and rods. The microbiota in diseased and healthy implant and control sites was very similar. It is suggested that peri-implant tissues behave very similarly to periodontal tissues and that peri-implantitis lesions should be considered as site-specific infections harboring a high number of periodontal pathogens, mainly Gram-negative anaerobic rods.

Aluminum Oxide↗
PubMed1990

Emotional and behavioral predictors of preschool peer ratings.

It was predicted that social cognitive, behavioral, and affective aspects of young children's social development would predict stable peer ratings of their likability. Measures of likability, emotion knowledge, prosocial and aggressive behavior, peer competence, and expressed emotions (happy and angry) were obtained for 65 subjects (mean age = 44 months). Sociometric ratings, particularly negative, were stable over 1- and 9-month time periods. Correlational analyses showed that emotion knowledge and prosocial behavior were direct predictors of likability. Prosocial behavior mediated the relations of gender and expressed emotions with likability (i.e., gender and expressed emotions were each related to prosocial behavior, and prosocial behavior was related to likability, but neither gender nor expressed emotions were related to likability with prosocial behavior partialled out). Knowledge of emotional situations similarly mediated the age-likability relation. Results uphold the early development of stable peer reputations and the hypothesized centrality of emotion-related predictors of likability.

Child, Preschool↗
PubMed1988

Intraoperative radiation therapy of hepatic metastases: technical aspects and report of a pilot study.

Surgical resection of hepatic metastases offers long-term survival, and possible cure, for selected patients with colorectal carcinoma. Fifty percent of patients considered candidates for resection are found to have disease confined to the liver. The resections necessary are often more extensive than predicted preoperatively, which provides an opportunity for innovative approaches using radiation therapy. The intraoperative radiation therapy technique presented here offers the ability to control multiple metastatic deposits in patients not deemed resectable. This is achieved using remote afterloading interstitial (Ir-192) radiation therapy to deliver tumoricidal radiation doses to limited volumes within the liver. The technique was used to treat 11 patients in a pilot study, delivering radiation doses of 20 Gy to the periphery of predetermined target volumes in a single treatment. The number of metastatic deposits treated ranged from 2 to 11 separate tumors with maximum diameters from 3 to 9 cm (median 6 cm). Hospitalizations were from 6 to 23 days (median 8) with only one patient experiencing a surgically related complication (wound dehiscence and pneumonia). There were no radiation related complications on follow-up to 18 months. Biopsies of two treated sites in a patient undergoing reoperation confirmed control of tumors by this procedure. This technique is offered as a standby procedure to patients undergoing exploration for hepatic resection at our institution.

Aged↗
PubMed1986

Dental implants.

Explore the source record for details and available documents.

Aluminum Oxide↗
PubMed1986

Modified radical mastectomy with immediate breast reconstruction.

The authors reviewed 100 consecutive patients with breast cancer treated by modified radical mastectomy and immediate breast reconstruction in order to assess the safety and efficacy of this procedure in terms of cancer control. The study began in 1978 and is continuing. The procedure involves a two-team approach with both the general surgeon and the plastic surgeon interviewing the patient preoperatively. Virtually all breast reconstruction involved the use of a submuscular silicone saline type of implant. The median follow-up is 36 months. Slightly over half of these cases were Stage 0 or Stage I. There have been eight recurrences, including five local or regional and three distant. No patient has died of her disease at this point. Cosmesis was equal to or superior to that seen in delayed breast reconstruction. There have been no hidden recurrences. Postoperative depression has been significantly less. We conclude that modified radical mastectomy with immediate breast reconstruction is a safe and effective alternative to modified radical mastectomy alone.

Adult↗
PubMed1980

The early serological detection of colonisation by Staphylococcus epidermidis of ventriculo-atrial shunts.

Simple quantitative serological tests demonstrating Staphylococcus epidermidis agglutinins and C-reactive protein were used for the early detection of ventriculo-atrial shunt colonization by this organism. Tests in normal children and adults in various age groups throughout life confirmed Bayston's ovservations that those tested attained a titre up to 1:160 TO S. epidermidis agglutinogen. In contrast, the titre in children with colonised shunts and in adults with S. epidermidis endocarditis, both conditions which are usually accompanied by bacteraemia, rose to much higher levels, sometimes up to 1:5120. The routine combination of both tests has proven to be of considerable diagnostic value, particularly in early or recent colonisation.

Adolescent↗
PubMed1978

Civilian ground and air transport of adults with acute respiratory failure.

The intermountain Respiratory Intensive Care Unit (IRICU), established in 1973 at the LDS Hospital in Salt Lake City, provides specialized care for adults and older children with severe respiratory failure in the intermountain West. Because of the large area serviced by the IRICU, a transportation system for the critically ill was developed. Our report describes the transport system, including team organization, techniques, and experiences. Of 44 attempted transports during the last three years, 43 (98%) were safely accomplished without obvious ill effect to the patient. Patients with severe respiratory failure, if their conditions are adequately stabilized, can be safely transported hundreds of kilometers by ground and air by a well-equipped and well-trained team of physicians and nurses.

Acute Disease↗
PubMed1977

Growth of a heterologous tumor cell line in neonatal rats with graft-versus-host disease.

The ability of a hamster tumor cell line (T20) to grow and exhibit type H virus particles was significantly enhanced in neonatal DA rats with graft-versus-host disease (GVHD). Tumor growth peaked on days 4 and 7 in control littermates receiving adult syngeneic cells or no cells at birth, respectively, and then subsequently disappeared. However, tumor nodules in animals with GVHD became significantly larger than those in controls by day 7 and continued to grow until death. In addition, a marked plasma cell infiltration was noticed in such rapidly growing tumors from animals with GVHD only. In the light of previous studies, evidence is discussed for an environment within animals with GVHD conducive for tumor cell growth because of a depletion of T-cell areas within their tissues.

Animals↗
PubMed1976

Ultrastructural features of the verruciform xanthoma.

The verruciform xanthoma, a rare lesion of the oral cavity, was studied by light and electron microscopy. The major cell type associated with the lesion was shown to contain appreciable amounts of lipid and was characterized as a macrophage. It was characteristic of the endothelial cells associated with subepithelial capillaries to exhibit multiple basal laminae. A rather unusual observation was the migration of lipid-filled cells into the stratum germinativum of the overlying epithelium.

Adult↗