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Biomedical subjects

D Harrison

Publications and source records attributed to D Harrison.

At least 145 records · Page 8Linked to original sources

Mediastinal lymph-node biopsy is a definitive staging procedure for bronchogenic carcinoma.

Mediastinal lymph-node biopsy has been performed as a staging procedure in most cases of bronchogenic carcinoma since 1965. This study was carried out to assess the results of staging by this method in 75 patients. Biopsy sites were marked with hemoclips. Three zones were defined: zone 3 (inoperable), beyond the midline and above the lower border of the aortic arch; zone 1 (operable), more than 3 cm from the carcinoma, ipsilateral to the tumour; and zone 2, between zones 1 and 3. Forty of 75 patients had biopsy specimens showing carcinoma. The proportion was highest in small cell anaplastic carcinoma and lowest in squamous cell tumours. Of the 40 positive biopsies 35 were from zone 3. All the positive biopsy specimens showing small cell anaplastic carcinoma were from zone 3. Positive specimens correlated strongly with other evidence of inoperability. Mediastinal lymph-node biopsy is a definitive staging procedure.

Adenocarcinoma↗

Ultrastructural and functional studies on prolonged myocardial preservation in an experimental heart transplant model.

The effect of ischemia with hypothermic cardioplegic preservation were studied in a heterotopic isograft rat heart transplant model. Hearts with ischemic time periods of 0.5, 4, 8, and 12 hours (n = 5 to 7 transplants per ischemic time period) were analyzed for structural and functional changes 50 days after transplantation. Postoperative recovery was prolonged with increasing duration of preservation times, but all transplants functioned normally 20 minutes and 50 days after transplantation. Function of right ventricular strips from graft and normal hearts were compared in a muscle bath. No differences were observed between baseline or isoproterenol-stimulated myocardium from all grafts or normal hearts. Electron and light microscopy studies of right and left ventricle and ventricular septum samples demonstrated marked fibrosis at 4, 8, and 12 hours of preservation with no differences between the 4, 8 and 12 hour grafts. There were no other differences in other features examined, including necrotic, mitochondrial, I-band, contractility, nuclear, endothelial cell, or intracellular lipid changes. We conclude that (1) except for significant fibrosis, transplants have normal structure and function after 4, 8, and 12 hours of preservation, (2) in assessing the efficacy of hypothermic cardioplegic preservation, chronic structural changes are more sensitive than functional changes, and (3) hypothermic cardioplegic preservation is feasible up to 12 hours but fibrosis may be the ultimate limiting factor in man.

Animals↗

Gastric emptying as a determinant of the oral glucose tolerance test.

Intraindividual variation in the results of repeated oral glucose tolerance tests in normal subjects is well recognized but incompletely explained. The present studies show that such variation can be produced by ingestion of the glucose solution during different phases of the normal fasting activity cycle of the upper gut. Such variation is not seen when glucose is administered intraduodenally during the same phases of activity. Gastric emptying shows similar variation with the activity cycle; larger volumes of solution were emptied from the stomach during activity than quiescence, thus presenting greater quantities of glucose solution to the small intestine for absorption. Metoclopramide and hyoscine butylbromide, drugs known to influence the rate of gastric emptying, reduced the variation in the glucose tolerance test. The data suggest na possible use of the glucose tolerance test for the assessment of gastric emptying.

Activity Cycles↗

Influence of congestive heart failure on prazosin kinetics.

The kinetics of oral prazosin was studied in 10 healthy normal subjects (NS) and in 9 patients with congestive heart failure (CHF). NS received a single 5-mg dose, and blood concentrations of prazosin (CB) were measured, using a specific HPLC assay, during an 8-hr period. CHF patients received a 2-mg dose after which CB was measured for 10 hr. These patients then received 2 to 5 mg prazosin every 8 hr for 48 hr. After the last dose of prazosin, CB was measured for 24 hr. After the initial dose, time to peak CB did not differ significantly between that of the NS (123 +/- 19 SEM min) and of patients with CHF (132 +/- 31.3 min). AUC/mg prazosin was greater (p less than 0.001) in patients with CHF (3,385 +/- 380 Ng x min/ml) than in NS (1,603 +/- 208 ng x min/ml). Elimination of prazosin from blood was slower in CHF patients (t1/2 = 374 +/- 33.4 min) than in NS (t1/2 = 144.5 +/- 4.3 min) (p less than 0.001). These data suggest that in patients with CHF the elimination of prazosin is substantially slower than in NS and therefore higher steady-state prazosin concentrations can be expected in CHF patients than in NS.

Administration, Oral↗

Interaction of Vinblastine with Calf Brain Microtubule protein.

The interaction of vinblastine with calf brain tubulin has been studied by velocity sedimentation, gel filtration, and fluorescence. It has been established that vinblastine induces the stable tubulin dimers to dimerize further to tetramers. The sedimentation patterns at low vinblastine concentration were analyzed by the ligand-induced dimerization theory of Cann and Goad ((1972) Arch. Biochem. Biophys. 153, 603-609). The association constant and stoichiometry for the binding of vinblastine to tubulin, determined by gel filtration and spectrofluorometry, were (2.3 +/- 0.1) X 10(4) liters/mol at 25 degrees and two vinblastine binding sites per tubulin dimer of molecular weight 110,000. The binding of vinblastine to tubulin is characterized by an enthalpy change of 5.8 kcal/mol and a positive unitary entropy change. Binding of vinblastine did not induce any significant conformational changes in tubulin as monitored by circular dichroism. However, the vinblastine-tubulin complex displayed an ultraviolet difference spectrum, which appears to reflect mostly the transfer of vinblastine to a less polar environment. Besides binding vinblastine, tubulin was shown to bind vincristine with identical free energy and stoichiometry and to have a single binding site for 8-anilino-1-naphthalene sulfonic acid per tubulin dimer, which is independent of those for vinblastine.

Animals↗

The significance of enzyme histochemical patterns in carcinomas of the large intestine in man.

The activities of 13 enzymes in 40 carcinomas of the large bowel have been studied using histochemical techniques. Five enzymes-non-specific esterase, monoamine oxidase, succinate dehydrogenase, cytochrome oxidase, and acid phosphatase-commonly show much less activity in the tumours than in adjacent normal colon. The tumours have been classified based upon the number of enzymes which show marked reduction in activity in each tumour (types 1-5). The enzyme histochemical type and the size of the tumours have been jointly correlated with the presence of lymph node metastasis. Small type 1 or 2 tumours do not appear to be associated with metastatic disease. Small type 5 tumours were commonly associated with secondary carcinoma in the lymph nodes. Large tumours (greater than 25 sq cm surface area) of any histochemical type were frequently associated with lymph node metastasis. Discussion of the possible reasons for these findings and their clinical significance is presented.

Acid Phosphatase↗

The questionable value of total glossectomy.

In a personal series of 104 patients with squamous cell carcinoma of the tongue, 14 patients were treated with total glossectomy and laryngectomy, and 2 were treated with total glossectomy alone. The high rate of local recurrence that occurred when partial glossectomy followed curative radiotherapy suggests that in selected patients total glossectomy is of value. Patients with more extensive tumors requiring total laryngectomy are rarely cured and the procedure entails serious rehabilitation problems.

Adult↗