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Biomedical subjects

J D Cooper

Publications and source records attributed to J D Cooper.

At least 271 records · Page 15Linked to original sources

Development of a cytochrome P-450 monooxygenase system in clonogenic hemopoietic cells.

We characterized the presence of the monooxygenase arylhydrocarbon-hydroxylase (AHH), in mouse bone marrow cells taken directly from animals and from bone marrow colony culture. Using a standard radio-isotopic assay it was found that AHH activity was present in mouse bone marrow cells and that there was demonstratable activity in preparations taken directly from differentiated erythroid and myeloid colony cultures. Murine colonies of erythroid (CFU-E) and granulocytes (CFU-GM) were grown and AHH activity determined in non-induced and 3-methylcholanthrene (3-MC) induced cultures. Addition of 3-MC to erythropoietin dependent CFU-E was found to induce AHH activity above controls in a dose dependent manner, with 75 micrograms generating a maximal effect. CFU-E taken from different incubation periods (1-4 days) revealed that AHH was maximal in 2 1/2 day cultures and thereafter declined. In contrast, maximal AHH activity was obtained from 6-7 day CFU-GM and 40 micrograms of 3-MC stimulated the activity by 88%. These results demonstrate that AHH is present in normal mouse bone marrow cells and developing hemopoietic colonies, and that induction of AHH may indicate an important role for these cytochrome P-450 monooxygenases in cell development and differentiation as well as in the metabolism of various drugs.

Animals↗

A prospective evaluation of magnetic resonance imaging, computed tomography, and mediastinoscopy in the preoperative assessment of mediastinal node status in bronchogenic carcinoma.

Computed tomography, magnetic resonance imaging, chest roentgenography, and mediastinoscopy were compared prospectively as staging modalities to assess mediastinal node status in 84 patients with presumed operable bronchogenic carcinoma. Computed tomography was associated with a sensitivity of 71.0%, a specificity of 87.7% and an overall accuracy of 82.1%. Magnetic resonance imaging did not provide any advantage over computed tomography in the assessment of mediastinal node status. The accuracy of computed tomography was not dependent on cell type of the primary tumor. Although chest roentgenography had a sensitivity of 80.7%, the overall accuracy of 57.1% was unacceptably low. The sensitivity (87.1%), specificity (100%), positive (100%) and negative (93.0%) predictive values, and accuracy (95.2%) of mediastinoscopy exceeded those observed with all other modalities. We continue to recommend mediastinoscopy as the most accurate staging investigation in the routine management of patients with bronchogenic carcinoma.

Carcinoma, Bronchogenic↗

Automatic preparation of human serum samples for analysis of the drug enoximone and its sulphoxide metabolite using high-performance liquid chromatography.

A method for the estimation of the cardiotonic drug enoximone and its major sulphoxide metabolite, in serum, is described. The method uses a new technique for the preparation of biological material prior to the separation of analytes using high-performance liquid chromatography. This technique has been described as the automated sequential trace enrichment of dialysates (ASTED). The sample preparation process operates concurrently with the chromatographic separation. Aliquots of 500 microliters of serum are required for the analysis of serum from patients who have received a single 75-mg dose of enoximone. Within- and between-run coefficients of variation were found to be 2.8 and 3.9% for enoximone and 2.5 and 3.7% for enoximone sulphoxide. These values were obtained from estimating serum supplemented with enoximone and its metabolite, at concentrations of 0.5 and 1.0 mg/l, respectively.

Autoanalysis↗

Experimental en bloc double-lung transplantation.

A technique of en bloc double-lung transplantation through a median sternotomy has been developed. Hypothermic circulatory arrest was used after surface cooling in 7 puppies (mean weight, 3.1 kg; range, 1.5 to 4.1 kg). A double lung block, consisting of the two lungs, distal trachea, the main pulmonary artery, and a large cuff of left atrium, was removed from weight-matched donors. After the arrest of the circulation by inflow occlusion, bilateral pneumonectomies were performed in the recipient. The donor double-lung block was then implanted with anastomoses at the distal trachea, the posterior left atrium, and the main pulmonary artery. All animals were successfully rewarmed and had excellent hemodynamic function and gas exchange for periods of up to 24 hours. If primate experiments with long-term survival confirm these initial results, this procedure may have a role in the treatment of patients with end-stage respiratory disease but acceptable cardiac function.

Animals↗

Precision cautery excision of pulmonary lesions.

We have used a cautery dissection technique, initially described by Perelman, to facilitate nonanatomical pulmonary resections in certain instances in which the anatomical location of the lesion made wedge excision by standard methods difficult or impossible. With the precision cautery technique, the raw surface of the lung is left charred and allows minimum or no air leakage following the procedure. We have found this method a useful addition to existing techniques for pulmonary resection.

Electrocoagulation↗

Prospective evaluation of mediastinoscopy for assessment of carcinoma of the lung.

Between 1979 and 1984, mediastinoscopy was performed on 1,000 of the 1,500 patients admitted to the Thoracic Surgical Service of the Toronto General Hospital with the diagnosis of carcinoma of the lung. In 144 cases, concomitant anterior mediastinoscopy was also performed. Abnormal mediastinal nodes were found in 296 (29.6%). The overall complication rate was 2.3%, with no deaths. Mediastinoscopy revealed diseased nodes in 24% of patients with squamous cell carcinoma, 29% with adenocarcinoma, 54% with small cell undifferentiated carcinoma, 31% with large cell undifferentiated carcinoma, and 12% with bronchoalveolar carcinoma. Abnormal mediastinal nodes were found with equal frequency in right- and left-sided tumors and occurred in 31% of tumors in the main bronchus, 25% of upper lobe tumors, and 17% of lower lobe tumors. Of the 704 patients having negative results of mediastinoscopy, 590 were subjected to thoracotomy. Ninety-three percent underwent resection (85% curative, 7% palliative) and 7% had unresectable tumors. Of the resections, 20% were pneumonectomies. At thoracotomy, 52 of the 590 patients with negative mediastinoscopic results were found to have abnormal mediastinal nodes. Sixty-two of the 296 patients with positive results of mediastinoscopy were selected for thoracotomy. Eighty-six percent had resectable lesions (67% curative, 18% palliative) and 14% unresectable. The pneumonectomy rate in this group was 35%. These current data support our previous opinion that routine mediastinoscopy can be done with negligible morbidity and provides essential information for the classification and management of cancer of the lung.

Adenocarcinoma↗

Investigations of long-term treatment with perhexiline maleate using therapeutic monitoring and electromyography.

Experience is reported with 41 patients taking perhexiline maleate for angina pectoris for periods of up to 70 months, while serum concentrations of the drug were monitored, and liver function tests and electromyographic tests were made before and during treatment. Severe side effects did not occur unless serum perhexiline levels were greater than 1.5 mg/L. The drug seems effective for prolonged dosage, and the monitoring of weight, liver function test results, and serum concentrations should prevent or reduce toxicity. A starting dose of 100 mg daily is recommended. The drug is not recommended for routine use in angina pectoris.

Adult↗

Therapeutic monitoring of the anti-anginal drug perhexiline maleate.

Patients taking oral doses of perhexiline maleate have been examined. Measurement of serum perhexiline concentrations established that different dose requirements between patients were necessary due to the different doses at which drug saturation was achieved. Measurement of serum perhexiline concentrations are essential if side-effects from the drug are to be avoided.

Angina Pectoris↗

Radiotherapy alone for patients with operable carcinoma of the lung.

Between 1966 and 1980, 72 patients with operable carcinoma of the lung were treated primarily with radiotherapy because coexisting, nontumor related medical problem, or patient refusal prevented thoracotomy. We compared results obtained in this group with results obtained by thoracotomy in 123 consecutive patients over the age of 70, who were assessed in a similar fashion, but who underwent thoracotomy. All patients in both groups had proven, nonsmall cell carcinoma of the lung without clinical, laboratory, or radiologic evidence of tumor spread. All patients in both groups had a negative staging mediastinoscopy, and bronchoscopic findings consistent with operability. Many of the patients treated with radiotherapy had less than a curative dose as their general medical condition prevented a course of radical radiotherapy. It is apparent, however, that the results of radiotherapy for patients with operable carcinoma of the lung may be disappointing and that for patients who are marginal in terms of operative risk, the benefits of surgical resection may warrant the risks involved.

Actuarial Analysis↗

Contribution of circulating formed elements to prostanoid production in complement-mediated lung injury in sheep.

Incubation of plasma with zymosan results in complement activation. Infusion of this "zymosan-activated plasma" (ZAP) into the superior vena cava in sheep results in pulmonary leukostasis, pulmonary hypertension with generation of thromboxane (TXB), and hypoxemia. To examine the contribution of circulating formed elements to TXB generated when ZAP is infused, we studied four pairs of sheep in a cross-circulation model. Acetylsalicylic acid (ASA) irreversibly acetylates cyclooxygenase and blocks TXB production. Four hours after an intravenous dose of ASA (10 mg/kg), no circulating ASA was detectable by high-pressure liquid chromatography. Infusion of ZAP in ASA-treated animals resulted in no pulmonary hypertension and no rise in serum TXB levels. Treated animals were then cross-circulated with untreated sheep through cannulas that attached a carotid artery of each animal to a jugular vein of the other, creating simultaneous arteriovenous fistulas between the animals. A roller pump maintained cross-circulation flow at 450 ml/min for 15 minutes. This resulted in greater than 80% mixing of the circulating blood volumes of each pair of animals, verified by measurement of an intravascular marker. After cross-circulation the ASA-treated animals were still unable to generate TXB in response to ZAP infusion. Untreated animals had a typical response when infused with ZAP after cross-circulation, with elaboration of large amounts of TXB. Since the treated animals with circulating, nonaspirinated formed elements showed no response and the untreated animals with similar blood composition had a normal response, we conclude that circulating formed elements do not contribute significantly to the TXB recovered from sheep infused with activated complement components.

Animals↗

The stability of the o-phthalaldehyde/2-mercaptoethanol derivatives of amino acids: an investigation using high-pressure liquid chromatography with a precolumn derivatization technique.

The investigation of the stabilities of o-phthalaldehyde/2-mercaptoethanol derivatives of amino acids using a precolumn reaction technique and a high-pressure liquid chromatographic procedure is reported. The amino acid derivatives are shown to be stable on the high-pressure liquid chromatography column. Optimal conditions for the development of these derivatives for their separation using this technique are recommended.

Aldehydes↗

Bronchial omentopexy in canine lung allotransplantation.

Impaired bronchial healing has been a major source of morbidity and mortality following clinical lung transplantation. Bronchial ischemia secondary to division of the systemic bronchial blood supply may be an important cause of these complications. Bronchial omentopexy was performed in conjunction with lung allotransplantation in 6 dogs. Revascularization of the distal bronchial circulation through the omental pedicle was demonstrated in all instances by postmortem injection studies done through the celiac artery. Bronchostenosis occurred in 1 dog. No other complications were encountered. In view of the frequency of bronchial anastomotic complications following human lung transplantation, the technique of bronchial omentopexy warrants serious consideration.

Animals↗

Experience with primary neoplasms of the trachea and carina.

From 1963 to 1983, 44 patients presented with a primary tracheal neoplasm that was amenable to surgical treatment. Forty-two of the 44 tumors were malignant. Thirty-three patients were managed by resection and primary anastomosis. The following resections were done: trachea only, 12; trachea plus carina, 13; trachea plus cricoid cartilage, four; and trachea plus larynx, four. There were two operative deaths in these 33 patients. Prosthetic reconstruction with heavy-duty Marlex mesh was done in six patients. Three of the six died of erosion of the innominate artery during the postoperative period. In three patients with nonresectable tumors, a silicone-coated Montgomery T-tube provided transient but worthwhile palliation. In two patients with nonobstructive adenoid cystic carcinoma involving the subglottis, irradiation was chosen as the initial treatment, since resection would necessitate laryngectomy. Resection, including laryngectomy, may be required in the future. The following points are emphasized: (1) A majority of operable neoplasms can be resected through a cervical collar incision and median sternotomy. Median sternotomy is the optimal operative exposure in most neoplasms necessitating resection of the carina. (2) Partial resection of the cricoid with sparing of the recurrent laryngeal nerves and larynx is possible in some patients with primary malignant tumors involving the proximal trachea and subglottic region. (3) In patients with adenoid cystic carcinoma, resection may afford excellent, long-term palliation even when the resection is incomplete. Pulmonary metastases are common in patients with adenoid cystic tumors. However, they usually progress slowly, may remain asymptomatic for many years, and are not necessarily a contraindication to resection of the primary tumor even when they are synchronous. Our experience suggests that adjunctive radiotherapy is beneficial in patients with adenoid cystic carcinoma.

Anesthesia, Endotracheal↗

Cyclosporin and bronchial healing in canine lung transplantation.

Long-term bronchial anastomotic healing has been assessed in the canine lung transplant model with cyclosporin as the primary immunosuppressant. Early bronchial revascularization was achieved by wrapping an omental pedicle around the bronchial anastomosis. Ten dogs underwent left lung transplantation and six survived 100 days or more before being put to death. No significant bronchial complications occurred. Late bronchostenosis was not seen, despite four biopsy-proved rejection episodes in three of the dogs surviving past 100 days. Histologically, all anastomoses were well healed at autopsy. Cyclosporin was shown to be an effective immunosuppressant in this model and was associated with prolonged survival and low morbidity. Transplant lung function was assessed at 100 days by contralateral pulmonary artery ligation in five dogs and was satisfactory in the three animals that had not had rejection episodes. The findings support our belief that bronchial anastomotic complications after human lung transplantation are mainly related to the effects of immunosuppression with steroids and to the ischemia resulting from division of the bronchial circulation at the time of transplantation.

Animals↗

Extracorporeal gas exchange, lung transplantation, and the artificial lung.

The potential for lung damage from mechanical ventilation may be much greater than has been realized in the past. Prior studies of extracorporeal support in adults were carried out after patients had been subjected to high airway pressure and hyperventilation for several days. The studies by Gatinoni supported by Kolobow would suggest that earlier application of extracorporeal gas exchange to remove CO2 may be more effective in salvaging the lung, particularly if applied before ventilator-induced lung damage has occurred. These challenging studies, combined with the successful application of extracorporeal support in infants, should stimulate new investigations of extracorporeal support in adult respiratory failure. Extracorporeal support may be a valuable adjunct to lung transplantation if transient pulmonary failure occurs following that operation. However, lung transplantation for acute respiratory failure in a patient who is being supported with ECMO is not recommended. The feasibiilty of an implantable lung has been demonstrated in animals for short periods of time. Continuing studies in this area should be encouraged, particularly before the establishment of a lungless animal preparation to determine some of the nonrespiratory functions of the lung.

Animals↗

Results of surgical treatment for thymoma.

Ten years' experience with surgical treatment of thymoma in 52 patients is reported, 25 patients with myasthenia gravis and 27 without. Twenty-five patients had noninvasive tumors (Stage I) and 27 had invasive tumors (Stages II and III). Of the 52 patients, 29 had surgical resection as the only treatment and the remaining 23 had surgical resection with adjunctive preoperative or postoperative radiotherapy. Currently, 39 patients are alive (20 with myasthenia and 19 without), 10 are dead (none dying of myasthenia or tumor), and three patients have been lost to follow-up. The mean follow-up time for all patients was 5.6 years. There were no operative deaths in this series. The 5 year cumulative survival rate for the entire group of 52 patients is 81%; for patients with myasthenia it is 92%; and for those without myasthenia, 71%. This series suggests that the prognosis following resection of thymoma relates primarily to the stage of the tumor and is not significantly influenced by the presence or absence of coexisting myasthenia gravis. The improved survival rate, in contrast to a 1973 report, is a reflection of improved long-term medical management of myasthenia gravis and better postoperative supportive care.

Female↗