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Biomedical subjects

J Pym

Publications and source records attributed to J Pym.

16 recordsLinked to original sources

Establishment and characterization of a panel of human lung cancer cell lines.

The establishment and characterization of 11 human lung cancer cell lines are described in this article. Nine of these cell lines were established over a 5-year period, from 1983 to 1988, from patients treated at the Kingston Regional Cancer Centre. These include eight definite or probable small cell lung cancer (SCLC) lines and one adenocarcinoma line. In addition, two other SCLC cell lines were characterized. All of the lines have been in continuous culture for more than 2 years. The clinical histories of the patients from whom the cell lines were derived are outlined here. Several features of the cell lines are presented, including the following: (1) a comparison of the histologic features of the cell lines with the original biopsy specimens; (2) the expression of various markers, including cytokeratin, carcinoembryonic antigen, calcitonin, and neuron-specific enolase; (3) activities of the enzymes l-dopa decarboxylase and the brain isoenzyme of creatine kinase; (4) growth characteristics; (5) cloning efficiency in soft agar; (6) tumorigenicity in nude mice; and (7) cytogenetic studies. These cell lines, obtained directly from patients with a spectrum of drug-sensitive and drug-resistant tumors, will be valuable in vitro models of sensitivity and resistance to chemotherapy in lung cancer.

Adenocarcinoma

Chemosensitivity testing of small cell lung cancer using the MTT assay.

A simple colorimetric test, the MTT assay, has been adapted for chemosensitivity testing of human small cell lung cancer cell lines, and fresh tumour samples. Optimal conditions for clinical chemosensitivity testing were determined using established SCLC lines. Nineteen different chemotherapeutic agents were tested, and sixteen of them were found to be cytotoxic in this assay system. The drug sensitivity of a panel of 16 SCLC cell lines was measured and compared. There was very little intraexperiment variation, but the interexperiment variation was significant. Cell lines which were derived from patients who had not received chemotherapy at the time the cell line was established were more sensitive (to all but one of the drugs) than lines derived from treated patients, and the differences were statistically significant for two of the drugs. One cell line, NCI-H209, which was derived from an untreated patient, stood out as being the most sensitive or among the most sensitive to all of the drugs tested. Another cell line, H69AR, which is a multidrug resistant subline of the cell line NCI-H69, was the most resistant to many of the natural product drugs tested. Multiple drug chemosensitivity testing was performed on eight fresh tumour samples from SCLC patients (five pleural effusions, one lymph node, and two primary tumours). It was possible to perform chemosensitivity testing on all of the clinical samples in which sufficient tumour cells were available. The drug sensitivity of the clinical samples was, in most cases, within the same range as for the cell lines. Since this assay is very rapid and simple to perform, it may have practical applications in clinical drug sensitivity testing of human tumours.

Antineoplastic Agents

Adrenoceptors of the human internal thoracic artery.

Adrenoceptor function in the human internal thoracic artery (ITA) was characterized in vitro using segments of the artery obtained during coronary bypass operations. Specimens were prepared as isolated arterial rings mounted in a tissue bath, and mechanical activity (isometric tension) was measured in response to drugs. The ITA responded to phenylephrine (PE), epinephrine, and norepinephrine with concentration-dependent contractions. The PE-induced contractions were antagonized by phenoxybenzamine, prazosin, and high concentrations of yohimbine. The ITA was not effectively contracted by clonidine in the concentration range normally associated with alpha 2-adrenoceptor stimulation. The beta-adrenoceptor agonist, isoproterenol, had a weak and variable effect on the ITA; samples from 9 out of 12 subjects did not respond to isoproterenol, whereas samples from 3 subjects responded with relaxations of between 33 and 42%. These in vitro studies indicate that the most important adrenoceptors of the human ITA are alpha-adrenoceptors; this may be relevant for the pharmacologic management of patients undergoing coronary bypass surgery using the ITA.

Adrenergic alpha-Antagonists

A possible role for antiphospholipid antibodies in acquired cardiac valve deformity.

We studied the frequency of antiphospholipid antibodies (aPL) in patients undergoing cardiac valve replacement, and present the results in the context of the pathology of the valve lesions. Forty-eight consecutive patients undergoing valve replacement were studied. Of the whole group, 15 (31%) had antibody levels greater than 2 SD above the mean for a control group of healthy persons and 11 (23%) had a level of greater than 3 SD. There was an increased frequency of elevated antibody levels in patients with valves showing fibrocalcific change and a significant association between aPL and valve thrombus. The possible role of these antibodies in the pathogenesis of the valve lesions is discussed.

Aged

Contemporary operative management of pulmonary metastases of colorectal origin.

The management of patients with metastatic disease from primary carcinoma of the colon and rectum is still controversial. To evaluate the results of resection of pulmonary metastases from patients with colorectal primaries, a retrospective study of all patients who underwent such resection was carried out at the teaching hospitals of McGill University and Université de Montréal. A total of 345 patients admitted with pulmonary metastases; 27 of them underwent pulmonary resection with the extent of the resection varying from wedge excision of the metastatic nodule to pneumonectomy. In 25 of the 27 patients the resection was considered curative. Eight of the 27 patients had resection of two metastatic lesions while the remaining 19 patients had resection of solitary lesions. The interval between resection of the primary colorectal malignancy and the resection of the metastatic lesion (disease-free interval) varied from 2 to 77 months with a median interval of 35 months. The five-year survival following resection of pulmonary metastases was 21 percent. A prolonged interval between treatment of the primary and resection of the pulmonary metastasis was associated with a longer survival. This retrospective study demonstrates that prolonged survival can be achieved following resection of pulmonary metastases from colorectal carcinoma.

Adenocarcinoma

Use of the MTT assay for rapid determination of chemosensitivity of human leukemic blast cells.

A microcytotoxicity assay employing a tetrazolium salt has been adapted for testing the response of human leukemic blast cells to a variety of chemotherapeutic agents. After exposure to various concentrations of drugs, the viability of fresh leukemic blast cells was measured using a tetrazolium salt, MTT, which is converted to blue formazan crystals by living cells. The amount of formazan produced was quantitated using a microtitre plate spectrophotometer. In the present study, optimal conditions for chemosensitivity testing of human leukemia samples were determined, and the relative chemosensitivity of five patient samples was tested.

Antineoplastic Agents

Cardiac tamponade complicating anaesthetic induction for repair of ascending aorta dissection.

A case is described of a 69-year-old woman with dissection of the ascending aorta who developed cardiac tamponade during induction of anaesthesia. The tamponade was diagnosed by a haemodynamic profile showing approximation of the central venous, pulmonary wedge and pulmonary arterial diastolic pressures, and was treated with rapid surgical intervention and drainage of the haemopericardium. Cardiac tamponade and dissecting aneurysms of the ascending aorta are conditions with contrasting anaesthetic considerations and the problems encountered are discussed.

Aged

Gastroepiploic-coronary anastomosis. A viable alternative bypass graft.

Although increasing use is being made of arterial grafts (the internal mammary arteries) for direct myocardial revascularization, it is frequently not possible to reach the posterior surface of the heart with the internal mammary as either a pedicle or a free graft. Since June 1984 we have used the right gastroepiploic artery in nine patients as a pedicle graft to the distal right coronary artery (four patients), the posterior descending artery (three patients), and the distal circumflex branches (two patients). Eight patients survived the operation. Celiac axis opacification confirmed patency in six and coronary angiography strongly suggested patency in the remaining two. All survivors are functionally in New York Heart Association Class I or II. The early angiographic and clinical results demonstrate the feasibility of using the right gastroepiploic artery as a bypass graft to coronary vessels on the posterior surface of the heart when traditional conduits are unsuitable. If its long-term patency as a living arterial graft is similar to that of the internal mammary arteries, the gastroepiploic artery may become the coronary bypass graft of choice for the distal right coronary and circumflex systems.

Aged

Simultaneous use of membrane oxygenation and high-frequency jet ventilation in acute pulmonary failure.

A 16-yr-old female suffering acute, rapidly progressive combined respiratory and cardiac failure that was unresponsive to conventional volume-cycled ventilation, was stabilized with the simultaneous short-term use of veno-venous membrane oxygenation and high-frequency jet ventilation. Percutaneously introduced cannulas afforded rapid vascular access for membrane oxygenation, minimal wound problems during the perfusion, and easy decannulation. This is the first reported combined use of high-frequency jet ventilation and extracorporeal membrane oxygenation, and the first reported percutaneous initiation of veno-venous bypass. The patient remained alive and well 4 months after therapy.

Acute Disease

Hemolytic anemia following insertion of Ionescu-Shiley mitral valve bioprosthesis.

Hemolytic anemia is a relatively common complication after the replacement of cardiac valves with mechanical prostheses; the prevalence rate varies from 38% to 85%, depending on the prosthesis implanted. However, cardiac valves fabricated from biologic material are associated with a reduced incidence of hemolytic anemia, and to the authors' knowledge this report is the first to document hemolytic anemia in a patient who had the mitral valve replaced with an Ionescu-Shiley valve. The anemia was not associated with evidence of hemodynamically important mitral regurgitation and was ultimately controlled by iron and folate supplements.

Aged

Permanent cardiac pacing after open-heart surgery: acquired heart disease.

Retrospective review of 5,942 patients who underwent open-heart surgery for acquired heart disease revealed that 123 patients (2.1%) required permanent cardiac pacing postoperatively; 4.6% of these underwent predominantly valvular surgery and 0.6% had coronary bypass. The most important factors appeared to be: 1) preoperative evidence of a conduction disorder; 2) advanced patient age; 3) dense calcium in the aortic annulus; 4) valvular surgery and, especially, tricuspid valve surgery; and 5) poor myocardial protection. Postoperative permanent pacing had a considerable impact on patient morbidity from maintenance operations; most complications were lead-related problems.

Adult

Initial experience with universal pacemakers.

Thirty-five patients were implanted with the Sequicor DDD pacemaker between September 1, 1981 and March 1, 1982. The mean age was 61.7 years (range, 17-88). According to their ECGs, the patients fell into two distinct groups--those with A-V block and those with sick sinus syndrome. Our initial experience has indicated an excellent electronic component function (except for 1 discrepant reed switch); high battery drain of the Sequicor; complications similar to those seen with DVI or VVI pacing; and an increase in the hemodynamic benefits resulting from DDD as compared to DVI or VVI pacing in 70% of patients.

Adolescent

The hemodynamic and metabolic response to pacing after aortocoronary bypass.

Long-term follow-up of aortocoronary bypass has shown good preservation of ventricular function. However, myocardial reserve in the immediate postoperative period may not be optimal. Nineteen patients who underwent elective aortocoronary bypass protected with cold potassium cardioplegia were studied in the early postoperative period at rest and during the stress of atrial and ventricular pacing. Performance was assessed by hemodynamic, metabolic and nuclear angiographic measurements. In the first 2--6 hours after aortic cross clamping, myocardial performance was preserved at rest and there was no evidence of ischemic metabolism. Atrial pacing at a rate of 119 beats/min caused a significant increase in cardiac index (p less than 0.01) without deterioration in hemodynamics, ejection fraction or metabolic status. At the same rate, ventricular pacing did not change the cardiac index and there was a decrease in hemodynamic function. Ejection fraction decreased from 56% to 44% (p less than 0.05) without a change in end-diastolic volume. Lactate, pyruvate and beta hydroxybutyrate extractions were changed to net production. Ventricular performance was preserved at rest immediately after aortocoronary bypass done with multidose cold potassium cardioplegia, with adequate reserve to meet the stress of atrial but not ventricular pacing. We conclude that the therapeutic implications of the type of pacing selected in the immediate postoperative period may be important.

Atrial Function

A new surgical technique to correct double chambered right ventricle associated with anomalous left anterior descending coronary artery.

A 42 year old woman with symptomatic double chambered right ventricle had the additional features of an anomalous left anterior descending coronary artery and attachment of the tricuspid valve to the area of subinfundibular stenosis which precluded conventional repair. A non-valved Dacron conduit was used to bypass the obstruction. The patient is asymptomatic two years later.

Adult