Biomedical subjects

M E Cowen

Publications and source records attributed to M E Cowen.

7 recordsLinked to original sources

PubMed1992

Mucin gel formed by tumorigenic squamous lung carcinoma cells has Le(a)-X oligosaccharides and excludes antibodies from underlying cells.

Cells of cloned lines of human squamous lung carcinomas elaborate large glycoproteins that are associated with their tumorigenic potential. Two groups of clones (called Le(a)-X-positive and Le(a)-X-negative) were studied that either do or do not express the Le(a)-X oligosaccharide associated with large glycoproteins and mucins secreted by these clones. Le(a)-X-positive cells elaborate a mucin gel complex associated with their apical surfaces, which appears as a mosaic of extracellular plates. Clones of this type are tumorigenic in nude rodents when injected s.c. or when introduced into the lungs via intrabronchial aerosol. By contrast, the Le(a)-X-negative clones do not form extracellular plates and are not tumorigenic in the lungs or subcutaneously. We demonstrate that the extracellular plates of Le(a)-X-positive cells exclude antibodies from interacting with the underlying squamous lung carcinoma cells and may therefore exert an immunoprotective effect. In support of this possibility it was found that: (a) There is a substantial inflammatory cell infiltrate associated with regressing nodules of Le(a)-X-negative cells in nude rodent lung and subcutaneous nodules, while there is no observable infiltration associated with progressing Le(a)-X-positive tumors. (b) In the brain (an immunoprivileged site) tumors develop and progress when either Le(a)-X-negative or -positive cells are introduced.

Animals↗

PubMed1992

Lung tolerance to hyperthermia by in vivo perfusion.

In vivo isolated lung perfusion is a novel technique for targeting anticancer therapy to the lung while avoiding systemic toxicity as normal lung toxicity from the antitumour therapy becomes the limiting factor. This study was performed to investigate the effects of hyperthermia on lung function in an intact animal model in which both acute and subacute toxicity could be monitored. Dogs underwent in vivo isolated lung perfusion. A control group was perfused to a lung temperature of 37 degrees C (group 1) and two other groups were treated in an identical manner except that the perfusion temperature was 43 degrees-44.8 degrees C in group 2 and greater than 45 degrees C in group 3. An assessment of lung injury was performed pre-perfusion, immediately post-perfusion and 2 weeks post-perfusion by measurement of extravascular lung water (Qev), serotonin uptake and wet weight to dry weight ratio. Our findings showed that the lung was tolerant to hyperthermia up to about 44 degrees C for 1 h. Analysis of 4 animals who survived perfusion above 3/44.0 degrees C showed a highly significant decrease in serotonin uptake between pre- and post-perfusion values (82.4 +/- 1.2 vs 40.4 +/- 3.9, P less than 0.02); at 2 weeks serotonin uptake had returned to normal in all 3 dogs. Fulminating pulmonary oedema developed at temperatures over 45 degrees C. Serotonin uptake may be a sensitive predictor of thermal lung injury.

Animals↗

PubMed1992

Endoscopy assisted microthoracotomy: initial experience.

BACKGROUND: Although thoracoscopy has been used for diagnostic and minor therapeutic procedures for many years, there have been few reports of its use in performing major intrathoracic procedures, which have traditionally required formal thoracotomy. METHODS: Twenty one patients (M:F 1.2:1; mean (SD) age 47.1 (18.8), range 17-75 years) underwent endoscopic intrathoracic surgery. Eight had unidentified peripheral masses on the chest radiograph, eight required lung biopsy, and five had recurrent or persisting pneumothoraces. Under general anaesthesia a laparoscope attached to a video monitor was introduced into the chest. One or two additional stab incisions were made as needed for the introduction of standard surgical or endoscopic instruments and staplers. RESULTS: There were no complications or deaths, though one patient developed a second pneumothorax seven days after endoscopic pleurectomy, necessitating open pleurodesis. All patients were discharged home from two to six days after surgery (mean (SD) 3.7 (1.2) days). CONCLUSION: Endoscopic thoracic surgery is a safe and useful technique for certain cases. It merits further investigation and assessment.

Adolescent↗

PubMed1991

Irradiated nude rat model for orthotopic human lung cancers.

The development of improved animal models for biological and preclinical studies of human lung cancer is important because lung cancer is the leading cause of cancer death in the United States. To determine whether the Rowett nude rat could serve as an orthotopic (organ-specific) model of this disease, nude rats (CR: NIH-RNU), with and without 500 rads of prior gamma-irradiation, were implanted intrabronchially with 10(7) cultured cells from 3 human lung cancer lines. Without irradiation, the NCI-H460 large-cell undifferentiated carcinoma had a 54% take-rate, whereas the NCI-H125 adenosquamous carcinoma and A549 adenocarcinoma had take-rates of 7 and 33%, respectively; irradiation increased the respective take-rates to 100, 83, and 90%. In irradiated rats, tumor age versus weight measurements showed progressive growth for all three tumors, with growth rates in the order: NCI-H460 greater than A549 greater than NCI-H125, requiring approximately 3, 5, and 9 weeks, respectively, for average tumor sizes to exceed 500 mg. The small-cell carcinoma cell line NCI-H345 was implanted only into irradiated rats and resulted in more slowly growing tumors. Histopathological study showed all model tumor types to have histological characteristics consistent with the clinical tumors from which the cell lines were derived. Each tumor type had a different growth pattern, with some of the the A549- and NCI-H125-derived tumors metastasizing to contralateral lung and/or regional lymph nodes. There was no evidence for immunological rejection in irradiated, tumor-bearing rats. Nonirradiated, implanted rats without gross tumor exhibited peribronchiolar mononuclear cell infiltration with or without fibrosis, suggesting prior immunological rejection. The successful orthotopic growth of these 4 human lung cancer cell lines in irradiated nude rats suggests that this model could be useful for biological and preclinical studies of human lung cancer, both in intact rats and via ex vivo perfusion of their tumor-bearing lungs.

Animals↗

PubMed1990

The results of surgery for atrial septal defect in patients aged fifty years and over.

We examined the cases of 31 patients over the age of 50 years undergoing operative closure of isolated ostium secundum atrial septal defect. The lesion had been diagnosed in all cases prior to cardiac catheterization. To assess the importance of pre-operative data on surgical outcome, the patients were first divided into three groups according to mean pulmonary artery pressure (PAP): less than 16 mmHg (Group A), 16-30 mmHg (Group B) and greater than 30 mmHg (Group C). Symptomatic improvement occurred in all groups but more patients in Group C, although symptomatically improved, remained short of breath and in atrial fibrillation than in Group A. Patients in Group A had a higher actual forced vital capacity expressed as a percentage of the predicted value (FVCa/FVCp) than patients in Group B or Group C (P less than 0.015). There was a good correlation between FVCa/FVCp and percentage oxygen saturation of the arterial blood (P less than 0.0009). This simple non-invasive investigation was therefore found to correlate with previously documented parameters, pulmonary artery pressure and percentage oxygen saturation of the arterial blood, affecting surgical outcome. Patients were also divided into groups according to FVCa/FVCp: less than 75% (Group 1), 50-75% (Group 2) and less than 50% (Group 3). Postoperative symptoms were more common in Group 3 than in Group 1. We conclude that respiratory function tests, as well as measurement of pulmonary artery pressures, are useful in predicting improvement following atrial septal repair.

Arrhythmias, Cardiac↗

PubMed1990

Use of enoximone in weaning from cardiopulmonary bypass following mitral valve surgery.

Mitral valve surgery is often complicated by a postoperative low cardiac output state. In addition, some patients may have pre-existing pulmonary hypertension. Conventional inotropes, such as dopamine and dobutamine, tend to increase pulmonary vascular resistance. However, enoximone has both inotropic and vasodilatory properties. Ten patients, who had undergone mitral valve surgery and in whom weaning from cardiopulmonary bypass was unsuccessful without inotropic support, were treated with enoximone, 1 mg/kg loading dose plus 10 micrograms/kg/min continuous infusion, to assist in weaning from bypass. A significant and sustained increase in cardiac index was achieved without an increase in heart rate. At the same time, mean arterial pressure, systemic vascular and pulmonary vascular resistances were significantly decreased.

Aged↗

PubMed1990

Thoracic empyema: causes, diagnosis, and treatment.

Thoracic empyema is a disease that has been recognized for centuries. The principles of management as stated by Hippocrates remain more or less unchanged. Diagnosis can be masked by the underlying cause, preemptive antibiotic treatment, or the now frequently associated debilitating diseases. With no other specific investigation, the main diagnostic test remains diagnostic thoracentesis. When an empyema is encountered, the objectives are to save life; eliminate the empyema, its complications, and chronicity; return pulmonary mechanics to normal; and reduce the duration of the hospital stay. The introduction of antibiotics has dramatically influenced the spectrum of the disease now encountered. If the original infection is adequately treated, empyema rarely occurs. Penicillin has removed the major cause of empyema, and further developments in antibiotics now mean that the majority of empyemas occur when patients are disabled by other disease processes or malnutrition, or where there remains a delay in medical attention. These patients are often less able to withstand the prolongation of the infective processes that is sometimes encountered with the staged approach to treatment. Developments in operative and postoperative care have meant that these patients can best be treated by more aggressive and definitive surgical management.

Empyema↗