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Biomedical subjects

M E Cowen

Publications and source records attributed to M E Cowen.

36 records · Page 2Linked to original sources
PubMed1996

A guide for planning community-oriented health care: the health sector resource allocation model.

The objective of this study was to demonstrate the value of a planning model for the design and evaluation of community health services. The health status of Washtenaw County, Michigan was modeled. Data were obtained from the Michigan Department of Public Health, Medstat Systems, and the medical literature for 32 diseases or conditions, representing approximately 85% of causes of death and 56% of medical payments (excluding medication costs). An expanded life-table approach was used for 16 age-and sex-matched cohorts exposed to a disease attack rate, access-to-care rate, case fatality rate, morbidity, and costs. Rates can be modified to reflect changes due to treatment, secular trends, or prevention programs. Two alternative delivery methods were considered to show the potential impact of reducing cardiovascular deaths (worksite initiative), or increasing utilization of services (lay health promotion) on county health status and costs over time. Deaths, bed days, and annual medical payments were the main outcome measurements. Cardiovascular and cancer conditions are and will be the primary causes of death in this population. The most important causes of bed days are musculoskeletal conditions, chronic obstructive pulmonary disease, accidents, strokes, and depression. The major health-care payments are for angina pectoris and/or other cardiac conditions, musculoskeletal conditions, accidents, prenatal care, and/or childbirth, and depression. The two alternative scenarios illustrate how reductions in mortality are not necessarily equated with similar improvements in morbidity or costs. This model presents an overview of the current and projected health status of a community. With such a planning tool, a community can better understand the impact of potential prevention or intervention programs, and help design its health-care system within the constraints of available resources.

Cause of Death↗
PubMed1995

Time-related effects of enzymatic disaggregation on model human lung carcinomas.

Enzyme cocktails used to prepare tumor cell suspensions may influence yield, viability, and cytology, thus time-related cocktail effects on model human lung carcinomas were examined. A549, NCI-H125, and NCI-H460 carcinomas were completely disaggregated at 25 degrees C over 2 h with either (mg/ml) collagenase/DNAase (C/D, 1/0.1), collagenase/hyaluronidase/DNAse (C/H/D, 1/0, 1/0.1), or polymyxa protease/DNAse (PP/D, 3/0.1). Trypan blue viabilities, total yields, viable yields, and flow cytometric percent tumor cells (TC) were measured every 20-30 min (n = 4-7 per tumor type). The final percentages of TC, mononuclear cells (MN), polymorphonuclear cells (PMN), lymphocytes, and necrotic cells were determined by cytology (n = 4-5 per tumor type). The time-dependent measurements showed that 1) disaggregation was progressive and complete with all cocktails; 2) viability was stable or increasing with all cocktails; 3) percent TC was stable for all cocktails, but lower for PP/D than C/D in final suspensions; and 4) PP/D gave lower final total yields, higher final viabilities, but the same final viable yields as the C cocktails, suggesting selective elimination of dead cells by PP/D. Final cytology measurements showed that PP/D gave a lower percent MN and a higher percent PMN than C cocktails. Cocktail effects may importantly influence cell suspension properties.

Animals↗
PubMed1994

Dose-related doxorubicin effect in an orthotopic secondary lung cancer screen.

Lung cancer is the leading cause of cancer-related death of both sexes in the United States and promises to be a major problem in the world community for decades. We are developing an orthotopic (organ specific) secondary screening system to measure the uptake and efficacy of new lung cancer agents. The elements of the system are: (1) orthotopic growth of a model human lung cancer (NCI-H460 large cell carcinoma) in the right caudal lobe of the nude rat; (2) 1-hr ex vivo pulmonary perfusion treatment of the tumor-bearing lungs; and (3) soft agar clonogenic assay of the enzymatically disaggregated tumor cells. This study characterizes dose-response aspects of the system. Perfusion of tumor-bearing lungs with 0, 1, 10, and 100 micrograms/ml doxorubicin resulted in a dose-related reduction in surviving fraction from 1.01 +/- 0.41 to 0.019 +/- 0.006 (P < 0.05) without significant treatment-related increases in lung weight or perfusion pressure. Tumor and lung drug levels were also dose-related, with lung levels exceeding tumor levels at all doses. The tumor drug level at the 100 micrograms/ml dose was 62 +/- 16 ng/mg. There was a strong negative correlation between the measured tumor drug level and surviving fraction in the clonogenic assay (R2 = 0.47, P = 0.0005). This new screening system is capable of demonstrating dose-related uptake and tumoricidal activity of doxorubicin on an orthotopic, model human large cell lung carcinoma. It may be useful for the secondary screening of agents active against human lung cancer.

Animals↗
PubMed1994

A Markov model of the natural history of prostate cancer.

The objective of this study was to lay a foundation for future cost-benefit analyses evaluating the public health impact of treatment and screening protocols for prostate cancer. Specifically we wanted to define the relative impact on cancer-specific mortality rates of the individual epidemiological components: pathological incidences by age groups, cancer progression rates, and the effect of competing causes of death, assuming expectant management (i.e. no definitive treatment). A biological model of prostate cancer incidence and progression was converted into a standard Markov tree where competing causes of death could occur. Weighted averages of progression rates were obtained from clinical studies. Separate cohorts of 30 year old black and white men were followed for 50 years. The model yielded cancer-specific mortality rates, overall mortality rates, and pathologic prevalences for both white and black males, consistent with the literature. Sensitivity analyses showed that of all the parameters studied, the pathological incidence of cancer in men under 50 years of age had the greatest impact on the cancer-specific mortality rates. Also important was the annual probability of progression of A1 lesions. However the other parameters including pathological incidence in older males, and progression from locally-extensive to metastatic lesions had much smaller effects. In summary, this model correlates the clinical literature with the epidemiology of prostate cancer and can be used for further decision analyses. We recommend that future research be done to more precisely quantify the pathological incidence of prostate cancer in men under 50-60 years of age. More certainty is also needed before generalizing the results of relatively small A1 series to millions of men, since A1 progression rates critically affect the eventual cancer-specific mortality. Enough uncertainty remains at this point however, that we cannot advocate widespread screening for prostate cancer until its merit be demonstrated either by the definitive long term study, or by examination of costs and quality-of-life-adjusted benefits.

Adult↗
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↗
PubMed1985

Malignant fibrous histiocytoma of the heart presenting as unilateral pulmonary thromboembolism and infarct.

A malignant fibrous histiocytoma of the heart located at the pulmonic valve and thrombotic occlusion of branches of the left pulmonary artery with pulmonary infarct were found at autopsy in a 77-year-old man. The thrombi contained malignant cells. The patient had undergone left upper lobectomy four years earlier for thromboembolism with infarct, and review of the slides from that procedure revealed similar malignant cells within thrombi. This case is remarkable for the slow growth of the neoplasm and the prolonged survival of the patient, without specific therapy.

Aged↗
PubMed1982

An education program that improves the psychomotor skills needed for metaproterenol inhaler use.

This is the first report assessing an education program's impact on teaching patients the psychomotor skills needed for proper use of the metaproterenol inhaler. Most patients do not use pressurized inhalers correctly. This inability could lead to suboptimal or ineffective therapy. Pharmacists provided a standardized education program to asthma patients and to those with chronic obstructive pulmonary disease for three clinic visits. Proper use of the inhaler was assessed by evaluating the patient's psychomotor performance for each visit before and after instruction. Of 19 patients, 18 demonstrated a mean improvement of 33.5 percent from preinstruction to postinstruction evaluation at the first visit (Student's t-test, p less than 0.0005). Both preinstruction and postinstruction scores demonstrated an upward trend for all three visits, the postinstruction scores always being higher than the preinstruction scores. These results indicate that our standardized education program helped improve psychomotor performance. Certain instructional aspects that need emphasis in future education programs have been identified.

Aerosols↗
PubMedDate not supplied

The danger of applying group-level utilities in decision analyses of the treatment of localized prostate cancer in individual patients.

The optimal management strategy for men who have localized prostate cancer remains controversial. This study examines the extent to which suggested treatment based on the perspective of a group or society agrees with that derived from individual patients' preferences. A previously published decision analysis for localized prostate cancer was used to suggest the treatment that maximized quality-adjusted life expectancy. Two treatment recommendations were obtained for each patient: the first (group-level) was derived using the mean utilities of the cohort; the second (individual-level) used his own set of utilities. Group-level utilities misrepresented 25-48% of individuals' preferences depending on the grade of tumor modeled. The best kappa measure achieved between group and individual preferences was 0.11. The average quality-adjusted life years lost due to misrepresentation of preference was as high as 1.7 quality-adjusted life years. Use of aggregated utilities in a group-level decision analysis can ignore the substantial variability at the individual level. Caution is needed when applying a group-level recommendation to the treatment of localized prostate cancer in an individual patient.

Aged↗
PubMedDate not supplied

Pharmaceutical cost growth under capitation: a case study.

Rising drug spending has generated concern among purchasers and policymakers. This paper compares drug cost growth in a capitated system with that in managed care systems that generally did not place physicians directly at risk for drug spending. We focus on cost growth because a substantial body of literature indicates that managed care interventions that reduce the level of costs may not influence the rate of cost growth. Drug cost growth under capitation initially was below that of other systems but still above targeted rates. Over time the capitation rates rose, the amount of risk transferred to physicians declined, and spending growth accelerated.

Adolescent↗