Biomedical subjects
Publications and source records attributed to J J Crowley.
The purpose of this paper is to provide an overview of the statistical problems that exist and procedures that are available when attempts are made to assess the possible harm which has been or might be caused by substances in the environment. These issues bear directly on important decisions of public policy such as those related to the establishment and enforcement of regulations.
In an effort to improve prediction of duration of survival in chronic lymphocytic leukemia, correlations between blood-cell morphology and survival were investigated. Blood films made on 108 patients at the time of diagnosis of chronic lymphocytic leukemia were reviewed by a single hematologist. Lymphocyte diameter and the fraction of lymphocytes containing nucleoli were both found to have an inverse correlation with survival. Bone-marrow aspirate films were available for 64 patients. Differential leukocyte counts showed that the median for marrow lymphocytes was 64%. Those patients with a greater than median proportion of lymphocytes on marrow aspirate had a shorter survival time than those with less than median.
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Three experiments on the induction of mammary neoplasms by total-body 11- to 100-rad neutron or 50- to 500-rad gamma-radiation of female Fischer or W/Fu rats are reported. Grafts of mammotropin-secreting pituitary tumor were used to elevate mammotropic hormone levels. The results (a) confirm and extend previous reports that neutrons are more efficient in carcinoma induction than are gamma-rays (the neutron relative biological effectiveness for first carcinomas was 3.68) and (b) demonstrate that the potentiation of carcinoma induction by adrenalectomy is reversed by glucocorticoid replacement. Statistical analysis of the data by procedures that take into account time at risk as well as tumor frequency indicates that multiple mammary tumors do not occur independently (i.e., a first mammary neoplasm significantly increases the probability of development of another neoplasm). The statistical procedure used in this analysis is presented.
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Seventeen patients received placebo medication during a 12-week run-in period, followed by four double-blind study periods of six weeks each, during which time placebo, 80 mg, 160 mg and 320 mg propranolol dosages were administered. Examination of the frequency of angina episodes and nonprophylactic nitroglycerin consumption revealed significant beneficial clinical responses for both the 160 and 320 mg dosages. Exercise testing also demonstrated increased exercise tolerance (320 mg dose) with a shift of the exercise end point from pain to fatigue in seven of 17 patients. The interrelationships between propranolol daily dosage, clinical response assessed by percent reduction in anginal episodes, beta-adrenergic blockade measured by percent reduction in exercise heart rate and serum levels were examined. In general, serum levels of 30 ng/ml, when drawn 90 to 180 minutes following the last oral dose, were required to achieve a 25% or greater reduction in angina frequency. Serum levels above 30 ng/ml were similarly correlated with a 20% or greater reduction in exercise heart rate at equivalent levels of exercise. Detailed examination of different patterns of clinical response with respect to beta-blockade, serum levels and oral doses are presented.
The appearance on magnetic resonance (MR) images of a primary amelanotic malignant melanoma of the nasopharynx is reported. The factors affecting the MR appearance of melanomas of the head and neck are reviewed. The case is compared with a previously reported case of primary nasopharyngeal melanotic melanoma, and the importance of considering the tumor in all nasopharyngeal neoplasms is emphasized.
A case of contrast extravasation during voiding cystourethrography (VCUG) in a patient without a history of renal failure or "unused" bladder is presented. The subject of extravasation during VCUG is reviewed.
The MR appearance of a case of genital tract tuberculosis is reported. The finding of a large amount of loculated fluid containing septations and debris on ultrasound along with bilateral hydropic fallopian tubes and a thickened omentum on MRI permitted the diagnosis to be suggested preoperatively. With increasing prevalence, such unusual manifestations of tuberculosis will be seen more frequently.
The twofold to threefold higher incidence of adverse drug reactions in elderly as opposed to younger patients is due mainly to more severe disease and the requirement for more complex drug treatment regimens. The incidence of adverse drug reactions increases with the number of prescribed drugs. Because of multiple drug use by the elderly, the potential for drug interactions is greater in this patient group. Surprisingly, the effect of age on the clinical pharmacology of drug interactions has not been thoroughly investigated. Our studies have shown that cimetidine inhibits and phenytoin induces the metabolism of theophylline to a similar extent in healthy male nonsmokers and smokers. Preliminary analysis of the results of a study to investigate the inhibition of theophylline metabolism by cimetidine and ciprofloxacin administered in combination to healthy male and female nonsmokers also does not show an age difference in response. Additional careful studies are needed to evaluate further the pharmacology and clinical importance of pharmacokinetic and pharmacodynamic drug interactions in the elderly.
PURPOSE: To report the long-term follow-up of Southwest Oncology Group-8269, a phase II North American cooperative group trial of concurrent cisplatin, etoposide, vincristine (PEV), and thoracic radiotherapy (TRT) for limited small-cell lung cancer (L-SCLC). METHODS: 114 eligible patients from 47 institutions enrolled between April, 1985 and March 1986. Patients had documented L-SCLC. Induction chemotherapy consisted of three cycles of PEV. TRT was administered at 1.8 Gy/fraction in 25 daily fractions to a total dose of 45 Gy, to begin concomitantly. Consolidative chemotherapy included two cycles of vincristine, methotrexate, etoposide, doxorubicin and cyclophosphamide. Prophylactic cranial irradiation (PCI) was concurrent with the 3rd cycle of chemotherapy. The PCI dose was 30 Gy in 15 fractions of 2 Gy/fraction. RESULTS: As of May 2000, 5 of 114 remain alive and progression-free with a minimum follow-up interval of 13.2 years, as of May 2000. The median follow-up interval is 14.2 years. Thirty eight patients died of causes other than SCLC and five patients are still alive and progression-free. Of the remaining 71 patients dying of SCLC, local failure (LF) occurred in 24% (17 patients), distant metastasis (DM) occurred in 35% (25 patients), simultaneous LF and DM occurred in 25% (18 patients), and was indeterminate in 16% (11 patients). Thus, LF was a component of failure in 49%. Twenty patients had the CNS as the initial site of failure. Eleven patients (10%) developed fatal second primary cancers, including two with acute myelogenous leukemia, two with squamous cell lung cancer, one each with breast, pancreas, prostate, renal cell, and myelodysplasia. One patient developed both a melanoma and non-Hodgkin's lymphoma. CONCLUSION: There are long-term survivors with concomitant TRT and PEV. LF and DM are common. Pattern of failure suggests needs to improve local and systemic control.
Two-dimensional echocardiography is the method of choice for imaging and diagnosis in patients with hypertrophic cardiomyopathy. However, ultrasound examination of the left ventricular apex by transthoracic echocardiography is often inadequate so that hypertrophy localised to this region may be missed. The purpose of this study was to evaluate the use of multiplane transoesophageal echocardiography in the diagnosis and assessment of apical hypertrophic cardiomyopathy. Six patients with apical hypertrophic cardiomyopathy underwent transthoracic and multiple transoesophageal echocardiography. Assessment of the proximal left ventricle was possible in all patients by both techniques and normal wall thickness measurements were obtained. Assessment of the distal left ventricle by multiple transesophageal echococardiography revealed hypertrophy of the apex (range 1.7-2.9 cm) and less marked hypertrophy of the distal segments of the left ventricle in all 6 patients (1.4-2.2 cm). Examination of the papillary muscles was also possible and hypertrophy was detected in 2 patients. By transthoracic echocardiography, hypertrophy was detected in the distal left ventricle of 5 patients and values were less than those obtained by multiplane transoesophageal echocardiography. No papillary muscle hypertrophy was seen. The apical segment was imaged in only 4 patients and maximum thicknesses of the apical segment were greater by multiple transoesophageal echocardiographic examination than by transthoracic echocardiography (mean 2.25 +/- 0.4 and 1.97 +/- 0.3 cm, respectively). We conclude that apical hypertrophic cardiomyopathy may be difficult to diagnose using transthoracic echocardiography because of inconsistent imaging of the apical segment. The distribution of hypertrophy may be inappropriately assigned and the severity of wall thickening underestimated. Multiplane transoesophageal echocardiography allows high resolution imaging of all segments of the left ventricle, particularly the apex.
PURPOSE: This phase II multi-institutional trial of the Southwest Oncology Group was designed to evaluate the efficacy and toxicity of docetaxel in chemotherapy-naive patients with extensive-stage small cell lung cancer. PATIENTS AND METHODS: Forty-seven patients with extensive-stage small cell lung cancer were entered onto the study. Treatment consisted of docetaxel, 100 mg/m2, as a 1-hour intravenous infusion repeated every 21 days, with protocol-specified dose reductions for toxicity. RESULTS: Forty-three patients were eligible. A total of 158 cycles of docetaxel were administered (median, three cycles; range, one to nine). Ten patients (23%) (95% confidence interval, 12% to 39%) achieved partial responses. The median progression-free and overall survivals were 3 and 9 months, respectively. Therapy was generally well tolerated. Grade 4 neutropenia occurred in 58% of patients. Febrile neutropenia developed in five patients (12%), and infection was documented in 14% of patients. There was one treatment-related death caused by pneumonia in a patient who had developed bilateral pneumothoraces. Other toxicities (grade 3/4) included malaise, fatigue, and lethargy (21%); nausea (19%); stomatitis (14%); edema (9%); and sensory neuropathy (9%). DISCUSSION: Docetaxel, at a dose of 100 mg/m2, is an active agent in the treatment of small cell lung cancer. Reversible neutropenia is the most common toxicity associated with this treatment. The overall survival (9 months) with this agent is comparable to that reported with other new chemotherapeutic agents in small cell lung cancer and warrants additional evaluation of docetaxel in combination therapy.