Accrual of patients into a multihospital cancer clinical trial and its implications on planning future studies

Little information exists on the population of cancer patients from which individual patients are selected for admission to a clinical trial. In fact, most reports of clinical trials of cancer chemotherapeutic agents begin by describing samples of treated patients but neglect to collect data and describe the population from which the samples were taken. In a multi-institutional VA Cooperative Study in which two different cancer treatments were compared, an attempt was made to screen all lung, colorectal, prostate, and head and neck patients seen at participating hospitals prior to randomization to a therapeutic regimen. Of a total of 2687 patients screened, 437 (16.3%) were randomized and 2250 (83.7%) were excluded for 2981 reasons. Protocol reasons were the basis for 68.6% of all exclusions, 21.3% were physician refusals, and 10.1% were patient refusals. The number of patients randomized did not correlate well with number of patients screened across participating centers. Patients admitted to the study tended to be younger and in better health than excluded patients. Overestimates of randomization rates projected initially from published information point to the need for improved screening data in the planning of future studies. Factors such as screening methods, physician acceptance of the experimental approach, number of competing protocols within each center, and cooperation among medical center departments and personnel all are important ingredients in any screening effort.     

Effect of Feeding Chlortetracycline on the Reservoir of Salmonella typhimurium in Experimentally Infected Swine

Swine were fed either a diet containing 110 mg of chlortetracycline (CTC) per kg (100 g/ton) or a control diet and were inoculated orally with Salmonella typhimurium that was either susceptible or resistant to CTC. The quantity, duration, and prevalence of fecal elimination of S. typhimurium, as well as the effect of CTC on the transmission of S. typhimurium from infected to uninfected swine, were determined. When animals were infected with CTC-resistant S. typhimurium, CTC increased the quantity (P < 0.05), duration (P < 0.05), and prevalence (P < 0.01) of fecal shedding, the transmission from infected to uninfected swine, and the recovery of the infecting organism at necropsy. When animals were infected with CTC-susceptible S. typhimurium, CTC reduced the quantity (between 7 and 10 days postinfection) (P < 0.01), duration (P < 0.05), and prevalence (P < 0.05) of fecal shedding, the transmission from infected to uninfected swine, and the recovery of the infecting organism at necropsy. Resistance to tetracycline was transferred in vivo to 4 and 6% of the susceptible infecting S. typhimurium recovered from the untreated and treated groups, respectively. The increased reservoir of S. typhimurium and the transfer of resistance to susceptible S. typhimurium have implications for both animal and public health.     

An experimental model for angina pectoris using krypton-81m. The dynamic balance between myocardial perfusion and metabolism.

16 anesthetized and open chest dogs were studied. Regional myocardial perfusion was assessed using a constant infusion of krypton-81m (half-life 13 sec) into the aortic sinuses and a gamma camera linked to a digital computer. The epicardial electrocardiogram was recorded and the plasma activity of creatine kinase was measured in serial blood samples from the aorta and a local coronary vein draining the area of myocardium supplied by the left anterior descending coronary artery (LAD). These parameters were observed throughout the whole period of a 5-h experiment. Two reversible snares were positioned on the middle portion of this artery. A critical narrowing of this vessel was produced and a peripheral venous infusion of isoproterenol (causing a 5--10% increase in heart rate and a 10--15% fall in blood pressure) was used to increase myocardial oxygen demand. During infusion there was both a relative and absolute fall in regional myocardial perfusion together with evidence of myocardial ischemia in the epicardial electrocardiogram. Provided the infusion was discontinued within 30 min (8 dogs) myocardial perfusion and the epicardial electrocardiogram returned to normal during a 5-h recovery period. In addition there was no efflux of creatine kinase activity from the ischemic area. When infusion was continued for 1 h (4 dogs) permanent alterations in myocardial perfusion and the epicardial electrocardiogram occurred and there was increased creatine kinase activity released from the area of myocardium by the narrowed vessel. Infusion for 40 min in 4 dogs produced permanent alterations in the parameters measured in 2 and complete recovery in the remaining 2. A further 4 dogs were studied in the same way but without a snare on the coronary artery. Isoproterenol given for 1 h produced no effects on any of the parameters either during or after infusion.     

Nonpapillary carcinoma in situ and atypical hyperplasia in cancerous bladders: Further studies of surgically removed bladders by mapping

Complete mapping of epithelium has been performed in 10 bladders surgically removed for cancer. In all cases, in areas adjacent to or distant from the visible tumors, nonpapillary carcinoma in situ and related lesions such as atypical hyperplasia could be demonstrated. More importantly, in 5 of the 10 bladders, areas of occult invasive carcinoma derived from such abnormal epithelia have been recorded. These findings fully confirm prior observations and raise the number of totally mapped bladders to 20. The histologic findings in the entire series of 20 cases are discussed and the distribution of cancer and precancerous lesions tabulated. It is suggested that the areas of the bladder most frequently affected by precancerous lesions are the left and right lateral walls and the posterior wall. The trigone and the dome are less frequently involved. The need for aggressive assessment of bladder epithelium in patients with tumors of the bladder and/or early radical treatment for patients with nonpapillary carcinoma in situ is discussed in light of these observations.