Selection of patients for cardiac evaluation before peripheral vascular operations

PURPOSE: This study evaluated the value of preoperative cardiac screening with dipyridamole thallium scintigraphy and radionuclide ventriculography in vascular surgery patients. METHODS: From July 1, 1989, to Dec. 31, 1991, we routinely (irrespective of the patient's cardiac history or symptomatology) performed dipyridamole thallium scintigraphy (DTS) and radionuclide ventriculography (RVG) in 394 patients being considered for an elective vascular operation. Patients with reversible defects on DTS underwent coronary arteriography. RESULTS: DTS results were normal in 146 patients (37%), showed a fixed defect in 75 (19%), and showed a reversible defect in 173 (44%). Patients with and without a history of angina or myocardial infarction had identical rates of reversible defects. Normal left ventricular function (> 50%) was noted in 76% of the patients; 17% had moderate dysfunction (35% to 50%) and 7% had a low ejection fraction (< 35%). The finding of severe coronary artery disease led to cardiac revascularization in 17 patients who had no prior history of cardiac disease and in 13 patients with a history of angina or myocardial infarction. Two deaths and nine major complications were associated with coronary arteriography and cardiac revascularization. Vascular procedures (144 aortic, 53 carotid, 146 infrainguinal) were ultimately performed in 343 patients, with a mortality rate of 1.7% (3.5% aortic, 0% carotid, and 0.7% infrainguinal bypass). The nonfatal perioperative myocardial infarction rate was 2.0%. We monitored all 394 patients for cardiovascular events, with a mean follow-up of 40 months. Patients who underwent cardiac revascularization had a 4-year survival rate of 75%, which was similar to those with a normal DTS. Late cardiac events were significantly more frequent in patients who had either a reversible DTS or RVG < 35%. CONCLUSIONS: Routine cardiac screening of vascular surgery patients had similar impact on patients irrespective of their prior history or current symptoms suggesting coronary artery disease. Routine screening did not result in substantial benefit. Screening studies such as DTS or RVG may be most useful as part of an overall risk versus benefit assessment in patients without active symptoms of coronary artery disease who have less compelling indications for vascular intervention (claudication, moderate-sized aortic aneurysms, or asymptomatic carotid disease).     

Pharmacokinetic monitoring and dose modification of etanidazole in the RTOG 85-27 phase III head and neck trial

PURPOSE: To prospectively evaluate the pharmacokinetic monitoring and drug dose adjustment of Etanidazole (Eta) in patients treated on the RTOG randomized trial for Stage III and IV head and neck cancer. METHODS AND MATERIALS: From June, 1986 to October, 1991, 521 patients were randomized to conventional RT alone or RT plus Eta. The primary goal was to determine whether the addition of Eta to conventional radiation therapy improves local-regional control and tumor-free survival. Of the 264 patients who received Eta, 233 had their drug exposure calculated and the Eta dose and schedule adjusted accordingly to prevent the occurrence of serious peripheral neuropathy. Drug exposure was assessed using the area under the curve (AUC) for a single treatment that was calculated by the integral over time of the serum concentration of Eta. The total drug exposure (total-AUC) was estimated by multiplying the AUC by the number of drug administrations. RESULTS: Eighteen percent of patients developed Grade I and 6% developed Grade II peripheral neuropathy. There was no Grade 3 or 4 peripheral neuropathy. There is a trend for an increased risk of neuropathy by single dose AUC. The minimal difference in incidence of neuropathy by single-dose AUC was due to the use of dose and schedule modification for patients with the higher values. CONCLUSIONS: The pharmacokinetics investigated in this study confirm previous work that monitoring Eta levels, with dose adjustment, allows it to be used safely in the clinic. In a subset analysis there was a statistically significant improvement in local-regional control and survival rates for patients with N0 and N1 disease, that will require confirmation (14). However, the clinical efficacy of Eta in this trial proved to be of little overall benefit.     

Pathophysiology of erectile dysfunction

During the past decade, our knowledge of the hemodynamics, functional anatomy, neurophysiology, and neuropharmacology of erectile function has evolved substantially. The change of smooth muscle tone has emerged as a key factor in erection and detumescence. However, future studies are needed to elucidate the cellular and molecular basis of erectile physiology. With insight into normal physiology we will understand the pathologic process and be able to treat it.     

Liquid assisted ventilation: an alternative ventilatory strategy for acute meconium aspiration injury

Evidence of surfactant inactivation by meconium has led to the use of exogenous surfactant therapy in the management of meconium aspiration syndrome (MAS). Liquid assisted ventilation has been shown to improve the cardiopulmonary function in lungs with high surface tension. We compared exogenous surfactant therapy with liquid assisted ventilation in the management of experimental acute meconium aspiration injury. Thirty-two newborn lambs were ventilated at peak inspiratory pressures of 13-16 cm H2O, positive end expiratory pressure of 3-4 cm H2O, fractional inspired oxygen concentration (FiO2) of 1.0, and a respiratory frequency range between 30 and 35 breaths/min. Baseline arterial blood gases, pulmonary function, and arterial blood pressure measurements were taken. All lambs were given 2-3 ml/kg of an unfiltered 25% meconium solution. Lambs were then randomized into either gas-ventilated meconium control, or one of three treatment groups: 1) surfactant; 2) partial liquid ventilation (PLV); or 3) total liquid ventilation (TLV) for 4 hours after meconium injury. All treated groups demonstrated a significant increase in arterial oxygenation (P < 0.05); surfactant and PLV-treated lambs demonstrated significantly decreased arterial PCO2 (P < 0.05). Compliance in all groups increased compared with injury values; compliance of the TLV group increased more than in all other treatment groups (P < 0.05). In addition, lung histology of the TLV group demonstrated clear, intact alveolar epithelium and homogeneously expanded alveoli, while no such improvement was evident in the other groups. These data suggest roles for both exogenous surfactant therapy and liquid assisted ventilation techniques in the management of MAS.     

Mutual influence of plasmid profile and growth temperature on the lipid composition of Yersinia pseudotuberculosis bacteria

Glioblastoma multiforme (GBM) is the most malignant glial brain tumor in humans. The fact that deleted copies of chromosome 10 are observed frequently in primary GBM tumors supports the hypothesis that one or more tumor suppressor genes located on chromosome 10 occupy crucial growth control checkpoints for glial cells. Deletion mapping in primary GBM tumors using the loss of heterozygosity (LOH) test has implicated the 10q24-10qter region as one possible site for a gene. We report here on the molecular cytogenetic analysis of chromosome 10 abnormalities in a human GBM cell line, JBSA. LOH testing showed that JBSA cells were hemizygous for chromosome 10. Molecular cytogenetic analysis showed that the undeleted homologue was involved in a reciprocal translocation t(7;10)(p21;q22). The translocation breakpoint on chromosome 10 lay within band q22 between D10S19 and D10S4. The fact that JBSA cells lack one homologue of chromosome 10 and carry a translocation breakpoint on the remaining one, proximal to the smallest region of overlap reported in primary tumor deletions, suggests that 10q22 may be another possible site for a tumor suppressor gene involved in GBM.     

Patient responses to request for written permission to review medical records

2,163 patients of 55 physicians in one county, were sent letters asking for their written permission to have their medical records audited by the University of Michigan research team. The overall positive response rate was 64.1% for one county. Differences in response rates were statistically significant among specialties, among diagnoses, and among individual physicians.