Definitive radiotherapy for early glottic carcinoma: prognostic factors and implications for treatment.

PURPOSE: Treatment and disease-related factors were analyzed for their influence on the outcome of patients treated definitively with irradiation (RT) for early glottic carcinoma. METHODS AND MATERIALS: One hundred two patients with stage T1 or T2 glottic carcinomas were treated definitively with RT from December 1983 through September 1993. Median follow-up time was 63 months. Factors analyzed for each patient included age, sex, stage, anterior commissure involvement, surgical alternative, histologic differentiation, field size, total dose, fraction size, and total treatment time. Survival analysis methods were employed to assess the effects of these factors on local control and complication rates. RESULTS: The 5-year local control rates by stage were as follows: T1a, 92%; T1b, 80%; T2a, 94%; and T2b, 23%. By univariate analysis, factors found to have a significant impact on local control were stage, surgical alternative, fraction size, anterior commissure involvement, and overall treatment time. By multivariate analysis, stage, field size, and fraction size were the only significant factors that independently influenced local control. CONCLUSION: The inferior control rate for stage T2b lesions has implications for treatment. Our study supports the conclusion of reports in the literature showing that low fraction size negatively influences outcome in patients with early glottic cancer.

Reductase inhibitor monotherapy and stroke prevention.

BACKGROUND: Epidemiologic evidence and meta-analyses of data from early clinical trials suggest that lowering the levels of cholesterol does not reduce the events of stroke. These analyses have not included more recent clinical trials using reductase inhibitors. OBJECTIVE: To conduct a meta-analysis of the effect of reducing cholesterol levels on stroke in all reported clinical trials of primary (n = 4) and secondary (n = 8) prevention of coronary heart disease that used reductase inhibitor monotherapy and provided information on incident stroke. RESULTS: Analysis of combined data from primary and secondary prevention trials showed a highly statistically significant reduction of stroke associated with the use of reductase inhibitor monotherapy (27% reduction in stroke; P = .001). Analysis of secondary prevention trials alone disclosed a similar statistically significant effect (32% reduction in stroke; P = .001). A smaller nonsignificant reduction in stroke was noted in the primary prevention trials (15% reduction in stroke; P = .48). CONCLUSIONS: Reductase inhibitors now in use for lowering cholesterol levels are more potent and have fewer side effects than the cholesterol-lowering agents previously available. They appear to reduce stroke, most notably in patients with prevalent coronary artery disease, which may be partly due to the effects of lowering the levels of cholesterol on the progression and plaque stability of extracranial carotid atherosclerosis or the marked reduction of incident coronary heart disease associated with treatment.

Definitive radiotherapy for early glottic carcinoma: prognostic factors and implications for treatment.

PURPOSE: Treatment and disease-related factors were analyzed for their influence on the outcome of patients treated definitively with irradiation (RT) for early glottic carcinoma. METHODS AND MATERIALS: One hundred two patients with stage T1 or T2 glottic carcinomas were treated definitively with RT from December 1983 through September 1993. Median follow-up time was 63 months. Factors analyzed for each patient included age, sex, stage, anterior commissure involvement, surgical alternative, histologic differentiation, field size, total dose, fraction size, and total treatment time. Survival analysis methods were employed to assess the effects of these factors on local control and complication rates. RESULTS: The 5-year local control rates by stage were as follows: T1a, 92%; T1b, 80%; T2a, 94%; and T2b, 23%. By univariate analysis, factors found to have a significant impact on local control were stage, surgical alternative, fraction size, anterior commissure involvement, and overall treatment time. By multivariate analysis, stage, field size, and fraction size were the only significant factors that independently influenced local control. CONCLUSIONS: The inferior control rate for stage T2b lesions has implications for treatment. Our study supports the conclusions of reports in the literature showing that low fraction size negatively influences outcome in patients with early glottic cancer.

Differences in insulin suppression of free fatty acid levels by gender and glucose tolerance status. Relation to plasma triglyceride and apolipoprotein B concentrations. Insulin Resistance Atherosclerosis Study (IRAS) Investigators.

Most discussions of relations of insulin resistance to coronary heart disease risk factors have focused on insulin-stimulated glucose uptake, but insulin suppression of plasma free fatty acid (FFA) levels is also important in lipid and lipoprotein metabolism. To identify groups with impaired insulin suppression of FFAs, we studied a multiethnic cohort of 1521 women and men at four US centers that comprise the Insulin Resistance Atherosclerosis Study (IRAS): 682 with normal glucose tolerance, 352 with impaired glucose tolerance, and 487 with non-insulin-dependent diabetes. The FFA level 2 hours after a 75-gm oral glucose load adjusted for fasting FFAs was used as the measure of insulin suppression. After adjustment for age, center, ethnicity, body mass index, and fasting and 2-hour insulin levels, 2-hour FFA levels were significantly higher in men than women and in persons with impaired glucose tolerance and non-insulin-dependent diabetes mellitus versus normal glucose tolerance. The gender difference was largely accounted for by differences in central obesity as measured by waist-hip ratio; the difference by glucose tolerance status was not affected by central obesity, suggesting a different mechanism. In multivariate regression analyses, 2-hour FFA levels were strongly related to fasting triglyceride and apoB levels, respectively, after adjustment for age, fasting and 2-hour insulin concentrations, and fasting FFA concentrations. In summary, elevated plasma apoB and triglyceride concentrations associated with male gender and with glucose intolerance are partly accounted for by differences in the ability of insulin to suppress FFA concentrations.

Dietary fat and insulin sensitivity in a triethnic population: the role of obesity. The Insulin Resistance Atherosclerosis Study (IRAS)

From the Insulin Resistance Atherosclerosis Study (IRAS), 1173 men and women of African-American, non-Hispanic white, and Hispanic ethnicity with no history of diabetes were included in an evaluation of the cross-sectional relation of habitual dietary fat intake with insulin sensitivity (SI) as assessed by minimal-model analysis of a 12-sample, insulin-modified frequently sampled intravenous-glucose-tolerance test. Dietary intake was measured by a food-frequency interview modified to enhance sensitivity to food choices within the three ethnic groups. Percentage of energy from total fat was associated with rank of SI (SI(rank); r = -0.06, P = 0.03), with log fasting insulin (r = 0.10, P < 0.001), and with BMI (r = 0.10, P < 0.001). Multiple-linear-regression models included SI(rank) as the dependent variable, dietary fat (g/d) as the primary independent variable adjusted sequentially for total energy, other covariates, body mass index, and waist-hip circumference ratio (WHR). For all subjects combined, total fat intake was inversely related to SI(rank), but this association was not significant (P = 0.14) and was attenuated by adjustment for body mass index and WHR (P = 0.44). The association of total fat (g/d) with SI(rank) differed significantly (P < 0.01) for obese compared with nonobese individuals. Higher fat intake was associated with lower SI(rank) among obese (beta = -1.40, P = 0.03) but not among nonobese persons (beta = 0.16, P = 0.80). Among the obese (body mass index < or = 63), adjustment for body mass index largely accounted for the observed association of dietary fat with SI(rank). These findings were generally consistent for monounsaturated, polyunsaturated, and saturated fats. Among individuals already at increased risk for non-insulin-dependent diabetes mellitus because of obesity, high intake of dietary fat may worsen insulin sensitivity. This effect may be mediated by the relation of dietary fat to obesity.

A cloud adult: the Staphylococcus aureus-virus interaction revisited.

BACKGROUND: Nasal carriage of Staphylococcus aureus is common among health care workers, but outbreaks caused by such carriers are relatively uncommon. We previously reported outbreaks of S. aureus skin infections that affected newborn infants and were attributed to an S. aureus nasal carrier who had had an associated upper respiratory tract infection (UR) during the outbreak period. OBJECTIVE: To investigate the contribution of a nasal methicillin-resistant S. aureus (MRSA) carrier (physician 4) who contracted a URI to an outbreak of MRSA infections that involved 8 of 43 patients in a surgical intensive care unit during a 3-week period. DESIGN: An epidemiologic study of an outbreak of MRSA infections and a quantitative investigation of airborne dispersal of S. aureus associated with an experimentally induced rhinoviral infection. SETTING: A university hospital. PARTICIPANTS: 43 patients in a surgical intensive care unit and 1 physician. MEASUREMENTS: Molecular typing was done, and risk factors for MRSA colonization were analyzed. Agar settle plates and volumeric air cultures were used to evaluate the airborne dispersal of S. aureus by physician 4 before and after a rhinoviral infection and with or without a surgical mask. RESULTS: A search for nasal carriers of MRSA identified a single physician (physician 4); molecular typing showed that the MRSA strain from physician 4 and those from the patients were identical. Multivariate logistic regression analysis identified exposure to physician 4 and duration of ventilation as independent risk factors for colonization with MRSA (P < or = 0.008). Air cultures showed that physician 4 dispersed little S. aureus in the absence of a URI. After experimental induction of a rhinovirus URI, physician 4's airborne dispersal of S. aureus without a surgical mask increased 40- fold; dispersal was significantly reduced when physician 4 wore a mask (P < or = 0.015). CONCLUSIONS: Physician 4 became a "cloud adult," analogous to the "cloud babies" described by Eichenwald and coworkers who shed S. aureus into the air in association with viral URIs. Airborne dispersal of S. aureus in association with a URI may be an important mechanism of transmission of S. aureus.

Arterial microsphere concentrations in cats are not affected by changes in hematocrit.

BACKGROUND AND PURPOSE: Acute anemia may lead to erroneously low arterial reference sample concentrations of radioactive microspheres, depending on the sampling rate and the size of the artery from which the reference samples are withdrawn. Because this error would lead to falsely high cerebral blood flow values in studies involving hemodilution caused by hemorrhage and fluid resuscitation, we studied the effects of hematocrit, withdrawal rate, and vessel location and size on arterial microsphere concentrations in anesthetized adult cats. METHODS: Cats were anesthetized with ketamine, isoflurane, and nitrous oxide; both brachial arteries were cannulated with polyethylene tubing, as was the abdominal aorta through the femoral artery. Sequential left atrial microsphere injections were made using several doses of each of five isotopes. The rate of reference sample withdrawal from the three sampling catheters was randomized to 1.03 mL.min-1 or 2.06 mL.min-1. We analyzed the ratio of the number of microspheres in paired reference samples using the factors hematocrit, rate of withdrawal, and site. A ratio less than 1 indicates an underestimation of arterial microsphere concentration, which would lead to erroneously high cerebral blood flow values. The procedure was repeated after isovolemic hemodilution with 10% hetastarch to hemoglobin levels approximating 85%, 70%, 55%, and 40% of baseline. RESULTS: No significant effects of hematocrit on ratios of microsphere concentrations existed at any withdrawal rate or site. Ratios of microsphere concentrations in reference samples withdrawn slowly (1.03 mL.min-1) from the aorta and ratios of microsphere concentrations withdrawn either rapidly (2.06 mL.min-1) or slowly from the brachial arteries were significantly (P < .001) less than 1. CONCLUSIONS: Hemodilution did not affect microsphere concentrations in arterial reference samples at any withdrawal site or rate and therefore does not affect the accuracy of microsphere blood flow determinations. However, slow withdrawal from a large vessel may underestimate actual microsphere concentrations.

Prognostic factors and treatment outcome for patients with locally recurrent endometrial cancer.

BACKGROUND: Women who do not receive adjuvant irradiation after hysterectomy for endometrial carcinoma (EC) are at risk for developing a pelvic recurrence. Disease- and treatment-related factors were examined for their impact on disease-specific survival (DSS) and pelvic control (PC) in patients with locoregional recurrences to whom salvage radiotherapy was administered. METHODS: Forty-five patients with pelvic/vaginal recurrences of EC were treated at a single institution between 1973 and 1991. The median follow-up period was 89 months. Multiple patient-, disease-, and treatment-related factors were examined with univariate and multivariate analysis for their impact on DSS and PC. Kaplan-Meier methods were used to estimate outcomes. RESULTS: Overall DSS and PC was 51 and 54% at 5 years, respectively. Univariate analysis revealed the following factors to impact on outcome (P < or = 0.05): age (DSS, PC), vaginal stage of recurrence (DSS, PC), size of recurrence (DSS, PC), time interval from hysterectomy (DSS, PC), initial grade (DSS), location of recurrence (PC), and radiation boost technique (PC). CONCLUSION: Women in whom endometrial cancer recurrences develop can be salvaged with aggressive radiotherapy consisting of external beam therapy followed by a radiation boost. Close follow-up after the initial hysterectomy is important because patients with low-volume recurrence limited to the vagina have the best outcome.