BACKGROUNDThe best treatment for advanced head and neck cancer remains unclear. Proponents of various therapeutic regimens continue to debate this issue with inconclusive and frequently biased data and with carefully selected patients in controlled trials to support their approach. To assess the outcome of patients in a real-world situation, we reviewed a prospectively maintained database of patients with head and neck cancer.METHODSWe reviewed data from 591 consecutive patients with stage III or IV squamous cell carcinoma treated at a university medical center from January 1, 1992, through December 31, 2000, and analyzed survival using the Kaplan-Meier method.RESULTSOverall survival was 48%, 40%, and 33% at 2, 3, and 5 years, respectively. We found a significant death rate due to comorbid conditions. The primary tumor was treated surgically (with or without postoperative radiation) in 363 patients, with survival of 55%, 46%, and 38% at 2, 3, and 5 years, respectively. The tumor was treated primarily with radiation therapy (with or without neck dissection) in 193 patients, with survival of 40%, 33%, and 27% at 2, 3, and 5 years, respectively. Overall survival in the surgical group was better than in the radiation group (P =.005, log-rank chi 2 test). The radiation group was subcategorized into those who underwent radiation because the tumor was so advanced as to be unresectable (n = 86), because they were too unhealthy to undergo radical surgery (n = 23), and because they elected radiation therapy (n = 84). Survival in each of the radiation subgroups at 2, 3, and 5 years was 28%, 20%, and 14%, respectively, in the unresectable group; 34%, 22%, and 11%, respectively, in the unhealthy group; and 57%, 53%, and 46%, respectively, in the elective group. Thus, survival in the elective radiation subgroup exceeded that of the surgical group, although not statistically. We analyzed data regarding T and N stages, age, race, surgical margin status, postoperative radiation therapy, chemotherapy, radiation dose, and tumor site. Multivariate analysis of the surgical group and elective radiation subgroup showed that N stage and age were the strongest predictors of survival and that the method of therapy was not significant. For oropharyngeal cancer, the patients in the elective radiation subgroup did as well as the surgical group. Many patients were noncompliant with portions of therapy, with a resulting reduction in survival.CONCLUSIONSThe data demonstrate the value of analyzing a consecutive series of patients with advanced head and neck cancer. By including patients with comorbidities and those who are noncompliant, we determined a realistic expectation of patient outcomes. By including all patients, the data dramatically show the impact of age, comorbidity, and advanced stage on survival. The survival of patients who underwent elective radiation therapy in combination with neck dissection was similar to that of patients treated with primary tumor surgery. This was particularly true for oropharyngeal tumors. The site and stage-specific data are useful in counseling patients with advanced head and neck cancer regarding treatment choices.

OBJECTIVE Our specific aim in the 16 year prospective NHANES I epidemiologic follow-up study (NHEFS) was to assess the important roles of modifiable dietary and behavioral factors in causation and prevention of deaths and hospitalizations for coronary heart disease (CHD). METHODS Using NHEFS 16 year follow-up data (1971 to 1987), we studied 5811 subjects, 1958 with and 3853 without CHD events, using logistic regression. RESULTS In age groups 40 to 49, 50 to 59, 60 to 69, and 70 to 74 years (at study entry in 1971-4), the numbers of men and women were respectively 597 and 1019, 570 and 619, 932 and 1042, and 486 and 546. The following factors were independently positively associated (p < .05) with CHD: age, serum cholesterol, body mass index, cigarette use, and region (Midwest, Northeast). The following factors were independently negatively associated (p < .05) with CHD: gender (female), race (black), fish intake, alcohol, high school education, moderate exercise, and moderate and heavy habitual physical activity. Subjects with serum cholesterol > 249 mg/dl benefitted less (p = .04) from fish intake than those with 209 to 249 or < 209, and benefitted less (p = .03) from alcohol intake (CHD incidence [%]): [see text] CONCLUSIONS These associations emphasize the important role of modifiable dietary and behavioral factors in the causation and prevention of CHD.

Our specific aim in a 10-year prospective study of 772 Cincinnati firemen (predominantly aged 26 to 46 years) was to determine the prevalence, attributes, and etiology of persistent hypobetalipoproteinemia, defined by entry low-density lipoprotein cholesterol (LDLC) less than 75 mg/dL. A second specific aim was to cross-sectionally assess hypocholesterolemia (defined by total serum cholesterol [TC] < 130 mg/dL) in 1,314 white and 165 black men aged 26 to 46 years in the National Health and Nutrition Examination Survey (NHANES I). The 141 black and 631 white firemen had 4,973 person-years of follow-up time (median, 7.1 yr/man). Of 772 men, 44 (5.7%) had entry LDL levels less than 75 mg/dL; they had a mean follow-up time of 7.3 yr/man. Of these 44 men, there were 12 (1.8% of the cohort) with entry LDLC less than 75 mg/dL, and at least 67% of their follow-up LDLC levels were less than 75. Their mean entry TC and LDLC levels were low (130 and 58 mg/dL), mean triglyceride (TG) was low (63 mg/dL), and mean high-density lipoprotein cholesterol (HDLC) was high (60 mg/dL), LDLC remained at less than 75 mg/dL in 81% of their follow-up samples. Their mean entry and follow-up cholesterol and LDLC did not differ (P > .1, 130 v 133 mg/dL and 58 v 63 mg/dL). Compared with 32 men with entry LDLC less than 75 mg/dL but with less than 87% of follow-up LDLC less than 75 mg/dL, the 12 men with persistently low LDLC had lower mean Quetelet indices and diastolic blood pressure at entry (2.36 v 2.58, P = .056; 73 v 80 mm Hg, P = .03) and on follow-up study (2.45 v 2.69, P = .04; 72 v 79 mm Hg, P = .05). Of 12 men with persistently low LDLC, two had truncated apolipoprotein (apo) B (familial hypobetalipoproteinemia, two had the apo E genotype 2/3, and two had acquired hypobetalipoproteinemia that antedated mortality from melanoma by 9 years and from alcoholism by 2 years. Comparable to white and black firemen aged 26 to 46 years, 2.9% and 3.6% of whom had entry serum TC less than 130 mg/dL, of 1,314 white and 165 black men in the NHANES I study (aged 26 to 46), 1.8% and 3.6% had hypocholesterolemia (entry TC < 130 mg/dL). Daily mean calorie, fat, and protein intake (grams per day) did not differ (P > .05) in men with entry TC less than 130 mg/dL compared with those with TC 130 to 230 or greater than 230 mg/dL. Hypocholesterolemia in white and black men in NHANES I could not be attributed to hypocaloric intake or to protein, fat, or carbohydrate undernutrition. There appear to be racial differences in the prevalence of hypocholesterolemia. Blacks comprised 18% of the firemen's cohort but 42% of those with persistent hypobetalipoproteinemia; among NHANES I subjects, 3.6% of blacks were hypocholesterolemic versus 1.8% of whites. Unless persistent hypobetalipoproteinemia reflects an underlying disease, alcoholism, etc., it is often heritable, and may be associated with a reduced likelihood of coronary heart disease (CHD) and with increased longevity.

Inactivation of tumor suppressor genes, including p53 and retinoblastoma(Rb), are commonly found in all cancers, including head and neck squamous cell carcinoma. Alterations at either p53 or Rb, however, are only weakly associated with tumor aggressiveness. In many cancers loss of heterozygosity (LOH) at multiple loci is associated with decreased survival. The polymerase chain reaction and highly informative microsatellite markers were used to compare DNA from matched sets of 63 head and neck squamous cell cancers and normal tissue for LOH at the p53 and Rb loci. At p53, 50 were informative, with LOH occurring in 19 (38%). Of the 57 that were informative at Rb, LOH occurred in 21 (37%). Of the 46 that were informative at both p53 and Rb, LOH occurred in 10 (22%) at both loci. When LOH for p53 and Rb individually was compared to stage, differentiation, and survival, there was no correlation. However, the patients with LOH at both loci had a significantly poorer survival ( P = .009). This strongly supports the contention that simultaneous alterations of these two tumor suppressor genes favor tumor aggressiveness and can be used as a prognostic indicator.

STUDY OBJECTIVE:To determine pulmonary function test (PFT) profile and respiratory muscle strength (RMS) of a group of obese individuals who did not have evidence of obstructive airway disease or other underlying diseases affecting their respiratory system.DESIGN:Prospective, open.SETTING:PFT laboratory, VA Medical Center.PARTICIPANTS:Sixty-three consecutive obese (body mass index greater than 27.8 kg/m2) male subjects without overt obstructive airway disease (FEV1/FVC ratio greater than 80%).MEASUREMENTS AND RESULTS:Standard PFTs and maximum static inspiratory (PImax) and expiratory (PEmax) mouth pressures were determined. RMS was calculated from the following formula: (PImax+PEmax):2. Two distinct groups were identified, those with normal maximum voluntary ventilation (MVV) (> 80% predicted) and those with low MVV. Both inspiratory and expiratory flow rates (FVC, FEV1, forced expiratory flow at 50% vital capacity [V50], maximum inspiratory flow rate [MIFR]), lung volumes (vital capacity [VC], inspiratory capacity [IC], expiratory reserve volume), PImax, and RMS were significantly lower, and residual volume/total lung capacity (RV/TLC) ratio was significantly higher in obese subjects with low MVV compared with those in whom MVV was normal. MVV correlated significantly with FVC, FEV1, V50, MIFR, TLC, VC, IC, RV/TLC, and RMS; the strongest correlation was with MIFR (r = 0.76, p < 0.0001).CONCLUSIONS:Standard PFTs allow recognition of a subgroup of obese subjects without overt obstructive airway disease who have more severe lung dysfunction, the marker of which is a low MVV. Peripheral airway abnormalities may be responsible for these observations.

Since 1984, coronary heart disease (CHD) risk factors have been prospectively assessed among Cincinnati firefighters free of CHD at study entry. In total, 806 firemen with a mean age of 37 years at entry have been followed for 6.4 years on average, contributing 5,173 person-years. CHD risk factors were measured every 1-4 years and included weight, blood pressure, cigarette use, fasting glucose, and lipid profile. When, in aggregate, these CHD risk factors were found to be in a high risk range, suggestions were made serially to reduce CHD risk. A composite high CHD risk factor score led to an exercise electrocardiogram (ECG) with thallium scan, which was repeated every 1-4 years. Myocardial infarction (MI) occurred in 7 men, with 1.35 MIs/1,000 man-years; 15 others developed CHD, with 4.25 MI + CHD/1,000 man-years. The firefighters' MI event rate (1.35 MIs/1,000 man-years) was lower (but not significantly, p > 0.1) than that for employed 30- to 39-year-old men free of CHD at entry (2.07/1,000 man years), who had an average follow-up of 5.4 years in the NHANES I study. At study entry, the 22 men who later developed CHD (vs. the 784 who did not develop CHD) were older (p = .0001), smoked more (p = .0001), and were more likely to have first degree relatives with CHD before age 60 (p = .017). After covariance adjusting for age, race, and Quetelet index, men with CHD (vs. those CHD free) had higher systolic and diastolic blood pressures (p = .0001, .0001), higher LDL cholesterol (p = .04), higher total cholesterol (p = .014), and higher triglycerides (p = .03). By Poisson regression, significant independent predictors of CHD events were age (p = .0007), cigarette smoking (p = .001), diastolic blood pressure (p = .056), and family history of CHD at age < or = 60 (p = .048). Men who later developed CHD and those without CHD did not differ by history of smoke inhalation (p > 0.3). The calculated ratio of savings to cost attributable to the program per year was 5.9/1 ($258,500/$43,600). In the current study, firefighting as an occupation was not associated with increased CHD event rates. CHD events that did develop were, for the most part, associated with modifiable CHD risk factors.

NaCl cotransport carrier is known to be involved in transepithelial fluid absorption and secretion in various tissues. Recent studies indicate that Na-K-2Cl cotransport carrier also exists in the choroid plexus cells and that inhibition of the carrier decreases cerebrospinal fluid (CSF) production. In this study, we used large-dose intravenous furosemide, an inhibitor of Na-K-2Cl carrier, to determine the effects on cisternal CSF ionic composition in acute respiratory acidosis. In pentobarbital-anesthetized mechanically ventilated dogs, renal pedicles were ligated to prevent furosemide-induced diuresis. The experimental group (group II, n = 7) received 400 mg/kg of furosemide intravenously, and group I (control group, n = 7) received the vehicle. In group II, serial serum and CSF furosemide concentrations were approximately 10(-3) and 10(-5) mol/l, respectively. During 5 h of acute respiratory acidosis in both groups, the mean arterial PCO2 increased approximately 25 Torr, with comparable changes in CSF PCO2. In both groups, CSF [HCO3-] and [H+] rose approximately 3 meq/l and 20 neq/l, respectively. Changes in CSF [Na+], [K+], [Cl-], and [Na(+)-Cl-] were also similar and were not significantly different from each other when the two groups were compared. These data show that furosemide at the dose that inhibits NaCl cotransport carrier does not significantly alter ionic composition of cisternal CSF.

This study provided an assessment of the effects of lead on early growth in rats based on structural equation modeling and nested analysis of variance (ANOVA). Structural equation modeling showed that lead in drinking water (250, 500, or 1000 ppm) had a direct negative effect on body weight and tail length (i.e., growth) in female rats during the first week of exposure. During the following 2 weeks of exposure, high correlation between growth measurements taken over time resulted in reduced early postnatal growth. By the fourth week of exposure, reduced growth was not evident. Mating began after 8 weeks of exposure, and exposure continued during gestation. Decreased fetal body weight was detected when the effects of litter size, intrauterine position, and sex were controlled in a nested ANOVA. Lead exposure did not appear to affect fetal skeletal development, possibly because lead did not alter maternal serum calcium and phosphorus levels. The effect of lead on individual fetal body weight suggests that additional studies are needed to examine the effect of maternal lead exposure on fetal development and early postnatal growth.

Objective: Our specific aim in the prospective, longitudinal assessment of 8,251 subjects in the National Health and Nutrition Examination Survey, NHANES I, followup study was to assess the important roles of modifiable dietary and behavioral characteristics in the causation and prevention of coronary heart disease (CHD).Methods: Using NHANES I prospective 10 year followup data, we studied 8,251 subjects; 492 with cardiovascular events and 7,759 without events during the followup period (1971-75 to 1982-84). Using general linear models and logistic regression, we assessed the relationships of CHD risk factors to CHD morbidity and mortality.Results: By logistic regression, the following factors were independently, significantly, and inversely associated with coronary heart and vascular disease deaths and hospitalizations: alcohol intake, dietary riboflavin, dietary iron, serum magnesium, leisure time exercise, habitual physical activity, and female gender. Positive significant independent determinants of CHD events included cigarette smoking, sedimentation rate, Quetelet index, maximum body weight, and age.Conclusions: These associations emphasize the important role of modifiable dietary and behavioral characteristics in the causation and prevention of CHD.

The histologic significance of various changes in the bile ductal structures as observed by cytokeratin immunoperoxidase assay was studied in 122 patients with alcoholic liver disease (ALD) as a part of a large Veterans Administration Cooperative Study on alcoholic hepatitis. Four types of morphologic changes in the biliary structures were observed: 1) proliferation of interlobular bile ducts in the portal tracts; 2) marginal bile ductular proliferation at the periphery of the portal tracts; 3) appearance of bile duct type cells ("oval cells") in the liver parenchyma; and 4) metaplasia of bile duct epithelium to cells resembling hepatocytes. These bile ductal changes correlated strongly with liver fibrosis (p = 0.0003; 0.0003; 0.05; 0.0035, for 1, 2, 3, and 4, respectively), cirrhosis (p < 0.0001 for all four parameters), portal inflammation (p < 0.0001 for 1, 2, and 4; p = 0.0024 for "oval cells"), and with overall histologic severity scores (p < 0.0001; p = 0.0001; p = 0.0017; p = 0.0005, respectively). However, these changes did not correlate significantly with fatty change, parenchymal degeneration and necrosis, cellular infiltrate or Kupffer cell hyperplasia, suggesting that they are probably not the direct consequences of liver cell necrosis. Periportal piecemeal necrosis correlated significantly with both portal bile duct (p = 0.0041) and marginal (p = 0.0078) bile ductular proliferation. Among all these changes, only marginal bile ductular proliferation correlated significantly with Mallory bodies present both in the hepatocytes (p = 0.05) and the bile ducts (p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

ABSTRACT— The histologic significance of various changes in the bile ductal structures as observed by cytokeratin immunoperoxidase assay was studied in 122 patients with alcoholic liver disease (ALD) as a part of a large Veterans Administration Cooperative Study on alcoholic hepatitis. Four types of morphologic changes in the biliary structures were observed: 1) proliferation of interlobular bile ducts in the portal tracts; 2) marginal bile ductular proliferation at the periphery of the portal tracts; 3) appearance of bile duct type cells (“oval cells”) in the liver parenchyma; and 4) metaplasia of bile duct epithelium to cells resembling hepatocytes. These bile ductal changes correlated strongly with liver fibrosis (p = 0.0003; 0.0003; 0.05; 0.0035, for 1, 2, 3, and 4, respectively), cirrhosis (p<0.0001 for all four parameters), portal inflammation (p<0.0001 for 1, 2, and 4; p = 0.0024 for “oval cells“), and with overall histologic severity scores (p<0.0001; p = 0.0001; p = 0.0017; p = 0.0005, respectively). However, these changes did not correlate significantly with fatty change, parenchymal degeneration and necrosis, cellular infiltrate or Kupffer cell hyperplasia, suggesting that they are probably not the direct consequences of liver cell necrosis. Periportal piecemeal necrosis correlated significantly with both portal bile duct (p = 0.0041) and marginal (p = 0.0078) bile ductular proliferation. Among all these changes, only marginal bile ductular proliferation correlated significantly with Mallory bodies present both in the hepatocytes (p = 0.05) and the bile ducts (p = 0.01). Both marginal bile ductular proliferation and “oval cells” correlated significantly with clinical severity of the liver disease as determined by high serum bilirubin and prolonged prothrombin time (Maddrey's discriminant function). This study suggests that: 1) a variety of important morphologic changes occur in the bile ductal structures in ALD, particularly when fibrosis and cirrhosis develop; 2) “oval cells” and bile duct metaplasia are frequent in ALD and appear to be significantly related to the development of fibrosis and cirrhosis; 3) bile ductules are an integral component of piecemeal necrosis in ALD; 4) some of the bile ductal changes may influence the clinical outcome of patients with ALD.