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1. Concerns about the future are a major source of stress for older adults. 2. Contrary to popular opinion, older adults are capable of coping with threats to their well-being. 3. Health care providers can assist older adults in identifying the issues of concern to them and planning strategies to either prevent or minimize the losses they expect to occur in the future.

Background: Clinical trials of hyperfractionated radiation therapy and induction chemotherapy followed by standard radiation therapy have shown improved survival in patients with unresectable nonsmall cell lung cancer (NSCLC). Radiosensitization may improve local tumor control when chemotherapy is given concurrently with hyperfractionated radiation therapy, but also may increase toxicity. A Phase I/II trial, Radiation Therapy Oncology Group 90-15, was designed to evaluate whether this strategy could improve survival with acceptable toxicity and be part of a Phase III trial of chemoradiation sequencing., Methods: Vinblastine (5 mg/M2 weekly x 5 weeks) and cisplatin (75 mg/M2 days 1, 29, and 50) were given during twice-daily irradiation (1.2 Gy, 6 hours apart) to 69.6 Gy in 58 fractions in 6 weeks. Eligible patients had American Joint Committee on Cancer (AJCC) Stage II (unresected) or IIIA-B NSCLC and Karnofsky performance status 70 or greater; there were no weight loss restrictions., Results: Of 42 eligible patients, 76% had greater than 5% weight loss, 45% had T4 primary tumors, and 62% were Stage IIIB. All protocol treatment was completed in 53%. Acute toxicity was predominantly hematologic with 19 of 42 (45%) having Grade 4 toxicity or higher, three (7%) with septic death. Ten of 42 (24%) had Grade 3 or higher esophagitis. There were two (4.7%) patients with Grade 3 or higher (1 lung and 1 esophagus) and two (4.7%) with Grade 4 or higher (1 lung and 1 hematologic) late toxicities. Median survival time was 12.2 months, with an overall 1-year survival of 54%, an estimated 2 year survival of 28% and a 1-year progression free survival of 38%., Conclusions: For patients with unresectable nonsmall cell lung cancer, who were not selected on the basis of weight loss, concurrent hyperfractionated irradiation and chemotherapy had more intense acute toxicity than hyperfractionation alone, but late toxicity was acceptable. One and 2-year survival rates were 54 and 28%, respectively.

Background: A Phase I/II randomized dose-seeking trial was performed to document the severity, time course, and significance of white matter changes seen on serial imaging scans (magnetic resonance imaging, computed tomography) associated with bis-chlorethyl nitrosourea (BCNU) and hyperfractionated cranial irradiation., Methods: Long term survivors (> or = 18 months) were identified from a prospective randomized dose-escalation Phase I/II trial designed to evaluate twice-daily radiotherapy for supratentorial high grade malignant gliomas. All scans were reviewed by a neuroradiologist who had no information about the prescribed dose and fractionation. In the trial, patients were assigned to receive 64.8 Gy, 72.0 Gy, 76.8 Gy, or 81.4 Gy (all fractionated as 1.2 Gy twice a day [bid]), or 48.0 Gy or 54.4 Gy (both in 1.6-Gy bid fractions). Bis-chlorethyl nitrosourea was administered every 8 weeks for 1 year. Of 747 randomized patients, 177 had analyzable scans. The scans reviewed were those acquired preoperatively, immediately postoperatively, 3, 6, 12, and 18 months after radiotherapy. Radiographic endpoints included no white matter change (Grade 0), minimal patchy white matter foci (Grade 1), start of confluence of white matter disease (Grade 2), large confluent areas (Grade 3), confluence with cortical/subcortical involvement (Grade 4), leukoencephalopathy (Grade 5), and possible necrosis (Grade 6) according to the classification of F. Fazekas et al. The effects were scored relative to the baseline preoperative scans. The dose pairs of 48 Gy and 54.4 Gy, 64.8 Gy and 72 Gy, and 76.8 Gy and 81.4 Gy were grouped together for analysis (low, intermediate, and high dose, respectively). Toxicity was analyzed in three ways: Grade 2 or worse, Grade 3 or worse, and Grade 6., Results: Grade 2 or worse changes were observed in 26.6, 27.6, and 40.4% of patients in the low, intermediate, and high dose groups, respectively. Grade 3 or worse changes were observed in 8.3, 20.0, and 36.5% of patients in the low, intermediate, and high dose groups, respectively. Grade 6 changes were observed in 1.6, 4.6, and 19.2% of patients in the low, intermediate, and high dose groups, respectively. No statistically significant differences were observed among treatment groups when toxicity was evaluated as Grade 2 or worse. For toxicity of Grade 3 or worse, an chi-square test revealed P values of 0.04 (low vs. intermediate dose), 0.09 (intermediate vs. high dose), and 0.0005 (low vs. high dose). With the endpoint of possible necrosis (Grade 6), P values were 0.21 (low vs. intermediate dose), 0.05 (intermediate vs. high dose), and 0.003 (low vs. high dose). The median time to radiographic appearance of an effect (15 months) was not influenced by total dose or fraction size., Conclusions: A well described toxicity scale for white matter injury was applied successfully to patients with malignant glioma treated with definitive irradiation. Severe white matter changes continued to increase significantly as the total dose of hyperfractionated cranial irradiation was escalated. The time to onset of the white matter abnormalities appeared to be independent of dose. An ongoing Radiation Therapy Oncology Group study will allow correlation of white matter injury with prospective neuropsychometric testing.

Ruminants learn to avoid many foods that contain toxins by associating the flavor of the foods with aversive postingestive feedback. We hypothesized the emetic system is a cause of aversive feedback, and three experiments were conducted to determine whether antiemetic drugs (diphenhydramine, metoclopramide, dexamethasone) would attenuate food aversions caused by the toxicant lithium chloride (LiCl). Lambs were assigned to one of four treatments: antiemetics plus LiCl (A + L), antiemetics alone (A), LiCl alone (L), or neither antiemetics nor LiCl (C). The LiCl was administered immediately after sheep ate oats, wheat, and milo in Exp. 1, 2, and 3, respectively. The antiemetics were given 1 h before and at the time LiCl was administered to sheep. Lambs that received antiemetics (A and A + L) consistently ate more grain than lambs that did not receive the drugs (C and L) (Exp. 1, P < .08; Exp. 2, P < .05; Exp. 3, P < .08), and there was no interaction between antiemetics and LiCl. Thus, the results of all three experiments were consistent with the hypothesis that antiemetic drugs attenuate food aversions caused by the toxicant LiCl because sheep receiving antiemetic drugs (Group A + L) ate more grain than sheep not receiving the drugs (Group L). In addition, we suggest aversive postingestive feedback limited intake of grain because sheep receiving antiemetic drugs (Group A) ate somewhat more grain than sheep not receiving the drugs (Group C).

Precise reporting of surgical staging and operative data in multi-institutional protocol studies could provide a number of benefits: 1) fewer cases would be discarded because of inadequate data, 2) staff review time would be reduced, 3) there would be assurance that participating surgeons were performing similar operations on similar tumors, 4) the resulting precision in stratification should improve the likelihood of achieving accurate comparison of the treatment options under study, and 5) by comparing the surgical parameters with local-regional control of disease, the specific factors that have a statistically significant correlation with outcome could be identified. This paper presents a computer-based, anatomically oriented reporting instrument that should improve the reliability of surgical data available to multi-institutional protocols.

The Radiation Therapy Oncology Group (RTOG) has embarked on seven phase II or phase III multicentre clinical trials involving a quality of life component. Each quality of life trial used questionnaires or examinations that have been tested for reliability and validity by independent investigators. Each trial includes questionnaires that examine the patient's physical, functional, social, and emotional status, and that measure a specific quality of life issue pertinent to the patient's diagnosis or treatment. Two trial designs have been implemented for studies with quality of life endpoints. One design involves companion trials to the primary treatment study pertaining solely to the quality of life endpoint. The second design integrates the quality of life component into the primary trial design. The RTOG has found a need for education of individuals and institutions expected to administer and obtain the quality of life data. Once the data have been collected several methods for the analysis of the quality of life data are available. However, there is no one best method for analysing quality of life data, thus more than one method should be used in order to provide insight into the data.

To better understand some of the mechanisms that control selection of novel foods differing in postingestive consequences, we offered goats current season's (CSG) and older (OG) growth twigs from the shrub blackbrush (Coleogyne ramosissima). CSG is higher than OG in nitrogen (1.04% v. 0.74%) and it is more digestible in vitro in goat rumen fluid (48% v. 38%). Nevertheless, goats acquire a preference for OG because CSG contains much higher levels of a condensed tannin that causes a learned food aversion. When CSG and OG were offered to goat naive to blackbrush, the goats did not choose either OG or CSG exclusively, but when they finally (1) ate more CSG than OG within a meal (averages of 44 g and 16 g, respectively) and (2) ate enough CSG within the meal to acquire an aversion (average of 44 g), they ingested less CSG than OG from then onward. Accordingly, the change in food selection resulting from postingestive feedback was influenced by the amount of each food ingested within a meal. This was further shown when we varied the amounts of CSG and OG that goats ingested within a meal, and then gave them by gavage the toxin lithium chloride (LiCl). They subsequently ate less of the food eaten in the greatest amount, regardless of whether it was CSG or OG. The salience of the flavor (i.e., taste and odor) of CSG and OG also played a role in the acquired aversion to CSG. Salience evidently was due to a flavor common to both OG and CSG that was more concentrated in CSG. We conclude that the relative amounts of different foods ingested within a meal, and the salience of the flavors of those foods, are both important variables that cause goats to distinguish between novel foods that differ in postingestive consequences.

Purpose: The purpose of this study was to determine whether or not for patients with squamous cell carcinomas of the head and neck, a surgical resection leaving positive margins followed by postoperative adjuvant therapy improves the outcome compared to a matched group of patients treated with definitive radiotherapy alone., Methods and Materials: From January 1985 through January 1990 a consortium of national cooperative groups (Radiation Therapy Oncology Group, Cancer and Leukemia Group B, Eastern Cooperative Oncology Group, Northern California Oncology Group, Southeast Group, and Southwest Oncology Group) conducted a phase III clinical trial testing the efficacy of adjuvant chemotherapy for patients with resectable, squamous cell carcinomas of the head and neck. One hundred and nine patients were excluded from this study due to positive surgical margins. These patients have been followed prospectively with regards to local/regional tumor control, development of distant metastases, and survival. The postoperative treatment of these patients was not specified by the protocol but the majority of patients received postoperative radiotherapy +/- chemotherapy. These patients were compared with a matched group of patients from the Radiation Therapy Oncology Group head and neck database of patients treated with definitive radiotherapy alone using a standard fractionation schema. Matching parameters included primary tumor site, T-stage, N-stage, Karnofsky performance status, and age., Results: Actuarial curves are presented for local/regional control and survival. At 4 years the local/regional control rate is 44% for the positive margin patients compared to 24% for the patients from the data base (p = 0.007). However, there is no significant difference between the survival curves (p = 0.76) with respective median survivals being 18.1 months vs. 17.9 months and 4-year survivals being 29% vs. 25%., Conclusion: While an incomplete excision followed by postoperative therapy does not seem to improve survival compared to treatment with radiotherapy alone, it appears to yield significantly better local/regional control. This would argue for its applicability in selected palliative settings. A follow-up, Phase III trial for patients with advanced tumors may be warranted to test traditional resectability criteria.

Background: Despite notable technical advances in therapy for malignant gliomas during the past decade, improved patient survival has not been clearly documented, suggesting that pretreatment prognostic factors influence outcome more than minor modifications in therapy. Age, performance status, and tumor histopathology have been identified as the pretreatment variables most predictive of survival outcome. However, an analysis of the association of survival with both pretreatment characteristics and treatment-related variables is necessary to assure reliable evaluation of new approaches for treatment of malignant glioma., Purpose: This study of malignant glioma patients used a non-parametric statistical technique to examine the associations of both pretreatment patient and tumor characteristics and treatment-related variables with survival duration. This technique was used to identify subgroups with survival rates sufficiently different to create improvements in the design and stratification of clinical trials., Methods: We used a recursive partitioning technique to analyze survival in 1578 patients entered in three Radiation Therapy Oncology Group malignant glioma trials from 1974 to 1989 that used several radiation therapy (RT) regimens with and without chemotherapy or a radiation sensitizer. This approach creates a regression tree according to prognostic variables that classifies patients into homogeneous subsets by survival. Twenty-six pretreatment characteristics and six treatment-related variables were analyzed., Results: The years). Patients younger than 50 years old were categorized by histology (astrocytomas with anaplastic or atypical foci [AAF] versus glioblastoma multiforme [GBM]) and subsequently by normal or abnormal mental status for AAF patients and by performance status for those with GBM. For patients aged 50 years or older, performance status was the most important variable, with normal or abnormal mental status creating the only significant split in the poorer performance status group. Treatment-related variables produced a subgroup showing significant differences only for better performance status GBM patients over age 50 (by extent of surgery and RT dose). Median survival times were 4.7-58.6 months for the 12 subgroups resulting from this analysis, which ranged in size from 32 to 256 patients., Conclusions: This approach permits examination of the interaction between prognostic variables not possible with other forms of multivariate analysis., Implications: The recursive partitioning technique can be employed to refine the stratification and design of malignant glioma trials.

Purpose: The purpose is twofold: (1) to identify the malignant glioma patients treated in a trial of hyperfractionated radiotherapy (RT) and carmustine (BCNU) who may have been eligible for a stereotactic radiosurgery (SRS) boost; and (2) to compare survival of such patients with that of those considered SRS-ineligible., Patients and Methods: From January 1983 to July 1989, 778 malignant glioma patients were enrolled on Radiation Therapy Oncology Group (RTOG) 83-02, a randomized phase I/II hyperfractionated RT dose-escalation trial with BCNU chemotherapy. The SRS criteria used in a single-institution trial were applied to these patients; they are: Karnofsky performance status (KPS) of greater than 60; well-circumscribed tumor less than 4.0 cm; no subependymal spread; and a location not adjacent to brainstem or optic chiasm., Results: Eighty-nine patients (11.9%) were identified as potentially SRS-eligible. The median survival times (MST) and 18-month survival rates of the 89 eligible and 643 ineligible patients were 14.4 versus 11.7 months and 40% versus 27%, respectively (P = .047). The MST and 18-month survival rate of the 544 SRS-ineligible patients with KPS greater than 60 were 12.1 months and 29%, respectively, and were not statistically inferior to the survival of the SRS-eligible group (P = .21). Multivariate analysis revealed age, KPS, and histopathology to be strongly predictive of survival, and SRS eligibility was also significantly predictive (P = .047)., Conclusion: SRS-eligible patients enrolled on RTOG 83-02 had survival superior to that of the SRS-ineligible group, and this advantage is mainly due to the selection of a subgroup with a high minimum KPS.

Background: Although there have been occasional reports of improved response with greater doses of irradiation for unresected brain metastases, dose escalation has not been systematically studied in a cohort of patients with solitary brain metastasis. The current study examines this group of patients to evaluate dose escalation using accelerated hyperfractionated radiation therapy (XRT) with regard to survival, patterns of failure, and toxicity., Method: Radiation Therapy Oncology Group (RTOG) 85-28, a Phase I/II randomized trial of accelerated hyperfractionated XRT for patients with unresected supratentorial brain metastases, enrolled 153 patients with solitary brain metastasis. Whole brain dose was 32 Gray (Gy) administered in 1.6 Gy fractions twice a day with an interfraction interval of 4-8 hours. Boost dose was escalated to total doses of 48.0, 54.4, 64.0, and 70.4 Gy., Results: Acute and late toxicities were acceptable. The median survival time and 1-year survival rates were 4.9 months and 20% at 48 Gy; 5.4 months and 33% at 54.4 Gy; 7.2 months and 28% at 64 Gy; and 8.2 months and 37% at 70.4 Gy, respectively. Comparison of the upper three dose treatment arms to the 48 Gy treatment arm revealed a superior survival time with doses of 54.4 Gy and greater (P = 0.05). Improvement in neurologic function appeared to increase with dose escalation, with 25% of patients experiencing improvement at doses of 48 Gy, 38% at 54.4 Gy, 50% at 64 Gy, and 63% at 70.4 Gy (P = not significant)., Conclusion: A radiation dose response for survival time appears to exist with the use of accelerated hyperfractionated XRT for patients with unresected solitary brain metastasis.

Background: The third and final randomization of Radiation Therapy Oncology Group (RTOG) 83-02 was performed to identify the maximal tolerated dose and potential efficacy of accelerated hyperfractionated radiation therapy (AHRT) in 1.6 Gy twice-daily fractions for adult malignant glioma., Methods: From December 1987 to July 1989, 304 patients with malignant glioma were stratified by age, performance status, and histologic findings and randomized to receive total AHRT doses of 48.0 or 54.4 Gy, with 80 mg/m2 of bis-chloroethyl nitrosourea (BCNU) for 3 days every 8 weeks. Distribution of other prognostic factors, including neurologic function, extent of surgery, tumor size, and sex, was comparable in each treatment arm., Results: One Grade 5 radiation therapy (RT)-related toxic effect was reported (in the 54.4-Gy treatment arm), and the incidence of late Grade 3-5 RT-related toxic effects at 18 months was 1% at 48.0 Gy and 4% at 54.4 Gy. The median survival times (MST) for the 48.0 Gy and 54.4 Gy treatment arms were 11.7 and 10.8 months, respectively, comparable to the MST in prior RTOG trials with a similar proportion of patients with glioblastoma multiforme (79%). For the 123 patients who were 60 years of age or older, the MST for the 48.0 Gy and 54.4 Gy treatment arms were 8.9 and 10.4 months, respectively, and compare favorably with the MST of 6.0 months reported with standard RT and BCNU treatment used for 101 patients who were 60 years of age or older in two prior RTOG malignant glioma trials (74-01 and 79-18). Although these results differ significantly (P = 0.0015), this contrast is not significant when adjusted by performance status., Conclusions: The maximum tolerated dose of AHRT has yet to be identified, and pursuit of this information may most benefit patients with malignant glioma who are 60 years of age or older.

There currently is inconsistent information regarding the role that musculoskeletal strength (one component of musculoskeletal fitness) may have in lipid and lipoprotein metabolism, and consequently the risk of cardiovascular disease. Results of existing studies have been conflicting and have been influenced by several weaknesses. We provide cross-sectional analyses of the relation between muscular strength and serum lipid and lipoprotein status in a group of 1,193 women and 5,460 men. The large proportion of patients were not involved in formal weight training. As part of a preventive medical examination, patients were tested for maximal upper and lower body strength (one repetition maximum (1RM) bench and leg press). Fasting serum total cholesterol (TC), low-density lipoprotein cholesterol (LDLC), triglyceride (TG), and high density lipoprotein (HDLC) were evaluated for their relation to muscle strength, after adjusting for simultaneous associations with age, body composition, and cardiovascular fitness. Results showed no association between muscular strength and serum TC or LDLC for either men or women and a direct association between upper and lower body strength and TG in men. The direct association between strength and TG in women was not significant. A statistically significant inverse association was seen between muscular strength and HDLC in men only. These data suggest no beneficial effect, and perhaps an adverse association of muscular strength on lipid and lipoprotein status.

Thirty-six sedentary, mildly obese (30-40% fat), premenopausal women (29-49 yr) were randomly assigned to one of two dietary regimens for an 8-wk double-blind, parallel study of the effect of moderate caloric restriction and macronutrient variation on maximal physical performance. Group 1 (N = 19) consumed 4186 kJ.d-1 (1000 kcal.d-1) with a diet composition of 40% fat, 40% carbohydrate (CHO), and 20% protein. Group 2 (N = 17) also consumed 4186 kJ.d-1 but varied the percent kilojoules to 20% fat, 60% CHO, and 20% protein. Maximal aerobic power was measured using a modified Balke protocol, strength was assessed using isotonic bench and leg press machines and a Cybex 340 isokinetic device during knee flexion and extension, and muscular endurance was taken as the number of sit-ups performed in 1 min. Pre- to post-testing revealed significant (P less than or equal to 0.05) reductions in body weight (group 1, -7.4 kg; group 2, -6.5 kg) within both groups. No significant changes were seen in maximal aerobic power within both groups. Strength measures for both groups showed a trend toward reduction but statistical significance was only evident in right knee extension for group 1 and left knee extension for group 2 (P less than or equal to 0.05). Sit-up number increased nonsignificantly for both groups. Between group differences were not found in any body weight, body composition, or physical performance index. We therefore conclude that in mildly obese women, maximal exercise performance is relatively unimpaired after 8 wk of caloric restriction with either of two diets differing moderately in their macronutrient content.

103 patients with the diagnosis of AAF were identified from the RT/BCNU arms of 3 RTOG malignant glioma trials. Pre-treatment tumor size was less than 5 cm for 48% and greater than or equal to 5 cm for 52%, and tumor sites were frontal lobe in 55%, temporal in 25%, and parietal in 16%. Surgery consisted of biopsy for 30%, partial resection for 56%, and total resection for 14%. Extent of surgery correlated with age, with 81% of patients less than 40 undergoing partial/total resection vs. 60% of those over 40 (P = 0.019). The median survival time (MST) of patients undergoing partial/total resection was 49 mo., vs. 18 mo. for those biopsied only (P = 0.002). Patients with frontal location had longer MST than those with non-frontal lesions (MST: 49 vs. 25 mo., P = 0.047), while no survival difference was apparent by univariate analysis of tumor size. Multivariate analysis demonstrated that only younger age, frontal location, and smaller tumor size correlated significantly with extended survival. Extent of surgery was not predictive. The close correlation between young age and extensive surgery obscures the survival advantage for greater surgery seen with univariate analysis. Smaller tumor size and frontal location favorably influence outcome even when adjusted by age.

To test the efficacy of sequential chemotherapy as an adjuvant to surgery and postoperative radiotherapy for patients with locally-advanced but operable squamous cell cancers of the head and neck region, a randomized clinical trial was conducted under the auspices of the Head and Neck Intergroup (Radiation Therapy Oncology Group, Southwest Oncology Group, Eastern Oncology Group, Cancer and Leukemia Group B, Northern California Oncology Group, and Southeast Group). Eligible patients had completely resected tumors of the oral cavity, oropharynx, hypopharynx, or larynx. They were then randomized to receive either three cycles of cis-platinum and 5-FU chemotherapy followed by postoperative radiotherapy (CT/RT) or postoperative radiotherapy alone (RT). Patients were categorized as having either "low-risk" or "high-risk" treatment volumes depending on whether the surgical margin was greater than or equal to 5 mm, there was extracapsular nodal extension, and/or there was carcinoma-in-situ at the surgical margins. Radiation doses of 50-54 Gy were given to "low-risk" volumes and 60 Gy were given to "high-risk" volumes. A total of 442 analyzable patients were entered into this study with the mean-time-at-risk being 45.7 months at the time of the present analysis. The 4-year actuarial survival rate was 44% on the RT arm and 48% on the CT/RT arm (p = n.s.). Disease-free survival at 4 years was 38% on the RT arm compared to 46% on the CT/RT arm (p = n.s.). At 4 years the local/regional failure rate was 29% vs. 26% for the RT and CT/RT arms, respectively (p = n.s.). The incidence of first failure in the neck nodes was 10% on the RT arm compared to 5% on the CT/RT arm (p = 0.03 without adjusting for multiple testing) and the overall incidence of distant metastases was 23% on the RT arm compared to 15% on the CT/RT arm (p = 0.03). Treatment related toxicity is discussed in detail, but, in general, the chemotherapy was satisfactorily tolerated and did not affect the ability to deliver the subsequent radiotherapy. Implications for future clinical trials are discussed.

Objective: We studied whether the quantity and quality of walking necessary to decrease the risk of cardiovascular disease among women differed substantially from that required to improve cardiorespiratory fitness., Design: A randomized, controlled, dose-response clinical trial with a follow-up of 24 weeks., Setting: A private, nonprofit biomedical research facility., Participants: One hundred two sedentary premenopausal women, 20 to 40 years of age, were randomized to one of four treatment groups; 59 completed the study (16 aerobic walkers [8.0-km/h group], 12 brisk walkers [6.4-km/h group], 18 strollers [4.8-km/h group], and 13 sedentary controls). Eighty-one percent were white, 17% black, and 2% Hispanic., Intervention: Intervention groups walked 4.8 km per day, 5 days per week at 8.0 km/h, 6.4 km/h, or 4.8 km/h on a tartan-surfaced, 1.6-km track for 24 weeks., Main Outcome Measures: Fitness (determined by maximal oxygen uptake) and cardiovascular risk factors (determined by resting blood pressure and serum lipid and lipoprotein levels)., Results: As compared with controls, maximal oxygen uptake increased significantly (P less than .0001) and in a dose-response manner (aerobic walkers greater than brisk walkers greater than strollers). In contrast, high-density lipoprotein cholesterol concentrations were not dose related and increased significantly (P less than .05) and to the same extent among women who experienced considerable improvements in their physical fitness (8.0-km/h group, +0.08 mmol/L) and those who had only minimal improvements in fitness (4.8-km/h group, +0.08 mmol/L). High-density lipoprotein cholesterol also increased among the 6.4-km/h group, but did not attain statistical significance (+0.06 mmol/L; P = .06). Dietary patterns revealed no significant differences among groups., Conclusion: Thus, we conclude that vigorous exercise is not necessary for women to obtain meaningful improvements in their lipoprotein profile. Walking at intensities that do not have a major impact on cardiorespiratory fitness may nonetheless produce equally favorable changes in the cardiovascular risk profile.

The achievement of chronic blood pressure (BP) control in persons with mild hypertension is of central strategic concern in the prevention of hypertension-related morbidity and mortality. Epidemiologic and longitudinal studies suggest that regular participation in physical activity may be beneficial both in preventing hypertension and in lowering an already elevated BP. Moreover, preliminary analyses from our center suggest that cardiorespiratory fitness and, by inference, aerobic exercise may be of benefit in reducing mortality rates in hypertensive patients. When prescribing exercise with the intention of reducing an elevated BP and attenuating the risk for coronary artery disease, several factors must be considered to optimize the likelihood of a safe and effective response. These factors include specific safety aspects, and the type, frequency, intensity, and duration of exercise. In this respect, we recommend that aerobic exercise be performed at an intensity corresponding to 55 and 85% of the maximal heart rate and that the duration and frequency of training be modulated to achieve a weekly energy expenditure of between 14 and 20 kcal/kg of body weight. For those patients who require drug therapy, the interaction between the specific antihypertensive agent and exercise must also be considered.

A retrospective analysis of the effect of local control on the development of distant metastases was performed in 2648 patients with carcinoma of the head and neck selected from the RTOG database. The 5-year time-adjusted incidence of distant metastases was 21% for patients who were in local-regional control at 6 months after the start of treatment, compared to 38% for local-regional failure patients (p less than 0.001). The incidence of distant metastases detected between the interval of 6 months to 2.5 years after treatment was significantly increased in patients with tumors of the oral cavity, oropharynx, supraglottic larynx, and glottis who developed local-regional failure within this time period, compared to those who remained locally controlled (19% distant metastases for local-regional failure vs 7% for local-regional control (p less than 0.001)). In contrast, there as no difference in the incidence of distant metastases in patients with carcinoma of the nasopharynx or hypopharynx regardless of the local-regional disease status. A Cox proportional hazards regression analysis demonstrated that local-regional control was the most significant variable affecting the development of distant metastases, followed by tumor site, N-stage, and T-stage. For all tumor sites, except for the hypopharynx and nasopharynx, improvements in local-regional control are likely to improve survival. Tumors of the hypopharynx and nasopharynx have a higher probability of micro-metastatic dissemination at the time of initial diagnosis, and until effective methods to treat disseminated disease are developed, the effect of local control on survival will not be readily discerned.

Recently, a procedure has been established for the determination of the maximally accumulated oxygen deficit (MAOD) (Medbo et al., J. Appl. Physiol. 64:50-60, 1988) as an indicator of anaerobic capacity. We hypothesized that, if MAOD were a valid indicator of anaerobic capacity, it should distinguish between aerobically and anaerobically trained athletes and correlate with other existing anaerobic testing measures. Subjects were four distance and five middle distance runners, three sprinters, and four controls. The subjects ran for 2-3 min at 125-140% of VO2max until exhaustion, and the accumulated O2 deficit for that run was calculated by an extrapolation procedure. Subjects also performed the Wingate cycle ergometer test and runs of 300, 400, and 600 m. (Only athletes performed the runs.) Post-exercise blood lactates were obtained following the supramaximal treadmill run. MAOD (in O2 equivalents-ml.kg-1) was higher for the sprinters (78) and middle distance runners (74) than for the long distance runners (56) and control subjects (56) (P less than or equal to 0.05), indicating a greater anaerobic capacity for the former two groups. Consequently, the relative anaerobic contribution was larger for the sprinters (39%) and middle distance runners (37%) than for the long distance runners (30%; P less than or equal to 0.05). Significant correlations were found between MAOD and both Wingate power and treadmill work for all subjects and between Wingate power, Wingate capacity, treadmill work, and 300 m time for the athletes, suggesting that relationships do exist among MAOD and other anaerobic test measures. Potential use of MAOD as an indicator of anaerobic capacity is therefore promising and should be further explored.

The literature on the distinction between primary and secondary depression is reviewed. The research data indicate that less severe, non life-threatening suicidal thoughts and behaviours occur more often in patients with secondary depression than in those with primary depression and that the prognosis for secondary depression after somatic forms of therapy is poorer than that for primary depression. The data also suggest that secondary depressives, unlike primary depressives, suffer from chronic dysphoria. It is concluded that, because the available evidence suggests that there are no qualitative differences between the episodes of primary and secondary depression, future research should concentrate on investigating the characteristics of different groups of patients with secondary depression rather than on comparisons between primary and secondary depression in general.

Over the past 30 years, mortality rates from coronary artery disease (CAD) have decreased by more than 30% in the United States. However, CAD remains the major public health problem in this country. There is now substantial evidence linking exercise training to a reduced risk for CAD and for mortality after myocardial infarction. The actual mechanism by which physical activity aids in reducing the risk for developing or dying from CAD has still to be elucidated. Several highly plausible mechanisms have been postulated, including decreased myocardial oxygen demand, increased myocardial oxygen supply, reduced propensity toward ventricular arrhythmias, reduced platelet aggregation, increased plasma fibrinolytic activity, and modification of multiple CAD risk factors. Irrespective of the precise mechanism, it now appears that lower levels of physical activity are needed to reduce the risk for CAD than are needed to optimize cardiorespiratory fitness. In this regard, we recommend that the type, frequency, intensity, and duration of exercise training be modulated to achieve a weekly energy expenditure of between 14 and 20 kilocalories per kilogram of body weight. Although aerobic activities should be emphasized, muscle strengthening and flexibility exercises should also be incorporated into the training program in order to promote musculoskeletal health.

This is a report of a 10-year median follow-up of a randomized, prospective study investigating the optimal sequencing of radiation therapy (RT) in relation to surgery for operable advanced head and neck cancer. In May 1973, the Radiation Therapy Oncology Group (RTOG) began a Phase III study of preoperative radiation therapy (50.0 Gy) versus postoperative radiation therapy (60.0 Gy) for supraglottic larynx and hypopharynx primaries. Of 277 evaluable patients, duration of follow-up is 9-15 years, with 7.6% patients lost to follow-up before 7 years. Loco-regional control was significantly better for 141 postoperative radiation therapy patients than for 136 preoperative radiation therapy patients (p = 0.04), but absolute survival was not affected (p = 0.15). When the analysis was restricted to supraglottic larynx primaries (60 postoperative radiation therapy patients versus 58 preoperative radiation therapy patients), the difference for loco-regional control was highly significant (p = .007), but not for survival (p = 0.18). In considering only supraglottic larynx, 78% of loco-regional failures occurred in the first 2 years. Thirty-one percent (18/58) of preoperative patients failed locally within 2 years versus 18% (11/60) of postoperative patients. After 2 years, distant metastases and second primaries became the predominant failure pattern, especially in postoperative radiation therapy patients. This shift in the late failure pattern along with the increased number of unrelated deaths negated any advantage in absolute survival for postoperative radiation therapy patients. The rates of severe surgical and radiation therapy complications were similar between the two arms. Because of an increased incidence of late distant metastases and secondary primaries, additional therapeutic intervention is required beyond surgery and postoperative irradiation to impact significantly upon survival.

Chronic essential hypertension is a major public health problem afflicting an estimated 15 to 30% of persons from most Western industrialised countries. Persons with mild hypertension (diastolic blood pressure between 90 and 104mm Hg and/or systolic blood pressure between 140 and 159mm Hg) represent the overwhelming majority of hypertensive individuals in the general population. The achievement of long term blood pressure control in these individuals is of central strategic concern in the prevention of hypertension-related morbidity and mortality. Epidemiological studies suggest that regular participation in physical activity may be beneficial in preventing hypertension. The findings of epidemiological studies are supported by a recent meta-analysis of 25 longitudinal aerobic training studies, in which the average sample-size-weighted reductions in resting systolic and diastolic blood pressures were 10.8mm Hg and 8.2mm Hg, respectively. Moreover, preliminary analyses from our centre suggest that cardiorespiratory fitness and, by inference, aerobic exercise training may be of benefit in reducing mortality rates in hypertensive patients. When compiling an exercise prescription with the intention of reducing an elevated blood pressure and attenuating the risk for coronary artery disease, several factors must be considered in order to optimise the likelihood of a safe and effective response. Specifically, the 5 basic components of the exercise prescription for patients with mild hypertension are safety aspects, the type of exercise to be performed, and the frequency, intensity and duration of exercise training. For those patients who require pharmacotherapy, the interaction between the specific antihypertensive agent and exercise responses must also be considered. We recommend that aerobic exercise training be performed at an intensity corresponding to 60 to 85% of the maximal heart rate and that the duration and frequency be modulated to achieve a weekly energy expenditure of between 14 and 20 kcal/kg of bodyweight.

The development of lesions in adult and neonatal New Zealand White rabbits following intradermal inoculation of Shope fibroma virus was studied by immunofluorescence for viral antigens. T-cells, and immunoglobulin. In adults a self-limiting local fibroxanthosarcomatous tumor was rejected within 10-12 days in association with a dense infiltration of T-cells. In neonates expanding skin lesions were associated with systemic presence of virus in the reticuloendothelial system. In surviving infected neonates, granulomas formed at the site of infection after 3 weeks. These reactions may have limited further dissemination of the virus. These results support the hypothesis that the progressive disease produced by Shope fibroma virus in neonatal rabbits may be due to the inability of the reticuloendothelial system to clear infectious virus.

Seventy-four neonates with respiratory distress syndrome had cytologic study of tracheal aspirates. Thirteen, all of whom were receiving intravenous lipid and nothing orally had abundant macrophages with foamy cytoplasm, positive for intracytoplasmic lipid by Sudan black stain, in the tracheal aspiration specimens. Cytologic surveillance of tracheal aspiration specimens may be a useful method of monitoring infants receiving intravenous lipid infusions.

The Bowman-Birk protease inhibitors from soybeans and chick peas suppress in vitro malignant transformation. This fluorescent microscopy study is designed to visualize the cellular site of action of these protease inhibitors. Binding and internalization of active protease inhibitors occur over a time course of 2 h. The rate and character of fluorescent micrographs obtained are compared to insulin as a positive control. Internalization of both molecules is completely blocked at 4 degrees C. Interpretation of the fluorescent micrographs in conjunction with biochemical data suggests the anticarcinogenic action of Bowman-Birk type protease inhibitors may involve receptor-mediated endocytosis resulting in the internalization of both the protease inhibitors and a membrane-associated protease.

Diaphragm strength was measured as maximal transdiaphragmatic pressure (Pdi) during airway occlusion in 38 infants aged 11.6 +/- 0.5 (S.E.) months postconception (mpc), range 8-21 mpc. All infants were asymptomatic at the time of study and required no mechanical ventilatory assistance. Ten infants had previous surgical correction of abdominal wall defects (gastroschisis/omphalocele); 10 infants had previous surgical correction of congenital diaphragmatic hernia; and 18 infants had no thoracic or abdominal surgery. The mean maximal Pdi for all infants was 72 +/- 3 cmH2O. There were no significant differences between the three groups. All infants with a maximal Pdi of less than 60 cmH2O were aged less than 10 mpc. After 13 mpc there was no significant increase in maximal Pdi. Between the ages 8-13 mpc there was a significant positive correlation between maximal Pdi and age postconception (r = 0.87, P less than 0.0005), reflecting a developmental pattern of increasing maximal transdiaphragmatic pressure in infants during crying.

Diaphragm muscle strength was measured as maximal transdiaphragmatic pressure during airway occlusion in ten near-miss sudden infant death syndrome infants aged 4.1 +/- 0.6 (SE) months post-term, range 2 to 7 months, and ten control infants aged 4.5 +/- 0.8 months post-term, range 0.8 to 8 months. In the near-miss sudden infant death syndrome group, the mean maximal transdiaphragmatic pressure was 106 +/- 6 cm H2O, range 78 to 132 cm H2O, compared with a mean maximal transdiaphragmatic pressure 86 +/- 4 cm H2O, range 69 to 106 cm H2O, in the control group. Diaphragm strength is normal or increased in near-miss sudden infant death syndrome infants.

The parameters of cell-mediated immune responses of adult rabbits infected with Shope fibroma virus (SFV) were characterized by measurement of the size of local draining nodes, number of cells per lymph node, mitogen responses of lymphocytes, and kinetics of virus-specific cell-mediated lymphocytotoxicity (CML). In addition, the cytolytic effector population was characterized. After intradermal injections, tumors appeared within 3-4 days, reached maximum size in 10-12 days, and then regressed completely with 24 days. The size of local popliteal lymph nodes, in particular the diffuse cortex (paracortex), and the number of cells per node increased during tumor growth but then declined as the tumor regressed. Maximum specific CML to SFV-infected kidney cell monolayers (RK-13) occurred 10 days after inoculation of SFV and correlated with the initiation of tumor regression. Adult cytotoxic lymphocytes passed through nylon wool, and most of their activity was removed by treatment with antithymocyte globulin plus complement. Cytotoxic T-cells from SFV tumor-bearing rabbits killed only targets infected with SFV and not targets uninfected or infected with vaccinia virus. Therefore, T-cell-mediated virus-specific CML appeared as a major immune effector mechanism that correlated with tumor regression. However, antibody-dependent cell-mediated and NK cytotoxicity were also demonstrable. The presence of different cell-mediated cytotoxic mechanisms suggested a heterogeneity of effector mechanism.

The late B-cell proliferative phase of the in vitro antibody response by rabbit spleen cells is highly susceptible to suppression by activated T cells. The in vitro antisheep erythrocyte plaque-forming cell (PFC) response by spleen cells from normal or primed rabbits can be suppressed by adding concanavalin A (Con A), Con A-prestimulated peripheral blood or spleen lymphocytes, or supernates from Con A-prestimulated peripheral blood lymphocytes. The suppression is not mediated by a direct interaction of Con A with responding cells as shown by the effectiveness of prestimulated cells. Primed spleen cultures remain sensitive to Con A suppression as late as 72 h after initiation, and the addition of Con A after 24-72 h rapidly stops the increase in the number of PFC. T cells are required for Con A addition to be effective but the suppression can be induced at a time when T-helper cells are no longer necessary. Further, the suppressive effect of Con A addition is abrogated by specific antisera to rabbit T cells. We propose that Con A activates suppressor T cells which then exert their effects on proliferating PFC or their immediate precursor B cells. The early inductive or recruitment phase of the response is probably not blocked by suppressor cells. Also, there is an apparent relationship between the number of proliferating B cells and the number of suppressor cells required. Finally, the difficulties in inducing a stimulatory effect by Con A and the prolonged period that Con A addition is suppressive suggests that the rabbit has relatively more and/or longer-lived suppressor cells than the mouse and may be a particularly useful species for studying suppressive phenomena and their mechanisms.