Response of mouse hepatoma cell methylenetetrahydrofolate polyglutamates to folate deprivation.

The behavior of methylenetetrahydrofolate polyglutamate conjugates in cultured mouse hepatoma cells which were starved of folate has been investigated. Folate deprivation caused methylenetetrahydrofolate levels to decrease an order of magnitude. This diminished pool consisted essentially completely of the octaglutamate form. Replenishment of the media with folate caused a slow recovery to normal levels of methylenetetrahydrofolate with undetectable quantities of shorter chain length polyglutamates observable during recovery. Leucovorin, on the other hand, caused a much more rapid recovery to normal levels and gave rise to the early appearance of short chain length polyglutamate intermediates.

Combined small-cell and non-small-cell lung cancer.

Nine (2%) of 429 small-cell lung cancer (SCLC) patients seen at Vanderbilt University between 1977 and 1983 had a combined subtype SCLC at diagnosis (ie, small-cell carcinoma plus squamous cell or adenocarcinoma). Staging procedures and chemotherapy treatment were uniform for all 429 patients. The diagnosis of combined histology was established via bronchoscopy (six patients), needle aspiration biopsy (one), lymph node biopsy (one), and thoracotomy (one). The clinical characteristics of the combined subtype patients were similar to patients with other subtypes of SCLC (ie, there were no differences in median age, sex, performance status, and stage of disease). However, patients with a combined subtype histology had a higher incidence of peripheral lesions on chest x-ray (56% v 14%, P less than .001) and a lower median lactate dehydrogenase (LDH) (301 IU/L v 341 IU/L, P = .0002) at diagnosis. The overall response to chemotherapy (57% v 78; P = .5) and the median survival (8 months v 10 months; P = .4) of the combined subtype patients were similar to patients with other subtypes of SCLC. Two (22%) combined histology patients survived greater than or equal to 5 years. Both had had surgical resection in addition to chemotherapy. These data suggest that the combined subtype of SCLC is clinically similar to pure SCLCs and that surgery may play a prominent role in the management of these tumors. The possibility of a combined histology tumor should be considered in patients thought to have SCLC on the basis of limited biopsy material, such as a needle aspiration or bronchial biopsy, and when the primary lesion is peripherally located on chest x-ray.

An immunologic assessment of brain-associated IgG in senile cerebral amyloidosis.

Frontal and occipital lobes were taken within four hours of death from four senile patients (77-94 years) and frozen at -70 degrees C. After thawing at room temperature, gray and white matter were separated and subjected to sequential elution at pH 7.4 and pH 2.5. The eluates were processed for isoelectric focusing on 2.5% polyacrylamide gels and stained with silver nitrate; immunoblotting was done on agarose gels and stained by immunoperoxidase for IgG and light chains. Quantitation of the amount of IgG present in neutral and acidic eluates was performed by immunonephelometry and ELISA. Only the neutral eluates contained significant amounts of IgG, which were usually polyclonal. These data indicate that IgG associated with senile cerebral amyloid are not bound to any brain or vascular component and the data do not support the occurrence of an intraparenchymal immune response.

High-dose chemotherapy and peripheral blood stem cell infusion in patients with non-Hodgkin's lymphoma: results of outpatient treatment in community cancer centers.

The outcomes for patients with non-Hodgkin's lymphoma (NHL) treated with high-dose chemotherapy (HDC) and peripheral blood stem cell (PBSC) infusion by practicing oncologists in community cancer centers in the United States were determined. Eighty-three patients with NHL, who had failed conventional chemotherapy, underwent mobilization of PBSC with chemotherapy and a recombinant growth factor in an outpatient facility. At a median of 40 days (range 26-119) after mobilization chemotherapy all received carmustine (300 mg/m2 x 1), etoposide (150 mg/m2 twice a day x 4 days), cytarabine (100 mg/m2 twice a day x 4 days) and cyclophosphamide (35 mg/kg x 4 days) (BEAC) followed by infusion of unmanipulated PBSC in an outpatient facility. The probabilities of treatment-related mortality, relapse/progression, overall survival (OS) and event-free survival (EFS) at 3 years for all 83 patients were 0.07, 0.57, 0.49 and 0.38, respectively. The probabilities of relapse/progression, OS and EFS at 3 years for 28 patients who had failed primary induction chemotherapy were 0.55, 0.42 and 0.38, respectively. The probabilities of OS and EFS for 27 patients in untreated first relapse were 0.52 and 0.44, respectively, as compared to 0.56 and 0.32, respectively, for 18 patients who had reinduction attempts prior to receiving mobilization chemotherapy (P = 0.81 for OS and 0.99 for EFS). No significant risk factors for the outcomes of TRM, relapse/progression, OS or EFS could be identified. These data demonstrate that approximately 40% of patients with NHL who have failed conventional chemotherapy become long-term disease-free survivors after mobilization chemotherapy, high-dose BEAC and PBSC infusion administered in an outpatient setting in community cancer centers, with the major cause of failure being relapse. Results obtained in this study are comparable to published data in similar patient populations receiving therapy as inpatients, suggesting that clinical trials involving well-tested HDC regimens can be carried out safely in this setting.

Caffeine alters ventilatory and gas exchange kinetics during exercise.

The purpose of these experiments was to determine the effects of oral caffeine ingestion on the kinetics of oxygen uptake (VO2), expired carbon dioxide output (VCO2), and expired ventilation (VE) in the transition from rest to exercise. Nine male subjects underwent three repetitions of constant load cycle ergometer exercise (approximately 80% ventilatory threshold) on two occasions. A single blind experimental procedure was followed, with one trial being performed 60 min after the subject ingested caffeine (7 mg X kg-1), while the second trial required the subject to ingest a placebo with the treatment order being counterbalanced. Ventilation and gas exchange were monitored by open circuit techniques. The data from three repetitions of the same protocol were pooled and modeled with a single-component exponential function incorporating a time delay: (formula; see text) Kinetic analysis of VO2 revealed no significant difference (P greater than 0.05) in the mean response time between treatments. In contrast, the mean response time for VCO2 and VE were longer (P less than 0.05) for the caffeine trial when compared to the control experiment. These data suggest that caffeine will influence both VCO2 and VE kinetics in the transition from rest to work and should be considered by investigators when planning experiments to study ventilatory and gas exchange kinetics during exercise.

Sequential treatment including high-dose chemotherapy with peripheral blood stem cell support in patients with high-risk stage II-III breast cancer: outpatient administration in community cancer centers.

The authors determined outcomes for patients with localized high-risk breast cancer undergoing sequential outpatient treatment with conventional-dose adjuvant therapy, chemotherapy, and growth factor mobilization of peripheral blood stem cells (PBSC) and high-dose chemotherapy (HDC) with PBSC support in community cancer centers. Ninety-six patients with stage II-IIIB noninflammatory breast cancer with 10 or more positive lymph nodes and a median age of 46 years (range, 22-60 years) were treated with: 1) doxorubicin, 5-fluorouracil, and methotrexate (AFM), four courses at 2-week intervals; 2) cyclophosphamide (4 g/m2) and etoposide (600 mg/m2) (CE), followed by filgrastim (6 microg/kg per day) and PBSC harvest; and 3) cyclophosphamide (6 g/m2), thiotepa (500 mg/m2), and carboplatin (800 mg/m2) (CTCb), followed by PBSC infusion. All 96 patients received AFM, 95 (99%) received CE, and 95 (99%) received CTCb with a median hospital stay of 12 days (5-34 days) for all phases of treatment. Sixty-nine patients (72%) are alive, 55 (57%) without relapse at a median follow-up of 53 months (range, 37-77 months). One patient (1%) died of acute myeloid leukemia and all other deaths were associated with recurrent breast cancer. The probabilities of event-free survival (EFS) at 4 years for patients with or without locally advanced disease were 0.37 and 0.69, respectively (p = 0.004), and 0.71 and 0.48 for patients who were estrogen/progesterone receptor (ER/PR) positive or ER/PR negative, respectively (p = 0.016). In multivariate analyses, locally advanced disease (relative risk, 2.3; p = 0.021) and ER/PR-negative hormone receptor status (relative risk, 2.2; p = 0.014) were the only adverse risk factors for EFS identified. Patients with zero, one, or two of these adverse risk factors had 4-year EFS of 0.80, 0.56, and 0.33, respectively. The sequential administration of AFM, CE, and CTCb followed by PBSC in an outpatient community setting was well tolerated in patients with high-risk stage II-III breast cancer. More intensive or more novel treatment strategies will be required to decrease relapses in patients who have ER/PR-negative tumors and/or have locally advanced disease.

A comparison of single-versus multi-modal exercise programs: effects on aerobic power.

The purpose of this study was to compare the effects of a 10-week single mode (SM) training program (walk/jog) versus a multimode (MM) training program (walk/jog, cycle, arm crank) on peak aerobic power (VO2 peak) during three ergometry modes. Twenty Ss were stratified initially according to gender and then randomly assigned to either of the treatment groups. Seven additional Ss served as controls. Peak VO2 was determined during treadmill running, cycle ergometry and arm crank ergometry prior to and after ten weeks of training. Training for the SM group (N = 9) consisted of walk/jog three days per week for five weeks at approximately 50-60% peak VO2 and an energy cost of approximately 2400 kJ per week, then increased to approximately 3200 kJ for the duration of the study. Training for the MM group (N = 8) was isoenergetic to the SM group. However, the training differed in that subjects exercised one day walk/jog, one day cycling, and one day arm cranking. Controls were tested twice with no treatment between. Post-training VO2 peaks for the three ergometry modes were analyzed with an analysis of covariance, utilizing pre-training scores as a statistical covariate. The post-training SM VO2 was found to be significantly greater than either the MM or C when testing on the treadmill. No other comparison was statistically significant. These data support the concept that a conditioning program can become sufficiently variable so that expected increases in aerobic power are not produced, despite the fact that isoenergetic training is undertaken.(ABSTRACT TRUNCATED AT 250 WORDS)

Coagulation and fibrinolytic responses to exercise and cold exposure.

This study examined the effect of acute cold exposure on coagulation (PTT) and fibrinolysis (ELT), and the effect of cooling on subsequent exercise-induced coagulation and fibrinolytic responses. Ten male volunteers were tested at 5 degrees C and 28 degrees C on alternate days. Each subject began by sitting quietly for 60 min. Each then exercised on a cycle ergometer at 50 W for 5 min followed by 150 W for 10 min. Venous blood samples were taken before rest, after rest, and after exercise for each temperature on each of the two days. PTT, ELT, and hematocrit (HCT) were determined at each interval. Rectal temperature (Tre) and mean skin temperature (Tsk) were assessed at 15-min intervals throughout. Tsk was stable under neutral conditions but declined rapidly in the cold environment. Tre response was more complex but was significantly different for one contrast only (CE less than NE). ELT was shortened to 74, 62, and 44% while HCT increased to 107, 107, and 111% of pretest values for CR, NE, and CE, respectively. No significant change was noted for PTT. It is concluded that acute cold exposure as well as exercise stress results in an increase in ELT activity of blood; simultaneous enhancement of the coagulation status of the blood in response to stress is not inextricably linked to an elevation of fibrinolytic activity, a result that questions the importance of the Hageman factor dependent pathway between coagulation and fibrinolysis.

Hypoxia: a stimulus for tissue plasminogen activator release in humans?

Six healthy male volunteers between the ages of 22 and 33 years inspired normoxic (20.9% O2) and hypoxic (10% O2) gas mixtures continuously for 15 min on separate days while resting supine. The order of testing was counterbalanced. Heart rates (b.min-1), minute ventilation (L.min-1), transcutaneous PO2 (mm Hg) and euglobulin lysis times (min) were determined at the onset and at regular intervals. Heart rates and minute ventilation increased significantly with most of the change occurring by min 5. Transcutaneous PO2 declined exponentially but stabilized by min 10. Euglobulin lysis time response was highly variable with individual changes from 2-38% observed. Further, the group appeared to fall into two classes that could be described as responders versus non-responders. The variability of these data suggest that hypoxia may not be a direct cause of tissue plasminogen activator release into the circulation but that susceptible individuals may exhibit a substantial fibrinolytic response to hypoxia. Those factors that explain the variability require further elucidation.

A review of physical exercises recommended for VDT operators.

This paper presents an evaluation of exercises that have been recommended for the prevention of musculoskeletal discomfort among VDT/office workers. 127 individual exercises were analysed for their suitability for performance in VDT workplaces. Additionally, each exercise was judged in terms of its safety and its compliance with principles of physiotherapy. Results showed that, in the majority of cases, the prepared instructions for the exercises were satisfactory and the exercises could be readily performed at the workstation. However, over a third of the exercises were conspicuous and potentially embarrassing to perform, and half would significantly disrupt the work routine. Additionally, a number of the exercises posed potential safety hazards, exacerbated biomechanical stresses common to VDT work, or were contraindicated for persons with certain health problems. These findings suggest a need for greater attention to both the practical and the therapeutic aspects of exercises promoted for VDT users.

Relationship between perceptual style and ability to reproduce a standard work task.

The present study examined the relationship between perceptual style and perception of physical effort. Perceptual style of 10 men and 10 women was assessed by the rod-and-frame apparatus. Perception of physical effort was defined as the difference in heart-rate responses between a standard work task and the subject's self-selected task. Heart-rate response on the pre-selected standard work task on a cycle ergometer (600 kpm.min.-1) was extremely variable, ranging from 111 to 188 beats per minute (M = 153 +/- 23.5). However, average error between heart rate during the standard work task and the subjects' self-adjusted workload was extremely low (range 0 to 18 beats per minute; M = 5.4 +/- 5.5 beats per minute). Pearson correlation of .78 showed a moderate relationship between heart rate and rating of perceived effort, but was nonsignificant (-.12) between perceptual style and perception of physical effort. The data confirm the absence of a significant relationship between perceptual style (i.e., field dependence-independence) and ability to reproduce a standard work task. In addition, these results suggest that there has been possible bias in studies of relationships between heart rate and rating of perceived effort or workload and rating of perceived effort during incremental testing.

Exercise efficiency during arm ergometry: effects of speed and work rate.

The purpose of this investigation was to determine the effects of increasing work rate and speed of movement on efficiency during steady-state arm crank ergometry (ACE). Ten men exercised at speeds of 50, 70, and 90 rpm and four power outputs (15, 30, 45, and 60 W). O2 uptake determinations were made using open-circuit spirometry and energy expenditure was calculated from the respiratory exchange ratio. Gross (work accomplished/energy expended), work (unloaded cranking as base-line correction), and delta (measurable work as base-line correction) efficiencies were computed. A curvilinear relationship was found to exist between work rate and energy expenditure, which dictates that both delta and work efficiency will decrease with increments in work. Work (range 20-29%) and delta (range 14-30%) efficiencies decreased with increases in power output. The result that gross efficiency (range 6-15%) increased with increments in work was due to the decreasing effect of the resting metabolic rate on the total energy expended. Gross, work, and delta efficiencies were lower (P less than 0.05) at 90 rpm when compared with the same work rate at 50 and 70 rpm. Although all of the exercise efficiencies tended to be lower at 70 rpm compared with work at 50 rpm, the difference was significant (P less than 0.05) only at 45 and 60 W. These data suggest that delta and work efficiencies during ACE are decreased with increments in either speed or power output. However, gross efficiency increases as a function of power output but decreases as a function of speed of movement.

New differential medium for the isolation of Corynebacterium vaginale.

A new differential medium for isolation of Corynebacterium vaginale is described. This opaque medium containing 1% corn starch allows detection of C. vaginale by the zones of clearing developing around the colonies.