Multi-chemothermoimmunotherapy for human colon adenocarcinoma in vitro.

Effective adjunctive therapies for colorectal carcinoma are clearly needed. We evaluated the cytotoxic responses in vitro of human colon carcinoma cell lines to combined modalities: 5-fluorouracil/leucovorin (5-FU/LV), carboplatin (CP), tumor necrosis factor (TNF) and hyperthermia (HTX). Cytotoxicity was evaluated in a cell proliferation assay using crystal violet staining. 5-FU/LV was administered 2-3 days before TNF and CP, followed 1 h later by HTX. These cell lines were relatively resistant to HTX alone (42 degrees C for 2 h), but were heterogeneous in their responses to various doses of the other single agents. This heterogeneity was also evident for combined modalities: the HCT-15 cell line exhibited significant supra-additivity for selected doses of CP, TNF and 5-FU/LV, which was further enhanced by hyperthermia. In contrast, the HT-29 cell line did not demonstrate a strong pattern for supra-additivity, whereas the DLD-1 cell line had an intermediate response. Thus, our results suggest one approach to develop effective and dose-sparing multimodality therapeutic regimens for colon adenocarcinoma.

Effect of naloxone on luteinizing hormone secretion in premenstrual syndrome.

OBJECTIVES: To investigate the theory of brain opioid activity disregulation in premenstrual syndrome (PMS) and to discover the changes of central beta-endorphin activity during the menstrual cycle in PMS patients. DESIGN: Prospective study. SETTING: University-based PMS clinic. PATIENTS: All the patients and controls were between 20 and 45 years of age, with regular menses for at least six previous cycles. All the patients demonstrated at least 30% score increase in designated symptoms on the Visual Linear Analog Scale during the luteal phase compared with the follicular phase. In contrast, the score changes in the controls were < 30%. INTERVENTIONS: All subjects underwent LH-releasing hormone (LH-RH) stimulation test on days 2 to 3 of the cycle. Five naloxone infusions were administered on days 7 to 8 and 10 to 11, 1 day, 3 to 4 days, and 12 to 13 days after the LH surge as detected by the ovulation prediction kit. MAIN OUTCOME MEASURES: Luteinizing Hormone levels were recorded for 1 hour, followed by naloxone infusion at 2 mg/h for 4 hours. Blood samples were collected for LH tests every 15 minutes for 1 hour before, during, and for 1 hour after the infusion. RESULTS: All subjects had similar LH response to LH-RH. The integrated area of LH response to naloxone as expressed by percentage of the baseline on each of the 5 days did not show significant differences between the patients and the controls. CONCLUSIONS: The central beta-endorphin changes, if any, in PMS patients could not be demonstrated in our study.

Periovulatory beta-endorphin levels in premenstrual syndrome.

OBJECTIVE: To determine whether changes in peripheral beta-endorphin levels during the periovulatory phase are associated with symptoms of premenstrual syndrome (PMS). METHODS: Twenty-one PMS patients and ten controls were studied. All were in general good health and had no history of psychiatric disorders. They were between 21-44 years of age, had had regular menses for at least six previous cycles, and were carefully selected by charting the Visual Linear Analogue Scale and basal body temperature daily for 1 month. After an overnight fast, the subjects had blood drawn between 8:00 and 10:00 AM daily for 8 days, starting on the tenth day of the menstrual cycle, for one cycle. Beta-endorphin and LH were measured by radioimmunoassay. The day of the LH peak was defined as day LH 0. The beta-endorphin levels were expressed as the number of days before or after the LH surge. RESULTS: Beta-endorphin levels throughout the periovulatory phase were lower in PMS patients than in controls, and the differences were more remarkable on LH days 0 and 4. CONCLUSION: Our data suggest that an aberration of normal changes in beta-endorphin activity in PMS patients may occur around the time of ovulation.

The role of home environment in infant diarrhea in rural Egypt.

In 1982 and 1983, a descriptive environmental survey was conducted in 317 households with newborn infants in rural Bilbeis, Egypt. The incidence of infant diarrhea in these households was ascertained by twice-weekly home visits for a 1-year period (1981-1982). Using univariate and multivariate analyses, the authors identified household factors that were statistically associated with infant diarrhea incidence, including number of children in the house under 4 years of age; number of persons per household; incidence of diarrhea in other family members; having a dirt (vs. concrete) dining room floor; having multiple living areas in the house; having a house or roof in need of repair; using well water rather than tap water for cooking or bathin; the absence of a sewer for waste bathwater; food being left out at room temperature between meals; and having many rodents in the house. Two practices involving interaction with the environment appeared to be protective: butchering of cattle by the family for home consumption, and protection of the infant from flies by a veil during napping. The combined household variables explained 25% of the variance in the total incidence of diarrhea. Categories of variables that accounted for most of the total variance explained by environmental factors are, in decreasing order: house structure (28%); water usage (24%); toilet and bathing area (12%); animal management (11%); food preparation area (10%); hygiene (8%); and wastewater management (6%). This approach may be useful in identifying environmental characteristics whose change would reduce diarrheal illness among infants.

Comparison of a food frequency questionnaire using reported vs standard portion sizes for classifying individuals according to nutrient intake.

Individual intakes of retinol, carotene, vitamin C, and folacin calculated from a food frequency questionnaire using reported portion size were compared with intakes calculated using standard portion size information. Data from a case-control study to determine the association of nutrient intake and risk of cervical dysplasia were supplemented by standard portion size information from the US Department of Agriculture and reanalyzed. Significant mean differences were found between intake calculated from reported portion size data and that calculated from standard portion size data for all nutrients. Correlation of nutrient intakes obtained by the two methods of data collection ranged from .73 to .92. Calculation of the rho statistic, measuring the consistency of classification of participants into groups of high, medium, and low nutrient intake, led to values ranging from .55 to .71, indicating some misclassification of study participants. To determine the effect misclassification had on the study outcome, odds ratios were calculated using nutrient amounts obtained from both methods of collecting portion size data. Results indicate that replacing reported portion size data with standard portion size data may lead to conflicting outcomes for specific nutrients in research concerning the relationship between diet and disease.

Seasonal characteristics of and age at menarche.

Several patterns in menarche are evident over time and across populations which vary by ethnicity, socioeconomic status and altitude of residence: peak occurrence of menarche in January and August with a possible minor peak in April; troughs in the occurrence of menarche to either side of the peak months; and secular trends in season and age patterns of menarche. Contradictory patterns in season of menarche with respect to age at menarche and season of menarche with respect to season of birth are still unresolved. Further research is yet required to evaluate the role of the variety of endogenous and exogenous variables and their interactions on menarche in order to more fully develop an appropriate understanding of the chronobiology of developmental and reproductive phenomena in women and their dependence upon environmental quality and temporal cues.

Seasonal characteristics of and age at menarche.

Data from approximately 600 U.S. women were analyzed for seasonality in menarche. Data were converted to the ratio of observed (O) to expected (E) cases, based on an equal distribution of events over the year, per considered time span of the year. The greatest O/E ratio in menarche (1.55) occurred during January, followed by August (1.43) and July (1.24). The lowest O/E ratio in menarche occurred in February and May (0.68). Seasonal patterns in menarche were detected for the separate cohorts of women born during the 1940s, 1950s, and 1960s, with a shift from a December-January peak in menarche for those born in the 1940s and 1950s to an August-September peak for those born in the 1960s. Girls who were younger (8-14 yrs) at menarche exhibited a seasonal difference in the peak number of menarches by about 6 months in comparison to the pattern for girls who were older (15-17 yrs). Girls who experienced menarche during August-October were statistically significantly younger (p less than 0.05) than those born during the other three seasons. Season of birth was not statistically significantly associated with season of menarche. Overall, no 12-month pattern was substantiated by cosinor analysis in the month of menarche. However, a 6-month rhythm was detected in menarche for women born between 1940 and 1960 (p = 0.004, A = 29% M, phi = January and July).

Measurement and significance of antibodies against GM1 ganglioside. Report of a workshop, 18 April 1989, Chicago, IL, U.S.A.

Twelve laboratories from the United States, Canada, France, Italy and Switzerland participated in a workshop to compare assays used to measure anti-GM1 antibodies, and to discuss the clinical significance of these antibodies. A panel of test samples containing varying amounts of anti-GM1 antibody was prepared by mixing varied proportions of normal serum with a serum containing a monoclonal IgM antibody that bound GM1 ganglioside. Enzyme-linked immunosorbent assay (ELISA) data were supplied by eight laboratories and ten laboratories classified the sera as negative, weakly or strongly positive. Most laboratories correctly identified the two samples that contained the highest quantities of antibody, but there was considerable disagreement on the classification of the three samples with moderate or small amounts of antibody. The sensitivity of the assays varied considerably. The more sensitive assays did not use detergent in the washing buffers, and incubated the human serum with the antigen at 4 degrees C overnight. Several investigators have identified a subset of patients with lower motor neuron disease or multifocal neuropathy who have high titers of anti-GM1 antibodies. Many patients with neurological and non-neurological diseases have low to moderate levels of anti-GM1 antibodies, and the significance of these antibodies is unclear. There was general agreement that standardization of the ELISA assays is urgently required, and that distribution of a reference high-titered antiserum would facilitate this process.

A mortality study of employees at a synthetic rubber manufacturing plant.

A mortality follow-up study was conducted of workers employed at a synthetic rubber manufacturing plant in Baton Rouge, Louisiana. Interest in the potential health effects of exposure to methyl chloride, one of the substances used in the manufacturing process, provided the impetus for this study. The study cohort consisted of 852 male process workers who had worked at least 1 month during the period from startup of operations in 1943 through December 31, 1978. Mortality from all causes was lower than expected when compared with the U.S. male population. No excess mortality from any specific cause of death was found in the study population after analysis by level and duration of exposure.

Temporal patterns of reported single-vehicle car and truck accidents in Texas, U.S.A. during 1980-1983.

Reported single car and truck accidents due specifically to driver 'fatigue' for the 4-year span of 1980-1983 were analyzed for 24-hr, 7-d and 1-yr patterns. Three types of data were examined: (1) accidents in rural Texas, (2) accidents only in San Antonio, the fourth largest city in Texas and (3) accident ratio (number of accidents per time interval divided by traffic volume for the interval) in this city. A statistically significant seasonal variation of relatively low amplitude with peaks in May and July was detected only for accidents in rural areas. High-amplitude periodicities of 7 d were evident in all the data sets, with a peak on the weekend. A very prominent 24-hr pattern was detected as well, with the acrophase determined by single cosinor around 0300. A slight secondary peak in accidents, around 1500, was evident in the data from the rural areas. This secondary peak represented a 12-hr rhythm in addition to the 24-hr. Overall, features of the temporal patterns in accidents over 24 hr and over the year in urban and rural areas differed only slightly. Accident ratios yielded results similar to accident frequencies. However, with regard to the rural data, the shape of the 24-hr temporal pattern varied with driver age; older drivers exhibited a flatter curve with a more pronounced afternoon rather than early morning (around 0300) peak.

Ventilatory functions of normal children and young adults: Mexican-American, white, and black. III. Sitting height as a predictor.

We studied the ventilatory functions of 1800 normal children ranging in age 7 to 20 years. Boys and girls of black, white, and Mexican-American ethnic groups were represented adequately. The FVC and FEV1 of normal black children were fully 1 SD lower than those of white children with the same standing height. Such racial differences could not be corrected by a scaling factor, because the differences vary with sex and also with height as the children grow. Using sitting height as a predictor greatly reduced the racial differences of ventilatory functions and permitted the application of one set of prediction equations for children of all three groups.

Circannual rhythm in human sperm count revealed by serially independent sampling.

Sperm concentration and total sperm counts from single semen and samples from each of 4435 patients requesting vasectomy between September 1972 and December 1977 were analyzed for circannual (about 1 year) rhythmicity. Although large temporal variations were found both between years and within years, a trend was noted for higher sperm concentration during the winter than during the summer. When the entire series of data were analyzed by months, a strong circannual pattern was apparent, with the highest sperm counts between February and March and the lowest counts during September. To the authors' knowledge, this is the first report of a circannual rhythm in human sperm concentration and total sperm count. The data must be considered preliminary, but if confirmed by other investigators studying comparable populations, the influence on clinical investigations will be profound.

Circadian variation in the susceptibility of male Balb/C mice to ifosfamide.

At each of 6 different timepoints during a single 24-h span, a different subgroup of male Balb/C mice, previously standardized to a 12:12 LD schedule (L from 0600 to 1800) was challenged by one of a series of 5 different dosages of ifosfamide (450, 550, 650, 750 and 850 mg/kg) administered by a single i.p. injection. The measured endpoint of response was the number of deaths per experimental group within 96 h after the administration of the drug. The LD10, LD50 and LD95 (with 95% CL) were calculated by probit analysis. A statistically significant circadian rhythmicity was detected among each of the estimated LD% doses by single cosinor analysis. Male Balb/C mice 5 to 6 weeks of age were most susceptible to the toxic effects of ifosfamide during the middle and late hours of the rest span and most tolerant of the drug during the final hours of the activity span. The acrophase of the best fitting cosine approximation of the dosages required to produce 50% mortality was 03(49), 3 h and 49 min after the midpoint of the daily activity span (00(00)). The experimentally determined LD50's, with 95% CL, ranged from 792 mg/kg (703 mg/kg, 891 mg/kg) at 0500 to 596 mg/kg, (552 mg/kg, 643 mg/kg) at 1700, with a mesor (24-h time series mean) of 694 +/- 14 mg/kg.

Factors affecting conjugal violence.

This study presents information on 30 couples involved in marital violence within a sample of 60 couples who were seeking psychiatric assistance for marital conflict. Both univariate and multivariate analyses were used in data analysis. Key variables identifying battered wives were frequent alcohol use by their husbands, frequent marital arguments, a low educational level, and frequent legal drug use. Abusing husbands were characterized by backgrounds of family violence, frequent alcohol use, a low education level, and frequent marital arguments.

Ventilatory functions of normal children and young adults--Mexican-American, white, and black. II. Wright peak flowmeter.

A study was undertaken to establish the normal values of peak expiratory flow rate using the WPFM in three ethnic groups. This report is based on the testing of 1,805 healthy students 7 to 20 years of age in the Houston public schools. Significant differences of WPFR are noted among the three races, and between boys and girls. Prediction equations and regression lines are presented for each sex/race group. The performance of the WPFM is compared with that of the spirometer.

Ventilatory functions of normal children and young adults--Mexican-American, white, and black. I. Spirometry.

This is a study of the ventilatory functions of 1,805 normal Mexican-American, white, and black students of six public schools in Houston, Texas, with ages ranging from 7 to 20. A roll-seal piston type spirometer was used. The best performed forced vital capacity curve of each student was selected by the computer program from which the following measurements were extracted: FVC, FEV1, FEV1/FVC ratio, PEFR, and MMEF. Each student also had the peak expiratory flow rate measured by the Wright peak flowmeter to establish normal values with this instrument. Significant differences of lung volume and flow rate exist among the three races, and between male and female subjects. Prediction equations and prediction curves for each race and sex are presented. The results of the present study are compared with those of previously published works.

A circadian susceptibility/resistance rhythm for potassium cyanide in male BALB/cCr mice.

Circadian rhythms in mortality and/or survival time following a single intraperitoneal injection of a LD50 of potassium cyanide were studied. In two investigations, different but comparable subgroups of inbred male BALB/cCr mice were treated at 4-h intervals (under conditions standardized for chronobiologic study) during 24-h spans. Mice were observed for exact time-to-death during the first hour after treatment as well as overall mortality during the entire 24-h post-injection span following each KCN treatment timepoint. In both studies, mortality from KCN exhibited a 24-h rhythm. Highest mortality occurred in mice injected at 1600 (80% mortality) in Experiment 1 and 2000 (100% mortality) in Experiment II. Lowest mortality occurred at 0400 (40% mortality) in Experiment I and 0800 (30% mortality) in Experiment II. The need to consider the circadian organization of physiologic function when bioassaying toxicity is discussed.