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Biomedical subjects

F Levi

Publications and source records attributed to F Levi.

At least 325 records · Page 18Linked to original sources
PubMed1988

Circadian and circannual rhythms of allergic rhinitis: an epidemiologic study involving chronobiologic methods.

Seven hundred sixty-five patients, living in France and suffering from allergic rhinitis (eg, with positive skin tests to various antigens), agreed to self-rate (visual analog scales), four times daily, symptoms such as sneezing, stuffy or blocked nose, runny nose, itchy nose, itchy eyes, wheeze, or cough. Despite acute symptoms, patients did not take medications of any kind by any route during 36 hours. Several statistical methods (eg, Student's t test, analysis of variance, cosinor, chi-square, etc.) were used to validate both circadian and circannual rhythms of these symptoms in the group as a whole, as well as in subgroups related to age, sex, etc. Large-amplitude circadian rhythms with early morning peak times (eg, approximately 6 AM) were validated for sneezing, stuffy nose, and runny nose (with p less than 0.0001) but not for wheeze or cough. Such time-dependent changes were related neither to age (from 10 to 80 years) nor to sex. However, small differences were observed in subgroups sorted with regard to duration of disease (old versus new cases), smoking habits, and geographic location (north versus south France). Reanalysis of data taking into account interindividual differences revealed that the respective peak times of the three major symptoms occurred in the early morning in about 60% to 70% of the patients. Annual changes were validated as well with the annual peak time being January to April. The proposed interpretation of both circadian and circannual rhythms suggests taking into account endogenous component rhythms (eg, involving metabolic, immunologic, and endocrine systems), since they contribute to time-dependent changes in the human susceptibility to antigens. In addition, the elevated severity of symptoms in the morning experienced by 60% to 70% of patients should serve as a guide to individually optimize dosing time(s) of medications, such as antihistamines.

Age Factors↗
PubMed1988

Trends in smoking and lung cancer mortality in Switzerland.

Patterns of cigarette smoking in Switzerland were analyzed on the basis of sales data (available since 1924) and national health surveys conducted in the last decade. There was a steady and substantial increase in cigarettes sales up to the early 1970s. Thereafter, the curve tended to level off around an average value of 3,000 cigarettes per adult per year. According to the 1981-1983 National Health Survey, 37% of Swiss men were current smokers, 25% were ex-smokers, and 39% were never smokers. Corresponding porportions in women were 22, 11, and 67%. Among men, smoking prevalence was higher in lower social classes, and some moderate decline was apparent from survey data over the period 1975-1981 mostly in later middle-age. Trends in lung cancer death certification rates over the period 1950-1984 were analyzed using standard cross-sectional methods and a log-linear Poisson model to isolate the effects of age, birth cohort, and year of death. Mortality from lung cancer increased substantially among Swiss men between the early 1950s and the late 1970s, and levelled off (around a value of 70/100,000 men) thereafter. Among women, there has been a steady upward trend which started in the mid-1960s, and continues to climb steadily, although lung cancer mortality is still considerably lower in absolute terms (around 8/100,000 women) than in several North European countries or in North America. Cohort analyses indicate that the peak rates in men were reached by the generation born around 1910 and mortality stabilized for subsequent generations up to the 1930 birth cohort. Among females, marked increases were observed in each subsequent birth cohort. This pattern of trends is consistent with available information on smoking prevalence in successive generations, showing a peak among men for the 1910 cohort, but steady upward trends among females. Over the period 1980-1984, about 90% of lung cancer deaths among Swiss men and about 40% of those among women could be attributed to smoking (overall proportion, 85%).

Adult↗
PubMed1988

Socioeconomic groups and cancer risk at death in the Swiss Canton of Vaud.

Data collected by the Cancer Registry of the Canton of Vaud, Switzerland, were used to estimate proportional mortality ratios (PMR) and mortality odds ratios (MOR) for various neoplasms according to social class and sector of occupation (agriculture versus others). Mortality ratios were elevated in lower social classes for cancers of the lung (MOR = 1.18 for social class IV or V vs I or II) and other sites strictly related to tobacco (mouth or pharynx, oesophagus and larynx; MOR = 1.70), and (though not significantly) for cancers of the stomach (MOR = 1.16) and uterus (MOR = 1.30 for cervix and 1.47 for corpus uteri). Furthermore, there was a strong negative social class gradient for thyroid cancer (a neoplasm with particularly elevated incidence and mortality in Switzerland), probably attributable to higher prevalence of iodine deficiency in lower social classes (MOR = 3.17). Positive social class gradients emerged for cancers of the intestines (MOR = 0.77 for social class IV or V), skin (MOR = 0.74) and prostate (MOR = 0.87). Agricultural workers showed decreased ratios for cancers of the lung (MOR = 0.75), cervix uteri (MOR = 0.72) and prostate (MOR = 0.80), and excess mortality from cancers of the upper digestive and respiratory sites (MOR = 1.22), stomach (MOR = 1.18), testis (MOR = 2.05) and lympho-haematopoietic neoplasms, particularly myeloma (MOR = 2.14).

Adult↗
PubMed1988

Childhood cancer in Switzerland: mortality from 1951 to 1984.

Cancer mortality among children in Switzerland was analysed using (1) age-specific and age-standardized (0-14) rates from 1951 to 1984 and (2) comparison of observed numbers of deaths over the period 1960-1984 with expected one obtained by application of age-specific rates for the period 1951-1959 to the population structure of subsequent 5-year calendar periods. Certified mortality fell about 60% for leukaemias, 21% for lymphomas, 66% for Wilms' tumours, 40% for bone sarcomas and 30% for other and unspecified sites. Thus, the overall decline in childhood cancer mortality in Switzerland was around 45%, slightly more marked in females (-48%) than in males (-42%), and more pronounced in younger children (over 50% before age 5). This corresponds to an absolute number of about 50 deaths from childhood cancer per year avoided in the early 1980s as compared with expected numbers computed on the basis of rates registered in the 1950s (30 deaths per year for leukaemias alone). The estimated total number of deaths avoided during the whole period 1960-1980 was 820 (430 leukaemias alone). Trends in childhood cancer mortality persisted steadily downwards in the early 1980s, suggesting that further progress is being achieved in the treatment of these neoplasms.

Adolescent↗
PubMed1988

Circadian and ultradian rhythms in blood glucose and plasma insulin of healthy adults.

The circadian and ultradian variations of blood glucose and plasma insulin have been characterized individually and as a group phenomenon in five healthy young adults studied while adhering as closely as possible to their usual routine of sleep, activity, meal content and timing. Three complementary methods were used to analyze the data: displaying raw data as a function of time; cosinor method according to Nelson and Halberg; and time series analyses as proposed by De Prins and Malbecq. The subjects were studied in the laboratory and their life routine were controlled, but very close to that of their habitual routine. They had mainly ultradian rhythms of blood glucose (mainly about 6 hr) and circadian rhythms of immunoreactive insulin (I.R.I.). Blood glucose ultradian rhythms seem to be mainly but not exclusively mealtime dependent, while I.R.I. circadian rhythms appear to be primarily endogenous in origin. Therefore, the role played by insulin in the control of blood glucose levels seems to be programmed on a circadian basis rather than by a time independent feedback phenomenon as postulated by the conventional homeostatic hypothesis. The advantage of this chronophysiologic approach is to consider circadian rhythms of both I.R.I. and insulin effectiveness as an adaptive phenomenon able to maintain blood sugar changes in the ultradian domain of rhythms.

Activity Cycles↗
PubMed1988

Diurnal rhythms in performance tests of school children with and without language disorders.

Time-of-day related changes on four tests used by speech therapists and four other performance tests, in addition to oral temperature, were documented in 16 school children (7-9 years of age). Six of them had language disorders and were receiving speech therapy. Children were synchronized with diurnal activity from around 0730 to around 2100 and nocturnal rest. For each child, at each test time point (e.g. 0900, 1100, 1530 and 1930) tests were performed three times, with two different speech therapists, in a random order, with only one session per day. Conventional methods (t-tested mean differences; ANOVA; correlation tests) were used for statistical analyses. Among 29 parameters (items) which were analyzed, only nine exhibited time-of-day related changes, mainly in speed to-perform measures. In most detected rhythms best performance occurred either at 1100 or at 1530 with no difference in subgroups except for the fastest performance of the sentence repetition test. With regard to the daily mean M, controls performed better than children with language disorders for the word (syllabic) repetition test (P less than 0.0004) but this was reversed for both computing and colouring skill tests (P less than 0.04 and less than 0.002). A difference related to sex (but not to language disorders) was observed in the Ms of speed in sign reproduction (P less than 0.0000) and sorting cards (P less than 0.01), with boys being faster than girls. In children, as in adults, time-of-day effects should be considered when the quantification of performance is desired.

Body Temperature↗
PubMed1988

[Swiss interregional epidemiologic study of the risk of cancer in the contralateral breast].

This epidemiologic investigation in three Swiss regions (Geneva, St. Gall-Appenzell, Vaud) included 5,193 women diagnosed as having a first primary breast cancer. The patients were followed up for ten years (the observation totalled 24,994 women-years). Overall, these results confirmed that the relative risk of a second breast cancer was greatly increased during the first year following the primary diagnosis, but this was largely due to simultaneously discovered contralateral tumours. Beyond the first year of follow-up, the relative risk of a second tumour was lower but still significantly greater than unity. No significant diminution of the excess risk was observed in the first 10 years of follow-up. Relative risk of a second breast cancer was generally higher before age 50, independently of the latency. The relative risk of a second breast cancer differed significantly from one region to another, possibly due to specific techniques of registration.

Adult↗
PubMed1988

Trends in cancer mortality in Switzerland, 1951-1984.

Trends in overall age-standardized, truncated (35-64 years) and age-specific (40 to 49) cancer death certification rates in Switzerland from 1951 to 1984 were analysed. There was a substantial rise in lung cancer mortality in males, with an over 100% increase in overall rates. Thus, in the early 1980's, lung cancer alone accounted for 26% of all cancer deaths in Swiss males. However, male lung cancer rates tended to level off in subsequent cohorts starting from younger middle age in the late 1960's. In females, lung cancer mortality was approximately ten times lower than in males, but rates had been consistently rising since the late 1960's in all age groups. Declines were observed for several neoplasms of the digestive tract: besides stomach (overall decline 68% in males, 77% in females), trends were markedly downwards also for oesophageal cancer in males (-57%), and there was some moderate fall for intestinal sites in both sexes and gallbladder in females. Several trends for other common neoplasms were similar to those observed in other developed countries, such as the declines for (cervix) uteri, the general stability for breast cancer, or the increases in pancreatic cancer and (melanoma) of the skin. A peculiar feature of Swiss data, besides the marked decline in oesophageal cancer in males, was the consistent downward trend in thyroid cancer for both sexes. Thus, overall age-standardized total cancer mortality over the last three decades was moderately upwards in Swiss males, but consistently downwards in females. Male trends were more reassuring in middle age, chiefly in consequence of the flattening in lung cancer rises. Possible interpretations of these trends in terms of aetiological hypotheses (i.e., changes in alcohol drinking and improvements in diet for oesophageal cancer, or reduced prevalence of iodine deficiency for thyroid neoplasms) are discussed.

Adult↗
PubMed1987

Effects of age, birth cohort and period of death on Swiss cancer mortality, 1951-1984.

Swiss death certification data over the period 1951-1984 for total cancer mortality and 30 major cancer sites in the population aged 25 to 74 years were analysed using a log-linear Poisson model with arbitrary constraints on the parameters to isolate the effects of birth cohort, calendar period of death and age. The overall pattern of total cancer mortality in males was stable for period values and showed some moderate decreases in cohort values restricted to the generations born after 1930. Cancer mortality trends were more favourable in females, with steady, though moderate, declines in both cohort and period values. According to the estimates from the model, the worst affected generation for male lung cancer was that born around 1910, and a flattening of trends or some moderate decline was observed for more recent cohorts, although this decline was considerably more limited than in other European countries. There were decreases in cohort and period values for stomach, intestine and oesophageal cancer in both sexes and (cervix) uteri in females. Increases were observed in both cohort and period trends for pancreas and liver in males and for several other neoplasms, including prostate, brain, leukaemias and lymphomas, restricted, however, for the latter sites, to the earlier cohorts and hence partly attributable to improved diagnosis and certification in the elderly. Although age values for lung cancer in females were around 10-times lower than in males, upward trends in female lung cancer cohort values were observed in subsequent cohorts and for period values from the late 1960's onwards. Therefore, future trends in female lung cancer mortality should continue to be monitored. The application of these age/period/cohort models thus provides a summary guide for the reading and interpretation of cancer mortality trends, although it cannot replace careful inspection of single age-specific rates.

Adult↗
PubMed1987

Circannual rhythm in natural killer activity and mitogen responsiveness of murine splenocytes.

Seasonal variations were observed in murine splenic natural killer (NK) cell activity and also in murine lymphocyte responsiveness to mitogens, namely, concanavalin A, phytohemagglutinin, and lipopolysaccharide. The maximum and minimum splenic NK cell activities were observed in January-February and July-August, respectively. Conversely, maxima and minima of lymphoproliferative responses to all the three mitogens occurred in April-June and January-February, respectively. Such variations, when inferential statistics are used, appeared to be accounted for by circannual and other low-frequency (infradian) bioperiodicities. More specifically, the circannual rhythm in murine NK cell activity was demonstrated in data from a total of 356 mice collected over a period of 5 years. The various components of the immune system are characterized by a multifrequency time structure. The understanding of the organization of the immune system along the yearly scale may have bearings on that of the seasonal incidence of numerous infectious diseases and on the success/failure of immunotherapy.

Animals↗
PubMed1987

Circadian time dependence of murine tolerance for the alkylating agent peptichemio.

Since the extent of host toxicity of cytostatics is considerably affected by dosing time, a chronopharmacologic approach was undertaken for optimizing the therapeutic index of the alkylating agent, peptichemio (PTC). In 4 studies involving a total of 463 male B6D2F1 mice, a highly statistically significant circadian rhythm characterized murine tolerance for PTC (8 or 10 mg/kg/day i.v. X 3 days). Six circadian stages were explored (3, 7, 11, 15, 19 and 23 Hours After Light Onset--HALO). Day-40 survival rate varied between 20% (PTC at 3 HALO) and 55% (PTC at 15 HALO) (chi 2 = 16.7; P less than 0.01). In each study, body weight loss was maximal in mice injected with PTC at 3 HALO and minimal in those treated at 15 HALO (P less than 0.01). In a further study involving 96 male B6D2F1 mice, the toxicity of PTC on several target tissues (bone marrow, spleen, small bowel, colon, liver, kidney and lungs) was investigated by histology and leukocyte count as a function of drug dosing time. A circadian rhythm in the susceptibility of the bone marrow, the spleen and the intestinal tract was demonstrated. Optimal murine tolerance for PTC resulted from dosing it at 15 HALO, e.g. in the first half of the activity span.

Animals↗
PubMed1987

Cigarette smoking and the risk of endometrial cancer.

The risk of endometrial cancer in relation to cigarette consumption was evaluated in a hospital-based case-control study of breast and genital neoplasms conducted in Milan, northern Italy. For the present analysis, 357 women (cases) with histologically confirmed endometrial cancer were compared to a group of 1122 women (controls) admitted for a large spectrum of acute conditions unrelated to smoking or to any of the known or potential risk factors for endometrial cancer. Compared with never-smokers, the multivariate relative risk estimates were for current 0.45 [95% confidence interval (CI) = 0.30-0.70] and 0.86 (95% CI = 0.50-1.46) for ex-smokers. The negative association of endometrial cancer with current smoking was not influenced by menopausal status as well as by other major identified potential confounding factors, i.e. menstrual and reproductive history, body mass index, oral contraceptive or estrogen replacement therapy use and family gynecologic cancer history. However, there was no evidence of a dose-risk effect, since the relative risks were similar in moderate and heavy smokers. The present study confirms that smoking is less frequent in cases hospitalized for endometrial cancer than in a comparison group of patients with non-smoking-related acute conditions. This negative association is perhaps explained in terms of reduced estrogen levels in smokers, though the influence and the importance of some uncontrolled selection bias (due, for instance, to longer hospital stay of smokers even when admission diagnosis was for non-smoking-related conditions) cannot be ruled out.

Adult↗
PubMed1987

Circadian changes in the pharmacokinetics of oral ketoprofen.

Several investigations which have taken treatment time into account have shown that the pharmacokinetic parameters, the therapeutic efficacy and even the toxicity of a large number of products may vary according to the administration schedule. The present study was carried out in order to evaluate any circadian changes in pharmacokinetic parameters of ketoprofen, a new non-steroidal anti-inflammatory drug (NSAID). This randomised crossover study consisted of a single oral dose of ketoprofen 100mg administered to 8 healthy male volunteers, mean age 27.2 years, at 07.00 hours, 13.00 hours, 19.00 hours or 01.00 hours in 4 study periods during the first 3 months of the year. The order of administration was randomised, with each subject acting as his own control. A total of 14 blood and 4 urine samples were taken over a 12-hour period. The peak plasma concentration was twice as high after drug administration at 07.00 hours (13.4 +/- 1 mg/L) than after other administration times (13.00 hours: 6.9 +/- 1; 19.00 hours: 7.2 +/- 0.7; 01.00 hours: 6.3 +/- 0.5 mg/L) [p less than 0.001]. The time to reach peak concentration was much longer after drug administration at 01.00 hours (135 +/- 16.7 min) than at 07.00 (73.1 +/- 14.1 min), 13.00 (75 +/- 16.5 min) or 19.00 hours (82.5 +/- 12.7 min) [p less than 0.05]. The lag time was significantly longer at 01.00 hours than at 13.00 hours (p less than 0.01). The absorption rate constant after treatment at 01.00 hours was less than at the other times of administration (p less than 0.05). The bodyweight-corrected area under the curve (AUC0-12) was greater after 07.00 hours than after 13.00 (p less than 0.01) or 19.00 hours (p less than 0.05) and greater after 01.00 hours than after 13.00 hours (p less than 0.05). The elimination half-life was significantly longer after administration at 01.00 hours than after 19.00 hours (p less than 0.05), while the total clearance was lowest at 07.00 hours. Cosinor analysis demonstrated statistically significant circadian rhythms for all pharmacokinetic parameters described above. The amount of ketoprofen eliminated in the urine was delayed, and was significantly greater after the administration at 01.00 hours than 07.00 hours or 19.00 hours (p less than 0.01). The relationship between absorption, diffusion and/or elimination mechanisms of the drug are discussed.

Administration, Oral↗
PubMed1987

Circadian rhythm in the membrane of circulating human blood cells: microviscosity and number of benzodiazepine binding sites. A search for regulation by plasma ions, nucleosides, proteins or hormones.

Circadian rhythms in both the number of peripheral type binding sites for benzodiazepines in platelet membranes and the microviscosity of the erythrocyte membrane were demonstrated in 7 healthy men. Neither variable appeared to be linked to each other, or regulated by the plasma concentrations of total or free cortisol, testosterone, potassium, magnesium, calcium, cAMP, cGMP or proteins or by the erythrocytic concentration of magnesium or potassium or by the plasma cAMP:cGMP ratio or by the ratio of intra-erythrocyte:plasma concentrations of potassium or magnesium. A highly significant negative correlation was found between the microviscosity of the erythrocyte membrane and the activity of the membrane-bound enzyme, methyltransferase I. Such a correlation was validated both on raw data and on 24 hr-means (r = 0.84; P less than 0.01). A circadian rhythm in the activity of this enzyme was also demonstrated. Moreover, a highly significant correlation was also found between plasma transcortin concentration (TRC) and microviscosity (r = 0.50, P less than 0.01), and between TRC and methyltransferase I activity (r = 0.61, P less than 0.01). Such findings may constitute clues towards the understanding of the regulation of the circadian rhythm in the fluidity of the red blood cell membrane in man and guide future steps with regard to the role of this rhythm upon the availability of drug binding sites at the cell surface.

Adult↗
PubMed1987

Comparison of once-daily evening versus morning sustained-release theophylline dosing for nocturnal asthma.

Eight diurnally active (approximately 0730-1100 hr) adults (41-61 yr) suffering from nocturnal asthma volunteered for a double-blind, cross-over randomized study of a once-daily dosing (600-900 mg/24 hr) of Armophylline (Rorer s.a., France), a sustained-release theophylline given either at 0800 hr or 2000 hr for 8-day durations. Study variables monitored daily were: (a) self-measured peak expiratory flow (PEF), heart rate, oral temperature and self-rated fatigue checked every 2 hr during the waking span as well as upon spontaneous nocturnal awakenings and (b) duration and subjective characteristics of sleep rated every morning. In addition, serum theophylline concentration (STC) plus the variables in (a) were sampled every 2 hr during the 24 hr of the eighth day of each timed treatment span. Rx at 0800 hr was associated with a nocturnal dip in PEF of 20 +/- 2.8% (X +/- S.E.M.) from the level achieved at the time of the diurnal crest; Rx at 2000 hr moderated the nocturnal fall; it was only 10 +/- 2.1% and within the physiologic limits of non-asthmatic persons. The STC peak height (Cmax) was greater (P less than 0.05) and time-to-peak (Tmax) shorter (P less than 0.005) with Rx at 0800 hr than at 2000 hr. With Rx at 2000 hr an STC plateau of approximately 12 hr resulted. A statistically significant correlation (r = 0.86; P less than 0.01) between PEF and the corresponding-in-time STC was observed with Rx at 2000 hr but not with Rx at 0800 hr. A small, but statistically significant, higher heart rate resulted from 2000 hr dosings in five out of eight subjects relative to the 0800 hr dosing. There were no differences in the sleep characteristics nor in oral temperature between dosing times. Once-daily (600-900 mg) SRT dosing at 2000 hr controlled the nocturnal dip of bronchial patency with no major side-effects in diurnally active adult patients with nocturnal allergic asthma.

Adult↗