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Biomedical subjects

G Y Nicolau

Publications and source records attributed to G Y Nicolau.

At least 19 recordsLinked to original sources
PubMed2001

Circadian rhythms of basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), cortisol, and melatonin in women with breast cancer.

BACKGROUND: Circadian rhythms in plasma concentrations of many hormones and cytokines determine their effects on target cells. METHODS: Circadian variations were studied in cortisol, melatonin, cytokines (basic fibroblast growth factor IbFGF], EGF, insulin-like growth factor-1 [IGF-1]), and a cytokine receptor (insulin-like growth factor binding protein-3 [IGFBP-3]) in the plasma of 28 patients with metastatic breast cancer. All patients followed a diurnal activity pattern. Blood was drawn at 3h intervals during waking hours and once during the night, at 03:00. The plasma levels obtained by enzyme-linked immunoassay (ELISA) or radioimmunoassay (RIA) were evaluated by population mean cosinor (using local midnight as the phase reference) and by one-way analysis of variance (ANOVA). RESULTS: Cortisol and melatonin showed a high-amplitude circadian rhythm and a superimposed 12h frequency. bFGF showed a circadian rhythm with an acrophase around 13:00 with a peak-to-trough interval (double amplitude) of 18.2% and a superimposed 12h frequency. EGF showed a circadian rhythm with an acrophase around 14:20, a peak-to-trough interval of 25.8%, and a superimposed 12h frequency. IGF-1 showed a high value in the morning, which is statistically different (t test) from the low value at 10:00, but a regular circadian or ultradian rhythm was not recognizable as a group phenomenon. IGFBP-3 showed a low-amplitude (peak-to-trough difference 8.4%) circadian rhythm with the acrophase around 11:00 and low values during the night. CONCLUSIONS: (1) Circadian periodicity is maintained in hospitalized patients with metastatic breast cancer. (2) Ultradian (12h) variations were superimposed on the circadian rhythms of the hormones and several of the cytokines measured. (3) Studies of hormones and cytokines in cancer patients have to take their biologic rhythms into consideration. (4) The circadian periodicity of tumor growth stimulating or restraining factors raises questions about circadian and/or ultradian variations in the pathophysiology of breast cancer.

Analysis of Variance↗
PubMed1996

Stimulation of the secretion of dehydroepiandrosterone by melatonin in mouse adrenals in vitro.

Adrenals of young adult male mice kept on a LD 12:12 lighting regimen for three weeks prior to study and harvested at four different circadian stages were incubated for 2 hours with 0.4 IU synthetic ACTH in 2 ml Krebs-Ringer buffer (KR), or with 50, 150, and 450 microM of melatonin in KR containing 0.4 IU ACTH. The addition of melatonin to ACTH leads to a dose dependent stimulation of production and/or secretion of DHEA into the incubation medium irrespective of the circadian stage of harvesting of the adrenals. This relationship is of interest in view of the simultaneous decrease of dehydroepiandrosterone and melatonin in the course of aging, and the effects of these compounds upon aging related changes.

Adrenal Glands↗
PubMed1993

Chronobiology in laboratory medicine.

A critical amount of information has accumulated over the last decades to allow the application of chronobiology to clinical and laboratory medicine. The tasks faced in laboratory medicine include the quantitative measurement of the multifrequency human time structure in health and disease. For this purpose, it is essential to choose an adequate sample size in order to obtain meaningful results and quantitative endpoints which can be interpreted by inferential statistical techniques. No statistical technique is applicable for all purposes and it is essential that the assumptions underlying each technique and its limitation are well known to the investigator. The multifrequency nature of the human time structure has to be kept in mind in order to avoid erroneous results. Time qualified reference ranges have to be established for high amplitude rhythms. Circadian and/or circannual rhythm alterations have been described as group phenomenon in subjects with epidemiologically determined risk states for common diseases, but will require much further studies for the application to individual subjects. Rhythm parameters are new endpoints in the evaluation of the human time structure in health. Alterations of these parameters may occur as cause or as consequence of disease. Recognition of rhythm abnormalities in disease are critical for a meaningful application of chronopharmacology. Time dependent changes in pharmacokinetics and pharmacodynamics have to be taken into account in the interpretation of drug level determinations. A considerable degree of individuality of timing has been documented in some frequencies. This individuality and the rhythm abnormalities found in disease require the study of reference or marker rhythms. If the complexity of the human time structure is clearly understood and its study pursued in a critical manner with quantitative endpoints, chronobiology opens a new dimension in laboratory and clinical medicine.

Adult↗
PubMed1992

Chronobiology of pituitary-thyroid functions.

One hundred ninety four children, 11 +/- 1.5 years of age and 166 elderly men and women, 77 +/- 8 years of age were studied over one or (in the case of some of the elderly subjects) over several (up to 4) 24-hours spans. All subjects were diurnally active and rested at night and followed their regular three meal pattern. The subjects were studied in subgroups of 20-25 during all four seasons of the year. During each study, blood was collected at 4 hour intervals over one 24-hour span (6 samples). Circadian and circannual variations were found and described by cosinor analysis in the children as well as in the elderly subjects. The children with endemic goiter (134) as compared to those without endemic goiter (60) showed a slight circadian phase advance in plasma total and free T3, a lower circadian amplitude of total T4 concentrations and the absence of a detectable circadian rhythm in free T4. The children with goiter showed a phase delay in serum TBG. There was no difference between the children with and without goiter in the circadian MESOR of any thyroid parameter or of TSH. The children with endemic goiter in the region of Dimboviţa, Romania, are in clinical and biochemically euthyroid condition with some slight poral abnormalities of thyroid function. Seasonal variations in children and elderly patients showed the highest values of TSH during summer and fall, while the highest values in the plasma concentrations of thyroid hormones were found during the cold season of the years. Thyroglobulin in the children showed a circadian rhythm but no seasonal variation.

Aged↗
PubMed1992

Iodine-enriched milk in goiter endemics.

Researches carried out at Cîmpulung-Lereşti-Lăicăi from the north of the Argeş County demonstrated an environmental iodine-deficiency that caused thyroid hypofunction in animals and, consequently, a decrease in the iodine level in the products of animal origin. Administration of KI, KIO3 or of sea weeds powder in the cows nutrition corrected the thyroid function, the quantitative increase in milk production and enrichment of milk in iodine.

Animals↗
PubMed1991

Circadian, weekly, and seasonal variations in cardiac mortality, blood pressure, and catecholamine excretion.

Time of occurrence of cardiac death due to arrhythmia, heart failure, or acute myocardial infarction was recorded in 86 elderly subjects, belonging to a group in whom circadian and circannual rhythms in blood pressure and urinary catecholamine excretion had been studied previously. All patients were retired, with no work responsibilities, and lived--closely-supervised in a home for the aged--on a routine that provided little differences between weekdays and weekends. Cardiac mortality showed a circadian variation, with a peak in the early morning hours, coinciding with the circadian peak in systolic and diastolic blood pressures. A weekly (circaseptan) variation in cardiac mortality was found, with the greatest number of patients dying on Mondays and the least on Thursdays. There were seasonal differences in cardiac mortality, with a peak in July and a broader peak during the cold season (December to February). The former coincides with the circannual peak in diastolic blood pressure, but is unrelated to the seasonal variation in norepinephrine excretion. Circadian, circaseptan, and circannual variations in cardiac mortality appear to be the expression of time-dependent, transient risk states for catastrophic cardiac events, which may lend themselves to preventive treatment.

Aged↗
PubMed1987

Peculiarities of the endocrine time structure in noninsulin-dependent adult-onset (type II) diabetes mellitus.

Twenty noninsulin-dependent elderly diabetic patients, ten of whom were treated by oral hypoglycemic agents and ten of whom were regulated by diet alone, and 20 clinically healthy subjects matched for age, sex, height, and weight were examined with six blood and six urine samples at 4-hr intervals over a 24-hr span. Plasma ACTH, cortisol, aldosterone, and dehydroepiandrosterone-sulfate (DHEA-S) were determined by radioimmunoassay (RIA); epinephrine, norepinephrine, and dopamine in urine were determined by high-pressure liquid chromatography (HPLC); and magnesium in urine was determined colorimetrically on a DuPont ACA. There were a number of changes in some of these functions in type II diabetic patients with and without oral hypoglycemic agents that appear to be of interest. The circadian mean in plasma ACTH concentration in diabetic patients with and without oral hypoglycemic agents is significantly higher than in matched nondiabetic controls. The plasma aldosterone concentration is similar in type II diabetics treated by diet only and in matched controls but is statistically significantly elevated in patients on oral hypoglycemic agents. Correspondingly, the urinary excretion of sodium in type II diabetic patients on oral hypoglycemic agents is lower than in matched controls. The plasma cortisol concentration is unchanged in type II diabetic patients treated by diet alone but shows a slight increase in patients on oral hypoglycemic agents. The circadian means of plasma DHEA-S concentration is slightly higher in diabetic patients with and without oral hypoglycemic agents than in matched controls. This elevation, however, does not quite reach the 95% level of statistical significance. Urinary norepinephrine excretion in type II diabetic patients is similar to that in matched controls. The urinary epinephrine excretion in diabetics with and without oral hypoglycemic agents, however, was lower than in controls, and the urinary excretion of dopamine was higher in the diabetics. The urinary magnesium excretion in type II diabetic patients was lower than in matched controls.

Adrenal Cortex Hormones↗
PubMed1987

Circadian and circannual variations of thyroid function in children 11 +/- 1.5 years of age with and without endemic goiter.

A group of 194 children 11 +/- 1.5 years of age from Tirgoviste, Romania, an endemic goiter area, were studied over a 24-hr span (six blood samples at 4-hr intervals) during all four seasons. One hundred thirty-four of the children had some clinical evidence of endemic goiter, and 60 had none. Total and free T3 and T4, reverse T3, thyroglobulin, thyroxin-binding globulin (TBG; three seasons only), and TSH were studied. The circadian rhythms were analyzed by cosinor and the circannual variations by ANOVA. Children with and without endemic goiter showed circadian rhythms in all functions studied except free T4 for which no statistically significant rhythm was detected in the children with goiter. There were differences in the acrophase of total T3, free T3, and TBG, with phase advance in the children with goiter in total T3 and free T3 and a phase delay in TBG. Mesor and amplitude showed no differences except in total T4 for which the amplitude in the children with goiter was statistically significantly lower than in the children without goiter. Children with and without endemic goiter showed seasonal variations in total T4 and free T4 as well as total T3, free T3, and reverse T3, with the highest values in the fall; in thyroxin-binding globulin the highest values were in the winter; and in TSH the highest values were in the summer. There was no significant seasonal variation in thyroglobulin. There was no difference in the circannual variation between children with and without endemic goiter.

Child↗
PubMed1987

Chronobiology of catecholamine excretion in different age groups.

Urine was collected at 4-hr intervals over a 24-hr span in 87 boys and 106 girls 11 +/- 1.5 years of age and over one or several 24-hr spans in 62 elderly men and in 85 elderly women 77 +/- 8 years of age. Epinephrine, norepinephrine, and dopamine were determined by HPLC. The data were analyzed by cosinor and by one-, two-, and three-way ANOVA. Children and elderly subjects showed circadian rhythms of urine volume and of the excretion of norepinephrine, epinephrine, and dopamine. While the urine volume was higher in the elderly subjects than in the children, norepinephrine, epinephrine, and dopamine excretion in the girls and epinephrine in the boys showed a statistically significantly higher mesor than in the elderly subjects of the same sex. There was a sex difference, with lower values in all variables in the girls and women compared to their male counterparts; the circadian amplitudes of norepinephrine, epinephrine, and dopamine in the girls and of epinephrine in the boys were higher than the circadian amplitudes in the elderly subjects. The circadian timing in urinary excretion between the elderly subjects and the children was different, with a consistent phase delay; the acrophase of the circadian rhythm in the elderly subjects moved in the night hours. In contrast, there was no age difference in the acrophase of norepinephrine and epinephrine excretion or in dopamine in the females. In the males, the circadian rhythm in dopamine excretion in the elderly subjects did not quite reach statistical significance at the P less than 0.05 level. Circannual variations with high values in winter and low values in spring and summer were found in norepinephrine excretion in boys, girls, and elderly women, but not in elderly men. In neither age group was there a statistically significant seasonal variation in epinephrine. Only in girls was a statistically significant circannual rhythm in dopamine excretion found, with highest dopamine values in the fall and lowest values in winter and spring.

Age Factors↗
PubMed1987

Circannual rhythms of laboratory measurements in serum of elderly subjects.

A total of 160 elderly subjects 77 +/- 8 years of age were studied in 201 24-hr profiles consisting of six blood samples collected at 4-hr intervals. The sampling sessions were spread over all four seasons. The circadian means were analyzed (one-way ANOVA) for the presence of circannual variations. Statistically significant circannual variations were found in the serum concentrations of albumin, bilirubin, calcium, chloride, CPK, globulin (calculated), glucose, LDH, potassium, sodium, triglycerides, uric acid, and total protein. The data presented indicate that many chemical constituents commonly measured in human serum and urine show seasonal variations in elderly subjects, some of which are large enough to present potential diagnostic problems. Others may not pose diagnostic problems in today's practice of laboratory medicine, but indicate seasonal changes in metabolic functions or, if endogenous in nature, circannual rhythms that may be of physiologic and pathobiologic importance. There is a need to quantify certain of these rhythms as a predictable portion of variability in laboratory values and presumably as an indicator of human health.

Aged↗
PubMed1987

Endocrine factors of blood pressure regulation in different age groups.

Systolic and diastolic blood pressures were measured and blood and urine were collected at 4-hr intervals over a 24-hr span in 194 diurnally active children 11 +/- 1.5 years of age and in 278 elderly subjects 77 +/- 8 years of age. Plasma aldosterone and cortisol were determined by radioimmunoassay, serum calcium and magnesium on a Dupont ACA, and urinary epinephrine and norepinephrine by high-pressure liquid chromatography. In the children, there was a slight but statistically significant positive correlation between the circadian means in systolic blood pressure and norepinephrine excretion and serum calcium, and between diastolic blood pressure and norepinephrine excretion and serum calcium and magnesium. In the elderly subjects, there was a positive correlation between the circadian mean in diastolic blood pressure and aldosterone. In contrast to the findings in the children, however, the elderly subjects showed a negative correlation between the circadian means in norepinephrine excretion and in systolic and diastolic blood pressures. These investigations indicate differences in the regulation of the blood pressure within the "usual range" between children and elderly subjects. This has to be kept in mind in the study of essential hypertension, a syndrome that may be caused by different mechanisms in different age groups.

Age Factors↗
PubMed1984

Circadian endocrine time structure in humans above 80 years of age.

The circadian rhythms in blood hormone concentrations of 17 pituitary, adrenal, pancreatic, testicular, and thyroid hormones were determined in 9 women and 5 men 81 to 91 years of age. Six samples over a 24-hr span were studied for each hormone. Even with the small sample available, 9 of the 17 hormones determined showed a statistically significant circadian rhythm as a group phenomenon (prolactin, estradiol, 17-hydroxyprogesterone, insulin, C-peptide, thyroid stimulating hormone, aldosterone, cortisol, dehydroepiandrosterone sulfate). No rhythm detection by population mean cosinor analysis at the .05 level was obtained in this relatively small group of subjects for adrenocorticotropic hormone, follicle stimulating hormone, growth hormone, luteinizing hormone, triiodothyronine, thyroxine, progesterone (determined in women only) and testosterone (determined in men only).

Adrenocorticotropic Hormone↗
PubMed1984

Circadian and circannual rhythms of hormonal variables in elderly men and women.

A group of fourteen men (73 +/- 5 yr of age), and eighteen women (77 +/- 7 yr of age) institutionalized at the Berceni Clinical Hospital, Bucharest, Romania, were studied over a 24-hr span once during each season (winter, spring, summer and fall). All subjects followed a diurnal activity pattern with rest at night and ate three meals per day with breakfast at about 0830, lunch at about 1300 and dinner at about 1830. The meals were similar, although not identical for all subjects during all seasons. On each day of sampling blood was collected at 4-hr intervals over a 24-hr span. Seventeen hormonal variables were determined by radioimmunoassay. Statistically significant circadian rhythms were detected and quantitated by population mean cosinor analysis in pooled data from all four seasons in both sexes for ACTH, aldosterone, cortisol, C-peptide, dehydroepiandrosterone-sulfate (DHEA-S), immunoreactive insulin, prolactin, 17-OH progesterone, testosterone, total T4 and TSH. In women, estradiol and progesterone also were determined and showed a circadian rhythm during all seasons. Total T3 and FSH showed circadian rhythm detection by cosinor analysis in the men only; LH showed no consistent circadian rhythm as group phenomenon in men or women. A circannual rhythm was detected using the circadian means of each subject at each season as input for the population mean cosinor in the women for ACTH, C-peptide, DHEA-S, FSH, LH, progesterone, 17-OH progesterone and TSH. In the men, a circannual rhythm was detected for ACTH, FSH, insulin, LH, testosterone and T3. There were phase differences between men and women in ACTH, FSH and LH. In those functions in which both the circadian and circannual rhythms were statistically significant, a comparison of the amplitudes showed in the women a higher circannual rather than circadian amplitude for DHEA-S. In 17-OH progesterone, TSH and C-peptide, the circadian amplitude in women was larger. In men, the circannual amplitude of T3 was larger than the circadian amplitude and in insulin the circadian amplitude was larger than the circannual amplitude. There was no statistically significant difference between the circadian and circannual amplitudes in the women in ACTH and progesterone and in the men in ACTH and testosterone.

Aged↗
PubMedDate not supplied

Chronobiologic reference values in clinical chemistry.

Circadian rhythms of 23 biochemical parameters were studied in the serum of 194 children 11 +/- 1.5 years of age, 43 young adult subjects 21 +/- 2 years of age and 200 elderly subjects 77 +/- 8 years of age. In the children and the elderly subjects, the investigations extended over all four seasons allowing also the study of seasonal variations or circannual rhythms. The circadian rhythms were characterized by population mean cosinor for each group and sex. The circannual rhythms were explored by single cosinor and one and two way analysis of variance applied to the circadian means obtained during each season, and by the comparison of the circadian rhythm parameters obtained during the four seasons by the parameter test described by Bingham et al. Circadian rhythms were found in most and circannual rhythms in many parameters. The rhythm characteristics are presented as cosinor summaries. A number of laboratory parameters show high amplitude rhythms in one or the other frequency studies and require time-qualified reference ranges for a meaningful use of these variables for clinical diagnosis. The majority shows small amplitude rhythms, which do not pose diagnostic problems, but are indicators of the complex time structure of the human organism.

Adult↗