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Biomedical subjects

Germaine Cornélissen

Publications and source records attributed to Germaine Cornélissen.

At least 19 recordsLinked to original sources

Cancer chronomics I. Origins of timed cancer treatment: early marker rhythm-guided individualized chronochemotherapy.

A 21-year old patient who presented in 1973 with a rare and highly malignant ovarian endodermal sinus tumor with spillage into the peritoneal cavity is alive and well today after receiving chronochemotherapy. During the first four courses of treatment, medications were given at different circadian stages. Complete blood counts and marker variables such as mood, vigor, nausea, and temperature were monitored around the clock and analyzed by cosinor to seek times of highest tolerance. Remaining treatment courses were administered at a time corresponding to the patient's best drug tolerance, rather than extrapolating the timing of optimal cyclophosphamide administration from also-implemented parallel laboratory studies on mice. Notwithstanding remaining hurdles in bringing chronochemotherapy to the clinic for routine care, merits of marker rhythm-guided chronotherapy documented in this and other case reports have led to the doubling of the two-year disease-free survival of patients with large perioral tumors in a clinical trial.

Animals↗

Cancer chronomics II. Origins of timing cancer treatment.

This paper is a memorial to Mikhail Victorovich Berezkin (MVB) (10 April 1940 - 16 January 2005), an enthusiastic advocate of chrono-oncology. It illustrates his early dose- and circadian time-response curves, limited as yet by a 4-timepoint approach, provides a list of his publications, and offers a succinct overview of individualized marker rhythm-guided oncotherapy.

Animals↗

Cancer chronomics III. Chronomics for cancer, aging, melatonin and experimental therapeutics researchers.

This position paper documents the merit of including for basic and clinical investigations the mapping of circadian and other rhythms and yet broader chronomes, time structures in and around us. Chronobiometry used herein relies on inferential statistical methods and on materials documented earlier. The circadian amplitude of melatonin is shown to relate both to cancer risk and to the presence of overt cancer, when no differences are found in the 24-hour average of melatonin. Optimization of treatment by timing, thoroughly documented along the circadian scale earlier, could be broadened to include optimization along the scale of the week, and eventually beyond. In both cases, reliance on marker rhythmometry is advocated. More generally, the limits of knowledge are expanded by considering already mapped spectral components and their characteristics that can be influenced by the dynamics of heliogeomagnetic signals heretofore unassessed.

Aging↗

Theodor Hellbrugge: 85 years of age - Ad multos transannos, sanos, fortunatos et beatos.

We honor Theo Hellbrugge's acclaimed endeavors in the rehabilitation, or rather the prehabilitation of handicapped children. So far, he has focused on obvious handicaps, and we trust that he will include concern for everybody's silent handicaps in the future by screening for abnormal variability inside the physiological range. Therein, we introduce cis- and trans-years, components of transdisciplinary spectra that are novel for biology and also in part for physics. These components have periods, respectively, shorter and longer than the calendar year, with a counterpart in magnetoperiodism. Transyears characterize indices of geomagnetic activity and the solar wind's speed and proton density. They are detected, alone or together with circannuals, in physiology as well as in pathology, as illustrated for sudden cardiac death and myocardial infarction, a finding calling for similar studies in sudden infant death syndrome (SIDS). As transyears can beat with circannuals, and depend on local factors, their systematic mapping in space and time by transdisciplinary chronomics may serve a better understanding of their putative influence upon the circadian system. Longitudinal monitoring of blood pressure and heart rate detects chronome alterations underlying cardiovascular disease risk, such as that of myocardial infarction and sudden cardiac death. The challenge is to intervene in a timely fashion, preferably at birth, an opportunity for pediatricians in Theo Hellbrugge's footsteps.

Journal Article↗

Approximate entropy in the electroencephalogram during wake and sleep.

Entropy measurement can discriminate among complex systems, including deterministic, stochastic and composite systems. We evaluated the changes of approximate entropy (ApEn) in signals of the electroencephalogram (EEG) during sleep. EEG signals were recorded from eight healthy volunteers during nightly sleep. We estimated the values of ApEn in EEG signals in each sleep stage. The ApEn values for EEG signals (mean +/- SD) were 0.896 +/- 0.264 during eyes-closed waking state, 0.738 +/- 0.089 during Stage I, 0.615 +/- 0.107 during Stage II, 0.487 +/- 0.101 during Stage II, 0.397 +/- 0.078 during Stage IV and 0.789 +/- 0.182 during REM sleep. The ApEn values were found to differ with statistical significance among the six different stages of consciousness (ANOVA, p<0.001). ApEn of EEG was statistically significantly lower during Stage IV and higher during wake and REM sleep. We conclude that ApEn measurement can be useful to estimate sleep stages and the complexity in brain activity.

Adult↗

Approximate entropy of the electroencephalogram in healthy awake subjects and absence epilepsy patients.

The approximate entropy (ApEn) of signals in the electroencephalogram (EEG) was evaluated in 8 healthy volunteers and in 10 patients with absence epilepsy, both during seizure-free and seizure intervals. We estimated the nonlinearity of each 3-sec EEG segment using surrogate data methods. The mean (+/- SD) ApEn in EEG was 0.83 +/- 0.22 in healthy subjects awake with eyes closed. It was significantly lower during epileptic seizures (0.48 +/- 0.05) than during seizure-free intervals (0.80 +/- 0.13) (P < 0.001). Nonlinearity was clearly detected in EEG signals from epileptic patients during seizures but not during seizure-free intervals or in EEG signals from healthy subjects. The ApEn of EEG signals estimated over consecutive intervals could serve to determine pathological brain activity such as that occurring during absence epilepsy.

Adult↗

Neuropeptide chronomics in clinically healthy young adults: circaoctohoran and circadian patterns.

Endothelin-1 (ET-1) undergoes an about 8-h (circaoctohoran) rather than a circadian variation in clinical health. Herein, 24 h plasma concentrations of vasoactive intestinal peptide (VIP), substance P (SP), neuropeptide Y (NpY), and cortisol used as reference, were obtained from 20 healthy young adults starting at 07:00 or 19:00 h. Like ET-1, SP and NpY undergo a circaoctohoran variation, whereas VIP is circadian rhythmic, peaking during the night, some 8 h prior to the circadian acrophase of cortisol. Maps of circadian and extra-circadian patterns may serve for screening, diagnosis and a better understanding of mechanisms underlying the etiology of various diseases.

Adult↗

Circadian phase difference of leptin in android versus gynoid obesity.

A circadian rhythm in serum leptin, measured every 4 h for 24 h, characterizes normal-weight women (N = 14), and women with gynoid (N = 17) or android (N = 26) obesity, peaking around midnight (P < 0.05), but differing by about 3 h between android and gynoid women (P < 0.01). Obesity is associated with a higher MESOR (rhythm-adjusted mean; P < 0.001) and a smaller relative circadian amplitude (P < 0.05). Gynoid obesity is associated with a larger circadian amplitude of cortisol (P < 0.05), whereas android obesity is associated with a larger circadian amplitude and a higher MESOR of insulin (P < 0.05). Understanding putative mechanisms underlying different body fat distribution may lead to improved chronotherapeutic measures.

Adult↗

A chronomic tree of life: ontogenetic and phylogenetic 'memories' of primordial cycles--keys to ethics.

A scientific optimization may become possible in ethics to the extent to which any reproducible since cyclic features of spirituality and of criminality become measurable. Should either or both the 'good' or the 'bad' be found to be at least passively influenced by cyclic physical environmental factors, as is putatively the case, these aspects of behavior may eventually become actively manipulable, perhaps utilizable for human survival. Toward this goal, chronomics has already mapped time structures in religious behavior that can lead to a study of underlying geographic/geomagnetic latitude-associated mechanisms. This paper, with further but clearly insufficient data, revealing the hurdle of relative brevity of the available time series constitutes a plea for much longer and denser worldwide time series, for further endeavors in various methods of analyses, some of which are promisingly available.

Animals↗

About 21-year hale cyclic signature in agriculture complement those in biomedicine.

Data on total cultivated area and total production of wheat and rye, barley and two-row barley, corn, soya and sunflower in Romania (1968-2000) are re-analyzed from the viewpoint of chronomics. An about 10.7-year component is detected with borderline statistical significance. A 3-component model consisting of cosine curves, with periods of 3.62, 2.48 and 2.15 years, accounts for 27% of the overall variability. Transdisciplinary chronomics is advocated to systematically map predictable dynamics in agriculture such as Hale-like cycles in corn and soja and their interactions with chronomes of external environmental factors.

Agriculture↗

Magnetic storm effect on the circulation of rabbits.

The ultrastructure of cardiomyocytes of rabbits was found to be drastically altered at a time coinciding with strong magnetic storms by comparison with that usually observed during quiet geomagnetic conditions. The circadian characteristics of systolic and mean pressure in the left and right ventricles of Chinchilla rabbits were assessed and compared between quiet and stormy magnetic conditions. Experiments repeated during four consecutive seasons at the times of equinoxes and solstices in the absence of magnetic storms were also examined for any circannual and/or transannual variation. The results have been interpreted in the broader context of non-photic influences on the circulation, fully supporting the presence of non-photic effects. The recording of magnetic activity in the laboratory, and until this is possible, the consultation of the physicists' routine recording of geomagnetic indices should become a sine qua non, since, as shown herein, magnetic storms can override the effect of the usually dominant synchronizer, the alternation of light and darkness.

Animals↗

Does exposure to an artificial ULF magnetic field affect blood pressure, heart rate variability and mood?

The aim of this study was to determine whether an artificial magnetic field with an amplitude and frequency equivalent to those of geomagnetic pulsations during geomagnetic storms could affect physiology and psychology. Three healthy volunteers wore anambulatory BP monitor and an ECG recorder around the clock for 12 consecutive weekends in Winnipeg, Manitoba, Canada. In a room shielded against ELF and VLF waves, they were exposed for 8 hours per week to either a 50 nT 0.0016 Hz or a sham magnetic field at one of six circadian stages. Real exposure randomly alternated with sham exposure. They provided saliva and recorded mood and reaction time every 4 hours while awake. Systolic (S) and diastolic (D) blood pressure (BP), and heart rate (HR) were recorded every 30 minutes. Spectral analysis of HR variability (HRV) was performed using the maximum entropy method and a complex demodulation method. For these variables, daily means were compared between real and sham exposure, using paired t-tests. Their circadian MESOR, amplitude, and acrophase were analyzed and summarized using single cosinor and population-mean cosinor. Circadian rhythms were demonstrated for HR, SBP, DBP for sham exposure, salivary flow rate, positive affect, vigor, and subjective alertness (p < 0.001, -0.02). One participant showed higher HR, lower LF, HF, and VLF powers, and a steeper power-law slope (p < 0.005, -0.0001) in an early night exposure to the real magnetic field, but not in other circadian stages. There was no significant difference between circadian responses to real and sham exposure in any variable at any circadian stage.

Adult↗

100 or 30 years after Janeway or Bartter, Healthwatch helps avoid 'flying blind'.

Longitudinal records of blood pressure (BP) and heart rate (HR) around the clock for days, weeks, months, years, and even decades obtained by manual self-measurements (during waking) and/or automatically by ambulatory monitoring reveal, in addition to well-known large within-day variation, also considerable day-to-day variability in most people, whether normotensive or hypertensive. As a first step, the circadian rhythm is considered along with gender differences and changes as a function of age to derive time-specified reference values (chronodesms), while reference values accumulate to also account for the circaseptan variation. Chronodesms serve for the interpretation of single measurements and of circadian and other rhythm parameters. Refined diagnoses can thus be obtained, namely MESOR-hypertension when the chronome-adjusted mean value (MESOR) of BP is above the upper limit of acceptability, excessive pulse pressure (EPP) when the difference in MESOR between the systolic (S) and diastolic (D) BP is too large, CHAT (circadian hyper-amplitude tension) when the circadian BP amplitude is excessive, DHRV (decreased heart rate variability) when the standard deviation (SD) of HR is below the acceptable range, and/or ecphasia when the overall high values recurring each day occur at an odd time (a condition also contributing to the risk associated with 'non-dipping'). A non-parametric approach consisting of a computer comparison of the subject's profile with the time-varying limits of acceptability further serves as a guide to optimize the efficacy of any needed treatment by timing its administration (chronotherapy) and selecting a treatment schedule best suited to normalize abnormal patterns in BP and/or HR. The merit of the proposed chronobiological approach to BP screening, diagnosis and therapy (chronotheranostics) is assessed in the light of outcome studies. Elevated risk associated with abnormal patterns of BP and/or HR variability, even when most if not all measurements lie within the range of acceptable values, becomes amenable to treatment as a critical step toward prevention (prehabilitation) to reduce the need for rehabilitation (the latter often after costly surgical intervention).

Chronotherapy↗

Circadian hypo- and hyper-amplitude-tension (CHAT) associated with putative pheochromocytoma and 12-hourly phenoxybenzamine treatment.

A 26-year-old white woman had an ablated sino-atrial node and ventricular pacemaker as an unusual feature of a pheochromocytoma-compatible history. Her status quo included, on three occasions, elevated 24-hour urinary epinephrine and metanephrine excretion. She monitored her blood pressure (BP) and heart rate (HR) at 15- to 60-minute intervals over several days, with interruptions, before and after the institution of 10 mg phenoxybenzamine per os every 12 hours (between 7:30 and 8:00 and between 19:30 and 20:00), with continued monitoring over several months. Her data were summarized for consecutive 3-day intervals by sphygmochron. Circadian parameters and original data are compared with gender- and age-specified reference values, yielding also non-parametric endpoints, such as the percentage time elevation, the extent of excess, and the timing of excess, that all can be acceptable for some days but unacceptable for other days. In her broader time structure, or chronome, cosinor analyses revealed a prominent and statistically significant circadian rhythm in BP and HR before and during the 12-hourly therapy. The 12-hour component of BP was more prominent during therapy than prior to it. A statistically significant decreasing trend occurred before therapy, and recurred during treatment. Chronomically interpreted monitoring revealed: 1) the persistence of a statistically significant circadian rhythm during 12-hourly phenoxybenzamine treatment; 2) days-long changes in BP MESOR, the duration of which could not be previously determined based on spotchecks; 3) changes in the circadian amplitude of BP, which can be either very small or very large, compatible with the diagnosis of intermittent circadian hyper-amplitude-tension (CHAT); and 4) a very wide range of BP and HR values, so that occasional (casual) measurements fail to convey the dynamics that may underlie this infrequently found clinical condition of an elevated catecholamine excretion compatible with a pheochromocytoma. All findings support the need for long-term monitoring of BP and HR that may account for controversy in earlier publications.

Adult↗