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Objective -The scope of this study is to detect whether or not the entropy (E) circadian rhythm (CR) is maintained preserved in sinusal R-R intervals (SRRI), its loss being the expression of a transition to an indeterministic chaos in heart rate variability (HRV). Methods - The E of SRRI was estimated in 14 type I diabetic pregnant women (DPW) in the first trimester of an apparently uncomplicated gestation (7 patients - mean age = 30.3 + 4.1 y - without clinical and laboratory evidence of cardiac autonomic neuropathy, and 7 patients - mean age = 30.7 + 3.6 y - with positive tests for a cardiac dysautonomia).The E CR was studied via the single cosinor method, and summarized via the population-mean cosinor method. Results - The E CR was found not to be preserved in both the investigated type I DPW, despite the occurrence of the SRRI CR. Conclusions -The loss of the E CR confirms that in type I DPW there is a transition to an indeterministic disorder in HRV due to the lack of an autocorrelated periodic chaos in cardiac pacing. Such an unphysiological neurovegetative regulation suggests a new silent cardiac dysautonomic syndrome, that we intend to call "minimum delirium cordis syndrome" (MDCS). Can the MDCS be regarded as a condition of cardiovascular risk? To answer this question, it seems justified to suggest that the study of the E CR should be added to the routine tests that are presently applied to clinical analysis of the Holter ECG, being the classic tests of linear analysis not methodologically suitable for detecting the indeterministic chaos of the MDCS.

1. The aim of the present study was to investigate the effects of a short (1 day) fast by testing biohumoral variables associated with the human circadian rhythm. 2. Fifteen clinically healthy male volunteers (32 +/- 8 years old) participated in the study. Subjects were fed a control diet for 7 days. The last day was a control day and the following 8th day was the fasting day. Each subject was asked to collect urine seven times over a 24 h period. Chemical and hormonal variables were measured in each fractionated urine specimen. The time- qualified urinary excretion rates were biometrically analysed using conventional and chronobiological methods. 3. During fasting, significant incremental changes were detected in the urinary excretion rates of potassium, aldosterone, 17-hydroxycorticosteroids and adrenaline and significant decremental changes were detected in the excretion rates of sodium, chloride, creatinine, urea nitrogen, uric acid, 17-ketosteroids, noradrenaline and dopamine. The circadian rhythmicity of the variables was well preserved and remained almost stable throughout the fasting phase. 4. Fasting affected the mean oscillatory levels and oscillatory amplitudes of variables, suggesting that nutrients may have played roles as tonic and phasic modulators on the mechanisms that physiologically regulate ircadian rhythmicity.

The study investigates the circadian rhythm (CR) of urinary 6-sulphatoxy-melatonin (aMT6s) in long-living (longevous) subjects and their progeny. The aim is to detect whether or not the melatonin CR is a physiological feature associated with healthy longevity. The aMT6s CR was investigated in 10 longevous subjects, 8 of their children and 9 of their grandchildren, all in good health. Control data were obtained respectively from 13 adult subjects and 9 young subjects, in good health, but characterized by a negative family history for longevity. All the subjects were born and living in the same city. The study was performed in the summer of 1996. The aMT6s CR was found to persist in longevous subjects, being characterized by a lower mesor and amplitude. The aMT6s CR was found not to show properties consistently different in children and grandchildren as compared respectively to their adult and young controls. Because of its preservation in longevous subjects, it can be argued that the melatonin CR is a physiological feature associated with healthy longevity. Because of the comparability of aMT6s CR in children and grandchildren, with respect to their controls without a positive family history of longevity, it can be argued that the melatonin CR is not a marker that can be used for an earlier identification of the candidates for longevity.

This study investigates within-day hunger sensation (HS) variability in Clinically Healthy Subjects Adapted to Living in Antarctica (CHSALA), as compared to their coeval subjects living in their mother country. The aim is to detect how the orectic stimulus behaves in those environmental conditions and occupational schemes, in order to investigate the individual synchronization to sleep-wake alternation and meal time schedule. HS was estimated via a self-rating score of its intensity on a Visual Analog Scale, repeating the subjective perception every 30 min, unless sleeping. The individual HS time-qualified scores (orexigram) were analyzed according to conventional and chronobiological procedures. The orexigrams of the CHSALA were seen to show a more cadenced intermittence during the diurnal part of the day, strictly related to the meal timing, and a preserved circadian rhythm as well. In addition, these orexigrams were resolved in a spectrum of harmonic components which indicated a subsidiary number of ultradian formants. These findings are convincing evidence that the individual orexigram may be used to investigate whether or not a single subject is synchronized to sleep-wake cycle, meal time schedule and socio-occupational routines, instead of using more complex and expensive techniques, involving automated equipments and biohumoral assays.

The present paper explores the relationships between anxiety, depression, hunger sensation and body composition in obese patients (OP). The aim is to detect whether or not there are abnormalities in these relationships in OP as compared to clinically healthy subjects (CHS). The study was performed on 22 CHS (2 M, 20 W; mean age = 24 +/- 2 years; mean body mass index = 21 +/- 2 kg/m2) and 48 OP (4 M, 44 W; mean age = 40 +/- 17 years; mean body mass index = 32 +/- 7 kg/m2). Anxiety and depression were found to be correlated, negatively, with the relative lean body mass, and, positively, with the fat body mass in OP but not in CHS. These findings corroborate the idea that anxiety and depression can reach an abnormal expression when obesity shows its worst loss in lean body mass and its highest expansion in adipocyte mass. As hunger sensation was found not to correlate with either anxiety or depression in OP, the opinion is expressed that the impairment of anxio-depressive integrity is a corollary of obesity rather than a primary affective disorder leading to obesity via an enhanced food intake.

Background This study investigated the blood pressure (BP) values over the day-night period in 11 noninstitutionalized patients affected by probable Alzheimer's disease (AD) in its early stage. The scientific aim was to detect whether the BP circadian rhythm (CR) was preserved, given the fact that CR disruption was observed in advanced or institutionalized AD patients. Methods The BP within-day values were gathered via noninvasive ambulatory monitoring. The BP time series were analyzed according to the chronobiological procedure, called Cosinor method with three harmonic components. Results The biometric analysis was able to document that BP changes over the 24-h scale in AD patients as a function of a significant CR. Such a preserved circadian regulation is, however, compromised in the second and third harmonic component, suggesting that the BP within-day variability is desynchronized by the environmental clues that act as synchronizers during the diurnal part of the day. Conclusions The preservation of the BP CR in the early stage of AD suggests using such a finding as a clinical tool for confirming the recent onset of the disease. As a matter of fact, it is presumed that the disease is not evolved enough to reach the suprachiasmatic nuclei, wherein is located the BP circadian pacemaker. The abolition of the ultradian components is another precocious sign that, in turn, indicates early-stage AD patients to be particularly compromised in their synchronization to diurnal cues, such as social routines, meal timing schedule, psycho-physical activity, and occupational schemes.

The aim of this study was to demonstrate that blood pressure (BP) has to be standardized according to its circadian variability, including the properties shown in its circadian rhythm. The BP time-qualified standards were derived from a sample of 644 clinically healthy normotensive Japanese subjects (320 males, 324 females; age range, 18-93 years), stratified by age-group and gender, who underwent noninvasive ambulatory monitoring according to a fixed protocol. The monitored data series shows that BP exhibits a within-day variability at any age of life in both males and females. Additionally, the monitored data series shows that BP exhibits a significant circadian rhythm at any age of life in both males and females. The age- and sex-related reference limits for the BP within-day variability constitute the time-qualified standards against which both the casual and monitored BP measurements can be compared in order to detect whether or not they are compatible with normotension. The reference limits for the BP circadian rhythm represent the rhythmometric standards against which the BP oscillatory curve can be compared in order to detect whether or not they are compatible with a physiological circadian rhythm.

Blood pressure (BP) is recursively variable during the day-night cycle because of a physiological circadian rhythm. The aim of this study is, therefore, to show how to construct the population reference limits (desms) for BP in its time varying 24-h pattern, starting from a small sample, in order to facilitate their use in a local context. The sample for standardization comprised 427 clinically healthy subjects (211 males and 216 females), ranging in age from 16 to 100 years, attending their routine activities. The procedure begins with the statistical biometry related to the sample, and proceeds with the computation of the BP desms related to (1) the time-qualified discrete values; (2) the parameters of circadian rhythm; (3) the daily pressure load. The pertaining rules are explained step by stop, allowing each one to prepare the proper local desms for BP 24-h pattern. These standards may be useful for validating the individual BP monitoring according to the upper limits of the circadian physiological variability in the diagnostic procedure for identifying hypertensive subjects.

Hunger sensation (HS) in humans physiologically shows intraday (circadian) and within-day (ultradian) recursivity. This intrinsic periodicity was investigated by applying the cosinor method and spectral analysis to the 24-hour profile of HS (orexigram) derived by a self-rating score (from 1 to 10 hunger units [HU]) recorded every half-hour. The study of circadian and ultradian recursivity on the orexigram was performed in 30 diabetic obese patients ([DOPs], 14 men and 16 women aged 22 to 62 years; body weight, 77 to 130 kg; body mass index, 31–47). The control group consisted of 30 clinically healthy subjects ([CHS], 15 men and 15 women aged 21 to 60 years; body weight, 65 to 72 kg; body mass index, 23 to 25). DOPs showed two types of orexigrams in which hunger was felt with limitation to the diurnal part of the day or with extension to the night, respectively. The type 1 orexigram was characterized by a normal spectrum and circadian rhythm. The type 2 orexigram was characterized by subsidiary ultradian components associated with an abnormal elevation of the circadian mesor and a significant delay of the circadian phase, as the spectral analysis was indicative of a structural difference in the frequencies that sustain the intraday and within-day recursivity of the HS. Accordingly, DOPs can be recognized by their orexigram as “eurectic” or “hyperrectic” to indicate subjects with a normal or an exaggerated HS, respectively, during the 24-hour span.

Objective Diabetic patients (DP) refer increased hunger sensation (HS) when hyperglycemic but not yet ketogenic. As HS shows a within-day (ultradian cyclicity) and intra-day (circadian cyclicity) repetitivity, its recursive pattern was investigated in patients with type 1 and type 2 diabetes mellitus (DM), in compensated and uncompensated metabolic stage. Method: HS was approached in its cyclic structure by means of spectral analysis (SA), and in its circadian rhythmicity by means of Single Cosinor analysis (SCA), applied to self-rated scores of HS given every 30 min to their HS (orexigram) by DP. Results: Exaggerated periprandial, interprandial, and/or nocturnal peaks of HS were seen in the orexigram of both the type I and type II DP. Specific alterations in HS periodogram were detected, structurally denoting a relative prevalence of the ultradian components along with the deamplification and loss of the circadian harmonics. Discussion: The increase of HS (hyperorexia) in nonketotic DM may be formally attributed to a mechanism of frequency multiplication and amplitude demodulation in the multifrequency bioperiodic structure which physiologically regulates the recursive pattern to the daily HS in human beings. © 1996 by John Wiley and Sons, Inc.

Objective To investigate the effects of chronic smoking on the 24 h blood pressure and heart rate pattern in normotensive subjects. Methods Twenty-five smokers and 25 age-, weight- and height-matched non-smokers, who were all clinically healthy young men, gave their informed consent to undergo non-invasive, automated, ambulatory blood pressure monitoring for 24 h. The smokers in this study consumed on average 25.4 cigarettes per day. The lifestyle of the two groups was comparable because they worked as clerks at the same company. The 24 h blood pressure and heart rate data were analysed according to chronobiological methods. Results Smokers were found to show a statistically significantly higher blood pressure versus non-smokers by day but not by night. Furthermore, smokers showed a slight increase in the mean level of circadian blood pressure rhythm versus non-smokers, accompanied by an amplification of one cyclic component of this periodicity. Conclusions The increase in diumal blood pressure in smokers might be regarded as the haemodynamic effect of chronic smoking in normotensive subjects. Such an effect seems to be substantiated pathophysiologically by an amplitude overmodulation of one of the harmonic components which confer the circadian blood pressure rhythmicity. Because the diumal increase in blood pressure persists for two-thirds of the day-night period, one can argue that this phenomenon in normotensive smokers might be a premonitory sign of future hypertension. Apart from this, one can hypothesize that the diumal increase in blood pressure might itself be a cause of target organ damage, given its consistent within-day duration and daily repetition.

The study investigates how the human body composition (BC) changes as a function of the day-night cycle. The BC was investigated using bioelec-trical impedance analysis (BIA) of 10 clinically healthy subjects (CHS), mon-itored in supine position (readings at 2-h intervals), avoiding mealtimes, di-etary abuses, and bladder and intestinal retention. Time series data were analyzed for their temporal characteristics and circadian rhythm (CR). Ail the variables of BC (lean body mass, fat body mass, body cell mass, total body water, intracellular and extracellular body water, sodium and potassium exchangeable pool) showed a within-day variability with nighttime crests. Such an oscillatory synchronism corroborates the hypothesis that the rest time plays a fundamental role, via its anabolic effects, in conferring the noc-turnal phase to the CR of the human BC.

A mathematical method is suggested for determining biological periodicities being based on the minimization of the area underlying the serial section (area of displacement) with which the chronogram of the presumably rhythmic variable is scanned. The investigated biological variable may be measured at equidistant or non‐equidistant intervals of time in a span which exceeds at least twice the assumptive period. The method allows to verify the supposed periodicity with its statistical significance, and to alternatively find the best fitting period in case the investigated process is really rhythmic. The periods investigated are returned with their statistical significance along with the mean, standard deviation, peak, trough and timing of the values enclosed within. The estimates are printed out along with a diagram of the raw data within the limits of the best fitted period.

This study deals with the non‐invasive ambulatory monitoring of blood pressure (BP) in obese patients. The individual data were analyzed by means of chronobiometric procedures which allow us to estimate the BP values in their within‐day discrete variability, circadian rhythmicity and daily pressure load (Daily Baric Impact). The estimates of time‐qualified values documented that both male and female obese patients show an elevation of BP values all over the 24‐h span. The cosine function revealed that the BP circadian rhythm in obese males and females is preserved but shows a higher level of oscillation. The measure of the area under this oscillation (aesor) provided evidence that the Daily Baric Impact is higher in obese patients as compared to non‐obese subjects. The spectral analysis, in turn, revealed that the BP 24‐h variability in obese patients is sustained by oscillatory components which are not detectable in the physiologic spectrum of resolution in harmonics, suggesting an abnormal tone...

Non-obese diabetic (NOD) mice spontaneously develop an autoimmune diabetes with higher incidence in females than in males. In order to elucidate possible factors involved in the different incidence of diabetes between male and female mice, we studied the progression of pancreatic beta-cell loss in relation to mononuclear cell infiltration of the pancreas (insulitis). We examined the pancreas of 76 NOD mice (39 males and 37 females) of different ages. The beta-cell content was assessed by immunoperoxidase staining of sections with an anti-insulin serum and the severity of insulitis was determined by haematoxylin staining of the same sections. A semi-quantitative criterion was used to grade both parameters. The results showed that females have a faster loss of beta-cell mass, which progressively decreases with the increase of severity of insulitis. In males, a medium to severe degree of insulitis is required before initial loss of beta cells occurs. Under the age of 10 weeks there was a significantly lower content of beta cells in females than males (2.84 +/- 0.03 vs 2.67 +/- 0.07; P = 0.02). Since we never observed a significant difference in the degree of mononuclear cell infiltration in age-matched males and females, these data support the hypothesis of weaker beta-cell resistance to immunological attack in female mice. Thus beta-cell sensitivity, in addition to immunological activity, is an important factor in the pathogenesis of insulin dependent diabetes.

Presently, the chronobiometric procedures are eminently descriptive estimating the biological rhythms in their parameters without computing the integral measure of their periodic oscillation. The evaluation of the rhythm as a global function is fundamental in biomedical science as its integral estimate allows the correlation with biological events whose expression depends on the effects of time. In order to provide an integration method for biological rhythms, it has been developed a periodic integration analysis, called Cosint method. Its mathematical basis is explained. The integral estimate is represented by the parameter AESOR, acronym of Area Estimating Statistic Of Rhythm, which corresponds to the area under the curve provided by the analytical fits of a cosine function to the time data series. The AESOR can be computed on the waveform profiles resulting from the fit of mono‐ or multiple‐component models of harmonic analysis. The AESOR may estimate the biological rhythms in their entire per...

Noninvasive ambulatory blood pressure (BP) monitoring is a developing method in clinical practice. Its interpretation needs reference standards stratified by age and gender. This study addresses ambulatory BP monitoring in elderly people with the purpose of quantifying the discrete and periodic variability of BP pattern over a 24-h period. The ABPM was performed in 92 clinically healthy subjects (45 men and 47 women) ranging in age from 76 to 102 years. The results refer to the time-qualified mean values with their dispersion, to the circadian rhythm with its parameters, and to the daily baric impact (BI) with its variability. The conclusion is drawn that BP preserves its nychtohemeral variability and circadian rhythmicity despite old age. The daily BP mean level and BI in older people in good health are comparable with those of young subjects, suggesting that humans surviving into old age are characterized by a eugenic control of their pressure regimen.

A 67-year-old man affected by prostate cancer was incidentally found to have a nodular enlargement of the left adrenal gland without apparent changes in hormonal status. The adrenal mass was found to be scintigraphically active, the radiolabelled compound being concentrated in its context with a consensual suppression of the contralateral uptake. The patient underwent a resection of the adrenal tumor. Histologically and biochemically, the adrenal mass was found to be a non-functioning adenoma. The radioisotopic uptake along with the non-hormonal activity prompted us to call this tumor “Pre -Cushing's syndrome” of the adrenal cortex.

The circadian rhythm (CR) of plasma renin activity (PRA), plasma aldosterone (PA), and plasma cortisol (PC) was investigated in 8 patients with kidney transplantation, and in 10 patients with heart transplantation. Ten clinically healthy subjects were studied as controls. The transplanted patients were all under cyclosporine treatment associated with prednisone (PDN). Time-qualified levels of PRA and PA were seen to be higher than normal in both groups of transplanted patients. The analysis of PRA and PA circadian rhythm provided evidence for a systematically higher level of within-day concentrations. The higher level of oscillation suggests the occurrence of a condition of hyperreninemic hyperaldosteronism. The higher levels of PRA and PA 24-h values show no periodicity. The finding suggests the abrogation of the rhythmic function for renin-aldosterone system. The disappearance of PRA-PA circadian rhythm seems to be attributable to a side effect of immunosuppressive therapy.

The time course of blood pressure in clinically healthy (pregnant and nonpregnant) women was followed by automatic ambulatory monitoring. Chronobiologic methods revealed the time course of dynamic rhythm characteristics as a function of gestational age. Differences were found between nonpregnant and pregnant women with an overall lowering during pregnancy of the rhythm-adjusted midline estimating statistic of rhythm (mesor).

The study of blood pressure (BP) monitoring in essential hypertensive patients recurrently suffering from nocturnal headache revealed a rhythmic elevation of sphygmomanometric values during the night. Such a finding was not detected in essential hypertensive patients suffering from occasional headache. The nocturnal elevation of BP was seen to be paralleled by the circadian peak of heart rate, suggesting that the disorder is a systemic phenomenon. Importantly, the headache episodes were seen to disappear after antihypertensive therapy that was adjusted to lower the nocturnal increase of BP. The therapeutic results suggested that the nocturnal headache was dependent on the phasic elevation of BP. The beneficial effects further suggested that the nocturnal headache and the nocturnal elevation of BP may represent a particular syndrome with a cause-effect relationship. The term "nocturnal headache-hypertension syndrome" is proposed.

Because of recent papers on "Cugini's syndrome", as a new nosographic cardiovascular entity, the writer of this article has seen of medical interest to interview Prof. Cugini in person for a better elucidation of this syndrome. It must be stressed that the syndrome we are dealing with has been identified by reviewing Cugini's investigations carried out in Italy between 1997-1999 on subjects considered to be normotensive at the casual Riva-Rocci sphygmomanometry but unexplicably showing initial signs of hypertensive organ damage. The syndrome consists of the binomium "Minimal change hypertensive retinopathy/Pre-hypertension", in that the apparently normotensive subjects were seen to be characterized by a minimally accentuated reflex of retinal arterioles, as it occurs in I Stage of Keith-Wagener-Barker classification for hypertensive retinopathy, being neither "truly normotensive" nor "truly hypertensive". As a matter of fact, these subjects were classified by Prof. Cugini as "pre-hypertensive" in that the 24-h values of their blood pressure (BP), measured via Ambulatory Blood Pressure monitoring (ABPM), were invariably below the upper reference limits given at that time by WHO, but, notwithstanding that, their systolic (S) and diastolic (D) daily average was significantly higher than in "true normotensive" subjects. Furthermore, at the chronobiometric analysis of the ABPM, these pre-hypertensive subjects resulted to have a well-phased BP circadian rhythm and an amplified oscillation in their 24-h BP values. Interestingly, Prof. Cugini documented that the clinical condition of "Pre-hypertension" could be also found in putatively normotensive subjects with an initial hypertensive damage of other target organs, suggesting that the "Cugini's syndrome" could be intended more extensively via the binomium, i.e., "Minimal change hypertensive cardiovascular damage/Pre-hypertension". Having statistically found a significant difference in BP 24-h mean values between "true normotensives" and "pre-hypertensives", it can be inferred that Prof. Cugini used the term "Pre-hypertension" to taxonomically indicate a para-physiological hemodynamic status characterized by an increase in BP 24-h mean values, quantifiable and documentable via ABPM, staying in between normotension and hypertension, describing with a large anticipation of time the "normal-high" grade of the classification reported years later in 2003 by JNC in its VII Report on arterial hypertension. Moreover, it is important to stress at the time of Cugini's studies the Stage I of hypertensive retinopathy was considered to be an initial sign of damage already indicative of a high BP regimen. But, even more important, it is to remark that at the time of Cugini's studies the term "Pre-hypertension" was used just to indicate a presumable stage of predisposition to develop hypertension in subjects with a positive familiarity for high BP. Therefore, Prof. Cugini transposed the meaning of the term "Pre-hypertension" from a merely putative preclinical asymptomatic status to an objective clinical symptomatic status documentable via the daily average of BP values, being associated with documentable signs of initial tensive target organ damage in subjects "falsely normotensive". With this connotation, the Cugini's syndrome shows the following indications: 1. in the presence of a minimal sign of hypertensive organ damage in subjects considered to be normotensive at the casual sphygmomanometry, it is mandatory to perform the ABPM with the suspicion not only of an "odd-hour hypertension" or a "non-dipping phenomenon" but also of a "pre-hypertension"; 2. in the presence of a pre-hypertension diagnosed at the ABPM, it is mandatory to perform an accurate investigation of cardiovascular organs susceptible to hypertensive damage with the suspicion of a Cugini's syndrome. Further studies are needed to verify whether or not the Cugini's syndrome needs to be preventively cured and which drugs have to be eventually used. A non-pharmacological treatment of life-style seems to be necessary.

To prevent iodine deficiency disorders, the World Health Organization, United Nations Children's Fund, and International Council for the Control of Iodine Deficiency Disorders established that for a given population median urinary iodine concentrations (UIC) must be 100-199 microg/L in clinically healthy subjects and 150-249 microg/L in clinically healthy pregnant women. We evaluated whether in the urban area of Rome, Italy, where a salt iodination program (30 mg/kg) was introduced since 2005, an increased demand of iodine during pregnancy is guaranteed.During 2006, 51 pregnant women at first trimester of a physiologic gestation were consecutively enrolled on presentation to evaluate UIC in morning spot urine samples. As controls, 100 age-matched clinically healthy non-pregnant women were evaluated.The median UICs were 182 microg/L (range 85-340 microg/L) and 74 microg/L (range 17-243 microg/L), respectively, in the control and pregnant groups. This difference was highly significant (P0.001). In particular, the UIC was found to be lower than adequate in 4% of control women compared with 92% of pregnant women. This difference of occurrences was highly significant (P0.001).This observational study demonstrated that, despite the adequate supplementation of iodine intake, most pregnant women appear not to be protected against iodine deficiency. If confirmed in larger case studies, this finding claims the attention of relevant professionals to monitor iodine nutrition during gestation, assuming that ordinary supplementation of iodine intake seems to be sufficient only in non-gestational conditions.

Biomedical research is frequently confronted with regression lines that directionally describe the trend of phenomena, each one represented by a set of correlated x and y data. There could be a need to verify whether the regressions lines of two (or more) phenomena are statistically comparable in their slopes and intercepts, in order to draw conclusions about the similarity or dissimilarity of the conditions under scrutiny. The parallelism test the principles and methodology of which are presented here addresses this problem. A program for microcomputers is supplied as a non-profit software that can be freely shared on the understanding that the copyright belongs to the authors of this article.

Blood pressure (BP) monitoring is a clinical reality because of the availability of non-invasive automated recorders. BP 24-h patterns were explored during physiologic pregnancies in order to obtain time-qualified standards for clinical use. Non-inferential and inferential reference boundaries were computed by using chronobiometric procedures. The computed confidence limits provide a set of reference standards that serves to optimize the diagnosis of pregnancy-induced deviation in BP 24-h patterns.

The study estimates the unpredictable disorder (chaos) within the 24 h pattern of sinus R-R intervals (SRRI) in clinically healthy pregnant women (CHPW) and clinically healthy non-pregnant women (CHNPW), in order to evaluate the early gestational changes in neurovegetative cardiac pacing. SRRI were provided by the 24-h Holter ECG of 10 CHPW and 10 CHNPW. SRRI were investigated by descriptive conventional statistics by means of the Time and Frequency Domain Analysis, and subsequently, in their chaotic component by means of entropy analysis. Both the SRRI and entropy were tested via the Cosinor method to better decipher whether or not the periodic disorder in heart rate variability is modified in pregnancy as a result of a gestational tonic resetting of the cardiac sympatho-vagal regulation. Cosinor analysis documented that the circadian rhythm of both the SRRI and entropy were preserved in CHNPW and CHPW. However, the circadian rhythm of SRRI and entropy in CHPW exhibited a significantly decreased 24 h mean. Via the analysis of the rhythmicity of entropy, this study has documented that the chaos in the 24 h pattern of SRRI is less prominent in CHPW than in CHNPW. Such a reduction of level in the deterministic periodic chaos of heart rate variability provides evidence that, in early pregnancy, a tonic elevation of the sympathetic activity regulates cardiac pacing.

Objective: The present study investigated the orexigram, the time-qualified self-rated estimate of hunger sensation (HS), in patients affected by morbid obesity (MO) with the aim of detecting how daily HS behaves before morbidly obese patients (MOP) undergo bariatric surgery (BS). This article is therefore a preliminary report as it is necessary to make subsequent comparisons with post-BS orexigrams. Preoperative orexigrams may be helpful in selecting the MOPs who are candidates for surgical treatment. Materials and Methods: Ten MOPs (five males and five females, with a mean age of 34±11 yr and a mean BMI of 49.32±7.26 kg/m2), and 19 clinically healthy control subjects (CHS: nine males and ten females, with a mean age of 24±2 yr and a mean BMI of 21.00±1.70 kg/m2) gave their informed consent to participate in the study. All of the study participants were asked to compile a 24-h orexigram, which was then biometrically analysed by means of: 1) conventional methods for parametric statistics; 2) rhythm analysis for their circadian rhythms; and 3) spectral analysis for their harmonic structure. Results: The orexigrams of the MOPs had significantly increased mean daily levels (daily hyperorexia), retained their circadian periodicity despite an increase in mesor, and were consistently modified in their ultradian spectral harmonic components. Conclusions: The results show that the studied MOPs complain of a daily hyperorexia that is still perceived circadically. This perception is a structured abnormality, as demonstrated by the consistent changes in the spectral analysis, and so MOPs can be diagnosed as being affected by so-called “hyperorectic obesity”. It will be interesting to see whether or not presurgical hyperorexia in MOPs is corrected by BS: if so, hyperorexia may become an additional indication, and presurgery orexigrams could be suggested as an additional means of selecting the hyperorectic MOPs who are candidates for surgical treatment.

Objective: The aim of this study was to investigate the daily pattern of hunger sensation (HS) in patients affected by a non-advanced form of cystic fibrosis (CF) in order to detect how the orectic stimulus (OS) behaves in fibrocystic patients (FP) who are obliged to eat frequently because of their pancreatic exocrine insufficiency. Materials and Methods: The study involved 27 out-patients (13 males and 14 females; mean age 18±4 years; mean BMI 18.77±2.17 kg/m2) with a non-advanced form of CF, and 19 clinically healthy subjects (CHS, 9 males and 10 females; mean age 24±2 years; mean BMI 21.00±1.70 kg/m2). The FP were used to eating frequent small meals between the three main meals of breakfast, lunch and dinner. All of the participants were asked to compile an “orexigram”, which was chronobiometrically analysed by means of: 1) conventional statistical methods; 2) rhythmometric analysis of circadian rhythm (CR); and 3) spectral analysis of the harmonic structure substantiating the within-day variability of HS. Results: HS in FP had 1) a significantly increased daily mean level; 2) a well-established CR, with a significantly increased oscillatory mesor and amplitude; and 3) a modified orexigram power spectrum affecting the ultradian harmonic components. Conclusions: Our results suggest that the orectic perception of CF patients is characterised by “daily hyperorexia”, with the maintenance of HS CR. This condition seems to be a structured abnormality insofar as there are visible changes in the orexigram spectral resolution, particular in the ultradian harmonic components whose oscillatory frequency is responsible for the diurnal pattern of HS. The hyperorexia of the investigated FP indicates that their frequent small meals are not sufficient to satisfy their HS, which may cause a vicious circle leading to progressively disrupted mealtime behaviour.

We studied the within-day determinations of some body composition (BC) parameters in clinically healthy elderly subjects with the aim of investigating their circadian rhythms (CR), which are known to vary in a circadian manner in clinically healthy young adults. The study involved six non-smoking, clinically healthy elderly males (mean age: 75 +/- 4 years; mean weight: 71.07 +/- 10.26 kg; mean height: 170 +/- 5 cm, mean BMI: 24 +/- 1 kg/m2). The BC parameters were determined by means of bioelectrical impedance analysis (BIA) at 2-hour intervals during the day and night, with the subjects lying horizontally in bed. The time-qualified BC estimates were analysed using the Cosinor method. The analysis revealed that the healthy elderly subjects had lost the CR of a number of the BC parameters, including fat body mass, cell body mass, extracellular body mass, total body water, extracellular body water, intracellular body water, and the Na and K exchangeable pools. However, they still retained the CR of body weight and lean body mass, with the expected nocturnal phase of oscillation. The abolition of the CR of the majority of BC parameters in the elderly suggests that human senescence is characterised by consistent changes in the daily rhythmic patterns of fat, water and electrolyte metabolism.

This investigation deals with the circadian rhythm (CR) of hunger sensation (HS) in obese patients before and after a four-week, moderately hypocaloric diet with a substitutive meal. The study was performed on 25 non-diabetic obese patients (5 males and 20 females, mean age: 39.7 +/- 7, mean BMI: 27.9 1.4 Kg/m2), whose obesity was not associated with impaired glucose tolerance (IGT), binge eating, nor endocrine diseases. Their daily HS profile (orexigram) was analysed chronobiometrically. The moderately hypocaloric diet with a substitutive meal reduced the daily HS by about 10% by the fourth week. This reduction was apparently due to a tonic and amplitude modulation of the HS CR and was not accompanied by its disruption. No conclusions, however, could be drawn with regard to its orectic and clinical effects beyond four weeks.

Hunger sensation (HS) is a signal whose levels change during the 24-h day. The daily mean level of HS was correlated with the human body compartments, as investigated by bioelectrical impedance analysis, to detect the relationship between the orectic perception and both the free fat mass (FFM) and the fat body mass (FBM) in 22 clinically healthy subjects (CHS) (2 M, 20 W, BMI: 18.5–24.0 kg/m2) and 48 obese patients (OP) (4 M, 44 W, BMI: 25.2–54.7 kg/m2). In CHS, the daily mean level of HS correlated positively with the FFM and negatively with the FBM. These correlations were not present in OP. This lack of relationships between HS and the body compartments where energy is maximally consumed (i.e., the FFM) and maximally stored (i.e., the FBM) indicates that the orectic response to energy expenditure and the orectic inhibition to fat accumulation are feedback mechanisms which are impaired in obesity.

Alterations of blood pressure and heart rate circadian rhythmic structure in non-blind patients affected by retinitis pigmentosa

The human hunger sensation (HS) is a perceptive signal characterized by day-night variability (DNV). This pattern was investigated with respect to its relations with the body compartments in 22 clinically healthy subjects (CHS, 11 males and 11 females, mean age: 24 +/- 2.5 years, mean BMI: 21 +/- 1.7). The DNV was investigated by means of conventional descriptive statistics and the single cosinor method (SCM). Both procedures were applied to the orexigram, i.e., the 24-h profile of the orectic stimulus (OS) provided by each subject, who self-rated his/her HS (from 1 to 10 hunger units) every half hour. Body composition was investigated by Bioelectrical Impedance Analysis (BIA) on the day when the orexigrams were compiled. It was found that the daily HS level correlates positively with the Free Fat Body Mass (FFBM) and negatively with the Fat Body Mass (FBM). These opposite relations indicate that HS is stimulated by the needs of the FFBM, and inhibited by expansion of the FBM, and provide further evidence of the existence of an "adipostat" anorectic mechanism.

Hunger sensation (HS) is a perception with a daily (circadian) and within-day (ultradian) recursive pattern. In human beings, circadian repeatability was investigated by means of the Single Cosinor method, while the ultradian recursivity was investigated by means of the spectral analysis, both applied to the 24-h HS profile (orexigram). Orexigrams were provided by each subject investigated, who self-rated her subjective orectic stimulus (OS) (from 1 to 10 hunger units) every half hour. The study was performed in 19 female patients aged 13-52 newly diagnosed as in the first episode of Anorexia Nervosa Restricting Type, with a BMI below 18.7. The control group consisted of 10 clinically healthy women aged 21 to 52 years with a BMI from 23 to 25. Two types of orexigrams were found. The first was characterized by a low profile with negligible ultradian variability, in which the HS circadian rhythm (CR) was still detectable, but the power spectrum (PS) was composed of unusual ultradian components associated with a very diminished amplitude for the circadian harmonics. The second was characterized by an almost regular profile, in which the ultradian variability was clearly detectable, the CR regularly fluctuated, and the PS was almost regularly composed. These findings indicate that anorectic patients (AP) can be recognized by their orexigram as "hyporectic", or "eurectic". Therefore, the term "anorexia" seems to be appropriate for AP who exhibit the first type of orexigram (anorectic aphagia nervosa), whereas the second identifying those who could be defined as suffering from "eurectic aphagia nervosa".

The study of the relationship between hypertension and cognitive decline is characterized by various difficulties of realization and, as a consequence, by incongruent results. One of the reasons for these difficulties may be explained by the occasional method of measurement of blood pressure (once a day). This study presents the results obtained in 27 normotensive and mild hypertensive subjects of both sexes (ages between 20 and 77 years) with a continuous blood pressure monitoring for 24 h. A noninvasive sphygmomanometric technique was used employing a portable recorder programmed to take a measure every 30 min. Both objective and subjective measures of memory, measures of attention efficiency, and IQ were correlated to the blood pressure measures. Continuous monitoring data of blood pressure were analyzed according to a model that included a macroscopic descriptive analysis, a microscopic rhythmometric analysis, and a microscopic integrative analysis where the effects of the interaction between level and duration of excess and the time of the day when the excess eventually appeared were considered. Results evidenced no differences in cognitive efficiency between those subjects identified with the traditional occasional measurement of blood pressure as hypertensives of mild severity and the normal subjects. Cognitive efficiency of our subjects was found correlated, independently from the clinical diagnosis, with the time of peak and with the duration of excess of their blood pressure when the results of the analyses on the continuous monitoring of blood pressure were considered.

In 46 female outpatients with android-type obesity, body mass index (BMI) 36.6 +/- 1.0, waist to hip ratio (WHR)0.86, and normal glucose tolerance (NGT) who were hypertensive at entry study [blood pressure (BP)140/90 mm Hg] and in 10 clinically healthy, nonobese, normotensive women, we evaluated the relationship between BMI, fat mass, WHR, fasting blood glucose, sum of blood glucose levels during oral glucose tolerance test and casual BP levels, 24-h ambulatory BP monitoring (ABP) parameters as the 24-hour mean, day-time mean, night-time mean and, by using a periodic model of cosine regression, MESOR (midline estimating statistic of rhythm), amplitude, acrophase, and baric impact. In android obese women, a negative correlation between ABP levels (day-/night-time, MESOR, and baric impact of systolic BP; night-time and MESOR of diastolic BP) and BMI has been documented. A positive correlation between systolic BP (casual, night-time mean, MESOR, amplitude, and baric impact), diastolic baric impact, and the WHR has been found. No correlation has been demonstrated between ABP monitoring parameters, and BMI, body fat, and WHR in the control group. Our data could suggest that, when enrolling obese subjects, it must be taken into account that obesity is a heterogeneous disorder. There are in fact obese subjects with normal or impaired glucose tolerance, as well as diabetics with moderate to severe obesity and with gynecoid or android-type obesity. In our android obese subjects with NGT, the WHR rather than the BMI was found to be a better predictor of hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

In human beings, hunger is a proprioceptive signal that shows intraday (circadian components) and within-day (ultradian components) recursivity. Both periodic components can be investigated by chronobiometric procedures by combining the Cosinor method with spectral analysis. A 24-hour profile of hunger sensation (HS) can be plotted on a 1-to-10 scale of intensity using self-rated scores performed every half-hour of the day. Circadian and ultradian components were studied in 60 patients affected by essential obesity (20 men and 40 women; mean age, 38.4 years; mean body weight, 101 kg) before and after treatment with dexfenfluramine (Isomeride®; Servier, Orleans, France) 15 mg orally twice daily, for 30 days. The control group consisted of 30 clinically healthy subjects (15 men and 15 women; mean age, 37.5 years; mean body weight, 69 kg). Chronobiometric analysis shows three patterns in obese patients, which suggests that HS may be normal (eurectic obesity), exaggerated (hyperrectic obesity), or diminished (hyporectic obesity). After dexfenfluramine administration, HS was showed a substantial decrease in the daily mean level. The spectrum of resolution in circadian and ultradian components was found to be maintained in eurectic obesity and partially readjusted in hyperrectic and hyporectic obesities. This demonstrates that dexfenfluramine acts not only as an anorectic but also as a chronizer by interfering with the recursive components of HS. The anorectic and chronizing effects suggest that dexfenfluramine is a “chronoanorectic drug” that interacts with the chronobiologic properties of the serotoninergic system.

The aim of this study was to quantify the degree of sub-clinical anxiety and depression in essentially obese patients (EOP) and normoponderal healthy subjects (NHS) in order to identify quantitative differences based on mean scores and percentages (the latter in cases showing a tendency towards pathological anxiety and depression indicated by a score ofor = 8). The study involved 69 EOP (age: 13-72 years; BMI:25.0 and35.0 kg/m2) and 66 NHS (age: 18-68 years; BMI:18.5 andor = 25.0 kg/m2). The scores, expressed in Anxiety Units (AU) and Depression Units (DU), were computed using ad hoc questionnaires (the ASQ and CDQ) validated for the Italian population. The mean scores of sub-clinical anxiety and depression in the EOP were significantly higher (both p = 0.001) than those of the NHS (6.33 +/- 2.38 vs 5.02 +/- 2.22 AU; 6.42 +/- 2.42 vs 5.02 +/- 2.03 DU), as were the percentages of cases with a tendency towards pathological anxiety and depression (42% vs 18%, and 43% vs 12%) (both p = 0.001). The significantly higher mean sub-clinical anxiety and depression score in the EOP indicate that a worse mood status is associated with obesity in a non-random manner. The significantly higher percentages of EOP with a tendency towards pathologic anxiety and depression indicate that obesity is a clinical condition that predisposes to the development of clinically relevant affective disorders.

The aim of this study was to investigate whether there is variation in blood pressure when we reapportion the percentage of total daily salt intake consumed at each of three regular meals. The study was conducted on seven clinically healthy normotensive female subjects who, in Stages LH and DH, consumed two-thirds of the normal daily salt intake (12 g/day) at lunchtime or at dinnertime, respectively. The total daily amounts of nutrients and dietary salt were similar in Stage-R (regulated salt intake), Stage-LH (a high-salt intake at lunchtime), and Stage-DH (a high-salt intake at dinnertime). The blood pressure response to the variation of sodium content in the meals was examined by means of noninvasive automated blood pressure monitoring (ABPM-630; readings every 15 or 30 min over 48h) and chronobiologic analysis. A significant shift of blood pressure circadian rhythm was observed in Stage-LH. Additionally, the 24-h mean level of blood pressure significantly increased when the prevailing salt intake was at lunch, and significantly decreased when the prevailing intake was at dinner. These opposite responses corroborate the view that the blood pressure susceptibility of human beings to salt intake varies during the day, showing its maximal expression at midday. Such a time-dependent sensitivity may be exploited for better nutritional prevention and treatment of arterial hypertension by reappor-tioning the salt intake so that two-thirds is consumed at dinner.

OBJECTIVE--To study the circadian pattern of plasma concentrations of vasoactive intestinal peptide (VIP) in patients with orthotopic heart transplants. Circulating VIP is known to have neural and immunological sources. PATIENTS AND METHODS--13 patients with orthotopic heart transplants were studied 12-53 months (mean 31.8 months) after operation. All were haemodynamically compensated and had no histological evidence of rejection. They were being treated with cyclosporin, azathioprine, and prednisone. Ten healthy individuals were studied as controls. Circulating VIP was assayed six times within a 24h period. Time qualified data were analysed by ANOVA and the cosinor method. Student's t test for unpaired data and Bingham's test for cosinor-derived parameters were used for statistical comparisons. RESULTS--Plasma concentrations of VIP were lower in the patients with orthotopic heart transplants than in the controls (p < 0.001). ANOVA and the cosinor method respectively showed a statistically significant within-day variability and circadian rhythm in the controls but not in the patients with heart transplants. DISCUSSION--The low plasma concentrations of VIP in the patients with heart transplants could be the result of the lack of contribution by the cardiac VIPergic fibres, a reduction of VIP release by the pharmacologically suppressed immune system, the inhibitory effects of cyclosporin on neural function and humoral secretions, and the effects of negative feedback on VIP release of high concentrations of atrial natriuretic peptide. The lack of the circadian rhythm suggests a structural disorder, which should be further investigated.

The aim of this study was to investigate the natural history of the circadian rhythm of blood pressure (BP) and heart rate (HR) in 10 patients with heart failure (class IV of the New York Heart Association), who underwent heart transplantation because of primary congestive cardiomyopathy. The control group was 10 age-matched clinically healthy subjects. The BP and HR monitorings were performed before and after transplantation. Preoperatively, analysis of variance and cosinor methods validated the occurrence of a statistically significant BP and HR circadian rhythm in cardiopathic patients. Over the 4 days after surgery, both the cosinor method and serial section analysis were unable to validate a 24-h periodicity for BP and HR in patients with heart transplants. Six months after surgery, the BP and HR circadian rhythm was not detected as well. One year after transplantation, the BP and HR circadian rhythm was statistically validated. The recovery of the BP and HR circadian rhythm 1 year after heart transplantation can be regarded as a clinical sign of a reacquired susceptibility to neurovegetative chronoregulation.