The inhibitory effect exerted upon the cyclic activity of the adrenal cortex by a synthetic steroid analog (dexamethasone-21-phosphate) administered at different circadian stages, has been studied previously. Reexamination of the same data by microscopic methods herein provides two sets of objective quantitative endpoints for further studies, namely 1. the characteristics of a rhythm isolated from a superimposed trend as well as noise, and 2. the endpoints of the trend itself. These endpoints quantify the effect of dose and, with the appropriate dose, the optimal timing for a given purpose may also be found.

Adrenal Cortex↗

PubMedDate not supplied

Toward a medical prolepsis by chronobiology.

Medicine today strongly aims at prevention and optimization of diagnosis and therapy Studies tried staging and standardization of clinical trials in diseases and made search of markers for early diagnosis, prognosis and therapy. Moreover, risk factors and other variables such as predictors are now investigated more often in groups or populations of apparently healthy subjects, especially for such diseases as atherosclerosis and neoplasia. This new aspect of increasing interest may be defined as medical prolepsis (from the Greek pi rho ómicron lambda eta psi iota zeta = anticipated idea). It includes early signals of disease (protopathology) as well as other signals the host shows as defence or alarm reaction. Hence, we suggest a chronobiological approach in this field, which allows to quantify health and reveals more subtle differences in many physiological variables. According to these views, we reported studies concerning humoral markers and other parameters considered as risk factors both in atherosclerosis and in some endocrine tumors.

Arteriosclerosis↗

PubMedDate not supplied

An attempt to establish early signals of peripheral arterial disease (PAD): the use of rhythm's parameters of peripheral blood flow (RF).

Rhythm parameters of peripheral arterial rest blood flow (RF) as a potential predictor of peripheral arterial disease (PAD) have been investigated. Three groups of subjects have been studied: a. six apparently healthy subjects; b. seven high risk (hypertension, diabetes, hypercholesterolaemia, hypertriglyceridaemia, erythrocytosis) subjects; c. four occlusive PAD selected patients with one 'pre-symptomatic' leg. RF has been measured by 'strain-gauge plethysmography' every min for 25 min, 4 times/day. Right fore-arm, right leg and left leg have been assessed. Data have been analyzed by 'single and population mean cosinor'. Significant circadian rhythms have been detected in apparently healthy subjects. Mesor and amplitude can differ according to single individual's area. Mesor is higher in upper limb. RF circadian rhythm parameters differ in subjects with various vascular risk load. Sometimes, PAD-symptomatic limb shows higher mesor than pre-symptomatic one, suggesting conditions of reactive post-ischemic hyperemia or a role of RF in PAD. Circadian dyschronia can be detected in PAD limbs but also in high risk subjects, perhaps an example of chronoprotopathology. These results suggest the possibility of a clinical use of RF rhythm parameters as predictors of vascular protopathology.

Adult↗

PubMedDate not supplied

[Patterns of ventricular late potentials in systemic sclerosis: a noninvasive method in the study of cardiac involvement].

The aim of our study was to ascertain the prevalence of ventricular late potentials (VLP) in systemic sclerosis (SSc) and their correlation with the immunologic patterns and cutaneous and pulmonary involvement of the disease. Ventricular late potentials, which are low-amplitude high-frequency signals present in the terminal portion of the QRS complex, express the delayed and fragmented depolarization of ventricular myocardial fibers. Observed in myocardial interstitial fibrosis, they are characteristic of the myocardial alterations occurring in SSc. Twenty-six patients with SSc (1 man, 25 women) with a confirmed lack of cardiac involvement (negative history and normal clinical, electrocardiographic, and echocardiographic findings) underwent signal averaged high resolution electrocardiography. Pulmonary involvement was evaluated by pulmonary function tests and high resolution computed tomography. The degree of cutaneous involvement was assessed by skin score. In the patients with SSc, VLP presence with time-domain analysis was 30.8% when a 25-250 Hz pass-band filter was used and 26.9% when a 40-250 Hz pass-band filter was used whereas with frequency domain analysis it was 23.1%. Ventricular late potentials were confirmed in 7.7% of the control subjects, no matter what filter or technique was used. No significant correlations among VLP, pulmonary involvement, skin score and specific antibody patterns were found. Although this technique requires further consolidation, it seems to have the potential for use as an early index of myocardial fibrosis.

Adult↗

PubMedDate not supplied

[Circadian variations of bilirubin in the blood].

A group of 12 presumably healthy subjects was standardized for 7 days with rest time extending from 22.00 to 05.00. Meals were scheduled at 08.00-08.30, 12.00-12.30, 17.30-18.00 and the amounts consumed were standardized and measured. Each subject was sampled at 4-hour intervals throughout one 24-hour period; this involved the measurement of body temperature, radial pulse, blood pressure. In addition a sample of blood was collected at each time point and subsequently total, direct and indirect bilirubin measurement was made on each sample of serum. All data were analized by macroscopic approach (chronograms) and by mean cosinor. A circadian rhythm is detected in total, direct and indirect serum bilirubin.

Adolescent↗

PubMedDate not supplied

Circadian study on serum gastrin in patients with duodenal ulcers and in a control group.

Two groups of subjects (one consisting of fourteen apparently healthy subjects, the other of fourteen patients with peptic ulcers) were kept for a least 7 days on the same living schedule (nocturnal sleep for 22(00) to 05(00) and meals standardized at 08(00)-08(30), 12(00)-12(30), 17(30)-18(00)). During 24 hors, samples of venous blood were obtained from each subject every 4 hours for the serum gastrin radioimmunoassay. The results were analyzed by mean cosinor method. The control group has a statistically significant circadian rhythm, while we were not able to detect a circadian rhythm in the patients with duodenal ulcers. The daily mean of serum gastrin levels appears to be significantly reduced in the ulcer group.

Adolescent↗

PubMedDate not supplied

Effect of melatonin on normal and sclerodermic skin fibroblast proliferation.

OBJECTIVE: We studied the effect of melatonin (MLT) (N-acetyl 5-methoxytryptamine) on the growth rate of normal skin fibroblasts and of fibroblasts from involved and apparently uninvolved skin of patients affected by systemic sclerosis (SSc). METHODS: The growth rate was evaluated on the basis of growth curves and a 3H-thymidine incorporation assay. RESULTS: Our results demonstrate that a dose of 200 micrograms/ml of MLT inhibits (> 80%) both control and SSc fibroblasts. Inhibition was dose-dependent and was greater than 70% for MLT concentrations of 100 micrograms/ml, 200 micrograms/ml and 400 micrograms/ml. 3H-thymidine incorporation was correlated with the effect on the growth curves (81% at 200 micrograms/ml of MLT). In contrast, at a low dosage of 6 micrograms/ml, MLT exerted a stimulatory effect on cell proliferation in all the cell lines analyzed. Cell viability was not affected by MLT at any of the concentrations tested. A recovery study indicated that replacement of MLT-containing medium with MLT-free medium resulted in a re-establishment of cell growth. CONCLUSIONS: These results suggest that MLT, at higher dosages, is a potent inhibitor of the proliferation of fibroblasts derived from the skin of healthy and SSc patients.

Cell Count↗

PubMedDate not supplied

Peripheral nervous system involvement in systemic sclerosis: the median nerve as target structure.

OBJECTIVES: To investigate the frequency and the main electrophysiological characteristics of the canalicolar passage nerve involvement in patients with systemic sclerosis (SSc). METHODS: Thirty-two SSc patients were enrolled in the study, classified according to the type (diffuse or limited) and the duration (> / < 5 years) of the disease. Sensory-motor nerve conduction studies (NCS) of the upper and lower limbs, in particular at the critical canalicolar points, were conducted by recording the Compound Muscular Action Potential (CMAP) and the Sensory Action Potential (sNAP). The following parameters were evaluated: Motor Nerve Conduction Velocity (MNCV) and Sensory Nerve Conduction Velocity; distal and proximal latency of the CMAP and the onset and peak latency of the sNAP; peak-peak amplitude and negative-peak area of the CMAP and sNAP; and the Terminal Latency Index (TLI) (Terminal Distance/MCNV x Distal latency). RESULTS: Four (12.5%) patients had a distal neuropathy of the upper limbs (one with monolateral and two with bilateral involvement of the median nerve and one bilateral involvement of the ulnar nerve). Fourteen (43.7%) patients showed a decrement of the median nerve TLI and seven (21.8%) of either the median or the ulnar nerve (Table I). Motor and sensitive conduction velocity and latency studies did not show a statistical difference between SSc patients and controls. The amplitude and area of the CMAP (distal and proximal), sNAP and of the median nerve TLI were significantly decreased in patients with respect to controls. CONCLUSION: Distal mononeuropathy of the median nerve was the most frequent result in our patients. The involvement of the peripheral nervous system seems to be strictly topographical, following the modifications of the tissues and vascular tone (Raynaud's phenomenon) at the upper acral level. The neurophysiological alterations detected in our study at the wrist level may not be linked merely to a compressive event but also to microvascular involvement. Nerve involvement closely connected with the pathogenesis and distribution of SSc should be considered when peripheral nervous system involvement is the initial symptom of the disease.

Adult↗