[Shared decision-making in metaclinical medicine: from informed consent to shared probability].

At the dawn of "metaclinical medicine" era, shared decision-making represents the overcoming of modern medicine guidelines and classical medicine experience. The patient's life plan, the doctor's health plan, the scientist's evidence-based plan, the administrator's plan and the beliefs of the society for healthcare options should be integrated into the shared decision-making process to avoid patient's unrealistic expectations, doctor's self-referential and defensive medicine, the science without compassion of the scientist, the administered medicine of the politician, the herd mentality of artificial intelligence. For a doctor who must evaluate according to science and conscience, it becomes difficult to make decisions about a patient who thinks that there can be "no decisions about me without me".

[Process to insulin for type 2 diabetes mellitus therapy].

In type 1 diabetes mellitus and in symptomatic and critical hyperglycemic states, insulin is a lifesaving drug; however, its value in long-term type 2 diabetes therapy, which represents more than 90% of diabetes, has not been assessed. This happens despite the fact that, in randomized studies on type 2 diabetes, insulin is used in two-thirds of cases when intensive hypoglycemic treatment is needed and in half of the patients when treatment is the standard one. This is a major issue from a clinical, economic and social-health organization point of view as insulin therapy is expensive and needs a complex organization.

[The patient in clinical research: disposable guinea pig or involved actor?].

Background: The request for informed consent to join a clinical trial often creates mistrust and hesitation in the patient who should be enrolled. In our study, we evaluated the reasons for refusing to participate in a clinical trial.

Methods: In the last 10 years of cardiovascular clinical research, we asked an informed consent to 2586 patients for intervention studies.

[Digitalis, a drug to be scrapped?].

We performed a comprehensive review of the scientific literature on the use of digoxin in heart failure and atrial fibrillation. In congestive heart failure (CHF) there is only one randomized trial with a statistical sample sufficiently large. In this trial (DIG trial), which enrolled patients with systolic left ventricular dysfunction in sinus rhythm, digoxin had a neutral action on mortality and modestly reduced the overall need of hospitalization.

General and unspecific damping by malignancy of the circadian amplitude of circulating human melatonin?

The circadian rhythm of serum melatonin of 39 cancer patients is compared with that of 28 healthy subjects matched by gender and age. Each subject provided 6 blood samples at 4-hour intervals for determination of melatonin by RIA. After log10-transformation, data series were analyzed by single and population-mean cosinor and compared between the two groups and among patients subgrouped by cancer site, stage and treatment.

Genetic and environmental influences on human cord blood leptin concentration.

Objective: To examine in a population sample of cord blood the time structure (chronome) of leptin, an adipocyte-derived hormone, and to assess any effect of a familial history of noninsulin-dependent diabetes mellitus and obesity, separately, on both the maternal and the paternal side.

Subjects And Methods: Leptin concentration was determined in cord blood from 93 infants. Effects of gender, gestational age, birth weight, maternal weight, familial antecedents of obesity and noninsulin-dependent diabetes mellitus, and circadian and about-yearly stage were assessed by linear regression and ANOVA.

Chronomes, time structures, for chronobioengineering for "a full life".

Week-long or longer monitoring of blood pressure and heart rate, coupled to time-structure analyses, can help detect disease-risk elevations, as a warning of the need for a preventive prehabilitation. Within the normal range of physiologic variation, computer methods quantify time structures, or chronomes, that can serve as reference values. The major applied purpose for mapping chronomes is the detection of disease-risk syndromes such as blood pressure "overswinging" and heart rate "underswinging.

[Melatonin and seasonal depression].

Melatonin (MEL) hypothesis in seasonal affective disorders (SAD) is supported by: a) historical hint; b) circadian and seasonal MEL periodicity with evidence that the SAD is related to photoperiod; c) relationship between incidence and severity of SAD and latitude; d) the response to bright artificial light (ineffective in depression) which mimics summer time; e) MEL administration can induce some symptoms of the SAD; f) several antidepressant drugs increase MEL plasma levels. Several of these findings are disproved: the light acts independently from the MEL, some antidepressant agents act without modifying MEL levels; a consistent alteration in MEL secretion within SAD has not been convincingly demonstrated. Relationship between incidence and severity of SAD and latitude suggests a new potential implication of MEL in SAD.

Endothelin-1 and Paget's bone disease: is there a link?

The abundance of endothelial cells in bone marrow and the proximity of these cells to osteoclasts and osteoblasts suggest a role for endothelin-1 (ET-1) on bone metabolism. In vitro, the direct contact with bone endothelial cells induces osteoclastic progenitors to differentiate into mature elements. Recently it has been reported that ET-1 inhibits osteoclastic bone resorption and cell mobility through a specific receptor on osteoclasts; other authors demonstrated that ET-1 exerts a mitogenic activity on osteoblast-like cells (MC3T3) by stimulating tyrosin phosphorylation.

[Melatonin: a popular hormone].

This contribution makes an attempt to critically reassess the impressive career of melatonin (MEL) from a stepchild of hormone research to a best-seller of drug marketing. Melatonin, the hormone of the pineal gland, provides temporal information on diurnal and seasonal variation to the body and brain and it is involved in the synchronization of many different aspects of circadian systems to the light-dark cycle. In addition to these receptor-mediated functions, MEL may act as a modulator of intracellular signal transduction to enhance or suppress the responses of many different cells to other incoming signals.

Influence of non-insulin-dependent diabetes mellitus on plasma endothelin-1 levels in patients with advanced atherosclerosis.

Endothelin-1 (ET-1) is an endothelium-derived vasoactive peptide with mitogen properties. Increased circulating ET-1 levels were found in patients with atherosclerosis as well as in patients with non-insulin-dependent diabetes mellitus (NIDDM) suggesting a role in the pathogenesis of these disorders. The aim of the present study was to ascertain the influence of the NIDDM on plasma ET-1 levels in patients with advanced atherosclerotic lesions.

Chronome assessment of circulating melatonin in humans.

Background: Melatonin (MEL) production occurs mainly during the dark span. A prominent circadian variation is demonstrated in both blood and urine in humans.

Materials And Methods: The circadian, circannual, age and gender patterns of MEL were concomitantly investigated in 40 men and 132 women, each providing blood samples every 4 hours for 24 hours for conventional and cosinor analysis.

Serum beta-endorphin increase after intravenous histamine treatment of chronic daily headache.

Histamine is able to induce spontaneous-like headache attacks in migraine and cluster headache subjects. Therefore, it has been considered as a possible agent in the pathogenesis of headache. Histamine desensitization is used for the treatment of cluster and other chronic headaches like migrains with interparoxysmal headache.

Vascular damage and not hypertension per se influences endothelin-1 plasma levels in patients with non insulin dependent diabetes mellitus.

Several reports indicate higher endothelin-1 (ET-1) levels in patients with non insulin dependent diabetes mellitus (NIDDM), although this finding has not been confirmed by other studies. The discrepancy may be partially explained by the frequent coexistence in NIDDM patients of other pathologies, such as essential hypertension, and by the presence of diabetic vascular complications or renal failure, able, per se, to increase ET-1 circulating levels. This study aimed to evaluate the influence of arterial hypertension and/or of diabetic angiopathy on ET-1 circulating levels in a group of NIDDM patients.

Evidence for bone mass and body fat distribution relationship in postmenopausal obese women.

The measurement of bone mass, a reliable predictor of osteoporotic fractures, in obese subjects has yielded conflicting results and bone mass has been reported to be elevated, normal or decreased. These observations indicate that factors other than body weight may be involved in the less risk for osteoporosis in obese subjects. In order to clarify the role of body fat distribution on bone density we studied sixty postmenopausal overweight/obese women with Body Mass Index (BMI) over 25 kg/m(2).

About-half-weekly (circasemiseptan) component of the endothelin-1 (ET-1) chronome and vascular disease risk.

Plasma ET-1 was measured around the clock on different calendar dates in healthy subjects and in subjects with diabetes and/or with high blood pressure and/or a history of vascular complications (HVDR). A transverse approach, with each subject contributing a single 24-h mean, assessed any about-weekly or half-weekly variation in ET-1. A circasemiseptan component resolved by single cosinor for nondiabetic (but not for diabetic) HVDR subjects (p = 0.

Endothelin-1's chronome indicates diabetic and vascular disease chronorisk.

Plasma endothelin-1 was measured around the clock in 72 subjects. Cosinor methods were used to assess circadian and other recurrent variation and trends, that is, the time structure (chronome) of this peptide. Multifactorial analyses of variance and linear regressions assessed chronome alterations associated with different risk factors: diabetes, obesity, high cholesterol, high blood pressure, vascular disease, smoking, and age.

Serum osteocalcin levels in postmenopausal obese women.

In epidemiology of osteoporosis, obesity is to be considered one of its protecting factors. However there are in the literature discordant opinions: some authors describe a protective effect of obesity on the trabecular bone, others on the cortical one, others no effects at all and others finally a positive influence on both the trabecular and the cortical bone. However, only few studies on obesity's impact on bone metabolism are available.

Angiopathy affects circulating endothelin-1 levels in type 2 diabetic patients.

To evaluate the role of endothelin-1 (ET-1), a vasoconstrictor and mitogenic peptide synthesized by endothelial cells, on the endothelial dysfunction in non-insulin-dependent diabetic (type 2) patients, we have measured the circulating ET-1 levels in 25 patients with and without clinically evident vascular complications and in a control group. Circulating ET-1 levels were significantly higher in diabetic patients with angiopathy than in diabetics without angiopathy and in controls (7.02 +/- 2.

Serum melatonin in multiple myeloma: natural brake or epiphenomenon?

Melatonin (MEL), the main hormone produced by the pineal gland, seems to exert antineoplastic activity both in vitro and in vivo. Moreover, several studies reported increased melatonin blood levels in cancer patients. Plasma melatonin concentrations were determined in 46 patients with multiple myeloma and in 31 age matched healthy subjects (57.

Daytime circulating melatonin levels in smokers.

Aims And Background: Melatonin secretion is required to be a potential inhibitor of the development and growth of tumors, and cigarette smoking is a well established risk factor for cancer at various sites.

Methods: Circulating melatonin levels of 20 smokers and 20 non smokers (controls), sampled at the same hour from awaking in order to obtain a comparable circadian synchronization, were compared.

Results: Our data showed higher melatonin circulating levels in smokers (17.

Differences in some circadian patterns of cardiac arrhythmia, myocardial infarctions and other adverse vascular events.

Background: Results from unpublished data on the incidence of adverse vascular events and from several published studies are reevaluated chronobiologically.

Methods And Results: Cosinor methods indicate 1. a circadian variation in the incidence of paroxysmal supraventricular tachycardia (PST), of broadly classified ventricular arrhythmia (VAr), and of atrial fibrillation (AF); 2.

Amplifying effect of sumatriptan on noradrenaline venoconstriction in migraine patients.

The venoconstrictive activity of sumatriptan and its interaction with noradrenaline (NA)- and 5-hydroxytryptamine (5HT) venoconstriction was studied in vivo in the hand vein of migraineurs. Sumatriptan, injected at increasing doses into the vein, caused local venoconstriction after a 500 microgram dose, comparable to that induced by 0.5-1 micrograms of 5HT.