Biomedical subjects
Publications and source records attributed to M Benvenuti.
Fifty outpatients suffering from rheumatoid disorders were treated with proglumetacin. Efficacy was classified as "good" or "very good" in 80% of cases. Besides this considerable efficacy, a tolerance classified as "good" or "very good" was observed in 86% of patients.
A possible role of prolactin in prostatic disease has been claimed, but the results are so far misleading. Among the several factors that influence serum prolactin levels, temporal variations, notably circadian, are prominent. This paper shows an impairment in serum prolactin, chronobiologically investigated, in 12 patients with benign prostatic hypertrophy and in 7 patients with prostatic carcinoma. However, a single serum sample cannot be sufficient and may sometimes be misleading if not plotted with an adequate temporal reference standard (chronodesm).
Bromocriptine mesylate lowers the serum concentration of prolactin and TSH in patients with prostatic hypertrophy as a function of drug administration time. The effect of a 2.5-mg dose in lowering these two hormones in presumably similar patients is statistically highly significant and relatively large at unusual test times (in the evening); at other, conventional test or administration times (early morning or midday), it is smaller, questionable, or not demonstrable with the dose and conditions used. Dosing without timing may lead to reduced effect or lack of effect, ambiguity and controversy, and lack of timing may account for the circumstance that an effect of bromocriptine upon TSH in human serum was not previously established. Rigorous assessment of the effect of bromocriptine mesylate upon circulating TSH and prolactin requires consideration of the entire spectrum of rhythms, ultradian and infradian as well as circannual. The circadian approach here analyzed represents a step toward that goal and indicates that the circadian frequency is a critical determinant of this response. Manipulation of TSH concentration in serum, in turn, is of interest in view of the demonstrated alteration of the circannual TSH rhythm in patients with prostatic cancer.
Classical epidemiology associates human breast cancer with several risk factors including, among others, so-called preclinical hypothyroidism, fibrocystic disease of the breast (FM), and hyperprolactinemia. Relationships among FM, hyperprolactinemia, and thyroid function are of interest because of the possibility of multiple risk combinations. Prolactin and TSH (the latter as a presumed index of preclinical hypothyroidism) undergo rhythmic changes and hence should be chronobiologically investigated. Serum samples obtained at 4-hour intervals throughout a 24-hour span from 23 healthy women and from 25 women with FM (histologically verified) here summarized suggest that circadian mesor-hyperprolactinemia is a feature associated with FM. In a broader context, however, such impressions and an often considered modest impairment of thyroid function in some patients must be viewed in the light of new chronobiologic rules. These include a reciprocity of the circannual amplitudes of TSH and prolactin in relation to breast cancer risk, revealed by cooperative studies. A yet broader chronoepidemiologic view reveals that the reciprocal relation of the circannual amplitudes of circulating TSH and prolactin is (sex) inverted in patients with cancer of the prostate.
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In order to define circadian states for an earlier diagnosis and for optimal response to treatment, the possibility of a circadian rhythm in serum PAP was investigated in subjects with and without prostatic cancer. Two groups of subjects were investigated: a. 12 patients affected by PCa, further subdivided in two subgroups: 1. without metastasis (6 patients) and 2. with metastatic disease (6 patients); b. 9 age-matched healthy control subjects. Controls and PCa patients were synchronized before starting the study with standardized meal times and nocturnal rest (22(00) to 06(00) ). Venous blood samples were drawn at prearranged hours (00(00), 04(00), 08(00), 12(00), 16(00), 20(00) ) for 24 consecutive hours. Each serum sample was assayed for PAP. Data on each group and subgroup were evaluated by conventional statistical analysis and by 'single' and 'population mean cosinor' to define rhythm parameters. PCa patients, as a single group, did not show a significant circadian PAP rhythm. A statistically significant circadian PAP rhythm was however detected in the subgroup without metastasis, on the contrary no rhythm was detected in the subgroup with metastatic disease. The potential of these rhythms as marker of cancer is noted.
As compared to control subjects, patients with duodenal ulcer show decreased levels of serum G and increased levels of serum Group I pepsinogen (PGI). On the other hand, pregnant women in their third trimester show an increased level of serum G and decreased levels of serum PGI. Gastrin stimulates gastric secretion and has a trophic effect on the parietal cells. Concentrations of PGI in serum reflect the capacity of pepsin-secreting cells which are, in turn, closely related to the parietal cell mass. Pepsinogen/G ratio (PGI/G) could represent the effective acid-peptic secretory capacity. This study suggests that for screening and clinical purposes PGI/G ratio provides a good potentially discriminatory marker of gastric secreting capacity reliably correlating and improving the diagnostic significance of single G and/or PGI serum levels.
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.
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.
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.
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