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Biomedical subjects

F Rovelli

Publications and source records attributed to F Rovelli.

At least 19 recordsLinked to original sources
PubMed2001

Thrombopoietic properties of 5-methoxytryptamine plus melatonin versus melatonin alone in the treatment of cancer-related thrombocytopenia.

Recent studies have shown that the hematopoietic system is under neuroendocrine control. In particular, thrombopoiesis has been proven to be stimulated by melatonin, and the pineal indole has been shown to be effective in the treatment of thrombocytopenia resulting from different causes. At present, however, there are no data concerning the possible thrombopoietic activity of pineal indoles other than melatonin. The present study was carried out to evaluate the effect of a concomitant administration of the pineal indole 5-methoxytryptamine in patients with cancer-related thrombocytopenia who did not respond to melatonin alone. The present study included 30 patients, who were randomized to receive melatonin alone (20 mg/day orally in the evening) or melatonin plus 5-methoxytryptamine (1 mg/day orally in the early afternoon). A normalization of platelet count was achieved in 5/14 (36%) patients treated with melatonin plus 5-methoxytryptamine and in none of the patients treated with melatonin alone (P < 0.05). Moreover, mean platelet number significantly increased only in the patients treated with melatonin plus 5-methoxytryptamine. This preliminary clinical study would suggest that 5-methoxytryptamine, a pineal indole, may also exert thrombopoietic activity. Further studies, however, will be required to establish whether 5-methoxytryptamine may play a direct thrombopoietic activity, or whether it may act by improving melatonin's efficacy.

5-Methoxytryptamine↗
PubMed2001

Anti-angiogenic activity of melatonin in advanced cancer patients.

OBJECTIVES: The anticancer activity of the indole melatonin has been explained to be due to its immunomodulatory, anti-prolferative and anti-oxidant effects, whereas at present no data are available about its possible influence on the angiogenesis, which has been shown to be one of the main biological mechanisms responsible for tumor dissemination. Vascular endothelial growth factor (VEGF) is the most active angiogenic factor, and the evidence of abnormally high blood levels or VEGF has been proven to be associated with poor prognosis in cancer patients. To investigate the influence of melatonin on angiogenesis, in this preliminary study we have evaluated the effects of melatonin therapy on VEGF blood levels in advanced cancer patients. MATERIAL & METHODS: The study included 20 metastatic patients, who progressed on previous conventional antitumor therapies and for whom no other effective treatment was available. Melatonin was given orally at 20 mg/day in the evening for at least 2 months. Serum levels of VEGF were measured by an enzyme immunoassay on venous blood samples collected at 15-day intervals. RESULTS: The clinical response consisted of minor response (MR) in 2, stable disease (SD) in 6 and progressive disease (PD) in the remaining 12 patients. VEGF mean levels decreased on therapy, without, however, statistical differences with respect to the pre-treatment values. In contrast, by evaluating changes in VEGF levels in relation to the clinical response, non-progressing patients (MR + SD) showed a significant decline in VEGF mean concentrations, whereas no effect was achieved in progressing patients. CONCLUSIONS: This study, by showing that melatonin-induced control or the neoplastic growth is associated with a decline in VEGF secretion, would suggest that the pineal hormone may control tumor growth at least in part by acting as a natural anti-angiogenic molecule, with a following opposition or angiogenesis-dependent cancer proliferation.

Adult↗
PubMed2001

A study of light/dark rhythm of melatonin in relation to cortisol and prolactin secretion in schizophrenia.

OBJECTIVES: Recent studies have suggested the involvement of the pineal gland and its main hormone melatonin (MLT) in the pathogenesis of psychiatric disturbances, namely the depressive syndrome. In contrast, the behavior of MLT secretion in schizophrenia is still controversial. MATERIAL & METHODS: The present study was carried out to analyze light/dark rhythm of MLT secretion in relation to that of cortisol and prolactin (PRL) in schizophrenic patients. The study included 13 schizophrenic patients, 8 of whom were untreated, while the other 5 patients were on neuroleptic therapy. Serum levels of MLT, PRL and cortisol were measured by RIA on venous blood samples collected at 8 A.M., 12 A.M., 8 P.M. and 1 A.M. The control group consisted of 20 age-matched healthy subjects. RESULTS: A physiological nocturnal increase in MLT levels occurred in 6/13 patients, whereas the other 7 patients showed an abnormally low MLT peak during the night. Moreover, both light and night mean levels of MLT were significantly lower in patients than in controls. In addition, mean nocturnal levels of MLT were significantly lower in chronic patients than in those evaluated at the onset of disease. Cortisol rhythm was normal in 11/13 patients, whereas PRL levels were abnormally high in 10/13 patients. CONCLUSIONS: This preliminary study would suggest that schizophrenia may be associated with a diminished secretion of MLT from the pineal gland, and pineal deficiency would be more evident in the chronic disease. Finally, pineal alterations have appeared to be associated with an altered secretion of PRL and cortisol, by suggesting that the schizophrenic disease may be characterized by marked neuroendocrine disturbances, whose physio-pathological and prognostic significance needs to be established by successive clinical investigations.

Adult↗
PubMed2001

A review on cancer--psychospiritual status interactions.

With the advances in the knowledge of neuroimmunomodulation, a new era of investigations about the chemical basis of the state of mind has been initiated. Both emotions and states of spiritual consciousness may influence immune functions and cancer growth. Stress, anxiety and depressive states are associated with immunosuppression and enhanced frequency of tumors. On the other hand, the states of sexual pleasure and spiritual joy enhance the immune efficacy, by counteracting tumor onset and dissemination. The biochemistry of pleasure and immunostimulation is mainly mediated by pineal indoles and cannabinergic substances, whereas that of stress, anxiety and depression is associated with enhanced production of adrenal steroids, opioids and catecholamines. The sexual repression would allow a progressive immunosuppression through a profound damage in the biochemistry of pleasure. Therefore, a better definition of psychospiritual status-associated neuroimmunochemistry could allow us to improve the immune dysfunction by acting on the same neuroendocrine secretions which are involved in mediating the psychic influence on the immunity, including that against cancer.

Emotions↗
PubMed2000

Paradoxical stimulation of prolactin secretion by L-dopa in metastatic prostate cancer and its possible role in prostate-cancer-related hyperprolactinemia.

OBJECTIVE: In addition to sex steroids, prolactin (PRL) may also stimulate prostate cancer growth. Abnormally high blood levels of PRL have been noted in metastatic prostate cancer patients. However, most studies have been limited to the evaluation of basal levels of PRL rather than to investigate its secretion in response to classical endocrine dynamic tests. This study was carried out to analyze PRL secretion in metastatic prostate cancer patients both at basal conditions and in response to L-Dopa and metoclopramide, which represents the most classical inhibitory and stimulatory tests for PRL secretion, respectively. METHODS: The study included 12 patients with metastatic prostate cancer. On separate occasions, PRL secretion was evaluated in response to L-Dopa (500 mg orally) and to metoclopramide (10 mg i.v. as a bolus). Serum levels of PRL were measured by RIA. RESULTS: Mean PRL concentrations significantly increased after metoclopramide administration, even though no PRL response occurred in 6 of 12 patients. L-Dopa was unable to reduce PRL levels, which, in contrast, paradoxically significantly increased in response to L-Dopa, with mean values comparable to those achieved after metoclopramide injection. CONCLUSION: By showing a paradoxical stimulatory effect of L-Dopa on PRL secretion and a lack of response to metoclopramide in some patients, this study would suggest the existence of evident alterations in the neuroendocrine regulation of PRL release in advanced prostate cancer.

Aged↗
PubMed1999

Pretreatment serum markers and lymphocyte response to interleukin-2 therapy.

Lymphocytosis is a marker of subcutaneous interleukin (IL)-2 therapy efficacy, whereas baseline elevated inflammatory indices were noticed in IL-2-resistant disease. The aim of this study was to analyse the relationship between pretreatment circulating values of IL-6, neopterin, sIL-2R, ESR and the changes in lymphocyte number in response to IL-2 administration. Twenty metastatic renal cell cancer patients were treated with subcutaneous IL-2 immunotherapy (6 000 000 IU day(-1) for 6 days per week for 4 weeks); tumour response consisted of partial response (PR) in four patients, stable disease (SD) in eight patients and progressive disease (PD) in eight patients. Abnormally high pretreatment values of each marker were found as follows: IL-6 in seven patients, neopterin in nine patients, sIL-2R in 13 patients. In response to IL-2 immunotherapy, a significantly higher mean increase in lymphocyte number and a higher percentage of patients with tumour response or stable disease were observed when pretreatment values of IL-6, neopterin and sIL-2R were within the normal range, in comparison to patients with high values for these markers. The pretreatment excess of these serum inflammatory markers seems to negatively influence both the host and tumour response to IL-2 administration, by preventing the IL-2-induced lymphocytosis and resulting in tumour progression. Further studies are requested to verify if overall survival and quality of life may depend on pretreatment host immune status and/or lymphocyte response after IL-2 administration.

Aged↗
PubMed1998

Ten-year follow-up of the first megatrial testing thrombolytic therapy in patients with acute myocardial infarction: results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto-1 study. The GISSI Investigators.

BACKGROUND: We conducted a 10-year follow-up of the 11 712 patients with acute myocardial infarction randomized in the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto-1 study, the first large trial assessing thrombolytic therapy. METHODS AND RESULTS: Information on survival at 10 years was obtained for the 93% of all randomized patients through the census offices of their towns of residence. The difference in survival produced by streptokinase and sustained up to 1 year was still significant at 10 years (log-rank test, P=0.02), with the absolute benefit of 19 (95% CI 1 to 37) lives saved per 1000 patients treated. The time dependence of the extent of the benefit was confirmed, as the higher mortality rate reductions found in patients treated earlier were still present at 10 years. In the overall population, most of the benefit was obtained before hospital discharge (RR 0.81, 95% CI 0.72 to 0.90), since no difference in survival between thrombolyzed and control patients discharged alive was found at 10 years (RR 0.98, 95% CI 0.90 to 1.06). However, a slight albeit nonsignificant divergence of the survival curves of patients randomized within the first hour was observed [90 (95% CI 34 to 146) lives saved per 1000 at 10 years versus 72 (95% CI 37 to 107) lives saved at hospital discharge]. CONCLUSIONS: The benefits of a single intravenous infusion of 1.5 million units of streptokinase in prolonging survival of patients with acute myocardial infarction is sustained up to 10 years, with a still-evident trend in favor of the patients admitted earlier.

Age Factors↗
PubMed1998

In vivo stimulation of IL-12 secretion by subcutaneous low-dose IL-2 in metastatic cancer patients.

Despite the well-demonstrated involvement of both interleukin 2 (IL-2) and interleukin 12 (IL-12) in the activation of host anti-cancer response, the knowledge of IL-2-IL-12 interactions has still to be better investigated. This study was performed to evaluate the effects of subcutaneous (s.c.) low-dose IL-2 on IL-12 secretion in metastatic cancer patients. The study included 19 evaluable metastatic renal cell cancer patients, who received s.c. low-dose IL-2 (6 MIU day(-1) for 6 days per week for 4 weeks) as a first-line immunotherapy of their metastatic disease. Serum levels of IL-12 were measured using an enzyme immunoassay on venous blood samples collected before the immunotherapy and at 1-week intervals. The clinical response consisted of partial response (PR) in four and stable disease (SD) in eight patients, whereas the other seven patients progressed. Mean serum levels of IL-12 observed in the overall patients significantly increased in response to IL-2 injection. Moreover, by evaluating IL-12 variations in relation to the clinical response, a marked significant increase in IL-12 mean values occurred in patients with response or SD, whereas the progressing patients showed a significant decline in IL-12 levels during IL-2 administration. Finally, IL-12 mean pretreatment values observed in patients who progressed were significantly higher than those seen in non-progressing patients. This study shows that low-dose IL-2 immunotherapy of cancer may stimulate the in vivo release of IL-12, and it would suggest that IL-2-induced IL-12 enhancement is associated with a favourable prognosis.

Adult↗
PubMed1998

Biotherapy with the pineal immunomodulating hormone melatonin versus melatonin plus aloe vera in untreatable advanced solid neoplasms.

The possibility of natural cancer therapy has been recently suggested by advances in the knowledge of tumor immunobiology. Either cytokines such as IL-2, or neurohormones, such as the pineal indole melatonin (MLT), may activate anticancer immunity. In addition, immunomodulating substances have also been isolated from plants, particularly from Aloe vera. Preliminary clinical studies had already shown that MLT may induce some benefits in untreatable metastatic solid tumor patients, whereas, for the time being, no clinical trial has been performed with aloe products. We have carried out a clinical study to evaluate whether the concomitant administration of aloe may enhance the therapeutic results of MLT in patients with advanced solid tumors for whom no effective standard anticancer therapies are available. The study included 50 patients suffering from lung cancer, gastrointestinal tract tumors, breast cancer or brain glioblastoma, who were treated with MLT alone (20 mg/day orally in the dark period) or MLT plus A. vera tincture (1 ml twice/day). A partial response (PR) was achieved in 2/24 patients treated with MLT plus aloe and in none of the patients treated with MLT alone. Stable disease (SD) was achieved in 12/24 and in 7/26 patients treated with MLT plus aloe or MLT alone, respectively. Therefore, the percentage of nonprogressing patients (PR + SD) was significantly higher in the group treated with MLT plus aloe than in the MLT gorup (14/24 vs. 7/26, p < 0.05). The percent 1-year survival was significantly higher in patients treated with MLT plus aloe (9/24 vs. 4/26, p < 0.05). Both treatments were well tolerated. This preliminary study would suggest that natural cancer therapy with MLT plus A. vera extracts may produce some therapeutic benefits, at least in terms of stabilization of disease and survival, in patients with advanced solid tumors, for whom no other standard effective therapy is available.

Adjuvants, Immunologic↗
PubMed1998

Immunomodulatory effects of IL-12 in relation to the pineal endocrine function in metastatic cancer patients.

In addition to IL-2, IL-12 would constitute one of the most promising cytokines in the treatment of human neoplasms. IL-2 has been proven to induce in vitro and in vivo several evident changes in the secretion of cytokines and various other immunoinflammatory substances. In contrast, very little data are available about the immune effects of IL-12 in humans. The present study was carried out to investigate the in vivo immunoinflammatory effects of IL-12 by analyzing the secretions of neopterin, soluble IL-2 receptor (SIL-2R), tumor necrosis factor alpha (TNF), IL-2 and IL-6 in relation to the neuroendocrine function of the pineal gland, which is one of the most important organs involved in neuroimmunomodulation. Pineal endocrine function was investigated by evaluating the whole daily urinary excretion of the main catabolite of its hormone melatonin, 6-sulfatoxymelatonin (6-MTS). The study was performed on metastatic renal cell cancer patients. Each course of IL-12 consisted of 1.25 microg/ kg b.w. subcutaneously in the morning once a week for 3 consecutive weeks. The study evaluated 10 IL-12 courses. Mean serum levels of neopterin, SIL-2R and TNF significantly increased in response to IL-12, whereas no significant change occurred in IL-6 and IL-2 mean concentrations. Finally, 6-MTS urinary excretion was significantly reduced by IL-12 injection, particularly during the dark phase of the day. This preliminary study would suggest that IL-12 may induce important changes in the in vivo immunoinflammatory response. Moreover, IL-12 administration would suppress pineal endocrine activity, thus confirming its previously suggested involvement in the neuroimmunomodulatory processes. Because of the fundamental role of the pineal gland in neuroimmunomodulation, IL-12-induced immune variations could depend at least in part on its action at central neuroendocrine sites.

Adjuvants, Immunologic↗
PubMed1998

Circadian secretions of IL-2, IL-12, IL-6 and IL-10 in relation to the light/dark rhythm of the pineal hormone melatonin in healthy humans.

It has been demonstrated that cytokine activities are under neuroendocrine control, recently mainly exerted by the pineal gland through the circadian secretion of its main hormone melatonin (MLT). It is mainly released during the night, but at present it is still unclear which relation exists between MLT and the circadian secretion of cytokines. This study was performed to evaluate the circadian secretion of IL-2, IL-6, IL-10 and IL-12 in relation to that of MLT. The study included 10 healthy volunteers whose venous blood samples were collected at 8 a.m., noon, 4 p.m., 8 p.m., 1 a.m. and 4 a.m. The mean levels of MLT were significantly higher during the night than during the light phase of the day. Similarly, IL-2 mean levels significantly increased during the night. IL-6 mean values were higher during the light period of the day without, however, any significant differences with respect to the nocturnal mean levels. Finally, no substantial circadian variation was seen in IL-10 and IL-12 mean concentrations. These results show that IL-2 secretion increases during the night, concomitantly to that of the pineal hormone MLT, whereas there is no evidence of a circadian secretion for the other cytokines. Since the pineal gland has been proven to stimulate IL-2 endogenous production, the nocturnal increase in IL-2 blood concentrations could depend at least in part on the promoting action of MLT, whose release increases during the dark period of the day.

Adult↗
PubMed1997

Interleukin-12 in early or advanced cancer patients.

Interleukin-2 (IL-2) and interleukin-12 (IL-12) may represent the most important antitumour cytokines in human neoplasms. IL-2 blood levels decrease in advanced solid malignancies, but currently there are no data on IL-12 secretion in cancer patients. This study was performed to obtain preliminary data about IL-12 secretion in patients with solid malignant tumours, either in relation to the extension of disease, or to other cytokines, including IL-2, IL-6 and IL-10. The study included 40 solid cancer patients, 24 of whom showed distant organ metastases. Cytokine serum levels were measured by an enzyme immunoassay of blood samples collected during the morning. No patient had abnormally low levels of IL-12, but the levels were high in 14/14 (35%) patients. Mean levels of IL-12 were significantly higher in metastatic patients compared with non-metastatic patients (P < 0.05). Moreover, metastatic patients with high blood concentrations of IL-12 showed significantly lower levels of IL-10 than metastatic patients with normal IL-12 values, while no difference was seen in IL-2 mean concentrations. IL-6 mean levels were lower in metastatic patients with increased IL-12 levels, but this was non-significant. This preliminary study shows that advanced solid cancers are not characterised by a diminished secretion of IL-12, but rather IL-12 levels tend to be abnormally high in metastatic cancer patients.

Adult↗
PubMed1997

Prevalence and correlates of echocardiographic determined left ventricular hypertrophy in 2318 asymptomatic middle-aged men: the ECCIS project. Epidemiolgia e Clinica della Cardiopatia Ischemica Silente.

It is well established that left ventricular hypertrophy is a strong and independent risk factor for cardiovascular morbidity and mortality. This study was designed to determine the prevalence and correlates of left ventricular hypertrophy (LVH) among a sample population of 2318 totally asymptomatic men aged 40-59. This sample is a subset of the participants in the ECCIS Project. Left ventricular mass was estimated by echocardiography. The following individual variables were employed in the multiple linear regression analyses: age, diastolic and systolic blood pressure at rest and at peak exercise, body mass index, body surface area, conditioning physical activity. Three indexes of left ventricular mass were used: left ventricular mass/height, left ventricular mass/body surface area and "adjusted left ventricular mass" derived from adjustment, using a regression model, of left ventricular mass by age, body mass index and body surface area. The sample was subdivided in 3 blood pressure classes; normotensive (n = 1605), borderline (n = 390) and hypertensive (n = 323). All the variables considered with the exception of diastolic blood pressure both at rest and peak exercise were significantly correlated with left ventricular mass. Upper normal limits for left ventricular mass indexed to height and body surface area and of adjusted left ventricular mass were 143 g/m, 129 g/m2, and 245 g respectively. The prevalences of left ventricular hypertrophy, as determined by the reference standard of left ventricular mass/height, left.ventricular mass/body surface area and adjusted left ventricular mass, ranged 2.7-3.2% in the normotensive group, 4.2-5.4% in the borderline group and 11.8-14.5% in the hypertensive group, and were lower using adjusted left ventricular mass index. The results of this study show that the prevalence of left ventricular hypertrophy using adjustment by age, body surface area and body mass index reduces variability of left ventricular mass associated with age and body size and may be useful for the correct identification of left ventricular hypertrophy and hypertensive heart disease.

Adult↗
PubMed1996

Health services: an Italian market.

One of the glories of Italy is its capacity to surprise. In out-of-the-way places extraordinary things are suddenly encountered; and this is hardly less true of science than of architecture or music or painting. Italian medicine can boast excellence in many quiet spots. Yet Italy's record in medical science and practice is perceived to be below par, and one reason may be a lack of central coordination--forgivable in a country that had fifty governments in half a century. The latest administration offers a rare chance of political stability and the prospect of reforms. In this profile of Italian medicine The Lancet's guide was Dr Giuseppe Remuzzi, whose central coordination was exemplary.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Iodine, thyroid function, and very low birth weight infants.

OBJECTIVE: Research was undertaken to test two hypotheses. First, during the early neonatal period, thyroid function of very low birth weight (VLBW) infants is suppressed by exposure to iodine-containing antiseptic solutions and/or iodized contrast media. Second, this suppression is more pronounced in small for gestational age (SGA) infants. METHODS: Urinary iodine concentration and thyroid function measurements were obtained prospectively from 44 VLBW infants with gestational ages at birth of 30 +/- 2.3 weeks and weights of 1223 +/- 231 g. Eleven of these infants were SGA. The infants were grouped according to iodine exposure: 18 infants had no increased exposure and served as control infants; 9 infants were exposed to an iodine-containing antiseptic (povidone iodine); 12 infants were exposed to an iodized contrast medium (iopamidol); and 5 infants were exposed to both agents. Urinary iodine and serum free triiodothyronine, free thyroxine, and thyrotropin were measured on days 1, 7, 14, 21, and 28 of life. RESULTS: During the period of maximum exposure (days 1 to 7), the concentration of iodine in the urine of study infants was 2 to 4 orders of magnitude greater than that in the urine of control infants (123 +/- 141 micrograms/L). During the subsequent 3 weeks, levels of urinary iodine in study infants returned to levels that were not significantly different from controls. On day 7 of life, iodine-exposed infants had a significantly higher mean thyrotropin level than control infants, whereas on day 28, free triiodothyronine and thyroxine levels were lower. Of the 26 iodine-exposed infants, 6 had transient hyperthyrotropinemia and 2 had transient hypothyroidism. When exposed to iodine, SGA infants had more labile thyroid function than normally grown iodine-exposed or control infants. These SGA infants had significantly lower levels of thyroid hormones in umbilical cord blood, increased production of thyroid hormones on day 14 of life, and lower levels again at 1 month. CONCLUSION: In VLBW infants, the use of iodine-containing antiseptic solutions and iodized contrast media results in massive uptake of iodine that is associated with alterations in thyroid function. It is reasonable to suggest that, whenever possible, iodized products should be avoided in VLBW infants, because their routine use results in exposure to excessive loads of iodine, which can be associated with hyperthyrotropinemia and hypothyroidism.

Anti-Infective Agents, Local↗