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Biomedical subjects

C Benedetto

Publications and source records attributed to C Benedetto.

At least 19 recordsLinked to original sources

[The role of aromatase inhibitors in the treatment of breast neoplasms. An evaluation of clinical efficacy and the tolerability profile].

Constant acquisitions regarding endocrine pathogenesis and the biology of breast neoplasms have led to the evolution of hormone manipulation as a therapeutic option in patients suffering from this disease. There has been a shift from ablative surgical procedures to the use of drugs offering greater clinical efficacy and an improved tolerability profile. Since the late 1970s tamoxifen has been regarded as the gold standard for hormone treatment in hormone-responsive breast neoplasm, but promising new endocrine agents are now being compared in random trials. Of these, the latest generation of aromatase inhibitors appears to gather the widest consensus on the basis of the results published to date. This article aims to review this new category of drugs, illustrating their rationale of use, the results obtained in the treatment of breast neoplasm and the main studies in which they are currently being investigated.

Adult↗

Thyroid autoimmunity and infertility.

We aimed to study the prevalence of thyroid autoimmunity in infertile women; to assess whether thyroid autoantibodies were associated with non-organ-specific autoantibodies; and to investigate the influence of this dysfunction on the couples' chances of pregnancy. We assayed serum levels of thyroid stimulating hormone (TSH), free thyroxine, and microsomal and thyroglobulin autoantibodies in 149 infertile women. In patients with serum TSH levels in the hypothyroid or hyperthyroid range and/or with thyroid autoantibodies, we performed thyroid ultrasound examinations and assayed some non-organ-specific autoantibodies. We compared the duration of infertility in infertile patients with normal thyroid (control group), with thyroid abnormalities, and with thyroid autoantibodies in euthyroidism. Thirty infertile patients (20.1%) had thyroid abnormalities. The prevalence of thyroid autoantibodies was 17.4%. In infertile patients with thyroid autoantibodies, we found a poor association with non-organ-specific autoantibodies. Only the women with thyroid abnormalities and ovulatory dysfunction had a mean duration of infertility significantly longer than that of the control group. When the data were analyzed for euthyroid women with thyroid autoantibodies, we found no significant variation in the duration of infertility. Although we found a high prevalence of thyroid autoantibodies in infertile patients, the presence of these autoantibodies per se did not reduce the chance of pregnancy.

Adult↗

Increased L-citrulline/L-arginine plasma ratio in severe preeclampsia.

OBJECTIVE: To evaluate nitric oxide (NO) production in patients with pregnancy-induced hypertension or preeclampsia and in controls. METHODS: Four groups of pregnant women were included: 17 patients with pregnancy-induced hypertension, ten with mild or moderate preeclampsia, 17 with severe preeclampsia, and 44 normotensive women matched for weeks of gestation at blood sampling with the cases. Plasma levels of L-citrulline and L-arginine were measured by using high-performance liquid chromatography. RESULTS: The mean plasma levels of L-citrulline and the ratio of L-citrulline to L-arginine, which reflects NO production, were higher in women with severe preeclampsia than in controls, patients with pregnancy-induced hypertension, and patients with mild or moderate preeclampsia. CONCLUSION: Nitric oxide production is enhanced in severe preeclampsia, possibly as a compensatory phenomenon for the increased synthesis and release of vasoconstrictors and platelet-aggregating agents.

Adult↗

Access to databases in complementary medicine.

Access to medical databases is a keystone for obtaining up-to-date and complete information for physicians. In the last few years, the rapid growth of the World Wide Web has given rise to an information revolution, enabling health care providers to gain access (often free) to an expanding volume of information that was previously inaccessible. Search engines and online databases assist the search for health information. In this article we examine the biomedical databases of primary interest in the field of alternative and complementary medicine, dividing them into Web accessible and nonaccessible databases and emphasizing the freely available ones. A further classification is major biomedical bibliographic databases specific to complementary medicine, and dedicated therapy or modality-specific databases.

Complementary Therapies↗

Serum allopregnanolone levels in pregnant women: changes during pregnancy, at delivery, and in hypertensive patients.

Allopregnanolone is a neuroactive steroid measurable in peripheral circulation. The aim of the present study was to investigate the presence and the possible changes in serum allopregnanolone and progesterone levels in pregnant women during gestation, at delivery, and in patients with chronic hypertension, with or without superimposed preeclampsia. We also evaluated allopregnanolone in cord blood. Three groups of pregnant women were studied: 1) healthy controls followed longitudinally throughout gestation (n = 14); 2) at vaginal or cesarean delivery (n = 66); and 3) with chronic hypertension (n = 12), with (n = 7) or without (n = 5) superimposed preeclampsia. Allopregnanolone and progesterone levels were measured in maternal and cord serum by RIA. In healthy pregnant women, serum allopregnanolone and progesterone levels progressively increased throughout gestation. Whereas no changes were found at vaginal delivery, serum allopregnanolone and progesterone levels were significantly lower at delivery by emergency cesarean section (P < 0.01). Umbilical cord serum allopregnanolone and progesterone levels in emergency cesarean were significantly lower than those found at vaginal delivery (P < 0.01). Patients with chronic hypertension, with or without superimposed severe preeclampsia, showed serum allopregnanolone levels significantly higher than those of healthy women at the same gestational age (P < 0.01). In conclusion, maternal serum allopregnanolone levels increased during normal gestation were lower in women who underwent emergency cesarean and higher in patients with chronic hypertension, with or without preeclampsia. Because allopregnanolone is active on the central nervous system and in the control of systemic blood pressure, an involvement of this neurosteroid in the adaptive processes induced by pregnancy is suggested.

Adult↗

Increased maternal serum activin A but not follistatin levels in pregnant women with hypertensive disorders.

Activin A levels are elevated in maternal serum of pregnant women with hypertensive disturbances. Because follistatin is a circulating binding protein for activin A, the present study was designed to evaluate whether serum follistatin and activin A levels also change in patients with hypertensive disorders in the last gestational trimester. The study design was a controlled survey performed in the setting of an academic prenatal care unit. Healthy pregnant women (controls, n=38) were compared with patients suffering from pregnancy-induced hypertension (PIH, n=18) or pre-eclampsia (n=16). In addition, the study included a subset of patients with pre-eclampsia associated with intrauterine growth restriction (IUGR, n=5). Maternal blood samples were withdrawn at the time of diagnosis (patients) or in a random prenatal visit (controls), and serum was assayed for follistatin and activin A levels using specific enzyme immunoassays. Hormone concentrations were corrected for gestational age by conversion to multiples of median (MoM) of the healthy controls of the same gestational age. Follistatin levels were not different between controls and patients, while activin A levels were significantly increased in patients with PIH (1.8 MoM), pre-eclampsia (4.6 MoM), and pre-eclampsia+IUGR (3.2 MoM, P<0.01, ANOVA). The ratio between activin A and follistatin was significantly increased in patients with PIH (1.5 MoM) and was further increased in patients with pre-eclampsia (4.5 MoM) and in the group with pre-eclampsia+IUGR (2.6 MoM). Follistatin levels were positively correlated with gestational age in control subjects (r=0. 36, P<0.05) and in patients with PIH (r=0.46, P<0.05) or pre-eclampsia (r=0.61, P<0.01), while activin A correlated with gestational age only in the healthy control group (r=0.69, P<0.0001). The finding of apparently normal follistatin and high activin A levels in patients with PIH and pre-eclampsia suggests that unbound, biologically active, activin A is increased in women with these gestational diseases.

Activins↗

Leptin expression in colorectal and breast cancer patients.

Leptin is a hormone which controls fat metabolism. Leptin plasma levels and adipose tissue mRNA expression were measured in cancer patients. Plasma levels were correlated with TNM staging, cachexia parameters, tumour markers and hormones. Breast and colorectal cancer patients showed blood plasma levels of insulin, TNF-alpha and tumour markers higher than controls. Breast cancer patients, but not colorectal cancer patients, had plasma levels and adipose tissue expression of leptin significantly higher than controls associated with elevated values of estrogen- and progesterone-receptors. These data suggest the possible use of leptin as a clinical marker.

Adenocarcinoma↗

Recurrent spontaneous abortion. Etiologic factors.

BACKGROUND: Spontaneous abortion is the most common complication of pregnancy. It may be unique, remaining random and having no consequences on the reproductive process, or it can repeat itself, starting a clinical picture known as recurrent spontaneous abortion or habitual abortion. The term of RSA syndrome is used to define the repetition of three or more consecutive abortions before the 24th week. METHODS: A population of 195 couples with recurrent spontaneous abortion were screened for genetic, metabolic, infective, morphological, endocrine and autoimmune factors. Eighty-five completed the investigation, 44 are being tested and 66 did not complete the diagnostic course. Causes of recurrent abortion were evaluated in relation to the period of abortion and number of embryo losses. RESULTS: Forty-six percent of patients who completed the investigation turned out to be sine causa, which is in accordance with the findings in literature. CONCLUSIONS: Couple with RSA require accurate counselling and it is fundamental to eliminate any pathologies that can be discovered so as to improve the likelihood of the pregnancy's reaching term.

Abortion, Habitual↗

The use of intravenous immunoglobulin in sine causa or alloimmune recurrent spontaneous abortion (RSA).

BACKGROUND: Recurrent spontaneous abortion (RSA) has an incidence of 0.5%-1%. It is thought that immune reaction disorders in the mother may evolve in unexplained RSA, which has a higher incidence in women over 40 years old. METHODS: Twenty-three patients with recurrent spontaneous abortion of unknown origin and two autoimmune cases were treated with intravenous specific immunoglobulins at the 5th-6th week of pregnancy and fifteen days later. RESULTS: After treatment, nineteen patients brought their pregnancy to term, five aborted, one is pregnant at present. CONCLUSIONS: The use of immunoglobulins seems to be efficacious in recurrent spontaneous abortion of unknown origin. Our results support the theory that this treatment is able to passively transfer the sparking off factor that allows the pregnancy to evolve.

Abortion, Habitual↗

Baroreflex control of heart rate is impaired in pre-eclampsia.

Autonomic nervous dysfunction, such as parasympathetic and sympathetic impairment, has been suggested as possible cause of pre-eclampsia, but the studies are not conclusive. Our purpose was to assess non-invasively if pre-eclampsia is associated with a decreased baroreflex function. Nine women with pre-eclampsia (PE), eight normotensive pregnant women, and seven healthy normotensive non-pregnant women were studied. Continuous finger blood pressure was recorded by a Portapres device in the left lateral recumbent position and active standing. Baroreflex gain was evaluated by cross-spectral analysis of systolic blood pressure and pulse interval. The result was that baroreflex gain at rest was lower in pre-eclamptic women both compared to non-pregnant and healthy pregnant subjects (P<0.05). Moreover, a decrease of the baroreflex sensitivity was present in all pregnant women in the orthostatic position (P<0.05). In conclusion pregnancy per se is associated with a decrease in the baroreflex control of the heart, whereas in pre-eclampsia, the baroreflex sensitivity is impaired further.

Adult↗

Activin A, inhibin A, inhibin B and parturition: changes of maternal and cord serum levels according to the mode of delivery.

OBJECTIVE: To evaluate whether activin A, inhibin A, and inhibin B levels in maternal and umbilical artery serum change according to the mode of delivery. DESIGN: Maternal and cord blood specimens were collected at term after spontaneous labour and vaginal delivery, or elective caesarean section. SETTING: Universities of Pisa, Turin, Naples and Udine. POPULATION: Forty-two healthy pregnant women, at 3940 weeks of gestation, divided into two subgroups: group 1 vaginal delivery (n = 21), were delivered of 10 female and 11 male infants; group 2 elective caesarean section (n = 21), were delivered of 11 female and 10 male infants. MAIN OUTCOME MEASURES: Serum activin A, inhibin A, inhibin B concentrations in maternal and umbilical cord blood. RESULTS: At vaginal delivery, maternal serum inhibin A and inhibin B levels were lower and activin A levels higher than at elective caesarean section. Maternal levels of activin A, inhibin A and inhibin B were constantly higher than in umbilical arterial blood, independent of the mode of delivery. No significant difference was observed in umbilical arterial serum levels of the three proteins between the two modes of delivery. Umbilical arterial serum activin A and inhibin A concentrations did not show a significant difference between male and female infants in either vaginal or caesarean section, but male infants showed inhibin B levels significantly higher than female, independent of the mode of delivery. CONCLUSIONS: In the presence of active labour, the human placenta secretes larger amounts of activin A and lesser amounts of inhibin A and inhibin B into the maternal circulation. Inhibin-related proteins in the fetal circulation do not show differences according to the mode of delivery, suggesting that they have a different method of production or metabolic rate compared with maternal activin and inhibins.

Activins↗

Urocortin stimulates placental adrenocorticotropin and prostaglandin release and myometrial contractility in vitro.

Urocortin is a new member of the CRF family. Multiple biological effects for urocortin have been shown in rats and in some in vitro models, showing a modulatory role in hormonal and behavioral functions. Human placenta expresses urocortin, but no information is available on the possible local biological actions. The aim of the present study was to evaluate the effect of urocortin on placental ACTH and prostaglandin (PG) secretion, as well as on myometrial contractility. Various in vitro models were used. For investigating the effect of urocortin on ACTH release, primary cultures of human trophoblast cells were used. Culture media, collected before and after 3 h exposure to different doses of urocortin and ACTH, were measured by RIA. Trophoblast tissue explants were incubated for 24 h in the presence of increasing doses of urocortin, and prostaglandin E2 (PGE2) levels were measured by RIA. Strips of myometrial tissue were incubated in an organ bath and connected to an isometric smooth-muscle transducer in the presence of urocortin, with or without prostaglandin F2alpha (PGF2a). In all these experiments, the effect of astressin (a CRF receptor antagonist) on urocortin-induced actions and the effect of equimolar doses of CRF were evaluated. A dose-related increase of trophoblast ACTH or PGE2 was induced by urocortin, whereas astressin inhibited urocortin-stimulated ACTH or PGE2 release. Equimolar doses of CRF showed a similar effect on both ACTH and PGE2. Urocortin increased PGF2alpha-induced myometrial contractility, and this effect was completely abolished by the addition of astressin. The present study showed that human urocortin stimulates placental secretion of ACTH and PGE2, and modulates myometrial contractility, suggesting a role for this peptide in placental and intrauterine CRF pathways.

Adrenocorticotropic Hormone↗

A two-stage screening test for pregnancy-induced hypertension and preeclampsia.

OBJECTIVE: To assess the benefit of uterine artery Doppler ultrasound examination with ambulatory 24-hour blood pressure (BP) monitoring as a two-stage screening test for women at risk for pregnancy-induced hypertension, preeclampsia, or fetal growth restriction (FGR). METHODS: Uterine artery Doppler ultrasound was performed at 20-22 weeks' gestation on women at risk for pregnancy-induced hypertension, preeclampsia or FGR who were referred to our antenatal clinics. Abnormal findings were rechecked at 24 weeks' gestation. We selected 180 subjects (90 with abnormal uterine Doppler and 90 with normal uterine Doppler) for 24-hour BP monitoring with a portable automated device, immediately after recruitment, and the midline estimating statistics of rhythm of systolic and diastolic BPs were calculated. RESULTS: The highest incidence of pregnancy-induced hypertension and preeclampsia, with or without FGR, occurred in patients with abnormal uterine Doppler and a systolic midline estimating statistic of rhythm of at least 111 mmHg or a diastolic midline estimating statistic of rhythm of at least 68 mmHg. The specificity and positive predictive value of abnormal uterine Doppler ultrasound alone were low (55 and 27%, respectively), whereas the association of abnormal Doppler ultrasound with both systolic and diastolic midline estimating statistics of rhythm equal or above the selected cutoff values increased the specificity and positive predictive value to 93 and 63%, respectively. CONCLUSION: In clinical practice, a first-stage test with uterine artery Doppler ultrasound at 20-24 weeks' gestation, followed by a second-stage test with ambulatory 24-hour BP monitoring in patients with abnormal uterine Doppler, might indicate women at risk of developing pregnancy-induced hypertension or preeclampsia.

Adult↗

A randomized comparison of vaginal prostaglandin E2 with oxytocin plus amniotomy for induction of labour in women with intermediately ripe cervices.

OBJECTIVE: To compare the effects of oxytocin and amniotomy or vaginal prostaglandin E2 (PGE2) for induction of labour. STUDY DESIGN: We conducted a randomized clinical trial. Eligible for the trial were women with normal pregnancy, parity 0-3, with intact membranes, >40 weeks of gestation documented by ultrasound examination before 20 weeks gestation, observed in a network of 13 general and teaching hospitals in Italy. Inclusion criteria were cervical Bishop's score 5-7, less than six uterine contractions per hour, single pregnancy, cephalic presentation, no history of cesarean section and uterine surgery. Eligible women were randomly assigned by phone to oxytocin plus amniotomy (163 women) or vaginal PGE2 2 mg, two doses at 6-h intervals (157 women). RESULTS: Overall, 50 women (15.6%) delivered by cesarean section, 22 (13.5%) randomized to oxytocin, and 28 (17.8%) randomized to PGE2 (not significant). Twelve hours after randomization, induction had failed in 26 women of the 163 randomized to oxytocin plus amniotomy (21.6%) and 34 out of the 157 randomized to PGE2 (15.9%): the difference was not significant. Neonatal outcome was similar in the two groups. CONCLUSIONS: This study did not find marked differences in labour and neonatal outcome between women randomized to oxytocin plus amniotomy or vaginal PGE2. A shorter induction delivery interval in the group receiving amniotomy and oxytocin after PGE2 priming was observed.

Administration, Intravaginal↗

Twenty-four hour blood pressure monitoring in early pregnancy: is it predictive of pregnancy-induced hypertension and preeclampsia?

OBJECTIVE: To investigate whether a chronobiological analysis applied to automated 24-hour blood pressure monitoring in early pregnancy provides objective parameters enabling detection of single patients at risk of pregnancy-induced hypertension or preeclampsia. METHODS: 24-hour automatic blood pressure monitoring was performed at 8-16 and 20-25 gestational weeks in 104 women at risk of pregnancy-induced hypertension or preeclampsia. The subjects were hospitalized to be synchronized to rest-activity and meal-timing schedules. All women were followed longitudinally until post-partum. Chronobiological analysis of blood pressure values was performed; sensitivity, specificity and predictive values of MESOR and hyperbaric index were also calculated. Incidence of pregnancy-induced hypertension or preeclampsia, gestational week at delivery and birthweight were recorded. RESULTS: Nine thousand nine hundred and eighty-four blood pressure measurements were analyzed. In patients who later developed overt hypertension, systolic and diastolic blood pressure MESOR, hyperbaric index and percent time elevation were already significantly higher in early pregnancy than in those who remained normotensive. The best sensitivity and specificity was obtained between 20-25 weeks of gestation with systolic single cosinor MESOR and Hyperbaric Index using as cut-off 103 mmHg (sensitivity: 88%; specificity: 75%) and 10 mmHg/24 hour (sensitivity: 70%; specificity: 92%), respectively. CONCLUSIONS: The chronobiological analysis applied to 24-hour blood pressure monitoring during pregnancy allows definition of objective cut-off values which can be particularly useful in the routine clinical practice when the risk of developing pregnancy-induced hypertension or preeclampsia must be calculated in the individual subject.

Adolescent↗

24-hour blood pressure monitoring to evaluate the effects of nifedipine in pre-eclampsia and in chronic hypertension in pregnancy.

OBJECTIVE: To investigate the effect of 7 to 14 days of therapy with nifedipine (sustained-release preparation) on the 24-hour blood pressure patterns of pregnant women with pre-eclampsia or chronic hypertension, and to test the utility of blood pressure monitoring in modulating the timing and dosage of the drug. DESIGN: 24-hour automatic blood pressure monitoring of pregnant women with pre-eclampsia or chronic hypertension before and after nifedipine treatment. SETTING: Centre for Prevention, Diagnosis and Treatment of Hypertension in Pregnancy, University of Turin, Italy. POPULATION: Sixteen pregnant women with pre-eclampsia and 17 with chronic hypertension. METHODS: 24-hour blood pressure monitoring was performed before the beginning of the therapy and after 7 to 14 days of treatment with sustained-release nifedipine. MAIN OUTCOME MEASURES: Chronobiological analysis of systolic and diastolic blood pressure values was performed; MESOR, amplitude, acrophase, hyperbaric index, percent time elevation and significance of rhythm were calculated before and after treatment. RESULTS: 6336 blood pressure measurements were analysed. Systolic and diastolic MESOR values were significantly decreased after nifedipine treatment both in pre-eclampsia and in chronic hypertension. However, the antihypertensive effect of nifedipine in pre-eclampsia was especially pronounced during evening and night, while in chronic hypertension it was more constant during the 24-hour period. 24-hour blood pressure monitoring allowed adjustment, when necessary, to the timing and dosage of nifedipine in accordance with the blood pressure patterns of each patient, using the hyperbaric index and percent time elevation as objective parameters for the evaluation of treatment efficacy. CONCLUSIONS: 24-hour blood pressure monitoring is a good method to optimise treatment, and confirms that nifedipine is useful for the control of maternal blood pressure in pregnancy.

Adult↗

Pathophysiological aspects of menstrual migraine.

We review the role of several biochemical and hormonal factors in menstrual migraine pathogenesis: ovarian hormones, aldosterone circadian rhythm, nocturnal urinary melatonin excretion, sympathetic autonomic system, prolactin levels and dopaminergic function, endogenous opioid tonus, platelet activity and arachidonic acid metabolites. In particular, we focus on certain aspects of platelet function and prostaglandin metabolism, taking into consideration the different behavior of platelet sensitivity to prostacyclin, intraplatelet 5HT, peripheral plasma concentrations of 6-keto-PGF1alpha and PGE2 in menstrual migraine sufferers and in control subjects during the menstrual cycle. A comprehensive view of the data suggests that a complex impairment of PG and 5HT metabolism, and of platelet function, may play a significant role in the pathogenesis of menstrual migraine. However, it is not yet clear whether these alterations are primary or secondary to neuroendocrine disorders.

Blood Platelets↗