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Biomedical subjects

M Guido

Publications and source records attributed to M Guido.

At least 109 records · Page 6Linked to original sources

Evaluation of ovarian and adrenal sources of androgens in women with polycystic ovary syndrome. Dexamethasone and GnRH-agonist administration.

Ovarian and adrenal production of androgens was evaluated in 18 patients with polycystic ovary syndrome (PCOS) by administering a combination of short-term dexamethasone (DEX) and long-term gonadotropin-releasing hormone agonist (GnRH-A). At day 6 of the cycle, blood samples were collected at 7 A.M. (basal) and 11 P.M. At midnight, 2 mg DEX was given orally, and blood samples were collected at 7 A.M. the following day (DEX1). Blood samples were obtained for 6 weeks at the same time after administration of a potent GnRH-A (400 micrograms/day given subcutaneously). Eight normal subjects served as controls. The amounts of androgens and 17-hydroxyprogesterone (17-OHP) suppressed by using DEX (adrenal-source suppression) and GnRH-A (ovarian-source suppression) were greater in PCOS patients than in controls. We differentiated PCOS patients as having a normal or an exaggerated response to DEX or GnRH-A administration; threshold values were considered average +2SD of the suppressed androgen amounts of controls. Three patients had an exaggerated response to GnRH-A treatment for androstenedione, testosterone and 17-OHP, while DEX inhibition was similar to controls. The remaining 15 patients had an exaggerated response to DEX for all three androgens; seven also had an exaggerated response to GnRH-A. Thus, the combination of GnRH-A and DEX permitted us to selectively study and identify adrenal and ovarian sources of hyperandrogenemia.

Adrenal Glands↗

Differential androgen response to adrenocorticotropic hormone stimulation in polycystic ovarian syndrome: relationship with insulin secretion.

OBJECTIVE: To investigate the relationship between insulin and adrenal androgens in patients with polycystic ovarian disease (PCOD). DESIGN: Patients with PCOD and a group of volunteers who attended the department during a period of 6 months were studied. SETTING: Department of Gynaecology and Obstetrics, Università Cattolica del Sacro Cuore, Roma, Italy. PARTICIPANTS: Healthy women with ovulatory cycles (hospital personnel, n = 8) and women affected by PCOD (n = 32) were studied on day 5 to 6 of their follicular phase. INTERVENTIONS: All women had an oral glucose tolerance test (OGTT) (75 g) on day 5 to 6 of the cycle. Then plasma samples were collected at 7.00 A.M.; at 11.00 P.M., 2 mg of dexamethasone (DEX) were orally administered with blood samples collected the day after at 7.00 A.M. (effect of DEX). Then adenocorticotropic hormone (ACTH, Synacten; Ciba-Geigy, Varese, Italy) 250 micrograms was injected intravenously (IV) and samples collected 60 minutes later (effect of ACTH). MAIN OUTCOME MEASURES: Plasma glucose and insulin concentration were assayed on OGTT samples collected at time 0, 30, 60, 90, 120, 180, and 240 minutes after glucose ingestion. Data are expressed as area under the curve. Cortisol, 17 alpha-hydroxyprogesterone (17-OHP), testosterone (T), androstenedione (A), and dehydroepiandrosterone sulphate (DHEAS) plasma levels were evaluated on the samples collected before and after DEX or ACTH administration. Data are expressed as absolute concentrations and percent increase in respect to values before the treatment. RESULTS: According to the OGTT response, 21 patients were classified as hyperinsulinemic and 11 as normoinsulinemic. The ideal body weight was greater in hyperinsulinemic patients. No differences in baseline hormone levels were found between the two groups. Only sex hormone binding globulin levels were significantly greater in normoinsulinemic patients (P less than 0.05). Also, the plasma concentration of all steroids after DEX were similar in both groups. Intravenous injection of ACTH significantly increased plasma androgens levels. Cortisol, DHEAS, and T enhancement did not differ in normoinsulinemic and hyperinsulinemic patients, whereas significantly greater A (P less than 0.01) and 17-OHP (P less than 0.05) plasma concentrations were observed after ACTH injection in hyperinsulinemic when compared with normoinsulinemic PCOD subjects. Control group after IV ACTH showed an increase of A and 17-OHP similar to those found in normoinsulinemic PCOD group. CONCLUSIONS: These data suggest that insulin could be involved in the androgen production by adrenal gland and it could influence the responsiveness of adrenal to its trophic hormones.

17-alpha-Hydroxyprogesterone↗

Chronic hepatitis B surface antigen-negative hepatitis after treatment of malignancy.

We reviewed the records of all patients with a diagnosis of malignancy who were treated at our center and who had not had chemotherapy for at least 18 months, to assess the prevalence of chronic hepatitis B surface antigen (HBsAg)-negative hepatitis, to assess the prevalence of a marker of hepatitis C virus infection, and to determine the severity of chronic liver disease. Of 557 eligible patients, 38 (6.8%) had chronic HBsAg-negative hepatitis. Of these 38 patients, 20 (52.6%) had a marker of hepatitis C virus infection. The prevalence of chronic HBsAg-negative hepatitis was higher in patients previously treated for leukemia than in patients treated for another malignancy (11.8% vs 4.6%; p = 0.004). The liver biopsy revealed chronic active hepatitis or cirrhosis or both in 8 (28%) of 28 patients with clinical chronic HBsAg-negative hepatitis. Four patients without hepatitis C virus infection who underwent liver biopsy had hepatitis B virus antigen in the liver, confirmed by immunohistochemistry studies. One patient uninfected with hepatitis C virus had hemochromatosis. We conclude that infection with hepatitis C virus was the major cause of chronic HBsAg-negative hepatitis in pediatric patients previously treated for malignancy; the cause remained unidentified in 30% of the patients.

Alanine Transaminase↗

Primary carcinoid tumor of the cystic and common bile ducts.

We report a case of primary carcinoid tumor arising at the confluence of the cystic and common bile ducts. The patient was a 64-year-old woman who developed a sudden onset of biliary colic and jaundice. Computerized tomography and nuclear magnetic resonance showed a mass lesion close to the head of the pancreas. At laparotomy a nodular lesion was found at the confluence of the cystic and common bile ducts. Microscopic observation revealed a type B-C carcinoid (Soga's classification) with positive immunoreactivity to chromogranin and cytokeratin. The presence of neurosecretory intracytoplasmic granules was demonstrated by electron microscopy. Flow cytometry showed diploid DNA content of the neoplastic cells with less than 5% of the nuclei in the S-phase region.

Bile Duct Neoplasms↗

Therapy for chronic hepatitis B with lymphoblastoid interferon-alpha and levamisole.

About one third of patients with chronic hepatitis B show a sustained response when treated with interferon-alpha. Combining interferon-alpha with immunomodulators might be a way to increase response rate. The aim of this study was to compare the efficacy of lymphoblastoid interferon-alpha given alone with its efficacy when combined with levamisole in chronic hepatitis B. Forty-five patients with HBeAg-positive chronic hepatitis were randomly selected (with stratification for ALT levels) to receive a 6-mo course of combination therapy with lymphoblastoid interferon-alpha (5 million units/m2 three times per week) and levamisole (150 mg three times per week) or lymphoblastoid interferon at the same dose regimen and a matching placebo. Final evaluation 18 mo after randomization revealed a loss of both HBeAg and hepatitis B virus DNA with ALT normalization in 38% of patients treated with interferon-alpha alone and in 10% of patients receiving combination therapy. The higher response rate observed in patients treated with interferon-alpha alone was maintained after stratification for basal ALT levels (i.e., higher [45% vs. 10%] or lower [31% vs. 9%] than three times the upper normal value). The length of time to sustained HBeAg clearance was significantly (p < 0.05) shorter in patients receiving monotherapy than in patients receiving combination therapy. Blinded histological assessment revealed improvement in 44% of patients treated with interferon-alpha alone compared with improvement in 6% of patients receiving combination therapy. These results indicate that levamisole has no additive effects when combined with interferon-alpha in the treatment of HBeAg-positive chronic hepatitis.

Adult↗

5-HT2 presynaptic receptors mediate inhibition of glutamate release from cerebellar mossy fibre terminals.

'Giant' synaptosomes originating from mossy fibre terminals and having sedimentation properties different from those of standard synaptosomes were obtained from rat cerebellum. Exposure of superfused giant synaptosomes to 15 mM KCl caused the release of endogenous glutamate in a largely (about 80%) calcium-dependent manner. The K(+)-evoked overflow of glutamate was inhibited in a concentration-dependent manner by 5-hydroxytryptamine (5-HT) and by the 5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI), but not by the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). The effects of 5-HT and DOI were quite potent, already reaching significant inhibition (about 25%) at 10 nM. The 5-HT2 receptor antagonist ketanserin counteracted the inhibitory effect of 5-HT. In cerebellar slices, ketanserin increased on its own the calcium-dependent K(+)-evoked release of glutamate and this effect was not prevented by tetrodotoxin (TTX). The results support the idea that cerebellar mossy fibres use glutamate as a transmitter and show that the release of glutamate can be inhibited via presynaptic heteroreceptors of the 5-HT2 type probably localized on the mossy fibre terminals.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Leukemia and liver disease in childhood: clinical and histological evaluation.

Seventy-two consecutive patients with acute lymphocytic leukemia (ALL) who had undergone liver biopsy within 3 months of completing chemotherapy were studied to evaluate histological features after 2 to 3 years of chemotherapy and to correlate liver disease to the treatment schedule, the number of transfused blood units, and the identified etiology. Fibrosis due to antiblastic drugs was the most frequent histological finding. Histological liver disease was not related either to the chemotherapy schedule or the number of transfused blood units. HBV with or without delta virus and HCV infections were related to a more severe histological liver disease. In about 40% patients with chronic liver disease, no etiology was demonstrated. Immunohistochemistry revealed HBcAg in the liver of 3 HBsAg-negative patients. In conclusion, liver biopsy could be useful in patients with persistent abnormal liver function tests after the completion of chemotherapy and in patients with markers for hepatotropic virus infection.

Alanine Transaminase↗

Histology and virus expression in the liver: a prognostic puzzle in chronic hepatitis B.

Forty chronic untreated paediatric carriers of hepatitis B virus (HBV) infection, with no other causes of liver disease, were biopsied on presentation, when the disease was in the active viral replication phase. After a period ranging from 1 to 13 years, all patients underwent a control biopsy. At the time of the last biopsy, 31 of the patients were anti-HBe positive, whereas 9 persisted in the active replication phase. In this latter phase, necrotic and inflammatory lesions and the presence of nuclear HBcAg were found significantly more frequently than when replication had terminated. The necrotic and inflammatory lesions detected in the first biopsy of patients who subsequently underwent anti-HBe seroconversion were significantly more severe than in patients failing to reach seroconversion. All patients who maintained viral replication showed generalized nuclear reactivity for HBcAg on presentation; such reactivity was also found in 16 of 31 (52%) patients who reached anti-HBeAg seroconversion. All these cases had piecemeal necrosis (PMN) in the biopsy. PMN may therefore be considered as a positive prognostic factor in that it identifies those patients who may seroconvert with significant remission of liver disease.

Adolescent↗

Interferon therapy of chronic delta hepatitis in patients cured of pediatric malignancies: possible harmful effect.

In our Pediatric Haemato-Oncology Unit, 42 young patients cured of their malignancy were left with chronic delta hepatitis. The severity of liver disease in many of these patients prompted us to start a pilot study on the effect of recombinant alpha 2b interferon, given at a dose of 5 MU/square meter thrice weekly. All nine patients included in the study (five males, mean age: 15 years) had well-compensated liver disease, including five cases with active hepatitis and cirrhosis. At the end of the 3rd month of therapy, two patients with cirrhosis developed a biochemical exacerbation leading to hepatic decompensation, which was fatal in one case. The reasons for this unfavourable outcome remain unclear. Basic immunological tests were normal, but one of the two patients was the single case with anti-liver-kidney microsome antibodies. On the other hand, both patients seroconverted from hepatitis B e antigen to antibody at the time of exacerbation, suggesting that liver damage could have been the result of cell-mediated cytotoxicity to hepatitis B virus antigens. The results of this study, which has been interrupted at the 4th month, suggest that interferon therapy for chronic delta hepatitis has to be considered cautiously in young patients cured of pediatric malignancies. In fact, no beneficial effect was seen and the treatment appeared to be harmful in at least two out of nine patients treated.

Adolescent↗

Epithelial dysplasia in atrophic gastritis. Bioptical follow-up study.

Fifty-nine cases of gastric dysplasia (46 of which were mild, 11 moderate and 2 severe) were studied in relation to their association with atrophic gastritis and intestinal metaplasia. Atrophic gastritis was found in 39 cases (28 of which were mild, 10 moderate and 1 severe). Dysplasia was considered "persistent" when found of the same degree in at least two consecutive check-ups after initial diagnosis (13 cases); it was considered "progressive" if found more severe or evolving as cancer (5 cases) or "regressive" if detected in a lesser degree or no longer detected (13 cases). Sixteen of the 18 persistent or progressive cases of dysplasia were associated with atrophic gastritis, whereas 10 of the 13 cases with regressive dysplasia revealed no concomitant pattern of gastric mucosa atrophy (p less than 0.005). These findings suggest that dysplasia represents a truly pre-neoplastic change particularly when associated with atrophic gastritis and which must therefore be more carefully monitored.

Adult↗

Long-term outcome of chronic type B hepatitis in patients who acquire hepatitis B virus infection in childhood.

Seventy-six children aged 1-13 years who were known to be positive for hepatitis B surface antigen and hepatitis B e antigen in serum for at least 6 months and who had biopsy-proven chronic hepatitis have been followed longitudinally for 1-12 years (mean, 5 years). Twenty-three of them are now young adults. Eight patients had acute type B hepatitis 12-24 months before entering the study, while 68 patients came to observation during a chronic phase. At the beginning of follow-up, all 76 children were positive in serum for hepatitis B virus DNA, and 44 (58%) had chronic active hepatitis, associated with cirrhosis in two cases. During follow-up, 23 (30%) patients remained hepatitis B e antigen-positive, most with unchanged biochemical and histological features. The other 53 (70%) cases seroconverted to hepatitis B e antibody and cleared hepatitis B virus DNA from serum, including 7 of 8 (87%) patients with acute hepatitis at presentation. After seroconversion, alanine aminotransferase levels normalized in all patients and remained normal in 49 patients (92.5%) throughout a mean observation period of 3 years. Five of these children, including 2 of 7 (29%) with previous acute hepatitis, eventually cleared hepatitis B surface antigen from their sera. Finally, 4 (7.5%) patients experienced a mild increase of alanine aminotransferase levels several months after seroconversion in the absence of hepatitis B virus replication or of delta virus superinfection. Clinical and virological parameters did not significantly differ between patients with or without acute onset; however, seroconversion occurred earlier, and the rate of hepatitis B surface antigen clearance was greater in the former than in the latter group. The present data indicate that approximately two thirds of children with hepatitis B e antigen- and hepatitis B virus DNA-positive chronic hepatitis clear hepatitis B virus DNA from their sera before reaching adulthood. After termination of viral replication, most patients achieve a sustained biochemical remission, suggesting the disappearance of disease activity. Reactivation of virus replication after hepatitis B e antibody seroconversion has never been observed in this series, although mild alanine aminotransferase level abnormalities could be detected in a minority of cases.

Adolescent↗

Clinical, virologic and histologic outcome following seroconversion from HBeAg to anti-HBe in chronic hepatitis type B.

Seventy consecutive HBsAg- and HBeAg-positive patients with biopsy-proven chronic hepatitis were followed prospectively with serial determinations of SGPT levels and hepatitis B virus serum markers including HBsAg, HBeAg, anti-HBe and hepatitis B virus DNA. During a period of 1 to 11 years (mean +/- S.D.: 5.0 +/- 2.3 years), 28 patients remained persistently HBeAg positive, most with continuing biochemical and histologic activity, while 41 cases seroconverted to anti-HBe. One patient became HBeAg and anti-HBe negative. After seroconversion, 87.8% of the cases showed sustained normalization of SGPT, and clearance of hepatitis B virus DNA from serum and histologic improvement was documented in 79% of the cases who had a control liver biopsy, while 15.8% developed cirrhosis. In two patients (4.9%), the disease remained active despite seroconversion, and both cases had evidence of continuing hepatitis B virus replication. Finally, reactivation of liver damage and of hepatitis B virus replication was observed in three additional patients (7.3%) who had transiently normalized SGPT after seroconversion. All 70 patients were analyzed for hepatitis delta virus markers, and only two persistently HBeAg-positive cases were found positive for antibody to hepatitis delta virus in serum, one also having hepatitis delta antigen in the liver. These findings indicate that, in chronic hepatitis type B, termination of virus replication is associated in most patients with biochemical and histologic regression of inflammatory activity. After anti-HBe seroconversion has occurred, virus replication and liver disease may persist or reactivate in a small proportion of patients thus giving origin to the well-recognized group of anti-HBe positive, hepatitis B virus DNA-positive chronic hepatitis type B.

Adolescent↗

Naltrexone effect on pulsatile GnRH therapy for ovulation induction in polycystic ovary syndrome: a pilot prospective study.

The aim of the present study was to analyze the opioid influence on LH pulsatility in polycystic ovary syndrome (PCOS) patients and to evaluate the effectiveness of a long-term opioid antagonist (naltrexone) treatment in improving the pulsatile GnRH therapy which is successful in this syndrome. Ten obese women affected by PCOS participated in the study. Patients were hospitalized during the early follicular phase and underwent an oral glucose tolerance test (OGTT) with 75 g of glucose and a pulse pattern study followed by a GnRH test (100 pg i.v.). All patients were then treated for ovulation induction with pulsatile administration of GnRH (5 microg/bolus every 90 min). Since pregnancies did not occurr in any patient, after spontaneous or progestin-induced menstrual cycles, all patients received naltrexone at a dose of 50 mg/day orally for 8 weeks and during treatment repeated the basal protocol study and the ovulation induction cycle with the same modalities. The naltrexone treatment significantly reduced the insulin response to OGTT and the LH response to GnRH bolus, whereas it did not affect the FSH and LH pulsatility patterns. Concerning the ovulation induction by pulsatile GnRH, naltrexone treatment was able to improve, although not significantly, the ovulation rate (60% pre-treatment vs 90% post-treatment). Furthermore, the maximum diameter of the dominant follicle and the pre-ovulatory estradiol concentration were higher after long-term opioid blockade (follicular diameter 19.5+/-1.76 mm pre-treatment vs 21.6+/-2.19 mm post-treatment, p<0.001; maximum estradiol level 728.7+/-288.5 pmol/l pre-treatment vs 986.4+/-382.1 pmol/l post-treatment, p<0.05). During the naltrexone-pulsatile GnRH co-treatment two pregnancies occurred. In conclusion, our data show that naltrexone-pulsatile GnRH co-treatment is able to improve the ovarian responsiveness to ovulation induction in obese PCOS patients when compared to pulsatile GnRH alone. This action seems to be related to a decrease of insulin secretion. Further randomized studies should be performed in order to obtain significant conclusions on the possible clinical application.

Adult↗

The hypothalamic-pituitary-luteal axis in women: effects of long-term orally active opioid antagonist (naltrexone) administration.

Aim of our study is to assess the effect of a long-term oral opiate antagonist treatment during the luteal phase on the hypothalamic-pituitary-ovarian axis. Fourteen normovulatory women participated to the study. Immediately after the ovulation, the patients were randomly divided in two groups: in the first one women received naltrexone 50 mg/die orally (Antaxone Zambon Italy) from day 1 of the luteal phase for 7 days. In the second patients were treated with placebo for the same period and served as control group. On day 7, patients were hospitalized for a pulse pattern study followed by a GnRH test. LH, FSH, Estradiol, Progesterone were assayed. The naltrexone administration strongly increased the number as well as the amplitude of the gonadotropin pulses. The circulating P levels were also significantly higher in treated patients. The GnRH injection significantly increases the gonadotropin secretion in all patients. The stimulated LH and FSH secretion was significantly greater in treated patients when compared to controls. Such discharge of LH determined a significant increase of progesterone production in controls, but failed to stimulate the corpus luteum in treated patients. In conclusion the present paper strengthen an important role of the opioidergic system in the regulation of GnRH pulsatility in luteal phase. Moreover, our findings confirms the sensibility of the corpus luteum to LH and the possibility to stimulate the P secretion during the luteal phase.

Adult↗

EEG spectral analysis in migraine without aura attacks.

In 16 patients suffering from migraine without aura, we examined quantitative EEG and steady-state visual evoked potentials (SSVEPs) at 27 Hz stimulation during the critical phase of migraine and in attack-free periods. The main spontaneous EEG abnormalities found during the critical phase were the slowing and asymmetry of the dominant frequency in the alpha range. The amplitude of the SSVEP F1 component was significantly reduced during the attack phase compared with the intercritical phase; in the latter condition the visual reactivity to 27 Hz stimulus was increased over almost the entire scalp compared with normal subjects. The EEG abnormalities confirm a fluctuating modification of alpha activity during the migraine attack, probably related to a functional disorder. The suppression of visual reactivity during the migraine attack could be related to a phenomenon of neuronal depolarization such as spreading depression, occurring in a situation of central neuronal increased excitability predisposing to migraine attacks.

Adult↗

Leukocyte chemotaxis and pyoderma gangrenosum.

Leukocyte chemotaxis (in five patients with pyoderma gangrenosum) was studied using a modification of the Boyden chamber method. In all patients the chemotactic response was significantly lower than in the controls. This abnormal chemotaxis was a result of an intrinsic neutrophil dysfunction. No significant difference was detected between the chemotactic response of leukocytes from patients with minimal or no skin involvement and those from patients with extensive lesions.

Adult↗

Safety and immunogenicity of conventional subunit and MF59-adjuvanted influenza vaccines in human immunodeficiency virus-1-seropositive patients.

In this study of influenza vaccination, 37 human immunodeficiency virus (HIV)-1-seropositive patients were randomized to receive either a vaccine with a conventional subunit or one adjuvanted with MF59. Blood samples were collected at the time of vaccination, and then 30 and 180 days later, to evaluate immunogenicity, CD4+ T-lymphocyte count and HIV-1 RNA levels. Seroconversion rates against the three viral strains included in the vaccine ranged between 44% and 72% and 53% and 68% for the adjuvanted vaccine and the subunit vaccine, respectively. Other criteria of the European Medicines Evaluation Agency were also met. Vaccination was not associated with serious adverse events. Local and systemic effects were mild and of short duration. CD4+ T-lymphocyte counts and viraemia levels were not negatively affected by vaccination. These results confirmed the safety and immunogenicity of these currently available vaccines in HIV-1-seropositive patients, thus supporting the recommendation for influenza immunization in this high-risk category.

Adjuvants, Immunologic↗