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Biomedical subjects

M Guido

Publications and source records attributed to M Guido.

At least 91 records · Page 5Linked to original sources
PubMed1996

Preconceptional and gestational evaluation of insulin secretion in patients with polycystic ovary syndrome.

The relationship between insulinaemia and obesity and glucose tolerance and the impact of pregnancy as risk factor for carbohydrate abnormalities were investigated in 91 consecutive patients with polycystic ovary syndrome (PCOS) aged 26-32 years. Fifteen normoglycaemic patients became pregnant within 6 months of the pregestational study using pharmacological induction of ovulation. Plasma concentrations of insulin and glucose after an oral glucose tolerance test (OGTT) were determined by immunoradiometric assay and glucose oxidase technique respectively. OGTT patients were classified according to their response as normoinsulinaemic (n = 46) or hyperinsulinaemic (n = 45). Impairment of glucose metabolism occurred in 12.1% (n = 11, 10 obese and one lean) of all PCOS subjects. Based on insulin secretion, 6.5% of normoinsulinaemic and 13.3% of hyperinsulinaemic patients had an impaired glucose tolerance and 2.3 and 2.2% respectively a non-insulin-dependent diabetes mellitus. Obese patients had higher values for area under the curve for insulin response to OGTT (I-AUC values) than lean patients, and the percentage above ideal body weight was greater in hyperinsulinaemic than in normoinsulinaemic patients. All hyperinsulinaemic (7/15) subjects who became pregnant developed an impairment of glucose metabolism during pregnancy. It is concluded that the PCOS population was at higher risk of developing carbohydrate abnormalities than the normal population of a similar reproductive age. Furthermore, those with abnormal insulin secretion at the pregestational stage may, during pregnancy, develop an impaired gestational glucose tolerance or gestational diabetes.

Adult↗
PubMed1996

Hepatitis C virus serotypes and liver pathology.

The present study aimed to analyze the pathology of chronic hepatitis C in relation to HCV serotype, and to speculate on possible differences in the pathogenesis of liver injury. Liver biopsies were investigated from 59 consecutive patients in whom hepatitis C virus genotypes were determined by a serological genotyping assay that detects antibodies directed to epitopes encoded by the NS4 region. A morphological study was performed in each case, semiquantitatively scoring necro-inflammatory and fibrotic liver lesions. The prevalence of HCV serotypes was as follows: 26 of the 59 patients (44%) had type 1 infection, 11 (19%) had type 2 and 20 (35%) had type 3. A significant association between intravenous drug abuse and serotype 3 infection was observed. Patients with HCV type 2 proved significantly older than patients with infection type 1 or 3, and more frequently they showed a more active liver disease, but no differences were found in the quality and acinar topographic distribution of all the morphological lesions scored. In conclusion, in chronic hepatitis C a more active liver disease can be related to HCV serotype 2 but the spectrum of liver lesions is independent of HCV types. From a morphological point of view, a different pathogenesis of liver injury related to different HCV types is unlikely.

Adult↗
PubMed1996

Evidence of a disturbance of the hypothalamic-pituitary-adrenal axis in polycystic ovary syndrome: effect of naloxone.

DESIGN: There are conflicting data on hypothalamic-pituitary-adrenal (HPA) axis function in women with polycystic ovary syndrome (PCOS). We have evaluated the HPA axis responses to naloxone in patients with PCOS compared to control subjects. PATIENTS: Twenty PCOS patients and 10 control women participated in the study. MEASUREMENTS: On days 5-6 of a spontaneous or progestin induced cycle each patient received an intravenous bolus (5 mg) of naloxone (time 0 min), followed by a 2-mg naloxone infusion in 100 ml of 0.9% saline over one hour. Samples were collected at -30, 0, 15, 30, 60, 90 and 120 minutes. ACTH and cortisol levels were measured in all plasma samples. RESULTS: PCOS patients showed significantly greater response than controls to naloxone of ACTH (peak value 261 vs 172% of basal value) and cortisol (peak value 237 vs 165% of basal value); also, ACTH and cortisol incremental areas were higher in PCOS patients (P < 0.05 and P < 0.04 respectively). The cortisol/ACTH ratio of AUCs percentage increase was found to be near unity for all patients without significant difference between PCOS and control groups, suggesting a direct correspondence between ACTH circulating levels and adrenal cortisol production. CONCLUSIONS: Polycystic ovary syndrome patients showed a hypothalamic-pituitary-adrenal axis hyper-responsiveness to naloxone infusion compared with control subjects. These data support the hypothesis that this disturbance could be central in origin.

Adolescent↗
PubMed1996

Different arrangement of human papillomavirus E2 binding sites distinguishes cutaneous types from those associated with mucosal lesions.

High-risk-type human papillomavirus DNA sequences are found in a high percentage of carcinomas from the uterine-cervix, with the viral E1-E2 gene region usually disrupted and the E6 and E7 oncoproteins consistently expressed. The E2 protein is known to repress early transcription from genital HPV promoters having a proximal E2 binding site (E2BS) close to the TATA box. On the contrary, the E2 protein activates cutaneous early promoters having a longer distance between these sites. Using an in vivo approach we analyzed the regulation, by the BPV-1E2 protein, of a natural HPV-18 promoter where proximal E2BS were placed at variable positions relative to the TATA box, and of heterologous promoters where E2BS was placed upstream of any other known DNA-binding elements. Our results confirm that the E2 protein represses or activates HPV early gene transcription depending on the distance between the TATA box and the proximal E2BS.

Animals↗
PubMed1996

[Undifferentiated gastric carcinoma of lymphoepithelioma type with Epstein-Barr virus].

We are presenting the case of a 62-year-old man with a gastric tumor which turned out to be an undifferentiated carcinoma lymphoepithelioma type. The epithelial nature of the cells was confirmed by immunohistochemistry. The presence of Epstein-Barr virus, limited to the epithelial cells, was demonstrated by in situ hybridization. These findings confirm data from the literature and support the possible etiopathogenic relationship between Epstein-Barr virus and undifferentiated carcinoma lymphoepithelioma type of the stomach. We are unaware of any other report of this type of neoplasm in our country.

Carcinoma, Squamous Cell↗
PubMed1995

Gastric epithelial dysplasia. How clinicopathologic background relates to management.

BACKGROUND: Gastric epithelial dysplasia (GED) in metaplastic mucosa is considered the most advanced preinvasive lesion in the multistep morphogenesis of intestinal-type gastric cancer (GC). The rate of GED's evolution into GC is still under debate and probably is related to pathologic and clinical parameters other than the dysplasia itself. The aim of this study was to evaluate whether clinical aspects (sex and age) and/or morphologic variables (GED grade, coexisting atrophic gastritis) are relevant to the outcome of dysplasia, with a view toward initiating the establishment of a rational follow-up protocol for practical GED management. METHODS: Ninety-three patients harboring GED (G1: 56, G2:34, G3:18) were followed for more than 12 months according to a previously-agreed protocol. Regression, progression, or evolution into GC were detected for each grade of GED. Multivariate analysis was used to check the independence of clinical and pathologic variables in the progression of GED into more severe dysplastic lesions and/or as risk factors for evolution into GC. RESULTS: Age, male sex, GED grade and grade of coexisting atrophic gastritis proved independent risk factors for GED progression, with no significant interactions. Only GED grade (G2 and G3) was significantly associated with carcinomatous evolution. In G1-GED, age and the grade of coexisting atrophy proved to be independent risk factors for carcinomatous evolution. CONCLUSIONS: In G1-GED, more stringent follow-up should be recommended for older patients with coexisting high grade atrophic gastritis; stringent follow-up is always mandatory for G2-GED; and a surgical approach is justified in G3-GED.

Adenocarcinoma↗
PubMed1995

Effect of opioid blockade on insulin metabolism in polycystic ovarian disease.

A total of 17 women affected by polycystic ovarian disease (PCOD) were studied to evaluate the involvement of endogenous opioids in the pathophysiology of the hyperinsulinism in PCOD by administering naltrexone, an oral opioid antagonist. An oral glucose tolerance test (OGTT) was performed at baseline (on day 5 of the cycle) and repeated after 6 weeks of naltrexone administration. Plasma glucose, insulin and connecting peptide (c-peptide) concentrations were evaluated in all samples. Based on their insulinaemic response to OGTT, patients were classified as hyperinsulinaemic or normoinsulinaemic. Naltrexone treatment significantly (P < 0.007) reduced the insulin response to OGTT in the hyperinsulinaemic group without affecting the c-peptide incremental area; in the normoinsulinaemic group there was a slight, but not significant, increase in both c-peptide and insulin incremental areas. The two groups showed similar c-peptide incremental areas after naltrexone treatment. There was no significant difference in the c-peptide:insulin incremental areas molar ratio between the two groups; after treatment, a significant increase in this ratio was observed in both groups. When we considered the data as an expression of the fractional hepatic extraction of insulin, we found a lower value for hyperinsulinaemic in comparison with normoinsulinaemic patients (not significant), and a significant (P < 0.01) improvement of this parameter in the hyperinsulinaemic group after naltrexone administration. In conclusion, we suggest that the contribution to hyperinsulinaemia in PCOD patients may be at least in part due to both increased pancreatic secretion and reduced hepatic removal of insulin. Chronic pharmacological inhibition of opioid tone could improve the insulin plasma concentration by acting chiefly on the liver metabolism of insulin in hyperinsulinaemic patients.

Adolescent↗
PubMed1995

HLA-DR expression in liver in human HIV infection.

In order to clarify the relationship between HLA-DR antigen expression in the liver and human HIV infection, we studied 66 non-autopsy specimens obtained from HIV-infected patients with and without AIDS; 33 biopsies from HIV-negative patients were considered for control purposes. All biopsies were immunohistochemically tested with monoclonal antibody TAL-1B5, reacting with the alpha-chain subunit of HLA-DR in the avidin biotin complex method. We found occasional and usually weak HLA-DR expression on hepatocytes and biliocytes. By comparison with controls, HIV-positive cases showed a significantly higher percentage of HLA-DR immunoreactivity on hepatic artery and portal vein endothelial cells. No relationship was demonstrated between HLA-DR endothelial expression and the CD4+ lymphocyte count or grade of portal/periportal inflammation in the liver. The biological significance of HLA-DR expression on intrahepatic vascular endothelial cells in HIV infection still remains to be clarified.

Adult↗
PubMed1995

Effect of corticotropin-releasing factor on the pituitary-ovary axis in human luteal phase.

In order to test the possible negative effect of corticotropin-releasing factor (CRF) on the pituitary-gonadal axis, two gonadotropin-releasing hormone (GnRH) tests, on two consecutive days, were performed in five normally cycling women in the midluteal phase of the menstrual cycle. The first GnRH test was performed after 2 h during which time basal blood samples were collected every 10 min. On the second day, the GnRH test was repeated after a 2-h CRF infusion which was continued throughout the GnRH test. Our results demonstrate that while CRF increases cortisol levels it affects neither the basal nor the GnRH-stimulated gonadotropin levels. Similarly, both basal and luteinizing hormone (LH)-stimulated progesterone concentrations were not modified by the CRF infusion thereby also excluding a possible direct effect of the peptide on corpus luteum steroidogenesis.

Adult↗
PubMed1995

The effect of interferon alfa and ribavirin combination therapy in naive patients with chronic hepatitis C.

BACKGROUND: Chronic hepatitis C may lead to cirrhosis and hepatocellular carcinoma in a subset of patients. Because response rates with interferon alfa therapy are unsatisfactory, new therapies are needed. METHODS: We conducted a three-arm, randomized trial in 45 interferon-naive men (mean age 40.6 +/- 12 years) with chronic hepatitis C to compare treatments: group A, ribavirin alone (15 mg/kg daily for 6 months); group B, interferon alone (3 MU thrice weekly for 6 months); and group C, interferon plus ribavirin at the above doses. Histologic outcomes of therapy were assessed by pretreatment and post-treatment liver biopsies. RESULTS: In group A, alanine aminotransferase levels normalized during therapy in 66% of those with HCV-1b and 34% of those with HCV-2a, but all patients relapsed after treatment ended. In group B, alanine aminotransferase levels normalized during treatment in 66%, 75%, and 100% of patients infected with HCV-1b, HCV-2a, and HCV-3, respectively; however, a sustained response was noted in only 25% of those with HCV-3. In group C, a sustained normalization of alanine aminotransferase with negative serum HCV RNA was seen in 20% of those with HCV-1b, 40% of those with HCV-2a, and 75% of those with HCV-3 12 months after therapy. One year after therapy ended, group C demonstrated a significant sustained response (47%) as well as a significant reduction in piecemeal necrosis and portal inflammation (p < 0.05). CONCLUSIONS: Combination therapy was significantly superior to ribavirin or interferon monotherapy in producing a sustained response in interferon-naive patients with chronic hepatitis C (p < 0.05). The results of our study suggest that ribavirin potentiates the effect of interferon therapy in chronic hepatitis C.

Adult↗
PubMed1994

Multiple-dose pharmacokinetics and safety of a potential memory-enhancing compound, CL 275,838, in healthy male volunteers.

The pharmacokinetics and safety of CL 275,838, a new potential memory-enhancing compound, were examined after 14 daily doses (50 and 100 mg) in 16 healthy male volunteers, age 20 to 59 years, in a randomized, double-blind, placebo-controlled, parallel group study. Trough blood samples (predose) were collected on days 2, 4, 7, 10, and 14, and further samples were drawn after the final dose (day 14) to define the multiple-dose kinetics of the parent compound and its metabolites II and IV. Intercurrent clinical events, vital functions, EEG, ECG, and cognitive tests (attention, verbal memory, and spatial memory) were considered as outcome measures of safety. Performance in cognitive tests was also studied to collect preliminary information on possible therapeutic action. Predose plasma concentrations of the parent compound and its two metabolites increased approximately in proportion to the dose, and accumulation was complete within 7 days, regardless of the dose. At steady state, mean Cmax and AUC of the parent compound and its two metabolites were dose related. Mean wash-out t1/2 was 18 to 20 hours for the parent compound, 22-23 hours for metabolite II, and 28-33 hours for metabolite IV; these elimination t1/2 are comparable for the two doses, and are similar to those observed in single-dose studies. For the 50-mg-dose group, predicted and observed average plasma concentrations (Css) of CL 275,838 and its two metabolites did not differ significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Gonadotropin-releasing hormone agonist versus human chorionic gonadotropin as a trigger of ovulation in polycystic ovarian disease gonadotropin hyperstimulated cycles.

OBJECTIVE: To compare the use of GnRH agonist (GnRH-a) versus hCG in triggering the follicular rupture in patients with polycystic ovarian disease (PCOD) in whom ovulation was induced by gonadotropins. DESIGN: Polycystic ovarian disease gonadotropin hyperstimulated cycles outcome was investigated in a prospective study. PATIENTS AND INTERVENTIONS: Thirty-three PCOD patients (40 cycles) with gonadotropin-induced mild to moderate degree of ovarian hyperstimulation received 5,000 IU IM hCG or 200 microg [corrected] SC GnRH-a. A subgroup of GnRH-a-treated patients received P for luteal support. Five GnRH-a-treated patients underwent a GnRH test during luteal phase. MAIN OUTCOME MEASURES: Echographic and endocrine characteristics both during the therapy and the luteal phase. RESULTS: There was a similar percentage of ovulation and pregnancy rate in both groups of patients. The ovarian enlargement during the luteal phase in the GnRH-a-treated patients was lower than in the hCG group. Progesterone plasma levels (at midluteal phase) and the length of luteal phase was significantly lower in GnRH-a-treated patients with respect to the hCG-treated group. These differences disappeared in patients receiving luteal support. After GnRH injection, LH secretion decreased in GnRH-a-treated patients with respect to controls; however, corpus luteum was able to respond with a normal increase of P production. CONCLUSION: The GnRH-a appears to be an effective alternative to hCG for inducing the follicular rupture in stimulated cycles in women who are at risk for developing ovarian hyperstimulation syndrome. However, GnRH-a administration can induce short luteal phase. This defect may be ascribed to the pituitary desensitization rather than to a direct effect on corpus luteum. Luteal phase support is needed to prevent luteal phase deficiency.

Adult↗
PubMed1994

A randomized controlled trial of thymopentin therapy in patients with chronic hepatitis B.

Strategies of treatment of chronic hepatitis type B are currently based on the use of either antiviral or immunomodulatory agents. A randomized, controlled trial was performed to assess the safety and efficacy of 6-month thymopentin therapy in 30 patients with chronic hepatitis B. Inclusion criteria were biopsy-proven chronic hepatitis, elevated alanine aminotransferase and serum HBsAg and HBV-DNA positivity for at least 12 months. At the conclusion of the study (1 year), HBV-DNA was negative and alanine aminotransferase had normalized in 13% and 20% of treated cases and in 20% and 27% of controls. None of the ten treated and one of the nine control patients who were initially HBeAg positive subsequently cleared HBeAg. None became HBsAg negative. A histologic improvement was noted in 27% of the treated patients compared with 18% of controls. These results indicate that this regimen of thymopentin therapy is not effective in treating chronic hepatitis B.

Adult↗
PubMed1994

Differential androgen response to adrenocorticotrophin hormone stimulation and effect of opioid antagonist on insulin secretion in polycystic ovarian syndrome.

To investigate the effect of a chronic anti-opioid treatment on the adrenal steroid production in polycystic ovarian syndrome (PCOS), 20 women affected by PCOS were studied before and after 6 weeks of treatment with an opioid antagonist. All women had an oral glucose tolerance test (OGTT) (75 g) on day 5 of the cycle. At 11.00 p.m. 2 mg of dexamethasone was orally administered and blood samples collected the following day at 7.00 a.m. Then 250 micrograms of adrenocorticotrophin hormone (ACTH) was injected i.v. and samples collected 60 min later. At this time a 6 week course of naltrexone treatment (50 mg/day orally) was started, following which the protocol was repeated on day 6-7 of the menstrual cycle. According to OGTT responses, 10 patients were classified as hyperinsulinaemic and 10 as normoinsulinaemic. No difference in baseline hormone concentrations was found, except for sex hormone-binding globulin, which was significantly greater in normoinsulinaemic patients (P < 0.02). The plasma concentration of all steroids after dexamethasone and ACTH administration was similar in both groups, except for androstenedione (P < 0.02) and 17 alpha-hydroxyprogesterone (17-OHP) (P < 0.05), which were significantly greater after ACTH injection in hyperinsulinaemic compared with normoinsulinaemic PCOS patients. Naltrexone treatment significantly (P < 0.001) reduced insulin response to OGTT in the hyperinsulinaemic group, while it did not affect the response in the normoinsulinaemic group; thus at the end of the treatment the two groups had the same insulin concentrations. Similarly, naltrexone abolished the difference between normoinsulinaemic and hyperinsulinaemic patients regarding androstenedione and 17-OHP response to ACTH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1994

Human immunodeficiency virus infection and hepatitis C pathology.

To investigate the possible influence of human immunodeficiency virus (HIV) infection on hepatitis C virus-related liver disease, liver morphology was evaluated in 160 HBsAg-negative patients with chronic hepatitis C, including 68 HIV-positive and 92 HIV-negative cases. No differences were detected in the severity of necro-inflammatory hepatic lesions between HIV-negative and HIV-positive patients when the CD4+ lymphocytes count exceeded 400 cells/mm3. In contrast, HIV-positive patients with CD4+ lymphocytes below 400 cells/mm3 showed a significantly lower grade of portal inflammation and piecemeal necrosis. These results suggest that liver lesions in hepatitis C may largely depend on immunomediated mechanisms.

Adult↗
PubMed1993

Single-dose safety and pharmacokinetics of a potential cognition-enhancing compound, CL 275,838, in healthy volunteers.

The pharmacokinetics and safety of CL 275,838, a potential cognition-enhancing compound, were studied after single escalating oral doses first in young healthy male volunteers and then in old (60-74 years) and very old (over 75 years) volunteers of both sexes. In all age groups absorption of CL 275,838 was rapid as assessed by the mean time to reach maximum plasma concentrations (Cmax) which averaged 1-2 hr, regardless of the dose administered. In young male volunteers both Cmax and area under the curve (AUC) increased proportionally with dose from 10 to 100 mg. Mean elimination half-lives (t1/2) of the parent compound (18-21 hr) and of its circulating metabolites II (20-22 hr) and IV (27-30 hr) were well comparable for the doses tested (50 and 100 mg). Age did not appreciably affect plasma Cmax of CL 275,838 or its two metabolites. Mean AUC and elimination half-life did not appreciably differ between old and very old subjects given 50 mg CL 275,838, with the limitations dictated by the small number of elderly subjects examined. Compared with younger volunteers receiving comparable doses, however, the elderly had higher mean plasma AUC of the unchanged compound and its two metabolites, although the parameter varied widely between subjects. The mean elimination t1/2 (+/- SD) was longer in the elderly (38.8 +/- 19.6, 50.5 +/- 24.5 and 41.7 +/- 12.1 hr, respectively, for the parent compound and its metabolites II and IV) than in the young subjects. The cause(s) of these variations and the possible clinical implications remain to be established.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗