Chronic HCV infection: epidemiological and clinical relevance.

Hepatitis C virus (HCV), first recognized as a cause of transfusion-associated acute and chronic hepatitis in 1989, plays a major role as a cause of chronic liver injury, with potential for neoplastic degeneration. It is mainly transmitted by the parenteral route. However, although with lower efficiency, it may be also transmitted by sexual intercourses and by the mother-to-child route. Epidemiological evidence shows that a wave of infection occurred in the 1945-65 period (baby boomers) in western countries. After acute infection, as many as 50-85% of the patients fail to clear the virus resulting in chronic liver infection and/or disease. It is estimated that, on a global scale, about 170 million people are chronically infected with HCV, leading to about 350.000 deaths yearly. Among western countries southern Europe, and particularly Italy, is among the most affected areas. The impact on the public health systems is noteworthy, with high number of hospitalizations due to chronic liver disease, cirrhosis or hepatocellular carcinoma. While waiting for a safe and effective vaccine to be made available, new promising direct-acting antiviral (DAA) drugs offer a better therapeutic scenario than in the past even for the poor responder genotypes 1 and 4, provided that effective screening and care is offered. However, the long and aspecific prodromic period before clinical symptoms develop is a major obstacle to early detection and treatment. Effective screening strategies may target at-risk groups or age specific groups, as recently recommended by the CDC.

Pilot dose-finding trial on interferon alpha in combination with ribavirin for the treatment of chronic hepatitis C in patients not responding to interferon alone.

BACKGROUND: Effectiveness of combination therapy with standard interferon alpha doses and ribavirin is far from being demonstrated in patients with hepatitis C non responders to interferon alpha monotherapy. Recent kinetic studies revealed that these doses may be suboptimal. AIMS: To find the criteria for optimisation of the interferon dose, to be used in combination with ribavirin in patients with hepatitis C non responders to interferon alpha monotherapy. PATIENTS: Sixty-three patients enrolled in a pilot controlled trial were treated for 6 months with ribavirin ([1000-1200 mg daily) and were randomised to concurrently receive interferon alpha 2b for 6 months at: 3 Million Units thrice weekly [group A (21 patients)], 5 MU thrice weekly [group B (21 patients)] and 5 million units daily [group C (21 patients)]. RESULTS: A sustained virological response was observed in: 1 patient from group A (5%), 2 patients from group B (9%) and 8 patients from group C (38%; p=0.02 vs group A; p=0.03 vs group B). Side-effects were not significantly different between the 3 groups. Multivariate analysis showed that infection by hepatitis C virus genotypes 2 or 3 and interferon alpha dosage of 5 million units daily were independent predictors of sustained response. CONCLUSIONS: These results suggest that higher interferon doses administered daily in combination with ribavirin could be more effective in those patients with hepatitis C who had not responded to interferon alone.

Liver fibrosis progression is related to CD4 cell depletion in patients coinfected with hepatitis C virus and human immunodeficiency virus.

A total of 204 patients with liver biopsy-proven hepatitis C virus (HCV) infection, 84 with and 120 without human immunodeficiency virus (HIV) coinfection, were studied, to evaluate variables possibly associated with the stage of liver fibrosis. All patients were injection drugs users, with a mean age of 32 years and an estimated duration of HCV infection of 12 years. Twenty-four patients (11%) had many fibrous septa with (5%) or without (6%) cirrhosis, 56 (27%) had few fibrous septa, and 124 (60%) had no fibrous septa. In all patients, an association was found between CD4 cell counts <500 cells/mm(3)and the presence of many fibrous septa (odds ratio, 3.2; P=.037), independent of HIV infection and other factors. These results suggest that HIV infection-induced CD4 depletion is independently associated with the severity of liver fibrosis in chronic HCV infection.

Mortality for liver disease in patients with HIV infection: a cohort study.

We undertook this study to assess the association between the various potential causes of liver disease in HIV-seropositive patients and mortality due to liver failure. Three hundred and eight in-hospital deaths were observed from 1987 to December 1995 in a prospectively followed cohort of 1894 HIV-seropositive patients. For each study subject, clinical data were evaluated to assess whether liver failure had substantially contributed to mortality. A case control study nested in the cohort was then performed, which compared demographic and clinical variables observed at enrollment and during follow-up between patients who died for liver disease as the main or concurrent cause of death (cases) and those who died as a result of illness related to AIDS or other causes (controls). Among 308 in-hospital deaths, liver failure was found the cause of death in 35 patients (12%); in 16 cases, it was the primary cause and in 19 cases it was concurrent. Multivariate analysis showed that in-hospital liver-disease-related mortality was independently associated with hepatitis B surface antigen reactivity (odds ratio [OR], 9; 95% confidence interval [CI], 3.8-21.7) and history of alcohol abuse (OR, 2.3; 95% CI, 1-5.2). Prevention and treatment of hepatitis B virus infection and alcohol intake are management priorities in HIV-seropositive patients.

Liver damage and kinetics of hepatitis C virus and human immunodeficiency virus replication during the early phases of combination antiretroviral treatment.

In order to assess the relationship between human immunodeficiency virus (HIV) RNA, hepatitis C virus (HCV) RNA, CD4, CD8, and liver enzymes during combination antiretroviral therapy, these parameters were measured in 12 HIV-HCV-coinfected patients (who were naive for antiretrovirals) on the day before and 3, 7, 14, 28, 56, and 84 days after initiating the following treatments: stavudine and lamivudine in all patients, indinavir in 6 patients, and nevirapine in 6 patients. HIV RNA declined rapidly, CD4 cells increased slowly, and CD8 cells and liver enzymes were stable. HCV RNA showed a transient significant increase at days 14 and 21 (7.33+/-0.16 [mean +/- SE] and 7.29+/-0.2 log copies/mL vs. 7+/-0.2 log copies/mL at baseline; P<.05). These changes were similar in both treatment groups. A 2-fold alanine aminotransferase increase was observed in 4 of 12 patients; 4 of 4 patients showed increased HCV RNA. The relationship between HCV RNA increase and HIV RNA decrease indicates virus-virus interference. An HCV RNA increase may cause significant liver damage only in a minority of patients.

Decrease of HCVRNA after three days of daily interferon treatment is predictive of the virological response at one month.

Early monitoring of HCVRNA during interferon treatment may allow clinicians to obtain important information that could help them to adopt therapeutic decisions in individual cases. The hepatitis C virus infection is highly dynamic and a daily high dose of IFN may induce a decline of viremia of 95+/-10% of baseline value after 24 to 48 hours of treatment. The importance of this early antiviral efficacy has not been understood. We have measured HCVRNA levels in 47 patients with chronic hepatitis C infection during interferon treatment to study HCVRNA kinetics and evaluate the predictive value of the early decay of viremia on the virological response after one month of treatment. Sixty percent of treated patients showed early virological response (EVR) and it was significantly associated with low HCVRNA levels and a genotype other than 1b. Finally, the absence of an 85% decline in HCVRNA levels after 3 days of treatment observed in 11 out of 45 patients (24%) was an absolute and very early predictor of the absence of EVR in the study population.

GH, IGFBP-1, and IGFBP-3 response to oral glucose tolerance test in perimenopausal women: no influence of body mass index.

OBJECTIVES: an increasing interest is being focused on the role of the somatotropic axis in the modulation of body weight and fat distribution, particularly in climacteric women. The influence of the glycometabolic state on the somatotropic axis in postmenopausal and in obese subjects has not been investigated. The aim of the present study is to evaluate whether menopause and body mass index (BMI) affect the response of growth hormone (GH), insulin-like growth factor-binding protein-1 (IGFBP-1) and -3 (IGFBP-3) to the oral glucose tolerance test (OGTT). METHODS: the study included 24 women, aged 45-55 years, categorized into 4 groups, premenopausal pre-obese (BMI = 28.5 +/- 0.8 Kg/m2) and normal body weight (BMI = 22.2 +/-1.1 Kg/m2), and postmenopausal pre-obese and normal body weight. All women underwent: (1) a biophysical evaluation with determination of waist/hip ratio; (2) an assessment of fat and lean tissue mass and body fat distribution by total body DEXA; and to (3) an OGTT. RESULTS: in response to OGTT plasma GH levels significantly decreased in all groups, but the relative decrease was more prominent in the lean subjects. A significant decrease of IGFBP-1 levels in response to OGTT was observed in all women, regardless of menopausal age and BMI, while IGFBP-3 levels did not significantly change in either group. CONCLUSIONS: in conclusion, the impact of both BMI and menopausal condition on GH, IGFBP-1, and -3 response to OGTT is limited to a blunted GH response in overweight women compared with normally-weighing ones. These findings appear to rule out the hypothesis that a common glycometabolic derangement may affect both the modifications of body weight and of the somatotropic axis observed in perimenopausal women.

Ultrasound evaluation of hepatic lymph nodes in patients with anti-hepatitis C virus antibody reactivity.

BACKGROUND: Portal lymphadenopathy is frequently found in inflammatory liver diseases. However, the mechanisms underlying portal lymphadenopathy are unknown. AIMS: To evaluate the prevalence of portal lymphadenopathy in patients with serum anti-hepatitis C Virus antibody reactivity and its relationship to clinical parameters. PATIENTS AND METHODS: The presence of portal lymphadenopathy was evaluated by upper abdominal Ultrasound by the same examiner in 114 patients with anti-hepatitis C Virus reactivity: 56 patients with normal liver enzyme activity and 58 randomly selected patients with increased liver enzyme activity undergoing liver biopsy. Laboratory tests were then performed in all patients the following day. RESULTS: Portal lymph nodes were found in a significantly higher percentage of patients with increased liver enzymes (74%) than in patients with persistently normal liver enzymes (29%: p < 0.01). Aminotransferases, gamma glutamyl transpeptidase levels and the percentage of patients with HCVRNA in serum and histological scores for piecemeal and lobular necrosis were significantly higher in patients showing hepatic lymph nodes. Multivariate analysis showed that only alanine aminotransferase and lobular necrosis were independently related to the presence of hepatic lymph nodes. A significant correlation was found between lymph node size, aminotransferase activity and lobular necrosis. CONCLUSION: Ultrasound-proven portal lymph node enlargement is an indirect sign of hepatocellular damage in patients with positive serum anti-hepatitis C Virus antibodies.

Endocrine, neuroendocrine and behavioral effects of oral dehydroepiandrosterone sulfate supplementation in postmenopausal women.

Aging in women and men is characterized by a progressive decline of circulating dehydroepiandrosterone (DHEA) levels and its sulfate ester (DHEAS). The improvement of wellbeing described in postmenopausal women treated with DHEA suggests that this steroid may exert specific actions on the central nervous system (CNS). The postmenopausal period is associated with several neuroendocrine modifications. The decrease of circulating levels of beta-endorphin is considered a hormonal marker of those changes. The aim of the present study was to investigate neuroendocrine and behavioral effects of three months of DHEAS supplementation in postmenopausal women. Postmenopausal women (n = 22) were divided in three groups: the first group was treated with oral DHEAS (n = 8) (50 mg/day), the second treated with the same dose of oral DHEAS + transdermal estradiol (n = 8) (DHEAS) 50 mg/day, estradiol 50 micrograms/patch) and the third with transdermal estradiol alone (n = 6) (50 micrograms/day). Before and after 1, 2 and 3 months of therapy, the following circulating steroid and protein hormone levels were evaluated: DHEA, DHEAS, androstenedione, testosterone, estrone, estradiol, 17-hydroxyprogesterone, sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH), luteinizing hormone (LH), beta-endorphin, growth hormone (GH) and cortisol, and a Kupperman score was performed. Before and after treatments, plasma beta-endorphin levels were evaluated in response to three neuroendocrine tests: (a) clonidine, an alpha 2-presynaptic adrenergic agonist (1.25 mg i.v.) (b) naloxone, an opioid receptor antagonist (4 mg i.v.) and (c) fluoxetine, a serotonin selective reuptake inhibitor (30 mg p.o.). In both groups of women treated with DHEAS, mean basal serum DHEA, DHEAS, androstenedione, and testosterone levels significantly increased after treatment, while no changes were shown in the group receiving estradiol alone. Serum estradiol, estrone, GH and plasma beta-endorphin levels significantly increased progressively for the three months of treatment, with higher levels for estrone and estradiol in subjects receiving estradiol alone or plus DHEAS. Serum SHBG, cortisol, and 17-hydroxyprogesterone did not show significant variations under any treatment. Serum LH and FSH levels showed a significant decrease in groups treated with estradiol alone or plus DHEAS at the second and third months. The Kupperman score showed that all treatments were associated with similar and progressive improvement. Before therapy clonidine, naloxone and fluoxetine stimuli failed to modify circulating beta-endorphin levels. After each of the treatments, the beta-endorphin response was completely restored and was similar, independent of the kind of therapy. Restoration of the beta-endorphin response to specific stimuli suggests that DHEAS and/or its active metabolites modulates the neuroendocrine control of pituitary beta-endorphin secretion, which may support the therapeutic efficacy of the DHEAS on behavioral symptoms.

Menopause and the central nervous system: intervention options.

The central nervous system is an important target for sex steroid hormones. During the climateric period the rapid decline of gonadal steroids causes neuroendocrine changes in different areas of the brain. The failure of gonadal hormone production brings specific symptoms due to the central nervous system derangement. At the hypotalamic level estrogen withdrawal gives rise to vasomotor symptoms, eating behavior disorders and altered blood pressure control. Psychological disturbances such as depression, anxiety, irritability and mood fluctuation are related to estrogen-induced changes in the lymbic system. The hypothesis of specific neuroanatomical and neurophysiological effects of estrogen on the brain may also explain the correlation between estrogen deficiency and cognitive disturbances such as Alzheimer's type dementia (AD). The increasing interest in the influence of sex steroids on brain function has focused attention on hormonal replacement therapy. Clinical and epidemiological studies have demonstrated that estrogen therapy exerts a positive effect on vasomotor instability and improves psychological disturbances. The positive effects of estrogen on mood are probably related to its stimulatory action on adrenergic and serotoninergic tone. Estrogen may influence the cognitive function through different biological actions. Estrogen administration increases total cerebral and cerebellar blood flow, cerebral glucose administration and improves cholinergic tone, a key neurotransmitter in learning and memory. The evidence suggests that hormone replacement therapy may reduce the relative risk of developing AD. Progestagens and androgen may also have a role in the control of mood disorders. At present, few data are available regarding the influence that selective estrogen receptor modulators, a new class of compounds, can exert on the brain.

High prevalence of peripheral neuropathy in hepatitis C virus infected patients with symptomatic and asymptomatic cryoglobulinaemia.

BACKGROUND: Fifty per cent of patients with chronic hepatitis C, show detectable cryoglobulinaemia, even though most of them do not show cryoglobulinaemia related symptoms. Peripheral neuropathy is present in most of the patients with symptomatic cryoglobulinaemia, where it may be the first clinical manifestation. The prevalence of peripheral neuropathy in patients with hepatitis C and cryoglobulinaemia is unknown. AIMS: To assess the prevalence of peripheral neuropathy in HCV infected patients with symptomatic or asymptomatic detectable cryoglobulinaemia. PATIENTS AND METHODS: Eighty-nine patients with HCV infection and detectable cryoglobulinaemia underwent electrophysiological studies. RESULTS: Electrophysiological evidence of peripheral neuropathy was found in 37% and was significantly associated with: the presence of cryoglobulinaemia syndrome, older age, higher rheumatoid factor reactivity and immunoglobulin M levels and reduced complement C4 activity. However, electrophysiological evidence of peripheral neuropathy was unrelated to cryocrit levels and type of cryoglobulinaemia and was found in 23/68 patients without any symptoms of cryoglobulinaemia other than pain and paresthesia. CONCLUSIONS: These findings suggest that peripheral neuropathy is frequent in patients with hepatitis C and detectable cryoglobulins. Neuropathy was found to be present in 1/3 of patients without other cryoglobulinaemia-related symptoms, thus a direct or indirect role of HCV, independent of cryoglobulinaemia, in the pathogenesis of nerve damage cannot be ruled out.

Treatment of chronic hepatitis D with interferon alpha-2b in patients with human immunodeficiency virus infection.

BACKGROUND/AIMS: Hepatitis delta virus (HDV) coinfection is frequent in patients infected with human immunodeficiency virus (HIV), and it may cause death independently of the development of full-blown AIDS. In order to evaluate the efficacy and tolerability of interferon alpha in the treatment of hepatitis delta in HIV-infected patients, and to compare them with those observed in anti-HIV-seronegative patients, we carried out an open uncontrolled trial on 21 HIV-uninfected and 16 HIV-infected patients without severe immunodeficiency. METHODS: All patients were treated with recombinant interferon alpha 2b (IFN) at doses of 10 million units thrice weekly for 6 months, and 6 million units thrice weekly for an additional 6 months. Patients showing alanine transaminase activity values persistently reduced by at least 50% from basal values received an additional 1-year course of 3 million units thrice weekly. RESULTS: Alanine aminotransferase normalization was observed in 19% of HIV-infected and 14% of HIV-uninfected subjects during the first year; in 12% of HIV-infected and in 9% of HIV-uninfected patients during the second year. Twenty-five percent of HIV-infected and 14% of HIV-uninfected patients stopped IFN because of poor compliance or side effects. Two years after stopping interferon treatment, one anti-HIV-seropositive and two anti-HIV-seronegative patients showed complete persistent biochemical, virological and histologic remission. CONCLUSIONS: Long-term efficacy and toxicity of IFN treatment seem not to be different in HIV-infected and -uninfected patients with delta hepatitis; given the overall poor rate of long-term response, IFN treatment could be considered only in immunocompetent HIV-HDV-coinfected patients, strictly selected because of rapidly evolving liver disease.

Somatotropic axis and body weight in pre-menopausal and post-menopausal women: evidence for a neuroendocrine derangement, in absence of changes of insulin-like growth factor binding protein concentrations.

The altered function of the somatotropic axis observed in perimenopause may underlie the changes in body weight and fat distribution. The aim of the present study was to evaluate, in pre-menopausal and post-menopausal women with body mass index (BMI) > or = or <25, the basal plasma levels of growth hormone (GH), insulin-like growth factor (IGF)-I and -II, IGF binding protein (IGFBP)-1 and -3, and the response of GH and IGFBP-1 and -3 to GH releasing hormone (GHRH) and GHRH plus arginine tests. GH and IGF-I basal concentrations were significantly higher in pre-menopausal than in post-menopausal women, while IGF-II, IGFBP-1 and IGFBP-3 concentrations did not vary significantly. IGFBP-1, but not IGFBP-3, concentrations were higher in lean than in obese patients. Insulin concentrations were significantly higher in obese patients, while no differences were observed between pre-menopausal and post-menopausal women. In all subjects, GH concentrations increased significantly during GHRH test; pre-menopausal and lean women showed a higher response compared to post-menopausal and obese women. The GHRH plus arginine test stimulated GH response in all women, irrespective of age and BMI. IGFBP-1 and -3 concentrations did not vary in response to GHRH or GHRH plus arginine tests. The somatotropic axis undergoes modifications in post-menopausal women, apparently not involving IGFBP-1 and -3. Arginine infusion restores the response of GH to GHRH, in both post-menopausal and obese subjects. A somatostatinergic hyperactivity at the climateric period may underlie the changes both in body weight and somatotropic axis.

Beta-endorphin response to oral glucose tolerance test in obese and non-obese pre- and postmenopausal women.

Beta-endorphin (beta-EP) is a neuropeptide involved in several brain functions, regulating the reproductive axis and behavioral changes. Estrogens play a modulatory role on circulating levels of beta-EP in women. Previous clinical studies have demonstrated high plasma beta-EP levels in obese subjects and increased beta-EP release after an oral glucose tolerance test (OGTT) in normal or obese women. The aim of the present study was to evaluate plasma beta-endorphin levels in response to an OGTT in pre- and postmenopausal obese and non-obese women, in order to investigate if the decrease in gonadal steroid levels at menopause could modify in a different manner the control of beta-endorphin release in response to glucose administration. A group of 24 normal women (age range 45-55 years) were included in the study. The patients were subdivided in four groups of six subjects each: group A, premenopausal women with body mass index (BMI) < 25 (control); group B, premenopausal women with BMI > 25 (obese); group C, post-menopausal women with BMI < 25 (control); group D, postmenopausal women with BMI > 25 (obese). All women were studied between 8.30 and 9.00 am, after overnight fasting, and underwent an OGTT. In obese premenopausal women, basal plasma beta-EP levels were significantly higher than in non-obese women (p < 0.01). In postmenopausal women, regardless of body weight, low basal plasma beta-EP levels were found. A significant increase in plasma beta-EP levels, at 30 and 60 minutes after oral glucose ingestion, was shown in control premenopausal women. No significant modifications to OGTT were shown in plasma beta-EP levels in the other three groups of women. In conclusion, while in premenopausal women the response of plasma beta-EP levels to OGTT is maintained, in postmenopause there is a lack of response to OGTT. This suggests that beta-EP release is dependent upon gonadal steroids, while it is only in part influenced by body weight.

Evaluation of the in vitro activity of seven selected antimicrobial agents to be used for the isolation of human intestinal spirochaetes.

This study aimed at making a comparative assessment of the growth of pure cultures of Human Intestinal Spirochaetes (HIS) in a control medium without antibiotics and in media including antibiotics (spectinomycin, rifampin, colistin, polymyxin B, amphotericin B, vancomycin, spiramycin) whose use had been indicated in the literature in connection with the isolation of HIS or animal intestinal spirochaetes. All the strains of HIS tested grew in media to which appropriate concentrations of those drugs had been added giving a final number of CFU/ml +/- 10 times the number of CFU/ml observed in the control medium. These results indicate that a selective medium to be used for the isolation of HIS may include appropriate concentrations of one or more of the following antibiotics: spectinomycin (100-1,000 micrograms/ml), rifampin (10-30 micrograms/ml), vancomycin (6.25 micrograms/ml), colistin (6.25 micrograms/ml), polymyxin B (5 micrograms/ml), spiramycin (1-10 micrograms/ml) and amphotericin B (0.05-35 micrograms/ml).

Hormonal replacement therapy affects calcitonin gene-related peptide and atrial natriuretic peptide secretion in postmenopausal women.

OBJECTIVE: Menopause is associated with critical changes in the cardiovascular system, and the possible effect of hormonal replacement therapy (HRT) on these changes is under investigation. The aim of our study was to evaluate in postmenopausal women the effects of HRT and clonidine on the response of plasma calcitonin gene-related peptide (CGRP) and plasma atrial natriuretic peptide (ANP) to the upright posture test and the saline infusion test respectively. METHODS: CGRP and ANP levels were measured with specific radioimmunological assays and expressed in pmol/l (means +/- S.E.M). DESIGN: Postmenopausal women (age 46-53 years) (n = 18) were studied before and after 3 months of HRT (n = 13) or clonidine treatment (n = 5). RESULTS: After HRT or clonidine treatment plasma CGRP levels (14.9 +/- 1.6 and 15.9 +/- 3.8 pmol/l) were significantly higher than before (9.8 +/- 0.6 and 10.5 +/- 1.6 pmol/l) (P < 0.01). The assumption of upright posture caused no change in plasma CGRP levels before treatment, while after HRT, but not after clonidine treatment, an increase in plasma CGRP levels was observed (P < 0.01 at 5 and 20 min). Basal plasma ANP levels significantly decreased after both HRT and clonidine treatment (P < 0.01). In untreated women the saline infusion test did not induce any change in plasma ANP levels; a significant response to the test was restored after HRT but not after clonidine treatment (P < 0.01 at 90 and 120 min). CONCLUSIONS: The results show that some of the adaptive responses modified by menopausal changes are restored by HRT but not clonidine treatment, suggesting a modulatory role for sex steroid hormones in cardiovascular function and salt and water balance.

Cooperative haemolysis between weakly beta-haemolytic human intestinal spirochaetes and Staphylococcus aureus.

Weakly beta-haemolytic spirochaetes related to human intestinal spirochaetosis produced a cooperative haemolysis together with S. aureus consisting of an enhanced haemolysis in the zone of the spirochaetal growth which was overlapped by the zone of activity of the staphylococcal beta-haemolysin. The cooperative haemolysis was observed in sheep blood agar media when the concentration of spirochaetes ranged from 1.5 x 10(3) to 1.5 x 10(8) CFU/ml and the concentration of S. aureus from 4 x 10(3) to 4 x 10(8) CFU/ml. With the increase of the distance between the streaks of the spirochaetes and S. aureus from 3 to 10 mm, the period of incubation needed to observe the cooperative haemolysis also increased from 18 to 72 hours. When the spirochaetes and S. aureus were streaked at the same time and when S. aureus was streaked earlier than the spirochaetes, the phenomenon was observed after anaerobic incubation of the plates for 24-72 hours but not after incubation in 10% CO2 under atmospheric conditions. A cooperative haemolysis was also observed between S. aureus and spirochaetes related to the porcine and avian intestinal spirochaetosis and the spirochaete causing swine dysentery when the same experimental conditions were used which allowed an observation of the phenomenon involving human spirochaetes and S. aureus.

Effects of hormonal replacement therapy on plasma sex hormone-binding globulin, androgen and insulin-like growth factor-1 levels in postmenopausal women.

Plasma sex hormone-binding globulin (SHBG) levels are important in the regulation of plasma free and albumin-bound androgens and estrogens. In postmenopausal women associated to the decrease of estrogen production, a decrease of plasma SHBG levels occurs. Hormone replacement therapy (HRT) in postmenopausal women modulates plasma SHBG levels, in relationship with the different regimens and routes of administration. The present study aimed to compare the effect of different HRT on plasma SHBG levels in relationship with the changes of plasma androgen [dehydroepiandrosterone sulphate (DHEAS), testosterone (T), androstenedione (A)] and insulin-like growth factor-1 (IGF-1) levels. In a retrospective study 443 postmenopausal women were studied and divided into 2 groups. The group 1 (n = 170) was subdivided in 4 groups of women as follows: A) treated with transdermal 17-beta estradiol + medroxyprogesterone acetate, B) treated with oral conjugated estrogens, C) treated with sequential HRT (estradiol valerate (EV) + norgestrel), and D) treated with a combined HRT (micronized estradiol (E2) + noretisterone acetate). Women of group 2 (n = 273) did not receive HRT and served as controls. All groups of women treated with different HRT showed plasma estradiol levels significantly higher than controls (p < 0.01), showing the highest values in women treated with oral HRT. Plasma SHBG levels were not significantly different between patients treated with transdermal 17-beta estradiol + medroxyprogesterone acetate and controls. On the other hand, all the groups of patients treated with oral conjugated estrogen with or without progestagens showed plasma SHBG levels significantly higher than controls (p < 0.01). Plasma SHBG levels were higher in the group treated with estrogen alone than in groups of women treated with sequential or combined HRT. Plasma DHEAS, T and A levels in patients treated with different HRT regimens were in the same range of levels as control women. Plasma IGF-1 levels were not significantly affected by the various HRT regimens and remained in the same range as controls. In conclusion, plasma SHBG levels increase following oral HRT while are not affected by transdermal HRT. Plasma IGF-1 and androgen levels are not influenced from oral or transdermal HRT.

Effects of a new estrogen/progestin combination in the treatment of postmenopausal syndrome.

Postmenopausal women were randomly given either oral calcium (500 mg/day, control group, n = 12) or a combination of estradiol valerate (EV, 2 mg/day for 21 days) with cyproterone acetate (CPA, 1 mg/day in the last 10 days of the treatment cycle, n = 19). EV+CPA reduced (P < 0.01) postmenopausal complaints, inducing regular withdrawal bleeds, with no hysteroscopic or hystologic evidence of endometrial hyperstimulation after 12 months of treatment. In the control group, spine bone mineral density (BMD) and the total body bone mineral (TBBM) decreased (P < 0.01), whereas urinary hydroxyproline excretion (OH-P/Cr), plasma bone Gla Protein (BGP) and lipid profile did not show any significant modification throughout the study. In the EV+CPA group, urinary OHP/Cr and plasma BGP levels decreased (P < 0.01) after 6 and 12 months, whereas both BMD and TBBM showed a small but significant (P < 0.01) increase. In this group, LDL cholesterol significantly (P < 0.01) decreased and HDL levels significantly (P < 0.01) increased after 6 and 12 months. In conclusion, the EV+CPA combination is effective in relieving menopausal symptoms, produces a good cycle control and a favourable lipid profile, preventing postmenopausal bone resorption.

Ultrasonographic bone characteristics during normal pregnancy: longitudinal and cross-sectional evaluation.

OBJECTIVE: We evaluated the pattern of bone density during pregnancy by radiation-free ultrasonographic densitometry. STUDY DESIGN: In a longitudinal study we measured bone mineral density in a group of 10 normal primiparous women, from the fourteenth to the thirty-eighth weeks of pregnancy. In a cross-sectional study bone mineral density was determined in a group of 85 normal primiparous women, in different weeks of pregnancy. RESULTS: In the longitudinal study ultrasonographic bone density was stable in the first part of pregnancy, whereas a significant (p < 0.05) decrease was evidenced during the third trimester. A negative correlation between bone density and weeks of pregnancy (p < 0.0001) was evidenced in the cross-sectional study. CONCLUSION: During physiologic pregnancy the calcium mobilization from the maternal bone stores to accomplish the fetal needs can cause a significant decrease in maternal bone density in the last trimester of gestation.