Electrophysiological features in acromegaly: re-thinking the arrhythmic risk?

BACKGROUND: Acromegaly is disease associated with a specific cardiomyopathy. Hitherto, it has been widely understood that acromegaly carries an increased risk of arrhythmia. PURPOSE: In this review we show that evidences are limited to a small number of case-control studies that reported increased rates of premature ventricular beats (PVB) but no more significant arrhythmia. In contrast, there are several studies that have reported impaired preclinical markers of arrhythmia, including reduced heart rate variability, increased late potentials, QT interval dispersion, impaired heart rate recovery after physical exercise and left ventricular dysynchrony. Whilst these markers are associated with an adverse cardiovascular prognosis in the general population, they do not have a high independent positive predictive accuracy for arrhythmia. In acromegaly, case reports have described sudden cardiac death, ventricular tachyarrhythmia and advanced atrio-ventricular block that required implantation of a cardio-defibrillator or permanent pacemaker. Treatment with somatostatin analogues can reduce cardiac dysrhythmia in some cases by reducing heart rate, PVBs and QT interval. Pegvisomant reduces mean heart rate. Pasireotide is associated with QT prolongation. In the absence of good quality data on risk of arrhythmia in acromegaly, the majority of position statements and guidelines suggest routine 12-lead electrocardiography (ECG) and transthoracic echocardiography (TTE) in every patient at diagnosis and then follow up dependent on initial findings.

Acromegaly and ultrasound: how, when and why?

BACKGROUND: Acromegaly is a rare disease caused by an excess of growth hormone and insulin-like growth factor 1. It is usually diagnosed because of typical signs such as macroglossia, acral enlargement, jaw prognathism and malocclusion. Systemic complications are a major cause of morbidity and mortality in acromegaly, and many patients remain undiagnosed for several years. Increased ultrasound (US) application in the general population, and including among acromegaly patients, has revealed many suggestive features which, taken together with clinical suspicion, could induce suspicion of this disease. PURPOSE: This review describes main US features in acromegaly. Echocardiography shows a typical cardiomyopathy, characterized by left ventricular hypertrophy, diastolic and systolic dysfunction, aortic and mitral regurgitation, and increased aortic root diameters. US preclinical markers of atherosclerosis, such as intima media thickness (IMT), seem also to be impaired. Visceromegaly and increased organ stiffness are other features of acromegaly, including enlarged prostate, kidneys, liver, and thyroid. In addition, other US findings are: renal cysts, micronephrolithiasis, impairment of renal haemodynamic parameters, gallstones and gallbladder polyps, hepatic steatosis, thyroid nodules, multinodular goiter, and polycystic ovaries. Musculoskeletal US findings are increased cartilage thickness, impaired density and elasticity of bones, nerve enlargement, carpal and cubital tunnel syndrome, and trigger finger. CONCLUSIONS: Acromegaly patients frequently present systemic complications and a diagnostic delay. US features of acromegaly are not specific, but could potentially have a key role in early detection of the disease in the presence of typical clinical features.

Ovarian 25OH-vitamin D production in young women affected by polycystic ovary syndrome.

INTRODUCTION: Vitamin D is involved in the regulatory mechanisms of ovarian function and is frequently low in PCOS patients. Since obesity and hyperinsulinemic state negatively influenced vitamin D levels, therefore, we evaluated the production of vitamin D at the ovarian level only in lean and normoinsulinemic PCOS subjects. Basal, GnRH analogue-induced ovarian production of 25OH-vitamin D (VitD) and a direct sampling at ovarian vein level were investigated. METHODS: Basal and GnRH analogue-induced hormone levels were evaluated at peripheral level in 45 subjects, aged 18-39 years, and in 22 healthy women with age- and BMI-matched as controls. In 12 PCOS patients, undergoing laparoscopy, a venous sampling at both peripheral and ovarian level was further done. All subjects presented low VitD levels, appropriate to the season and with no difference between PCOS and control subjects. RESULTS: GnRH analogue significantly stimulated plasma LH, FSH, 17-OHP and estradiol secretion (p from < 0.05 to < 0.001 vs basal levels), whereas no effect was observed on both serum AMH and VitD concentrations in all groups. A significant difference (p < 0.006), between peripheral and ovarian veins, was observed in both AMH and estradiol levels in PCOS subjects, while no gradient of VitD was detected. CONCLUSIONS: All patients presented with low VitD levels. The absence of any VitD variation, both at basal and after GnRH analogue administration, or at peripheral-ovarian vein gradient, suggests no pituitary-ovarian axis involvement in VitD production or its direct ovarian production in lean and normoinsulinemic PCOS subjects.

Guidelines versus real life practice: the case of colonoscopy in acromegaly.

PURPOSE: The aim of this study is to investigate guideline application and colonoscopy findings in real-life practice in acromegaly. METHODS: We conducted a retrospective observational non-interventional and cross-sectional analysis on 146 patients with acromegaly (ACRO) referred to our clinic. We evaluated colonoscopy data, focusing on the correlation between colonoscopy findings and hormonal/metabolic values. RESULTS: The total number of colonoscopies performed in ACRO patients increased from 6 in the period 1990-1994 to 57 in the period 2010-2014. Colonoscopy procedures were performed according to guidelines in 25% of ACRO patients at diagnosis, 51% at follow-up and 11% globally (both at diagnosis and follow-up). Among the 146 ACRO patients, 68% were subjected to at least one colonoscopy and in 32% of the cases a polyp was detected during the procedure. The presence of polyps was significantly associated with mean levels of growth hormone (GH), insulin-like growth factor 1 (IGF-1), fasting glucose and insulin levels (p < 0.05). Polyps were detected in 48% of untreated patients and in 26% of patients under treatment for acromegaly (p = 0.04). The general risk of polyps and adenomatous polyps in ACRO patients was higher compared to the control population of Veneto Region, Italy (odds ratio 1.33 and 1.16, respectively). No cancerous polyps were detected in our analysis. CONCLUSION: In real-life practice, adherence to ACRO colonoscopy clinical guidelines was lower than expected. Among patients who underwent colonoscopy, the prevalence of colon polyps was higher for ACRO patients, suggesting the need for new strategies to ensure adherence to colonoscopy guidelines.

A contribution to adequate use of freshwater sponges as a proxy in paleoenvironmental studies.

This paper provides a comprehensive review of the environments where freshwater sponges occur and evaluates the use of sponge spicules as a proxy in paleoenvironmental studies in the Neotropical region. The paper aims to: I) review the information about the ecology of inland sponges to facilitate the use of spicules as a paleoenvironmental tool; and II) identify possible incongruities in the use of this information in paleoenvironmental reconstructions that have been conducted in Neotropical regions. The study compiled data on 77 sponge species, specialist or generalist that occur under certain environmental conditions, such as: substrate type for growth, hydrodynamic types, as well as salinity and acidity concentrations. In addition, it provides a comparison of the paleoenvironmental conditions applied to reconstruction studies that have been carried out within this biogeographic region, highlighting incongruities regarding the current ecology of the sponges.

Venous outflow as a criterion of impairment of cerebral vascular reserve.

AIM: The purpose of this work is to evaluate if the asymmetry of venous outflow between the two hemispheres is a reliable criterion of impairment of the cerebral vascular reserve among symptomatic patients harbouring a spontaneous atherosclerotic occlusion of internal carotid artery. METHODS: From January 1995 to December 2007, 7 symptomatic patients, affected from occlusion of internal carotid artery, were submitted to a low-flow by-pass between the superficial temporal artery and the middle cerebral artery owing to the presence of an impairment of cerebral vascular reserve diagnosed by TC-Doppler, SPECT or perfusion-CT with acetazolamide challenge. Conventional angiography was always performed. Angiographic studies of these patients were reviewed in order to find out the presence of asymmetry of the venous outflow. In the same period 35 patients harbouring an occlusion of the carotid artery in the neck and a normal cerebral reserve underwent cerebral angiography in our departments in Monza. Angiographic studies, of this latter group of patients, were also retrospectively analyzed with the same purpose. RESULTS: All patients, with a poor cerebral reserve, showed an asymmetry of venous outflow >3 s omolateral at the carotid occlusion. Patients, with a normal cerebral reserve, showed an asymmetry of venous outflow <2 s. CONCLUSIONS: Asymmetry of venous outflow were correlated to an impaired cerebral reserve also in chronic conditions as atherosclerotic spontaneous occlusion of internal carotid artery. Our data are a further support to the reliability of this criterion in case of therapeutic sacrifice of internal carotid artery.

Sleep disorders and cognitive dysfunction in acromegaly.

PURPOSE: In the general population, sleep disorders are associated with an increased risk of cognitive impairment. The prevalence of sleep disorders, such as sleep apnea, in acromegalic patients is higher than in the general population, and they may have additional risk of cognitive impairment due to acromegaly treatment and comorbidities. We aim to study the relationship between sleep disturbances and cognitive dysfunction in a group of acromegalic patients. METHODS: We studied 67 consecutive acromegalic patients. We performed a neurocognitive assessment and patients completed the Acromegaly Quality of Life Questionnaire (AcroQoL), Epworth Sleepiness Scale, and Pittsburgh Sleep Quality Index. RESULTS: Of the 67 acromegaly patients in the study, 38.8% were male and median age at the neurological examination was 56 (IQR 48, 65). Approximately 6-10% of patients had impaired cognitive assessment, depending on the test. In linear regression models adjusted for age, sex, BMI, disease duration, and disease activity, poorer sleep quality was associated with lower global cognitive z-score (B = -0.03, 95% CI -0.06, -0.002). Daytime somnolence was associated with poorer physical AcroQoL sub-score (B = -0.04, 95% CI -0.08, -0.002). Sleep quality was associated with poorer overall AcroQoL (B = -0.03, 95% CI -0.05, -0.006), physical AcroQoL (B = -0.04, 95% CI -0.07, -0.005), psychological AcroQoL (B = -0.02, 95% CI -0.04, -0.001), and social AcroQoL (B = -0.02, 95% CI -0.04, -0.0009). CONCLUSIONS: In acromegaly patients, we found robust evidence that poor sleep quality is associated with poorer quality of life, and some evidence that it is associated with poorer cognitive function.

Relevance of DNA binding to the mechanism of anti-herpesvirus activity of benzhydrazone.

Benzhydrazone (1H-benz(f)indene-1,3(2H)-dione bis (amidino-hydrazone) (BH) is a synthetic compound with selective anti-herpesvirus activity. Its selectivity seems to stem from the inhibition of viral protein glycosylation and several hypotheses have been formulated to explain such an effect. Data presented here demonstrate that DNA binding is a prominent feature of BH. Interaction is taking place with a relatively high affinity constant and is more efficient for GC-rich viral sequences. Experiments with the cloned DNA fragments from a BH-resistant virus strain indicate that BH-DNA complex formation is drastically reduced as compared to BH-sensitive virus. The occurrence of the resistant phenotype in HEp-2 cells but not in Vero cells could be explained by differences in BH cytotoxicity. Changes in drug uptake and accumulation by cells following infection, in addition to GC preference, may also account for the degree of antiviral selectivity shown by BH.

Substrate utilization during exercise with glucose and glucose plus fructose ingestion in boys ages 10--14 yr.

We measured substrate utilization during exercise performed with water (W), exogenous glucose (G), and exogenous fructose plus glucose (FG) ingestion in boys age 10-14 yr. Subjects (n = 12) cycled for 90 min at 55% maximal O(2) uptake while ingesting either W (25 ml/kg), 6% G (1.5 g/kg), or 3% F plus 3% G (1.5 g/kg). Fat oxidation increased during exercise in all trials but was higher in the W (0.28 +/- 0.023 g/min) than in the G (0.24 +/- 0.023 g/min) and FG (0.25 +/- 0.029 g/min) trials (P = 0.04). Conversely, total carbohydrate (CHO) oxidation decreased in all trials and was lower in the W (0.63 +/- 0.05 g/min) than in the G (0.78 +/- 0.051 g/min) and FG (0.74 +/- 0.056 g/min) trials (P = 0.009). Exogenous CHO oxidation, as determined by expired (13)CO(2), reached a maximum of 0.36 +/- 0.032 and 0.31 +/- 0.030 g/min at 90 min in G and FG, respectively (P = 0.04). Plasma insulin levels decrease during exercise in all trials but were twofold higher in G than in W and FG (P < 0.001). Plasma glucose levels decreased transiently after the onset of exercise in all trials and then returned to preexercise values in the W and FG (approximately 4.5 mmol/l) trials but were elevated by approximately 1.0 mmol/l in the G trial (P < 0.001). Plasma lactate concentrations decreased after the onset of exercise in all trials but were lower by approximately 0.5 mmol/l in W than in G and FG (P = 0.02). Thus, in boys exercising at a moderate intensity, the oxidation rate of G plus F is slightly less than G alone, but both spare endogenous CHO and fat to a similar extent. In addition, compared with flavored W, the ingestion of G alone and of G plus F delays exhaustion at 90% peak power by approximately 25 and 40%, respectively, after 90 min of moderate-intensity exercise.

Arterial graft reconstruction in an aneurysm of the middle cerebral artery.

A case of a large aneurysm of the middle cerebral artery that was treated by resection of the aneurysm sac and reconstruction of the vessel is presented. The middle cerebral artery was reconstructed using a graft from the superficial temporal artery (STA). Cerebral vessel reconstructions are usually carried out with veins as grafts. This paper shows the possibility of using the STA as a graft. When a vessel reconstruction is contemplated, the skin flap should be planned in order to save the STA.

MRI indirect stereotactic targeting for deep brain stimulation in Parkinson's disease.

AIM: Stereotactic localisation of brain targets for functional neurosurgery might be obtained with different neuroimaging sources. Magnetic resonance (MR) might be of particular interest for its high definition of the various brain structures; unfortunately, magnetic field distortion and inaccuracy in imaging reproduction constrain the use of MRI in stereotactic surgery. METHODS: We present an experimental work devoted to the utilization of MRI in the targeting of the subthalamic nucleus for deep brain stimulation (DBS) in Parkinsonian patients. RESULTS: Experimental data were obtained after PVC phantom and fixed human brain measurements of the stereotactic coordinates of specific basal ganglia structures. Intrinsic and external sources of error and imaging distortion have been carefully corrected. Afterwards, 36 patients, operated for DBS in the subthalamus for Parkinson's disease (PD), have been investigated. MRI targeting proved to be clinically successful; comparing anatomical and neurophysiological findings, MRI targeting scattered from the neurophysiological targeting in a minority of cases. CONCLUSION: MRI targeting proved to be reliable for functional stereotactic surgery, pending careful and adequate quality control of the distortion and of the sources of error.

Prevalence of type 2 diabetes mellitus in Brazilian liver transplant candidates: negative association with HCV status.

Recently, an epidemiological association between hepatitis C virus (HCV) infection and type 2 diabetes mellitus (DM) has been reported in several studies, although many of them did not consider known risk factors in the pathogenesis of type 2 DM. The aim of this study was to assess the prevalence of type 2 DM among Brazilian HCV (+) and HCV (-) liver transplant candidates, analyzing known confounding factors for the development of type 2 DM. We conducted a cross-sectional study to evaluate the prevalence of type 2 DM among 106 liver transplant adult candidates, comparing 36 HCV (+) cirrhotic patients with 70 HCV (-) patients who developed cirrhosis from other causes. Type 2 DM was diagnosed after two consecutive fasting glucose values > or =126 mg/dL. The age, sex, and race distribution, severity of liver disease (Child-Pugh score), and family history of DM were similar in both groups, but the mean body mass index (BMI) was higher in the HCV (-) subjects (26.81 +/- 5.29 vs 24.0 +/- 4.71, P < .01) Most of the patients were Caucasians (70.75%). Type 2 DM was detected in 36.11% of HCV (+) group and in 25.71% of the HCV (-) (P = .27). A multivariate analysis revealed that family history of DM was the only significant independent predictor for DM (odds ratio = 2.55, 95% CI = 1.03 to 6.31, P = .04). In conclusion, our study did not show an association between HCV infection and Type 2 DM in Brazilian liver transplant candidates. It confirmed that the family history of DM was a determinant factor for the development of type 2 DM.

Prevalence of new-onset diabetes mellitus in Brazilian liver transplant recipients: association with HCV infection.

New-onset diabetes melittus (NODM) is a serious complication following transplantation. Recent studies suggest an association between hepatitis C virus (HCV) infection and DM both in nontransplant settings as well as after liver transplantation (LT). The aim of this study was to assess the prevalence of NODM among Brazilian LT recipients, analyzing possible risk factors including HCV infection. We conducted a cross-sectional study to evaluate the prevalence of NODM in 82 LT recipients with a posttransplant follow-up > or =1 year including 29 HCV-positive patients and 53 with other causes for liver disease. Patients were considered to meet the criteria for DM if they had two consecutive fasting glucose values > or =126 mg/dL or if they were taking insulin or oral hypoglycemic agents at the time of the study. The overall prevalence of NODM was 18.29% with a median interval of 20 months between LT and diagnosis of DM. The age, sex, and race distribution, immunosuppressive regimen, number of rejection episodes treated with pulse therapy, and family history of DM were similar in both groups. However, the frequency of BMI > or = 30 in the pre- and posttransplant periods was higher among patients who developed NODM (P = .02). Upon multivariate analysis of the entire cohort, HCV infection was the only significant predictor of NODM (OR = 4.31, CI = 1.17 to 15.84, P = .02). In conclusion, our study confirmed an association between HCV infection and NODM among Brazilian liver transplant recipients, suggesting that HCV infection may have a potential role in the pathogenesis of posttransplantation DM.

Prevalence of malnutrition in liver transplant candidates.

OBJECTIVE: To determine the prevalence of malnutrition among liver transplant (LT) candidates. MATERIALS AND METHODS: A prospective study evaluated 219 adult LT candidates including 141 men and 78 women. Cholestatic disease was present in 21 (Child: A = 1, B = 11, and C = 9) and noncholestatic disease in 198 (Child: A = 12, B = 93, and C = 93. The mean age was respectively 45.6 and 46.5 years. Anthropometric and biochemical assessments were performed for statistical analysis using Student t test (P <.05). RESULTS: In the noncholestatic group, 41.5% were obese according to keep a body mass index (BMI); 61.6% were depleted according to adequacy of tricipital skin fold (%TSF); and 71.1% were above normal levels for generalized adipose reserve (%F). In terms of adequacy of mid-upper arm muscle circumference (%MMC), 58% were depleted and 50.5% were depleted for the current body weight/usual body weight (%CBW/UBW). Otherwise 52.2% of current body weight/ideal body weight (%CBW/IBW) values were above normal. Serum albumin was below normal in 64.9% of cases. In the cholestatic group 62% were normal for BMI; 66.7% were depleted for %TSF; 77.8% were above normal for %F. As to %MMC, 47.6% were depleted and 47.6% were depleted for %CBW/UBW. Otherwise 47.6% were above normal weight for %CBW/IBW. Serum albumin was below normal in 53.9% and %MMC values showed statistically significant differences (P =.02) when compared with Child B and C in the noncholestatic group, as well as %F (P =.01) and serum albumin (P =.0002) in the cholestatic and noncholestatic groups. Serum albumin values also showed statistically significant differences (P =.0004) when noncholestatic Child B and C patients were compared. CONCLUSION: Patients with cholestatic disease were more affected by calorie depletion compared to noncholestatic patients who were more affected by protein depletion.

Donor quality of life after living donor liver transplantation.

Living donor liver transplantation (LDLT) for children and adults has gained widespread acceptance due to the severe organ shortage. LDLT provides potential recipients with timely transplantation, but this procedure engenders a potentially significant risk to the donor. This study analyzed medical, functional, and psychological donor outcomes after LDLT. Nineteen donors (mean age 33.9 +/- 12 years), who underwent hepatectomy for LDLT (13 right lobectomy for adult LDLT) from March 1998 to November 2002, were interviewed at a median of 13 months after donation (range, 2 to 58 months). According to the Clavien System classification, major complications occurred in three donors (16%), and minor in four (21%). The mean length of hospital stay was 5.7 +/- 1.6 days. Five patients (27%) needed rehospitalization. Complete recovery was achieved at a mean time of 8.5 +/- 3.5 weeks. All 19 donors were able to return to predonation activities. The donor's relationship to the recipient and to their families was improved after donation in all cases; 12 (63%) cited a positive psychological impact on their lives. About 90% would donate again and 84% would recommend donation to someone contemplating it. In conclusion, all donors are alive and well after donation and were able to return to their predonation occupation. Most of them felt that this experience changed their lives for the better and would donate again. Donor safety and quality of life should remain the priority in all donation processes.

Impact of successful liver transplantation on reproductive function and sexuality in women with advanced liver disease.

Abnormalities in the reproductive function and sexuality, which are common among women with advanced liver disease, may reverse after successful liver transplantation (LT). To analyze reproductive function and sexuality in women who underwent successful LT, we interviewed 28 recipients (mean age 44.17 +/- 13.6 years old) at a median posttransplant survival of 36.5 months (range, 6 to 110 months), with good graft function and obeying regular follow-up at our institution. In addition to medical records, all subjects answered a questionnaire on their menstrual pattern, sexual activity, contraceptive practice, pregnancy, and sexuality domain. Nineteen of 22 patients in the child bearing age (86.4%) recovered menstrual function at a median of 1 month after LT (range, 1 to 7 months). Twenty of 28 recipients (71.4%) were sexually active. The most frequent contraceptive practices were barrier methods and tubal ligation. There were four successful pregnancies (one twin) in three patients; five healthy babies were delivered. Overall, 70% of sexually active patients indicated satisfaction with their relationship, 75% had weekly intercourse, and 70% experienced orgasm with intercourse. Eighty percent expressed a desire to receive information concerning sexuality. In conclusion, LT has a positive impact on sexuality and reproductive function in female recipients. It would desirable that LT programs included information regarding these issues for this population.

Role of pyruvate dehydrogenase in lactate production in exercising human skeletal muscle.

The mechanisms responsible for lactate production with increased intensity of muscle contraction are controversial. Some investigators suggest that the mitochondria are O2-limited, whereas others suggest that lactate production occurs when O2 to the mitochondria is adequate and that the increased lactate production is due to a "mass-action effect" when pyruvate production exceeds the rate of pyruvate oxidation. Pyruvate dehydrogenase is a rate-limiting enzyme for pyruvate entry into the tricarboxylic acid cycle; its catalytic activity influences both pyruvate oxidation and lactate production. Since lactate dehydrogenase is an equilibrium enzyme, increased lactate production will be due to a mass-action effect exerted by increases in pyruvate concentrations. Because the equilibrium constant of the lactate dehydrogenase reaction markedly favors lactate over pyruvate, small increases in pyruvate concentration will result in large increases in lactate concentration. At higher exercise intensities, which are more reliant on glycogen as substrate, the rate of pyruvate production exceeds the catalytic activity of pyruvate dehydrogenase, and lactate production occurs. Studies using dichloroacetate, induced acid-base changes, diet and short-term endurance training, indicate that lactate production is related to complex interactions of metabolic pathways and not related to inadequate O2 supply. As pyruvate dehydrogenase plays a central role in the integration of carbohydrate and fat metabolism, and in the entry of pyruvate into the tricarboxylic acid cycle, this enzyme plays a key role in lactate production.

[Apoptosis as a mechanism of tissue injury in hepatobiliary diseases]. / Apoptose como mecanismo de lesão nas doenças hepatobiliares.

BACKGROUND: Cell death by apoptosis is a fundamental biologic process involved in many physiologic and pathophysiologic processes in the liver. OBJECTIVE: To review the process of apoptosis, its cellular mechanisms, its regulation by external factors, and its role in pathophysiologic process and specific diseases of the liver. CONCLUSION: An understanding of the cellular mechanisms of apoptosis and their dysregulation during pathophysiologic disturbances will help in understanding human liver diseases. The modulation of apoptosis may lead to novel therapeutic strategies for the treatment of a wide range of liver diseases.

[Amantadine-HCL in the treatment of chronic hepatitis C in non-responders to alpha-interferon. Effect on ALT serum levels and viral load]. / Cloridrato de amantadina no tratamento de portadores de hepatite crônica C não-respondedores ao alfa-interferon. Efeito sobre os níveis séricos de ALT e carga viral.

Due to the limited efficacy of alpha-interferon for chronic hepatitis C amantadine has been proposed as a possible alternative method of treatment. However, few studies about efficacy of amantadine in chronic hepatitis C are available with controversial results. Stimulated by recent data in the literature, we studied the effect of 100 mg of amantadine HCL (alone) PO bid, for a four month period on alanine aminotransferase serum levels and viral load in a cohort of 18 patients (14 males and 4 females) with chronic hepatitis C, non-responders to alpha-interferon. Inclusion criteria were: detectable serum HCV-RNA, alanine aminotransferase above the upper limit of normal, chronic inflammation on liver biopsy, no other associated chronic liver disease and written informed consent. Available biopsies showed initially four cases of cirrhosis, six of chronic persistent hepatitis and eight of chronic active hepatitis. The most prevalent HCV genotypes were 3a (n = 9, 52.94%) and 1b (n = 6, 32.29%). Viral load (Amplicor HCV Monitor, Roche, USA) and alanine aminotransferase levels were obtained at baseline and after four months of treatment. All patients enrolled into the study but one completed the treatment. One patient discontinued amantadine due to severe depression. No significant reduction was observed between baseline and final values of alanine aminotransferase (139.118 +/- 79.789 vs. 99.588 +/- 62.583 U/L, P = 0.059) and viral load (7.154 +/- 1.596 vs. 6.574 +/- 1.584 log copies/mL, P = 0.147). Amantadine alone was not effective neither eradicating viremia nor normalizing alanine aminotransferase levels in chronic hepatitis C non-responders to alpha-interferon patients. It is suggested that only a study with amantadine alone in-patients without previous treatments could determine its efficacy in comparison with alpha-interferon.

[Normalization of menstrual cycles and pregnancy after liver transplantation]. / Normalização dos ciclos menstruais e gravidez após transplante de fígado.

The objective of the present study is to evaluate the effects of successful liver transplantation on menstrual cycles abnormalities and on reproductive function of women with chronic liver disease. Twelve women with age between 17 and 54 years who underwent liver transplantation were evaluated. The following variables were analyzed: age, etiology of chronic liver disease, pattern of menstrual function and period of amenorrhea before and after transplantation, and occurrence of pregnancy after transplantation. The mean age of patients was 36 +/- 12.6 years. Patients with primary biliary cirrhosis did not have menstrual abnormalities before transplantation. The other patients presented amenorrhea for 3 months to 11 years before the transplantation. Rapid recovery of menstrual function was observed in all patients after the transplantation (3.1 +/- 1.2 months). Two patients became pregnant one and three years after the transplantation. It is concluded from this study that most women who present amenorrhea secondary to chronic liver disease have normal menstrual cycles in approximately three months following liver transplantation and they may become pregnant.