HCV NS3 sequencing as a reliable and clinically useful tool for the assessment of genotype and resistance mutations for clinical samples with different HCV-RNA levels.

OBJECTIVES: This study aims to evaluate the reliability and clinical utility of NS3 sequencing in hepatitis C virus (HCV) 1-infected patients who were candidates to start a PI-containing regimen. METHODS: NS3 protease sequencing was performed by in-house-developed HCV-1 subtype-specific protocols. Phylogenetic analysis was used to test sequencing reliability and concordance with previous genotype/subtype assignment by commercial genotyping assays. RESULTS: Five hundred and sixty-seven HCV plasma samples with quantifiable HCV-RNA from 326 HCV-infected patients were collected between 2011 and 2014. Overall, the success rate of NS3 sequencing was 88.9%. The success rate between the two subtype protocols (HCV-1a/HCV-1b) was similarly high for samples with HCV-RNA >3 log IU/mL (>92% success rate), while it was slightly lower for HCV-1a samples with HCV-RNA ≤3 log IU/mL compared with HCV-1b samples. Phylogenetic analysis confirmed the genotype/subtype given by commercial genotyping assays in 92.9% (303/326) of cases analysed. In the remaining 23 cases (7.1%), 1 was HCV-1g (previously defined as subtype 1a), 1 was HCV-4d (previously defined as genotype 1b) and 1 was HCV-1b (previously defined as genotype 2a/2c). In the other cases, NS3 sequencing precisely resolved the either previous undetermined/discordant subtype 1 or double genotype/subtype assignment by commercial genotyping assays. Resistance-associated variants (RAVs) to PI were detected in 31.0% of samples. This prevalence changed according to PI experience (17.1% in PI-naive patients versus 79.2% in boceprevir/telaprevir/simeprevir-failing patients). Among 96 patients with available virological outcome following boceprevir/telaprevir treatment, a trend of association between baseline NS3 RAVs and virological failure was observed (particularly for HCV-1a-infected patients: 3/21 failing patients versus 0/22 achieving sustained virological response; P = 0.11). CONCLUSIONS: HCV-NS3 sequencing provides reliable results and at the same time gives two clinically relevant pieces of information: a correct subtype/genotype assignment and the detection of variants that may interfere with the efficacy of PI.

Rapid virological response as a predictor of sustained response in HCV-infected patients with persistently normal alanine aminotransferase levels: A multicenter study.

Rapid virological response (RVR) is now considered the strongest predictor of sustained virological response (SVR) in patients with HCV undergoing antiviral treatment, and thus, shorter antiviral treatment for these patients has been suggested. However, no data exist on the predictive value of RVR in HCV carriers with normal ALT values. A total of 137 patients with persistently normal ALT treated with peginterferon alfa 2a and ribavirin were studied. Fifteen patients dropped out early because of side effects, and in 10 patients with HCV-1 treatment was discontinued because of lack of early virological response (EVR). RVR was observed in 68% of the patients (42% patients with HCV-1, 90% HCV-2 and 64% HCV-3). An end-of-treatment response was observed in 86% of the patients (68% HCV-1, 100% HCV-2 and 91% HCV-3). SVR was maintained in 91 patients (46% HCV-1, 97% HCV-2 and 82% HCV-3). Overall, 92% patients with rapid response did obtain HCV eradication vs only 38% of those without rapid response. HCV-1 patients with baseline HCV RNA <400×10(3) IU/mL were more likely to achieve RVR and SVR than those with higher HCV RNA levels. We conclude that patients with genotype 1 and normal ALT who achieve HCV RNA negativity at week 4 may have a higher probability of eradicating their infection. Because of the concomitant favourable demographic and virological features often found in this particular subset of patients, the duration of therapy in these people might be shortened in the case of RVR. Persistently normal alanine aminotransferase levels patients with genotype 2 or 3 have a high chance of achieving SVR, so retesting of HCV RNA during treatment may have no additional practical value in these subjects.

Management of chronic hepatitis in drug addicts: a systematic review.

Injection drug users constitute the largest group of person at high risk for acquiring chronic hepatitis C, B and Delta. In particular viral, host and environmental factors all seem to favour rapid spread of these infections among drugs addicts. Host factors include behaviours that expose individuals to hepatitis virus such as the shared use of drug preparation, injection equipment and not protected sexual relationship with other drugs users. While in some clinical studies adherence to treatment regimens was often poor and to treat chronic hepatitis in injection drug users was stated as futile, in other controlled clinical studies adherence and sustained biological response to antiviral treatment was slightly lower or similar to that reported in other groups of patients. In this review we describe the epidemiology, diagnosis and treatment of chronic hepatitis C, B and Delta in intravenous drug users.

Intensity of myocardial expression of inducible nitric oxide synthase influences the clinical course of human immunodeficiency virus-associated cardiomyopathy. Gruppo Italiano per lo Studio Cardiologico dei pazienti affetti da AIDS (GISCA).

BACKGROUND: Increased levels of tumor necrosis factor-alpha (TNF-alpha) and inducible nitric oxide synthase (iNOS) have been reported in patients with dilated cardiomyopathy. We investigated the myocardial expression of TNF-alpha and iNOS in patients with HIV-associated cardiomyopathy (HIV-DCM) compared with patients with idiopathic dilated cardiomyopathy (IDCM). METHODS AND RESULTS: Endomyocardial biopsy specimens from 82 HIV-DCM and 80 IDCM patients were processed for determination of the immunostaining intensity of TNF-alpha and iNOS and for virological examination. Negative controls were derived from autopsy myocardium specimens from 32 HIV-negative patients without known heart disease. The mortality rate for congestive heart failure between groups according to the intensity of iNOS staining was also evaluated. The mean intensity of both TNF-alpha and iNOS staining was greater in patients with HIV-DCM (0.81 and 1.007, respectively) than in patients with IDCM (0.44 and 0.49, respectively) and controls (0.025 and 0.027, respectively). The staining intensity of both TNF-alpha and iNOS was inversely correlated with CD4 count. The staining intensity of iNOS was greater in HIV-DCM patients with HIV/coxsackievirus B3 (CVB3) or with HIV/cytomegalovirus coinfection than in IDCM patients showing infection with CVB3 and adenovirus alone. The staining intensity of iNOS correlated to mortality rate, because it was higher in HIV-DCM patients and, in particular, in those with an optical density unit >1. CONCLUSIONS: Cytokine activation seems to play a significant pathogenetic role in both HIV-DCM and IDCM. In HIV-DCM patients, the state of immunodeficiency may favor the selection of viral variants of increased pathogenicity, influencing the clinical course of cardiomyopathy by enhancement of the inflammatory process.

One-step nested PCR for detection of 2 LTR circles in PBMCs of HIV-1 infected patients with no detectable plasma HIV RNA.

A highly sensitive nested PCR was carried out in order to detect 2 LTR circles as a marker of recent and ongoing viral replication in HIV-1 infected patients with HIV plasma RNA undetectable. This "in house" two-step nested PCR is very sensitive, but it is not feasible for routine tests and presents a high risk of contamination. In order to reduce the time of reactions and crossover contamination, the possibility was explored to carry out a single step nested PCR, in which the two successive amplification rounds are carried out in the same tube. This single step nested PCR has the same sensitivity of the two-step nested, is easy to conduct and requires a short time of reaction. The two different PCR methods were compared and the clinical use of monitoring 2 LTR DNA circles in HIV-1 infected patients with undetectable plasma viral load is discussed.

Clinical course of cardiomyopathy in HIV-infected patients with or without encephalopathy related to the myocardial expression of tumour necrosis factor-alpha and nitric oxide synthase.

OBJECTIVE: To define whether the development of encephalopathy influences the clinical course of HIV-associated cardiomyopathy (HIV-DCM) in relation to the myocardial expression of tumour necrosis factor-alpha (TNF-alpha) and inducible nitric oxide synthase (iNOS). DESIGN: Prospective study. SETTING: University hospitals and AIDS centres. METHODS: 115 HIV-infected patients with echocardiographic diagnosis of HIV-associated cardiomyopathy (34 with encephalopathy and 81 without encephalopathy) were followed for a mean of 24 +/- 3.2 months. All patients underwent endomyocardial biopsy for determination of myocardial immunostaining intensity of TNF-alpha and iNOS. Cerebrospinal fluid (CSF) from patients with encephalopathy was examined for the presence of viruses. Patients underwent clinical examination every 3 months and echocardiographic examination every 6 months. The intensity of TNF-alpha and iNOS immunostaining was also evaluated on postmortem cerebral tissue of patients who died of congestive heart failure (CHF). RESULTS: A greater impairment of echocardiographic parameters was observed in patients with HIV-associated cardiomyopathy after development of encephalopathy. These parameters tended to worsen progressively during the follow-up period and were inversely correlated with HIV-1 viral load, CD4 cell count, mini mental status score and the intensity of myocardial and cerebral TNF-alpha and iNOS staining. CSF specimens were available in 29 patients with encephalopathy. HIV-1 sequences were detected in CSF of all these patients with cytomegalovirus sequences in two. The mortality rate for CHF was greater among patients with encephalopathy (73% versus 12%). CONCLUSIONS: The development of encephalopathy has an adverse effect on the clinical course of HIV-associated cardiomyopathy. In the relationship between cardiomyopathy and encephalopathy, the activation of iNOS by TNF-alpha may have a significant pathogenetic role in HIV disease.

Clinical manifestation of HIV-related pulmonary hypertension.

In recent years, much more thought has been given to the pathogenic role of HIV and to the clinical manifestations of HIV-related pulmonary hypertension (HRPH), which currently represents one of the most severe events during HIV disease. HRPH occurs in early and late stages of HIV infection and does not seem to be related to the degree of immune deficiency. Many of the symptoms in HRPH result from right ventricular dysfunction: the first clinical manifestation is effort intolerance and exertional dyspnea that will progress to the point of breathlessness at rest. The diagnosis of HRPH can be made only after all etiologies for pulmonary hypertension have been excluded. Echocardiography has been proven to be an extremely useful tool for diagnosing HRPH, and Doppler echocardiography can be used to estimate systolic pulmonary artery pressure and to monitor the effects of therapy. Assessment of hemodynamic measures by catheterization remains, however, the best test for evaluating response to therapy. Cardiac catheterization is mandatory to characterize the disease and exclude an underlying cardiac shunt as etiology. Vasodilators have been extensively used in the treatment of pulmonary hypertension, since vasoconstriction is a determinant characteristic of this disease. However, HRPH remains a progressive disease for which treatment is often unsatisfactory and there is no cure. As new, more efficient antiretroviral treatment are introduced, clinicians should expect to encounter an increasing number of cases of pulmonary hypertension in HIV+ patients in the future.

Pathogenesis of HIV-related pulmonary hypertension.

Human immunodeficiency virus (HIV)-related pulmonary hypertension (HRPR) is a cardiovascular complication of HIV infection that has been recognized in the last years with increasing frequency. The etiology of HRPH is unknown. All the attempts to isolate HIV on pulmonary vessels in HRPH patients failed, and an indirect role for HIV in this disease has been hypothesized. Current theories on the pathogenesis focus on abnormalities of endothelial and smooth muscle cells of pulmonary vasculature. Endothelial and smooth muscle cell injury could be due to a high production or to a reduced clearance of cytokines in these patients. In fact, in several studies high levels of ET-1, IL-1alpha, IL-6 and PDGF in primary pulmonary hypertension (PPH) and in HRPH have been found. HIV gp 120 could induce the production of these cytokines by a stimulation of monocytes/macrophages. A high alpha1-adrenoreceptors stimulation of pulmonary vessels could be also implicated in the pathogenesis of HRPH. Chronic hypoxia is observed with increased frequency in HIV patients, and this could induce a chronic stimulation of alpha1-receptors of pulmonary vasculature with typical pathological changes. However, only a small percentage of HIV- patients develop HRPH. This observation suggests the existence of an idiosyncratic susceptibility to the development of vascular disease. This susceptibility could have a genetic basis, and might be determined by particular major histocompatibility complex alleles.

Left ventricular filling in young patients affected by insulin-dependent diabetes mellitus: a stress Doppler echocardiographic study.

BACKGROUND: The purpose of this study was to analyze diastolic function in two different populations of young patients affected by insulin dependent diabetes mellitus (IDDM), with and without systemic diabetic complications, and to compare the results obtained at rest with those obtained during isometric exercise. METHODS: Forty-five IDDM diabetic patients were studied. On the basis of presence or absence of systemic diabetic complications (nephropathy and retinopathy) patients were divided into two groups. Group I (20 patients) without and Group II (25 patients) with diabetic complications. Diastolic function parameters were measured by Doppler echocardiography at rest and during isometric exercise. The two groups were similar regarding age, metabolic control and insulin dosage but there were significant differences in diastolic and systolic blood pressure and heart rate between the two groups, the patients with complications showing higher values (p < 0.001, p < 0.005, p < 0.01 respectively). RESULTS: Group II already presented at rest alterations of diastolic function parameters respect to Group I with a marked increase of: peak velocity of late left ventricular filling (peakA cm/sec), (60.1 +/- 13.4 versus 48.4 +/- 8.9, p < 0.01); late left ventricular filling integral (A area), (6.5 +/- 1.4 versus 5.0 +/- 0.8, p < 0.05); late left ventricular filling integral over total filling (A area/total area), (0.31 +/- 0.06 versus 0.26 +/- 0.06, p < 0.01). There was a decrease of E/A ratio in Group II versus Group I (1.5 +/- 0.32 versus 1.9 +/- 0.5, p < 0.05). During isometric exercise these changes became even more pronounced in patients with complications and in this group there was a marked decrease of flow integral of early left ventricular filling over total filling (E area/total area), (0.57 +/- 0.09 versus 0.68 +/- 0.07, p < 0.01). CONCLUSIONS: In conclusion, young IDDM patients with complications show an impairment of diastolic function more pronounced than those without. These changes are more evident during isometric exercise. Stress Doppler echocardiography is a reliable tool to detect early diastolic dysfunction in diabetic patients.

Left ventricular filling in young patients affected by insulin-dependent diabetes mellitus: a stress Doppler echocardiography study.

BACKGROUND: The purpose of this study was to analyze diastolic function in two different populations of young patients affected by insulin dependent diabetes mellitus (IDDM), with and without systemic diabetic complications, and to compare the results obtained at rest with those obtained during isometric exercise. METHODS: Forty-five IDDM diabetic patients were studied. On the basis of presence or absence of systemic diabetic complications (nephropathy and retinopathy) patients were divided into two groups. Group I (20 patients) without and Group II (25 patients) with diabetic complications. Diastolic function parameters were measured by Doppler echocardiography at rest and during isometric exercise. The two groups were similar regarding age, metabolic control and insulin dosage but there were significant differences in diastolic and systolic blood pressure and heart rate between the two groups, the patients with complications showing higher values (p < 0.001, p < 0.005, p < 0.01 respectively). RESULTS: Group II already presented at rest alterations of diastolic function parameters respect to Group I with a marked increase of: peak velocity of late left ventricular filling (peakA cm/sec), (60.1 +/- 13.4 versus 48.4 +/- 8.9, p < 0.01); late left ventricular filling integral (A area), (6.5 +/- 1.4 versus 5.0 +/- 0.8, p < 0.05); late left ventricular filling integral over total filling (A area/total area), (0.31 +/- 0.06 versus 0.26 +/- 0.06, p < 0.01). There was a decrease of E/A ratio in Group II versus Group I (1.5 +/- 0.32 versus 1.9 +/- 0.5, p < 0.05). During isometric exercise these changes became even more pronounced in patients with complications and in this group there was a marked decrease of flow integral of early left ventricular filling over total filling (E area/total area), (0.57 +/- 0.09 versus 0.68 +/- 0.07, p < 0.01). CONCLUSIONS: In conclusion, young IDDM patients with complications show an impairment of diastolic function more pronounced than those without. These changes are more evident during isometric exercise. Stress Doppler echocardiography is a reliable tool to detect early diastolic dysfunction in diabetic patients.

Alteration of left ventricular filling evaluated by Doppler echocardiography as a potential marker of acute rejection in orthotopic heart transplant.

To evaluate the changes in left ventricular (LV) filling associated with acute cardiac rejection, serial Doppler echocardiographic (ED) examination were performed on the same day as endomyocardial biopsy (EMB) in 40 patients who underwent orthotopic transplantation. The diameters and wall thickness of the left ventricle were measured. The indexes of LV filling in the following parameters were measured by pulsed Doppler: isovolumic relaxation time (IRT), peak early mitral flow velocity (V max E), and pressure half-time (PHT). The patients were classified into three groups on the basis of EMB: Group I (19 patients without rejection), Group II (11 patients with mild or moderate rejection), and Group III (10 patients with severe rejection). In Group III rejection was associated with a significant increase of posterior wall thickness (P < 0.05), with a decrease of IRT (P < 0.05), and an increase of V max E velocity (P < 0.01) in comparison with Group I. In Group II, Doppler indexes were not statistically significant in comparison with Groups I and II. In conclusion, in transplant patients, a diagnosis of acute rejection can be suspected in severe rejection by use of echocardiography when the diagnosis is based on a multiparametric evaluation of different ED indexes (m-mode and Doppler indexes). Doppler echocardiography is a method with an excellent specificity but insufficient sensitivity; this is due to the influence of recipient atrial contraction timing on Doppler indexes of LV filling.

Influence of thrombolytic therapy on inferior acute myocardial infarction with concomitant anterior ST segment depression.

The purposes of this study were to analyze the prognostic significance of precordial ST segment depression and to determine whether thrombolytic therapy is effective for all patients with inferior acute myocardial infarction (AMI) or whether there is a different effectiveness for patients with concomitant anterior ST segment depression persisting for 24 hours or longer. Medical charts of 176 patients were studied. On the basis of ECG the patients were subclassified into three groups according to the presence, persistence, or absence of significant ST segment depression: Group 1: anterior ST segment depression persisting for less than 24 hours (45.4%); Group 2: anterior ST segment depression persisting for more than 24 hours (17.6%); Group 3: no anterior ST segment depression (37%). Age, Killip class, peak creatine kinase, hospital deaths, left ventricular ejection fraction, regional wall motion score, postinfarction angina, and ventricular/supraventricular arrhythmia of all patients were studied. Parameters of the three groups were compared: worse results were found in group 1 and the worst in group 2. This result is independent of thrombolytic therapy. Finally, the same parameters of thrombolyzed and nonthrombolyzed groups were compared: no statistically significant difference was observed. Among thrombolyzed patients the number of those with ST depression lasting more than 24 hours is lower than in nonthrombolyzed patients. It can be assumed that thrombolytic therapy in inferior AMI determines a shifting of patients from a worse prognosis group (ST segment depression persisting for more than 24 hours) to a better prognosis group (ST segment depression persisting for less than 24 hours).

Primary pulmonary hypertension in HIV patients: a systematic review.

The relationship between grade of pulmonary hypertension and factors associated with human immunodeficiency virus among patients with HIV infection is poorly documented. This report documents the most extensive attempt made thus far to determine whether a relationship exists between degree of pulmonary hypertension and the following conditions: HIV risk factor, degree of immunosuppression, presence or absence of AIDS, and presence or absence of liver cirrhosis. A retrospective study involving a search of the published literature on primary pulmonary hypertension among HIV cases from 1987 to 1998, using the Medline and Aidsline databases was conducted. Patients for whom secondary causes of pulmonary hypertension could be excluded were selected, and the following information for each was recorded: age, gender, risk factors for HIV infection, HIV disease stage according to the Centers for Disease Control, previous opportunistic and neoplastic diseases, CD4+ cell count (cells/L), presence or absence of liver cirrhosis, pulmonary systolic artery pressure level, and lung pathology specimens. Information about the patient's survival time was also recorded. Seventy-six patients were judged to have primary pulmonary hypertension and were included in the study. While no correlation was found between pulmonary systolic artery pressure level and CD4+ cell counts, a statistically significant difference was found between HIV-positive patients with and without AIDS as determined by the Centers for Disease Control criteria with regard to the degree of pulmonary hypertension, expressed as pulmonary systolic artery pressure level (85.4 +/- 17 mm Hg vs 71.8 +/- 15 mm Hg, p < 0.013). Although a higher PAPS was present in HIV cirrhotic patients, a statistically significant difference was not found between degree of pulmonary hypertension and evidence of hepatic cirrhosis (85 +/- 21 mm Hg vs 73.1 +/- 15 mm Hg, p < 0.062). Patients with AIDS and primary pulmonary hypertension present a higher degree of pulmonary hypertension than non-AIDS patients. Pulmonary hypertension associated with HIV seems to be related to a cytokine-related stimulation and proliferation of endothelium. High levels of cytokines present in AIDS patients can favor pulmonary hypertension, but the role of a host response to HIV--determined by one or more HLA subtypes--is suspected to enhance high cytokine production levels.

Role of human immunodeficiency virus in primary pulmonary hypertension--case reports.

Previous cases of pulmonary hypertension (PH) in human immunodeficiency virus (HIV) infection have been reported in the literature. The role of HIV in PH is still debatable. The purpose of this report was to analyze whether HIV plays a direct or indirect role in PH pathogenesis. Between February and November 1997, 56 HIV-infected patients with cardiac symptoms and signs were studied by serial color Doppler echocardiography. In four patients (7.1%), PH not related to other well-known associated conditions, was disclosed. In spite of a low serum HIV RNA viral load and a high-efficacy antiretroviral therapy, including a protease inhibitor in two patients, PH developed and worsened. It could be hypothesized that in some patients with an individual immunogenetic predisposition, a high secretion of cytokines and endothelin-1 stimulated by an unidentified pathogen different from HIV could lead to PH. Antiretroviral therapy seems not to prevent or reduce right ventricle pressure gradient in PH.

Gastrointestinal tubercular arteritis during HIV infection.

Although digestive tract is often involved in HIV disease, severe gastrointestinal bleeding rarely occurs. We describe a case of severe gastrointestinal bleeding associated with a mycobacterium tuberculosis arteritis of colonic tract. It is reported a morphology change of mesenteric arteries by mycobacterium tuberculosis revealed by angiography. The superselective embolization of branches mesenteric inferior artery resolved the important bleeding without surgical intervention. In AIDS patients, during intestinal tuberculosis, massive enteric-hemorrhage suggests for involvement of mesenteric arteries by mycobacterium tuberculosis. An angiography is basic to discover bleeding and if necessary for the therapeutic treatment.

Pulmonary cryptosporidiosis in patients with acquired immunodeficiency syndrome.

Several reports have showed Cryptosporidium species as a cause of intractable diarrhea and malabsorption in patients with acquired immunodeficiency syndrome (HIV). A case of chronic diarrhea in a drug addict woman associated with a symptomatic interstitial pulmonary infection due to Cryptosporidium parvum is described. This unusual C. parvum spread into the bronchial tree is underlined and a survey of the literature is made.

[Changes in diastolic function in heart rejection: role of Doppler echocardiography]. / Alteraciones de la función diastólica en el rechazo cardíaco: papel del ecocardiograma-Doppler.

In acute cardiac rejection, left ventricular diastolic function is altered. To study these abnormalities and their utility in cardiac allograft rejection, we studied 56 cardiac transplant recipients. All patients were assessed with endomyocardial biopsy and Doppler echocardiography done in the same day. A total of 163 Doppler studies were recollected. Cardiac transplant recipients were excluded during the early 6 weeks postoperative period. Totally, 100 biopsies were normal, 48 positive for mild rejection (Billingham Gde I-II) and 15 positive for moderate or severe rejection (Billingham Gde III-IV). Compared to negative biopsies, during acute rejection left ventricular wald thickness significantly increased (p < 0.05); isovolumic relaxation period and pressure half-time significantly decreased (p < 0.05, p < 0.001 respectively). Nevertheless, increase in peak early mitral flow velocity was only significantly associated with severe rejection (p < 0.001). Correlating only progressive shortening of isovolumic relaxation period parameter in the diagnosis of graft rejection, we forward a high sensibility (85%) and low specificity (57%). Thus, Doppler echocardiographic evaluation of left ventricular diastolic function provides a non-invasive tool for early detection of acute rejection monitoring after the early postoperative period.

[Correction of transposition of great vessels with and without associated congenital defects. Description of two clinical cases]. / Trasposizione corretta delle grandi arterie senza e con difetti congeniti associati. Descrizione di due casi clinici.

We describe two cases of corrected transposition of great vessel (L Transposition). The first case was diagnosed in a man of 70 years old and was not associated with other congenital defects. The second case regards a young man of 16 years old and congenital cardiopathy was associated with interventricular defect and left Ebstein disease. We discuss the different evolution of L Transposition according to the presence or not of other congenital defects and we analyse right ventricle behaviour when it is submitted systemic pressure. In the literature only 26 cases of L Transposition were described in patients over 40 years old. The first case represents a rarity and it shows how in the absence of associated congenital defects, the right ventricle is able to adapt to systemic pressure. Bidimensional echocardiography in the method of choice to diagnose and evaluate congenital cardiopathy in adult age.

[Cardiac rhabdomyoma in tuberous sclerosis. Presentation of a case]. / Rabdomioma cardiaco nella sclerosi tuberosa. Presentazione di un caso.

We report of a case of cardiac tumor in a three months old infant, examined with echocardiography because a murmur was noted on routine examination. Further investigations brought out the diagnosis of tuberous sclerosis. Spontaneous regression of the tumor mass occurred in the following months. No signs of cardiac dysfunction of CNS involvement appeared. The peculiarity of rhabdomyoma as an early manifestation of tuberous sclerosis is emphasized.

[Mycobacterium tuberculosis drug resistance in patients with HIV and pulmonary tuberculosis infections in Rome: 1987-1996]. / La farmaco-resistenza di Mycobacterium tuberculosis nei pazienti con infezione da HIV e tubercolosi polmonare in Roma: 1987-1996.

A retrospective chart review was performed on 118 HIV infected patients with pulmonary tuberculosis hospitalized between 1987 and 1996 in a tertiary care center for Infectious Diseases in Rome. The aims of this study were: a) to evaluate global prevalence of and risk factors for drug-resistant Mycobacterium tuberculosis and multidrug resistant tuberculosis; b) to assess trends in prevalence of drug-resistant tuberculosis over the 10-year study period. Prevalence of drug resistance of first Mycobacterium tuberculosis isolates was tested on Lowenstein-Jensen medium with the proportional method. Of the 118 patients studied, 83 had never been treated for tuberculosis and 35 had already been treated for at least 1 month. The overall prevalence of resistance to one or more drugs was 25% (17% in never treated patients vs 46% in already treated patients; p = 0.002). Five percent of isolates were resistant to both isoniazid and rifampin (1% in never treated patients vs 14% in already treated patients; p = 0.008). Resistance rates to individual drugs were: isoniazid 14%, rifampin 8%, ethambutol 0%, streptomycin 13%. During the study period no significant variations in prevalence of drug-resistant tuberculosis were found. In our area, empiric therapy should include 4 drugs: as well as isoniazid, rifampin and pyrazinamide, we recommend ethambutol. Surveillance of drug-resistant tuberculosis is needed. Directly observed therapy should be considered for HIV patients in order to prevent increases in drug resistance, relapses, and treatment failures.