Biomedical subjects
Publications and source records attributed to M Giuliani.
To investigate whether the signs of neurophysiological impairment observed in flight may be traced back to cytomorphology, we undertook a ground-based study focusing upon the architecture of cultured glial cells under simulated microgravity obtained by three-dimensional clinorotation.
CONTEXT: Nerve growth factor is a neurotrophic factor that promotes the survival of small fiber sensory neurons and sympathetic neurons in the peripheral nervous system. Recombinant human nerve growth factor (rhNGF) has demonstrated efficacy as treatment for peripheral neuropathy in experimental models and phase 2 clinical trials. OBJECTIVE: To evaluate the efficacy and safety of a 12-month regimen of rhNGF in patients with diabetic polyneuropathy. DESIGN: Randomized, double-blind, placebo-controlled phase 3 trial conducted from July 1997 through May 1999. SETTING: Eighty-four outpatient centers throughout the United States. PATIENTS: A total of 1019 men and women aged 18 to 74 years with either type 1 or type 2 diabetes and a sensory polyneuropathy attributable to diabetes. INTERVENTIONS: Patients were randomly assigned to receive either rhNGF, 0.1 microg/kg (n = 504), or placebo (n = 515) by subcutaneous injection 3 times per week for 48 weeks. Patients were assessed at baseline, 12 weeks, 24 weeks, and 48 weeks. MAIN OUTCOME MEASURES: The primary outcome measure was a change in neuropathy between baseline and week 48, demonstrated by the Neuropathy Impairment Score for the Lower Limbs, compared between the 2 groups. Secondary outcome measures included quantitative sensory tests using the CASE IV System, the Neuropathy Symptom and Change questionnaire, the Patient Benefit Questionnaire (PBQ), and a global symptom assessment, as well as nerve conduction studies and occurrence of new plantar foot ulcers. Patients also were evaluated for presence of adverse events. RESULTS: Among patients who received rhNGF, 418 (83%) completed the regimen compared with 461 (90%) who received placebo. Administration of rhNGF was safe, with few adverse events attributed to treatment apart from injection site pain/hyperalgesia and other pain syndromes. However, neither the primary end point (P =.25) nor most of the secondary end points demonstrated a significant benefit of rhNGF. Exceptions were the global symptom assessment (P =.03) and 2 of 32 comparisons within the PBQ, which showed a modest but significant benefit of rhNGF (P =.05 for severity of pain in the legs and P =.003 for 6-month symptoms in the feet and legs). CONCLUSION: Unlike previous phase 2 trials, this phase 3 clinical trial failed to demonstrate a significant beneficial effect of rhNGF on diabetic polyneuropathy. JAMA. 2000;284:2215-2221.
OBJECTIVES: To evaluate temporal trends of Kaposi's sarcoma (KS) and of the KS-related human herpesvirus (HHV-8) among homosexual men who seroconverted for HIV between 1984 and 1997. METHODS: The study participants were 387 homosexual men. Changes over a period of time were assessed by estimating KS incidence rates per 1000 person-years for the periods 1984-1989, 1990-1992, 1993-1995, and 1996-1997. The proportional incidence of KS as the AIDS-defining disease for the same periods was also calculated. To evaluate a cohort effect of calendar period, Kaplan-Meier curves were used to estimate the risk of KS by period of HIV seroconversion [i.e. before 1990 (median year of seroconversion) versus later]. Relative hazards for the four periods were estimated using competitive-risks models. We also estimated HHV-8 seroprevalence over the study period. RESULTS: Forty-eight participants developed KS. Between 1984 and 1995, the incidence rate of KS per 1000 person-years increased from 3.9 to 32.8, whereas the proportional incidence decreased from 33.3 to 24.3%. The risk of developing KS after HIV seroconversion did not change when comparing the seroconversion periods (i.e. before 1990 versus later). HHV-8 seroprevalence also remained stable. The rates of KS and the relative hazards dramatically decreased after 1995. CONCLUSIONS: Although KS incidence rates increased up to 1995, the proportional incidence decreased, due to the higher increase in rates of other AIDS-defining diseases. The finding that the risk of developing KS after HIV seroconversion remained stable over time is consistent with the stable trend of HHV-8 seroprevalence. The dramatic decrease in KS incidence rates after 1995 coincides with combined antiretroviral therapy.
This phase I, double-blind, randomized, placebo-controlled study evaluated the safety of single and multiple (daily for 7 days) subcutaneous administrations of recombinant-methionyl human neurotrophin-3 (r-metHuNT3) in healthy human volunteers at seven doses, ranging from 3 to 500 microg/kg/day. No serious or life-threatening adverse events occurred. The most frequently recorded adverse effects were mild injection-site pain, diarrhea, and elevation of liver function tests. No change in neurologic function was noted with these dosing regimens. We conclude that r-metHuNT3 is safe and well tolerated in the dosages used in this study.
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BACKGROUND: To date, few studies have provided information on risk factors for human t-lymphotropic viruses (HTLV) types I and II in European countries. In particular, few data are available from published studies conducted in STD centers. GOALS: To identify risk factors for HTLV-I and HTLV-II infection and to better distinguish the epidemiologic patterns of the two viruses in Italy. STUDY DESIGN: A cross-sectional study of individuals at high risk of sexually or parenterally transmitted infections attending a large STD center in an urban setting was conducted. Serologic tests for HTLV-I and II, HIV, hepatitis virus type B (HBV), hepatitis virus type C (HCV), and syphilis were performed. Information regarding at-risk behavior was collected using a specific questionnaire. RESULTS: From January 1994 to June 1996, 1,457 individuals were recruited; of them, 1,016 (69.7%) were males, 1,051 (72.4%) Italians, and 288 (19.8%) non-Europeans. One thousand seventy-five (74.8%) participants were noninjecting-drug-using heterosexuals, 285 (19.6%) were men who have sex with men, and 97 (6.6%) were injecting drug users (IDU). The mean age of the study participants was 33.6 (+/-10.5) years. Nine (0.6%) individuals were positive for HTLV-I antibodies and 9 (0.6%) for HTLV-II antibodies. The prevalence of HTLV-I among IDUs, men who have sex with men, and noninjecting-drug-using heterosexuals, was 2.1% (2/97), 1.4% (4/ 285), and 0.3% (3/1085), respectively. HTLV-II prevalence was 8.2% (8/97) among IDUs and 0.09% (1/1075) among noninjecting-drug-using heterosexuals. Among the nine HTLV-II-positive individuals, eight were Italian IDUs and one was a noninjecting-drug-using heterosexual man from India. None of the 285 men who have sex with men had HTLV-II antibodies. HTLV-infected individuals tended to be older than those who were uninfected. HTLV-I-infected individuals were more likely to be non-European and to have antibodies against Treponema pallidum. Injecting drug use tended to be independently associated with HTLV-II infection. CONCLUSIONS: The data suggest a role of sexual behavior in the spread of HTLV-I, which is more likely to be detected in individuals coming from endemic areas. Injecting drug use remains the most important risk factor for HTLV-II infection in Italy.
Abused drugs have several effects on sexual behaviour, which are related to the type, quantity, modality of assumption, and duration of abuse. Specifically, persons under the influence of drugs may fail to practice safe sex, increasing the risk of acquiring sexually transmitted diseases (STD) and of unplanned pregnancies. In recent years, many studies have been conducted to explore the association between drug use and the risk of STD, including HIV infection. The present paper is a review of these studies, which have been conducted in different parts of the world and among individuals with various modalities of drug assumption.
Epidemiological surveillance systems are an integral part of programmes geared towards disease control and therapy especially programmes for infectious diseases. In particular, the collection, analysis, and interpretation of data on the spread of sexually transmitted diseases provide the foundation for prevention and control programmes. During the last decade, the lack of data about the diffusion of the emerging STD, such as genital herpes, genital warts and non gonococcal genital infections, has conducted in Italy to set up a STD Surveillance System based on the reporting of cases from selected clinical sites. This report reviews the general principles and methods to be used in setting up of Italian STD Surveillance Project.
Legislation for the control of sexually transmitted diseases (STD) in Europe dates back several centuries, with laws specifying criteria for STD notification, diagnosis, and therapy, as well as guaranteeing treatment and medical visits at no cost. However, there still exist gross differences among European countries in terms of the geographical distribution of facilities and resources and in patients' access to services. This paper describes the STD legislation of the past 10 years for 14 European countries and compares this legislation with that in Italy.
The importance of specific programs for controlling and preventing sexually transmitted diseases (STD) has been widely recognized, considering that there exists no treatment that results in complection resolution of sexually transmitted viral pathologies, that many STDs have long periods of infectivity and clinical latency, and that there is a high risk of sequelae and of related oncogenesis. However, STD prevention can be quite complex, in that a variety of diseases with diverse clinical and epidemiological characteristics are currently defined as "STDs". One of the main aspects of STD prevention is the identification of population groups considered to be at risk of transmission and that play an important role in maintaining the current epidemic status of STDs in the general population (i.e., sexually promiscuous persons). As with other diseases, the prevention of STDs is generally classified into primary prevention and secondary prevention. Primary prevention consists of protecting healthy individuals from acquiring the infection and mainly consists of promoting safe-sex (including barrier methods), performing vaccination, and conducting information and education campaigns. The objective of secondary prevention is to prevent the disease from further evolving in persons who are already infected or ill, including the prevention of complications, by providing proper medical care and treatment. The main tools of secondary prevention of STDs are: early diagnosis of cases, early and targeted therapy, and management of sexual partners.
OBJECTIVE: To assess the distribution of specific sexually transmitted diseases (STD), including HIV-1 infection, among Italian adolescents with an acute STD and to evaluate these individuals behavioural characteristics. METHODS: The database of Italy's STD Surveillance System was used as the source of data. Data on all STD cases reported among individuals under 20 years of age were analysed. RESULTS: From September 1990 to December 1997, 57,046 cases of STDs were reported to the surveillance system; 1,757 (3.1%) of these were reported among adolescents, of whom 896 (51.0%) were males. The most commonly reported diseases among males were genital warts (30.7%) and non-gonococcal urethritis (18.5%); among females, the most commonly reported diseases were non-gonococcal vaginitis (39.1%) and genital warts (30.0%). Of the 555 males tested for HIV-1 antibodies, 28 (5.0%) were seropositive; of the 510 females tested, 17 (3.3%) were seropositive. The highest HIV-1 seroprevalence rates were found among intravenous drug users (IDU) (33.3% among male IDUs and 23.8% among female IDUs) and among homosexual males (17.6%). DISCUSSION AND CONCLUSIONS: In Italy, the impact of STDs among adolescents is not negligible, though the distribution of STDs among this population group differs from the distribution among adults. Moreover, the prevalence of HIV-1 among adolescents with STDs is similar to that among adults with STDs. This study's data suggest the need to further develop STD/HIV prevention programmes that specifically target youths.
OBJECTIVE: To determine changes over time in the proportion of individuals requesting HIV-1 testing represented by women and in the HIV-1 prevalence among women attending a centre for sexually transmitted diseases (STD) in Rome Italy. METHODS: We analysed the computerised clinical records of all women undergoing HIV-1 testing in two five-year periods (i.e., 1985-89 and 1993-97). RESULTS: In the period 1985-89, 2,605 individuals underwent HIV-1 testing; 605 (23.2%) of these individuals were women. In the period 1993-97, 5,981 individuals were tested; 2,015 (33.7%) were women. When analysing the proportion of women tested by exposure category, there was an increase in the proportion of non-drug-using heterosexual women (75.5% in 1985-89 vs. 84.6% in 1993-97) and of women from geographical areas endemic for HIV (1.8% vs. 5.5%, respectively), where as there was a decrease in the proportion of tested women represented by intravenous drug users (12.4% vs. 2.7%). Overall, the prevalence of HIV-1 infection among women decreased (8.8% in 1985-89 vs. 5.0% in 1993-97). When considering specific exposure categories, the prevalence increased among partners of HIV-1 infected males (8.7% vs. 36.5%) and among women from endemic areas (2.8% vs. 9.3%). DISCUSSION AND CONCLUSIONS: The increased proportion of women requesting HIV-1 testing, especially those reporting at-risk heterosexual behaviour, suggests that women are generally more informed with regard to the risks of sexual transmission. However, the increase in HIV-1 prevalence among women with an HIV-1-infected partner and those from endemic areas suggests that programmes for preventing sexual transmission need to be improved.
OBJECTIVES: To provide data on the incidence of HIV infection among repeat testers with sexually transmitted diseases (STD) in Italy. DESIGN: Retrospective longitudinal study. METHODS: Study participants, enrolled by 47 STD centres throughout Italy, included individuals with a newly diagnosed STD who were tested for HIV at the time of the STD diagnosis and who had a previous documented HIV-negative test. 'Seroconverters' were defined as those individuals who tested HIV-positive at the time of the STD diagnosis. The cumulative and the annual incidence of HIV in this population were estimated. RESULTS: Of 1950 patients, 47 were seroconverters, with an incidence rate of 1.7 per 100 person-years (PY) (95% confidence interval, 1.2-2.2). HIV incidence was higher among males than among females (2.5 versus 0.6 per 100 PY). The highest incidence rate was found among homosexual injecting drug users (IDU) (13.8 per 100 PY), whereas the lowest rate was observed among heterosexual non-IDU (0.4 per 100 PY). The annual incidence decreased from 1.8 per 100 PY in 1989 to 0.9 per 100 PY in 1996. CONCLUSIONS: Our results show that new HIV infections have occurred among STD patients in Italy since 1988, although a clear decrease in incidence has occurred since 1989. However, the rate of seroconversion appears to be alarmingly high in some high-risk groups. These findings suggest that there is a need for continued monitoring of new HIV infections among STD patients, and these individuals may represent a useful sentinel population for a better understanding of the HIV epidemic.
PURPOSE: Idiopathic polypoidal choroidal vasculopathy (IPCV) is a distinct clinical entity characterized by an edematous maculopathy and typical choroidal vascular change. The purpose of this study is to evaluate the use of optical coherence tomography (OCT) for diagnosing of this disease. METHODS: 4 patients affected by IPVC (mean age 71-84 years) underwent biomicroscopy with a three mirror conctact lens, fluorescein angiography (FA), indocyanine green angiography (ICGA) and OCT (Humphrey Zeiss) scan. RESULTS: in all 4 cases OCT tomograms acquired at the location of the typical choroidal abnormalities demonstrated by ICGA, revealed a characteristic hyper-reflectivity in the choroidal layers. CONCLUSION: ICGA is essential to diagnose IPVC, but OCT may be able to identify characteristic reflectivity patterns.
We evaluated the handling performance at implant, and the long-term atrial and ventricular electrical performance of a new generation using a very small surface area (1.2 mm2) steroid-eluting electrode (Medtronic CapSure Z). We compared the performance of CapSure Z to that of traditional passive fixation leads, with and without steroid elution. The study was conducted during 2 years of follow-up. We studied 188 patients (105 males and 83 females; mean age 71 +/- 7 years). All of the patients were implanted with a dual chamber pacemaker and the same type of lead in both chambers. Forty-one patients received CapSure Z leads, 25 patients received Target Tip leads (8-mm2 surface area; no steroid elution), 63 patients received CapSure leads (8-mm2 surface area; steroid elution), and 59 patients received CapSure SP leads (5.8-mm2 surface area; steroid elution). The four groups were homogeneous in regards to sex, age, cardiac disease, and reason for implant. At follow-up, the CapSure Z lead showed sensing values comparable to the other leads, with lower pacing thresholds and higher pacing impedance in both chambers. We evaluated the mean current drained from the pacemaker by the different types of leads when using safe, low energy output settings. We found that by using CapSure Z leads, the mean current was significantly lower than that of the other types of leads (0.42 microA for CapSure Z ventricular lead vs 0.85 for CapSure SP, 1.42 for CapSure, and 1.54 for Target Tip). Thus, the use of the CapSure Z lead, combined with low energy output programming, will increase pacemaker longevity compared to the use of traditional leads and standard output programming.
Infection by human herpesvirus 8 (HHV-8) is associated with the development of Kaposi's sarcoma (KS). Since regression of KS can be achieved by treatment of the patients with alpha interferon (IFN-alpha), we analyzed the effects of IFN-alpha or anti-IFN-alpha antibodies (Ab) on HHV-8 latently infected primary effusion lymphoma-derived cell lines (BCBL-1 and BC-1) and on peripheral blood mononuclear cells (PBMC) from patients with all forms of KS and from at-risk subjects. IFN-alpha inhibited in a dose-dependent manner the amplification of HHV-8 DNA in BCBL-1 cells induced to lytic infection with tetradecanoyl phorbol acetate (TPA). This effect was associated with the inhibition of the expression of HHV-8 nut-1 and kaposin genes that are induced early and several hours, respectively, after TPA treatment. In addition, IFN-alpha inhibited virus production and/or release from BCBL-1 cells. Inhibition of nut-1 and kaposin genes by IFN-alpha was also observed in BC-1 cells induced with n-butyrate. Conversely, the addition of anti-IFN-alpha Ab to TPA-induced BCBL-1 cells resulted in a larger number of mature enveloped particles and in a more extensive cytopathic effect due to the neutralization of the endogenous IFN produced by these cells. IFN was also produced by cultured PBMC from HHV-8-infected individuals, and this was associated with a loss of viral DNA during culture. However, the addition of anti-IFN-alpha Ab or anti-type I IFN receptor Ab promoted the maintenance of HHV-8 DNA in these cells that was associated with the detection of the latency-associated kaposin RNA. Finally, the addition of IFN-alpha reduced the HHV-8 load in PBMC. Thus, IFN-alpha appears to have inhibitory effects on HHV-8 persistent infection of PBMC. These results suggest that, in addition to inhibiting the expression of angiogenic factors that are key to KS development, IFN-alpha may induce KS regression by reducing the HHV-8 load and/or inhibiting virus reactivation.
In a group of 20 patients implanted with a single-lead VDD pacing system, a wide interindividual variability was found in P-wave amplitude changes occurring under dynamic conditions, even though they were of minor clinical relevance because constant atrial tracking was maintained.
Three hundred seventy-nine individuals [137 non-injecting drug using (non-IDU) heterosexuals, 130 homosexual men and 112 IDU] attending the human immunodeficiency virus (HIV) testing program of a sexually transmitted disease (STD) clinic in Rome were studied to estimate the prevalence and to identify the modalities of transmission of human herpesvirus-8 (HHV-8) infection. Serological analysis was performed by using an immunofluorescence assay able to detect anti-latent and anti-lytic HHV-8 antibodies. Twelve acquired immunodeficiency syndrome (AIDS)-Kaposi's sarcoma (KS) patients and 94 blood donors were tested as reference population groups. Anti-lytic antibodies were detected in 185 (48.8%) individuals; 52 of them (13.7%) also had anti-latent antibodies. Both anti-lytic and anti-latent antibody prevalence were higher among homosexual men (66.9% and 27.7%, respectively) than among IDU (49.1% and 8.0%, respectively) and non-IDU heterosexuals (31.4% and 5.1%, respectively), and tended to increase with age. Anti-lytic HHV-8 antibodies were associated with syphilis [odds ratio (OR)=3.81] but not with hepatitis C virus (HCV) seropositivity. HIV-infected homosexual men were more likely to have HHV-8 antibodies than those who were HIV-negative. When using anti-latent antibodies the direction of the OR remained the same, although the associations did not often reach statistical significance. Among AIDS-KS patients, 83.3% had anti-lytic and 66.6% had anti-latent antibodies. Among blood donors, 28% had anti-lytic antibodies and 2 of them (2.1%) also had anti-latent antibodies. Our data indicate that HHV-8 seroprevalence increases with age and is higher among homosexual men, particularly those infected with HIV. This is consistent with sexual transmission of HHV-8 infection. In addition, the presence of HHV-8 antibodies in HIV-negative non-IDU heterosexual contacts and in healthy blood donors is consistent with the high incidence of classic KS in Italy.