Recommendations of the Sleep Study Group of the Italian Dementia Research Association (SINDem) on clinical assessment and management of sleep disorders in individuals with mild cognitive impairment and dementia: a clinical review.

Clinical assessment and management of sleep disturbances in patients with mild cognitive impairment and dementia has important clinical and social implications. Poor sleep results in an increased risk of morbidities and mortality in demented patients and is a source of stress for caregivers. Sleep disturbances show high prevalence in mild cognitive impairment and dementia patients and they are often associated one to another in the same patient. A careful clinical evaluation of sleep disorders should be performed routinely in the clinical setting of individuals with cognitive decline. The Sleep Study Group of the Italian Dementia Research Association (SINDem) reviewed evidence from original research articles, meta-analyses and systematic reviews published up to December 2013. The evidence was classified in quality levels (I, II, III) and strength of recommendations (A, B, C, D, E). Where there was a lack of evidence, but clear consensus, good practice points were provided. These recommendations may not be appropriate for all circumstances and should therefore be adopted only after a patient's individual characteristics have been carefully evaluated.

Moderate alcohol use and health: a consensus document.

AIMS: The aim of this consensus paper is to review the available evidence on the association between moderate alcohol use, health and disease and to provide a working document to the scientific and health professional communities. DATA SYNTHESIS: In healthy adults and in the elderly, spontaneous consumption of alcoholic beverages within 30 g ethanol/d for men and 15 g/d for women is to be considered acceptable and do not deserve intervention by the primary care physician or the health professional in charge. Patients with increased risk for specific diseases, for example, women with familiar history of breast cancer, or subjects with familiar history of early cardiovascular disease, or cardiovascular patients should discuss with their physician their drinking habits. No abstainer should be advised to drink for health reasons. Alcohol use must be discouraged in specific physiological or personal situations or in selected age classes (children and adolescents, pregnant and lactating women and recovering alcoholics). Moreover, the possible interactions between alcohol and acute or chronic drug use must be discussed with the primary care physician. CONCLUSIONS: The choice to consume alcohol should be based on individual considerations, taking into account the influence on health and diet, the risk of alcoholism and abuse, the effect on behaviour and other factors that may vary with age and lifestyle. Moderation in drinking and development of an associated lifestyle culture should be fostered.

Prevalence of sleep disturbances in mild cognitive impairment and dementing disorders: a multicenter Italian clinical cross-sectional study on 431 patients.

BACKGROUND/AIMS: Sleep disturbances are common in the elderly and in persons with cognitive decline. The aim of this study was to describe frequency and characteristics of insomnia, excessive daytime sleepiness, sleep-disordered breathing, REM behavior disorder and restless legs syndrome in a large cohort of persons with mild cognitive impairment or dementia. METHODS: 431 consecutive patients were enrolled in 10 Italian neurological centers: 204 had Alzheimer's disease, 138 mild cognitive impairment, 43 vascular dementia, 25 frontotemporal dementia and 21 Lewy body dementia or Parkinson's disease dementia. Sleep disorders were investigated with a battery of standardized questions and questionnaires. RESULTS: Over 60% of persons had one or more sleep disturbances almost invariably associated one to another without any evident and specific pattern of co-occurrence. Persons with Alzheimer's disease and those with mild cognitive impairment had the same frequency of any sleep disorder. Sleep-disordered breathing was more frequent in vascular dementia. REM behavior disorder was more represented in Lewy body or Parkinson's disease dementia. CONCLUSION: A careful clinical evaluation of sleep disorders should be performed routinely in the clinical setting of persons with cognitive decline. Instrumental supports should be used only in selected patients.

Validity of a questionnaire for the semi-quantitative evaluation of dietary intake of hospitalised patients compared to weighed records.

BACKGROUND: Malnutrition in hospitalised patients is often underestimated. The present study aimed to evaluate the validity of a questionnaire for the semi-quantitative evaluation of food intake compared to weighed records in patients who were hospitalised for the rehabilitation of neurological disorders. METHODS: Food intake at breakfast, lunch and dinner was evaluated in 319 in-patients, by weighing the meals and the residuals, and using a semi-quantitative questionnaire, during five consecutive days. The questionnaire represented, for each offered food, the pictures of the nonconsumed quantities. The consumption of each food was determined by weighing foods that were served and the residuals after the meal. As a measure of validity of the questionnaire, the agreement over chance (kappa statistic) between the questionnaire and the weight was calculated. Considering the weight as the gold standard, the sensitivity and specificity of the questionnaire in detecting patients who consumed <50% or 75% of the meals was calculated. RESULTS: The agreement between the two measures was satisfactory (κ ≥ 0.70) or almost satisfactory (0.60 < κ < 0.70) for most of the foods, with the exception of fruit and the first course at dinner. The sensitivity and specificity of the questionnaire in detecting consumers of <50% or 75% of the offered foods were always >80%, except for bread and first course, as well as fruit at dinner. CONCLUSIONS: The present study shows that this semi-quantitative questionnaire on food consumption reproduces with sufficient precision the measures obtained by weighing. The questionnaire appears also to be a valid and suitable instrument for the identification of patients with poor food intake in a neurorehabilitation hospital.

An exploration of anger phenomenology in multiple sclerosis.

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) patients are often emotionally disturbed. We investigated anger in these patients in relation to demographic, clinical, and mood characteristics. PATIENTS AND METHODS: About 195 cognitively unimpaired MS patients (150 relapsing-remitting and 45 progressive) were evaluated with the State Trait Anger Expression Inventory, the Chicago Multiscale Depression Inventory, and the State Trait Anxiety Inventory. The patients' anger score distribution was compared with that of the normal Italian population. Correlation coefficients among scale scores were calculated and mean anger scores were compared across different groups of patients by analysis of variance. RESULTS: Of the five different aspects of anger, levels of withheld and controlled Anger were respectively higher and lower than what is expected in the normal population. Although anger was correlated with anxiety and depression, it was largely independent from these mood conditions. Mean anger severity scores were not strongly influenced by individual demographic characteristics and were not higher in more severe patients. CONCLUSIONS: The presence of an altered pattern of anger, unrelated to the clinical severity of MS, suggests that anger is not an emotional reaction to disease stress. An alteration of anger mechanisms might be a direct consequence of the demyelination of the connections among the amygdale, the basal ganglia and the medial prefrontal cortex.

Reduced oxygen due to high-altitude exposure relates to atrophy in motor-function brain areas.

BACKGROUND AND PURPOSE: At high altitudes barometric pressure is reduced and, thus, less oxygen is inhaled. Reduced oxygen concentration in brain tissue can lead to cerebral damage and neurological and cognitive deficits. The present study was designed to explore the effects of high-altitude exposure using a quantitative MRI technique, voxel-based morphometry. METHODS: We studied nine world-class mountain climbers before (baseline) and after (follow-up) an extremely high-altitude ascent of Everest and K2. We investigated the effects of repeated extremely high-altitude exposures by comparing mountain climbers' scans at baseline with scans of 19 controls. In addition, we measured the effects of a single extremely high-altitude expedition by comparing mountain climbers' scans at baseline and follow-up. RESULTS: A region of reduced white matter density/volume was found in the left pyramidal tract near the primary (BA 4) and supplementary (BA 6) motor cortex when mountain climbers at baseline were compared with controls. Further, when mountain climbers' scans before and after the expedition were compared, a region of reduced grey matter density/volume was found in the left angular gyrus (BA 39). CONCLUSION: These findings suggest that extremely high-altitude exposures may cause subtle white and grey matter changes that mainly affect brain regions involved in motor activity.

Amyloid beta and neuromelanin--toxic or protective molecules? The cellular context makes the difference.

Alzheimer's disease (AD) and Parkinson's disease (PD) share several pathological mechanisms. The parallels between amyloid beta (Abeta) in AD and alpha-synuclein in PD have been discussed in several reports. However, studies of the last few years show that Abeta also shares several important characteristics with neuromelanin (NM), whose role in PD is emerging. First, both molecules accumulate with aging, the greatest risk factor for AD and PD. Second, in spite of their different structures, Abeta and NM have similar characteristics that could also lead to neuroprotection. Metals are required to catalyze their formation and they can bind large amounts of these metals, generating stable complexes and thus playing a protective role against metal toxicity. Moreover, they may be able to remove toxic species such as oligopeptides and excess cytosolic dopamine. Third, both Abeta and NM have been implicated in parallel aspects of the neuronal death that underlies AD and PD, respectively. For example, both molecules can activate microglia, inducing release of toxic factors such as tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and nitric oxide (NO). A careful analysis of these parallel effects of Abeta and NM, including their seemingly paradoxical ability to participate in both cell death and protection, may lead to an improved understanding of the roles of these molecules in neurodegeneration and also provide insights into possible parallels in the pathological mechanisms underlying AD and PD.

Metallothionein-I-II and GFAP positivity in the brains from frontotemporal dementia patients.

Frontotemporal dementia regards a group of presenile progressive neurodegenerative form of dementias which includes Pick's disease, corticobasal degeneration, frontotemporal dementia with motor neuron disease, frontal lobe degeneration, dementia-parkinsonism-amyotrophy complex, familial non-specific dementia mapping to chromosome 3, non-Alzheimer degenerative dementia lacking distinctive histological features as well as a number other infrequent syndromes with dementia and focal neurological signs. The aim of this study was to investigate the regional distribution of metallothionein-I-II, an ubiquitary group of buffering proteins, in cases of frontotemporal dementia. The aim of the present study was to study the metallothionein-I-II expression in relationship to the expression in astrocytes of glial fibrillary acidic protein (GFAP) as we have already done in previous studies of Alzheimer's and Binswanger's diseases [31,32]. Our findings indicate that metallothionein-I-II expression in the most affected areas is likely to be regionally distinct and layer-dependent, in that it is highest in the deep layers of the frontotemporal cortex and the allocortex (hippocampus) while insignificantly immunopositive in the occipital cortex. In addition, the potential use of metallothionein-I-II as a new pharmacological approach to contrast some deleterious aspects of this disease has been also discussed.

Man-to-woman sexual transmission of the human immunodeficiency virus. Risk factors related to sexual behavior, man's infectiousness, and woman's susceptibility. Italian Study Group on HIV Heterosexual Transmission.

To investigate the risk factors for man-to-woman sexual transmission of the human immunodeficiency virus (HIV), we carried out a cross-sectional study of 368 women who were steady partners of HIV-infected men attending 16 Italian clinical centers. Information was collected from the medical records of the infected men and by direct interviews with the women. In a logistic regression analysis, the woman's awareness of her partner's seropositivity (odds ratio [OR], 0.2; 95% confidence interval [CI], 0.0 to 1.1), use of condoms (OR, 0.3; 95% CI, 0.1 to 1), and oral contraceptive use (OR, 0.5; 95% CI, 0.3 to 1.0) were negatively associated with transmission of the HIV infection. An increased risk was found in women having sexual intercourse more than twice a week (OR, 2.4; 95% CI, 1.2 to 4.9) and in women who had been sexually exposed to HIV for between 2 and 5 years (OR, 3.5; 95% CI, 1.8 to 6.7). The transmission rate was higher in couples who engaged in anal sex (OR, 2.8; 95% CI, 1.3 to 6.3); in women reporting vaginitis (OR, 4.9; 95% CI, 2.4 to 10.2) or genital warts (OR, 33.3; 95% CI, 4.5 to 244.1); and in those using intrauterine devices (OR, 3.1; 95% CI, 1.4 to 7.1). The risk for women was also associated with a CD4+ cell count lower than 400/mm3 in their partners. Knowledge of the HIV status of the partner led to increased condom use but did not induce a lower frequency of sexual intercourse or an avoidance of anal sex.

Antiretroviral treatment of men infected with human immunodeficiency virus type 1 reduces the incidence of heterosexual transmission. Italian Study Group on HIV Heterosexual Transmission.

OBJECTIVE: To determine the incidence of heterosexual human immunodeficiency virus type 1 disease transmission and the effect of zidovudine therapy on this risk of transmission. DESIGN: A cohort of 436 monogamous seronegative female sexual partners of human immunodeficiency virus type 1-infected males was followed up for 740 person-years with regular structured interviews and laboratory tests. PATIENTS: At enrollment of the women, 50% of their infected partners had one or more signs of disease progression (symptoms of acquired immunodeficiency syndrome, p24 antigen positivity, or CD4+ cell counts lower than 0.4 x 10(9)/L) and 15% were treated with zidovudine. MAIN OUTCOME MEASURE: Incidence rates of seroconversion were calculated and relative risks were estimated as incidence rate ratios. RESULTS: Twenty-seven women seroconverted during follow-up, and the incidence of seroconversion was 3.7 per 100 person-years. Seroconversion was about six times more frequent (relative risk, 5.8; 95% confidence interval, 2.2 to 15.3) in couples not using condoms. Men with signs of disease progression transmitted infection to their partners more frequently and were more frequently treated with zidovudine. When the risk of transmission was estimated accounting for disease progression, the rate of transmission in zidovudine-treated men was lower than in untreated men (relative risk, 0.5; 95% confidence interval, 0.1 to 0.9). CONCLUSION: Treatment of human immunodeficiency virus type-1 infected men with zidovudine reduces, but does not eliminate, heterosexual transmission of infection. Behavioral counseling that encourages sexual practices with a lower risk of transmission remains the most important method of prevention.

Mortality of intravenous drug users living in Milan, Italy: role of HIV-1 infection. COMCAT Study Group.

OBJECTIVES: To study the trend in mortality from 1980 to 1991 in a cohort of 2432 intravenous drug users (IVDU) enrolled between 1 November 1980 and 31 December 1988. In addition, to evaluate the impact of HIV-1 infection on mortality. DESIGN: The vital status of people enrolled in the cohort was ascertained at registry offices of the municipalities of residence. Cause of death was determined by reviewing death certificates, clinical records and autopsy reports. Within the cohort, the causes of death of HIV-1-infected subjects were compared with those of subjects of undetermined serologic status. SETTING: Municipalities of the metropolitan area of Milan. RESULTS: The cohort was followed-up for 16415 person-years (PY) and 413 deaths were observed up to 30 June 1991. Mortality was 25.2 per 1000 PY, 20.5 times greater than that of the general population of the same age and sex. The leading cause of death was drug overdose, followed by AIDS (death rates 9.2 and 8.8 per 1000 PY, respectively). Mortality remained under 16 per 1000 PY from 1981 to 1986, and then increased rapidly to 63.8 per 1000 PY in the first half of 1991. AIDS and overdose accounted for most of this increase, with AIDS becoming the leading cause of death from 1989. Mortality in HIV-1-infected IVDU was higher than in IVDU as a whole (48.0 versus 19.9 per 1000 PY), and the difference was entirely due to AIDS and infectious diseases. CONCLUSION: The overall mortality rate and the mortality for AIDS and overdose were markedly higher than in other European countries in the same risk group. HIV-1 infection does not appear to affect the mortality for causes other than AIDS and infectious diseases.

Soluble interleukin-2 receptor decrease in the sera of HIV-infected patients treated with zidovudine.

Laboratory parameters which are modified following administration of zidovudine are becoming increasingly useful in monitoring the efficacy of treatment of early stages of HIV-1 infection. The serum levels of soluble interleukin (sILR)-2 receptor, which have been reported to increase early in HIV-1 infection, were found to be significantly lower in 24 patients being treated with zidovudine than in 69 patients who were not treated, 28 of whom had CD4+ counts greater than 400 x 10(6)/l, and 41 less than 400 x 10(6)/l, respectively (P less than 0.0001). A prospective study group of 33 subjects treated with zidovudine demonstrated a decrease in sIL-2R during therapy (base values 2113 +/- 1131 versus 1444 +/- 728 after 90 days of therapy; P less than 0.0007). The reduction of sIL-2R was greater in those subjects were p24 antigen became negative during treatment. sIL-2R therefore seems to be a useful tool in the monitoring of therapy with zidovudine.

Redistribution of body fat in HIV-infected women undergoing combined antiretroviral therapy.

OBJECTIVES: To investigate the prevalence, metabolic features and risk factors of a particular pattern of fat redistribution (FR), characterized by a progressive enlargement of breast and abdominal girth associated with a wasting of the lower limbs, observed in HIV-infected women treated with combined antiretroviral (ARV) therapy. DESIGN: Cross-sectional study. SETTING: Outpatients attending the Institute of Infectious Diseases, University of Milan, Milan, Italy. PATIENTS AND METHODS: HIV-infected women treated with two or more ARV drugs, observed between December 1997 and February 1998. FR was confirmed by means of a physical examination and dual-energy X-ray absorptiometry (DEXA). The metabolic and endocrinological measurements in patients with FR were compared with those in FR-free women. RESULTS: FR was observed in 32 out of 306 women (10.5%). DEXA revealed more trunk fat (P < 0.01) and less leg fat (P < 0.001) in the patients with FR than in the matched controls. There were no significant differences in laboratory test results between the two groups. All of the FR patients were taking lamivudine-containing regimens; 20 of them were also taking a protease inhibitor (PI). The association of FR with lamivudine-including regimens was statistically significant (P = 0.017). Among the patients taking lamivudine, the risk associated with treatments including PI was 1.8 (95% CI 0.8-3.8, P = 0.12). A total duration of ARV therapy of more than 1000 days was associated with a greater risk of developing FR (OR 10.8; 95% CI 1.4-80.5; P = 0.0207). Stepwise logistic regression analyses indicated that prolonged ARV therapy and a viral load of more than 10000 copies per ml at the beginning of the last ARV regimen were the only variables that significantly and independently correlated with the risk of FR. CONCLUSIONS: The observed body modifications are caused by a redistribution of body fat without fat loss that is apparently not associated with hyperlipidemia, altered glucose metabolism or other endocrinological disorders. The development of FR in patients receiving only reverse transcriptase (RT) inhibitors suggests the presence of a PI-independent mechanism that deserves further investigation.

Clinical outcome and predictive factors of failure of highly active antiretroviral therapy in antiretroviral-experienced patients in advanced stages of HIV-1 infection.

OBJECTIVE: To verify the effectiveness of highly active antiretroviral therapy (HAART) and to identify any factors predictive of clinical outcome in a clinical setting. DESIGN: Observational study. METHODS: Treatment failure (i.e., the occurrence of new or recurrent AIDS-defining events, death or any definitive discontinuation) and the course of CD4+ cell counts and HIV RNA copies were evaluated in 250 heavily pretreated HIV-infected patients starting HAART [153 with indinavir (IDV), 55 with ritonavir (RTV), 43 with saquinavir (SQV)]. Univariate and multivariate analyses were performed to identify predictors of worse outcome. RESULTS: During a median follow-up of 8 months, 75 patients (30%) had treatment failure because of the occurrence of an AIDS-defining event or death (n = 24), inefficacy (n = 24), or severe intolerance (n = 27). Twenty new and six recurrent AIDS-defining events, and nine deaths occurred (six out of 20 AIDS-defining events and two out of nine deaths within 1 month of treatment). CD4+ counts were above 200 x 10(6)/l at AIDS diagnosis in only two patients. None of the SQV patients, 12 (7.8%) of the IDV patients, and 15 (27.3%) of the RTV-treated patients were considered non-compliant. The SQV-containing regimens independently correlated with treatment failure (relative risk, 2.46; 95% confidence interval, 1.20-5.03; versus IDV). Low compliance partially determined outcome in RTV-treated patients; both severe immunodepression and AIDS at baseline were predictive of treatment failure. There was a 10-fold increase in CD4+ cell counts in the patients treated with IDV and RTV; the best virological outcome occurred in IDV-treated patients, with 68.4% of patients showing undetectable HIV RNA copies after 6 months. CONCLUSIONS: HAART was effective in 70% of patients; low compliance and previous AIDS diagnosis represented predictive factors of therapy failure.

CD4 cell counts at the third month of HAART may predict clinical failure.

OBJECTIVE: To evaluate the influence of immunological and virological markers on clinical outcome in patients receiving their first highly active antiretroviral therapy (HAART) regimen. DESIGN AND METHODS: Observational study of 585 patients initiating HAART in a clinical setting. Clinical failure was defined as the occurrence of new or recurrent AIDS-defining events or death, and was analysed by means of intention-to-treat, univariate and multivariate analyses. An adjusted Cox regression model was used to evaluate the effect of 3-month CD4 cell counts on clinical outcome. RESULTS: Clinical failure occurred in 55 patients (9.4%) during a median follow-up of 483 days (range 33-1334 days): 45 new AIDS-defining events (ADEs) in 38, ADE recurrence in six, and death in 11. Twenty-four of the 45 new ADEs (53.4%) occurred during the first 3 months of HAART, and 11 of 45 (24.4%) in the presence of CD4 cell counts > 200 x 10(6) cells/l. The mean (median, range) CD4 counts were 144 x 10(6) cells/l (128, 4-529) in patients with and 322 x 10(6) cells/l (288, 14-1162) in patients without clinical failure (P < 0.0001). Moreover, the proportion of patients with mean CD4 cell counts < 200 x 10(6) cells/l was higher in those experiencing subsequent clinical failure (X2 test: 26.75; P < 0.00001). Multivariate analysis showed that baseline CD4 cell counts < 50 x 10(6) cells/l and AIDS at enrolment predicted failure; after adjusting for 3-month CD4 cell counts, this marker was the only one independently associated with clinical failure (hazard risk, 4.79; 95% confidence interval, 1.40-16.47). CONCLUSIONS: The 3-month immunological response is a reliable predictor of long-term clinical outcome.

A common variant of endothelial nitric oxide synthase (Glu298Asp) is an independent risk factor for carotid atherosclerosis.

BACKGROUND AND PURPOSE: Endothelium-derived NO is formed from L-arginine by endothelial NO synthase (eNOS) encoded by the NOS 3 gene on chromosome 7. Because several studies have indicated that NO plays a key role in the development of the atherosclerotic process, we investigated whether common variants in the eNOS gene are associated with an increased risk of plaque on carotid arteries. METHODS: We studied 375 subjects attending the hypertension center of our institution to be screened for arterial hypertension. The examined subjects were classified according to the presence of carotid plaques (intima-media thickness >/=1.5 mm), and 2 intronic (CA and 27-bp repeats) polymorphisms and 1 exonic (Glu298Asp) polymorphism of the eNOS gene were explored. RESULTS: Only the Glu298Asp polymorphism of eNOS was associated with the presence of carotid plaques (P:<0.05). In particular, there was an excess of homozygotes for the Asp298 variant among subjects with carotid plaques, whereas the number of subjects who had the Glu298 allele in exon 7 of the eNOS gene was equally distributed in both study groups. Interestingly, the risk of having carotid plaques was increased approximately 3 times in subjects who were homozygotic for the Asp298 variant compared with subjects who were homozygotic for the Glu298 variant and was independent of the other common risk factors (age, blood pressure, and smoking). CONCLUSIONS: Homozygosity for Asp298, a common variant of the eNOS gene, is an independent risk factor for carotid atherosclerosis in this study population.

Risk factors for woman-to-man sexual transmission of the human immunodeficiency virus. Italian Study Group on HIV Heterosexual Transmission.

A cross-sectional study of stable monogamous couples, recruited from 16 clinical and surveillance centers in Italy between 1987 and 1992, was carried out to investigate the risk factors of woman-to-man sexual transmission of human immunodeficiency virus (HIV). The male partners of all HIV-infected women attending the centers were invited to participate in the study. Of the 275 male partners who were tested for HIV and interviewed with use of a structured questionnaire, 51 were excluded because they had other possible risk factor for HIV infection, no established risk factor was found in the index case, or they had stopped engaging in sexual intercourse. Fourteen of the 224 men (6.3%) were seropositive for HIV. At logistic regression, the highest risks of transmission were for men practicing peno-anal intercourse [odds ratio (OR), 4.6; 95% confidence interval (CI), 1.0-22.2] and for men whose partner had acquired immune deficiency syndrome (AIDS) or a CD4+ lymphocyte count of < or = 400/mm3. No seropositive men were observed among those who were aware of the woman's HIV seropositivity since the beginning of the relationship or were partners of a zidovudine-treated woman. The results suggest that the risk factors described in man-to-woman and man-to-man HIV sexual transmission also operate in woman-to-man transmission.

Incidence and prevalence trends of HIV infection in intravenous drug users attending treatment centers in Milan and northern Italy, 1986-1990.

To assess the incidence and time trends of human immunodeficiency virus (HIV) infection among intravenous drug users (IVDUs) and to evaluate the opportunities for prevention, we studied IVDUs recruited from 23 drug dependence treatment centers in Milan and Northern Italy. Participants were screened for HIV antibodies, and seronegative subjects were enrolled. A preventive intervention, based on counseling and HIV antibody testing, was done, and participants were invited to the centers for follow-up visits. We enrolled 1,532 subjects between 1 January 1987 and 31 October 1990, and we observed 901 subjects for an average of 15.9 months. Forty-one cases of HIV infection occurred, giving a seroconversion rate of 6.1% in 1987, 4.1% in 1988, 2.2% in 1989, and 1.6% in 1990. HIV prevalence decreased from 54% in 1986 to 49% in 1989. Incidence rates were higher in areas with high prevalence. During follow-up, 35 to 55% of the subjects stopped injecting heroin intravenously altogether, and those who did not stop decreased the frequency of syringe sharing. This is probably the reason for the decline in seroconversion rates, while the apparent decline in prevalence may be due to the entry of new seronegative individuals and/or to differential withdrawal of HIV-positive individuals from the IVDU population to the heterosexual (non-IVDU) population.

Man-to-woman sexual transmission of HIV: longitudinal study of 343 steady partners of infected men.

To study incidence and risk factors of heterosexually transmitted HIV infection, we followed a cohort of 343 seronegative women, stable, monogamous partners of infected men whose only risk of acquiring HIV was sexual exposure to the infected partner. Nineteen seroconversions occurred in 529.6 person years (py) of observation, yielding an incidence rate of 3.6 per 100 py. The incidence rate was 7.2 per 100 py among women who did not always use or never used condoms and 1.1 among those who always used them [relative risk (RR) 6.6, 95% confidence interval (CI) 1.9-21.9]. Anal sex was associated with a risk increase in only those women not always using condoms (RR 1.4, 95% CI 0.4-4.8). No seroconversions were observed among 22 women using oral contraceptives. One of the women using intrauterine devices seroconverted. In couples who did not always use condoms, seroconversions occurred more frequently in partners of men with symptomatic diseases, with a low CD4+ cell number (< 400 per mm3) or with a detectable p24 antigen. In couples not always using condoms and where the man had a low CD4+ cell count, the joint presence of blood viral antigens and AIDS symptoms conditioned a fivefold increased risk of seroconversion of the woman (RR 5.4, CI 1.4-20.3). At multivariate analysis, women with longer relationships (> or = 1 year) showed a lower risk of seroconversion (RR 0.3, CI 0.1-0.8), and those partners of men positive for p24 antigen in serum had an increased risk of seroconversion (RR = 4.0, CI 0.1-0.8).

The occurrence of motor fluctuations in parkinsonian patients treated long term with levodopa: role of early treatment and disease progression.

The aim of this study is to evaluate what factors influence the risk of occurrence of motor fluctuations in patients with Parkinson's disease (PD) with particular reference to the role of early or delayed introduction of levodopa therapy during the course of the disease. One hundred twenty-five consecutive newly diagnosed patients with PD started levodopa treatment at the time diagnosis and were followed for 2 to 10 years. During follow-up, 60 patients had wearing-off or early morning akinesia. We estimated the cumulative time-dependent risk of motor fluctuation occurrence through a multivariable analysis. The risk was lower for patients with tremor-predominant PD, for those with shorter disease duration prior to levodopa, and for those who were relatively older at levodopa initiation. Our results suggest that, as far as motor fluctuations are concerned, disease prognosis is not influenced by early levodopa treatment. These observation support the introduction of levodopa as soon as there is a subjective need for the patients to maintain their level of social and work performance.