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Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology. © 2018 American Association for the Advancement of Science. All rights reserved.

In this retrospective study on 141 HIV-positive subjects, allergy was studied by a specific questionnaire and the Phadia-Top-Test, an in vitro screening test detecting specific IgE; both were correlated to the patient's history, clinical symptoms and the treatment used. Allergy was studied in reference to HIV-negative controls and in relation to the clinical and biological subgroups of HIV patients. The application of the x2 test demonstrated a high incidence of allergy and a specific relation to the HIV infection compared to the controls as well as in relation to the clinical stage of the infection. Atopy was not specifically related to the HIV infection despite the higher frequency found in the AIDS-IKEL group. A significant number (21%) of patients with T4 > 300/μ1 considered immunocompetent presented clinical manifestations of AIDS-IKEL and 100% of these patients were allergic. A significant number (19%) of patients with T4 < 300/μ1 considered immunodeficient were asymptomatic and 75% of them were allergic. Thus allergic symptoms may transiently be the only clinical manifestations in HIV infection and possibly a co-factor for the evolution of the disease due to the immunomodulatory function of the mediators, the cytokines and the proteases released during allergic reaction.

Cocaine remains the second most commonly used and trafficked illicit drug in the world after cannabis. This psychostimulant drug has become an essential part of the world drug scene with a different use among countries. Prevalence of cocaine use (lifetime, last year, last month use) is particulary high among males aged between 15 and 34 years. Five per cent of cocaine users will develop a substance- dependence during the first year of use, and 20% of these will become long-term cocaine-dependent patients. The number of patients entering drug treatment for primary cocaine use has been increasing in Europe for several years. Cocaine addiction is a worldwide public health problem, which has somatic, psychological, psychiatric, socio-economic and judicial complications. This article aims to provide the clinician with a detailed description of the clinical aspects, the adverse effects and the complications of cocaine addiction. Literature searches were conducted for the period from January 1985 to February 2012 using PubMed, EMBASE, PsycInfo, and Google Scholar.

In this retrospective study 141 HIV positive subjects were included. Allergy was studied by a specific questionnaire and the Phadia Top Test, an in vitro screening test for specific IgE. Both were related to the patients' history, clinical symptoms and the treatment used. Allergy was studied in reference to HIV negative controls and in relation to the clinical and biological subgroups of HIV patients. The statistical analysis (x 2 test) demonstrated a relationship between allergy and HIV infection and the clinical stage of AIDS-IKEL among patients with CD4300 microliters, which may suggest that allergy contributes to the functional deficiency of these cells. We also demonstrated a high frequency of hypersensitivity reactions (75%) in HIV asymptomatic patients with CD4300 microliters, which indicates that allergy could contribute to the early destruction of these cells. The allergic patients declared to be hypersensitive before contamination. Both mechanisms, functional deficiency and destruction of CD4 T-lymphocytes could be the result of the mediators, cytokines and enzymes released from the mast cells during IgE allergic reaction. Thus this study demonstrated that allergy could be a predisposing factor for the contamination and a polyvalent co-factor for the clinical and biologic evolution of HIV infection.

This multicenter retrospective study concerns 594 cases of HIV-1 positive patients. The majority were asymptomatic. Some had Aids-related complex and some had AIDS. They were all seen in seven hospitals of the western outskirts of Paris and in one Paris hospital between 1983 and 1988. There was a predominance of homosexuals and of cases of AIDS in the center of Paris. Intravenous (IV) drug users and asymptomatic cases were more numerous in the city outskirts, a reflection of the populations at risk around each hospital. The proportion of cases of AIDS was lower among IV drug users than among homosexuals or bisexuals probably due to the fact that the viral infection was discovered at an earlier stage in a population contaminated at a later date or to the tendency to ask for the test "systematically" in drug addicts. 22% of the cases were women with a sex ratio of 3.5. HIV infection was attributed to use of intravenous drugs in 51% and to heterosexual transmission in 18% of the women. But the incidence of heterosexual transmission increased significantly, essentially in women. Overall, the incidence of infection by the HIV 1 has decreased since 1986. A number of recent publications seem to indicate the same tendency. But this fundamental observation remains to be validated by further studies. The yearly incidence of AIDS increases. The 5 year calculated actuarial rate of probability of remaining asymptomatic decreased to 40% in 385 initially asymptomatic patients.

The fast growth of AIDS augurs, in the coming years, that the surgical complications will become more frequent. Of some 680 patients under medical treatment for HIV, in Laennec’s Hospital, 106 were op

The revelation of an acceptable rate of users still treated one year after initiation of a substitution program with high-dose buprenorphine (HDB) has contributed in the validation of the interest of the molecule in this indication. However the frequency of early drop-outs (after the first consultation), when treatment is set-up, is frequently evoked, although undocumented, by general practitioners.During analysis of a survey on the follow-up of opiate addicts starting substitution therapy with HDB, we attempted to assess the frequency of early drop-outs and identify the contributing factors.Among the 1085 patients included in the study and in whom induction therapy had been prescribed, 656 were assessed after 12 months' follow-up.Age, precariousness, lack of social support and partial access to care (lack of health insurance, previous contact with the prescriber) were significantly associated with early drop-out. The consumption of psychoactive products and their administration mode, during the 30 days prior to the first consultation of those loss to follow-up, also differed from those of patients who remained within the care system.Knowledge of the factors related to frequent early drop-out during induction of HDB substitution therapy, and bearing this in mind, would permit the organisation of more attentive management and hence reduce the drop-out rate.

Care for opioid users changed greatly in France in 1996 when general practitioners (GP) were allowed to prescribe high-dose sublingual buprenorphine (Subutex((R))) for maintenance treatment of major opioid dependence. In order to evaluate treatment benefits, a prospective epidemiological 2-year follow-up was initiated in May 1996 with the participation of 105 French GPs.A cohort of outpatient opioid users who started high-dose sublingual buprenorphine maintenance therapy at study onset or who had recently started were included in a prospective epidemiological study by GPs involved in management of drug abusers. Patients were followed for 2 years with collection of standardized information at 1, 3, 6, 12, and 24 months. The main evaluation criteria were follow-up by the same GP throughout the study and retention in the care system 2 years later. For patients who fulfilled these criteria, secondary end points were analyzed: information about buprenophine prescription, social status, and hepatitis B and C and HIV seroconversions.The 101 GPs included 919 patients and 909 were analyzed 2 years later. At study onset, a majority of the patients (70.6%) were taking an ongoing maintenance treatment, 10.5% had previously received such a treatment and the treatment was initiated for 18.8%. At the end of the study, 508 patients (55.9%) were still being followed by the same GP and 101 (11.1%) were followed by another healthcare provider (another GP, hospital or specialized center). No information about the care giver was available for 82 patients (9%). Among the other patients, 123 (13.5%) were lost to follow-up, 24 (2.6%) had moved, 23 (2.6%) were incarcerated, 11 (1.2%) had successfully discontinued drug usage and 7 (0.8%) had died. Other reasons for unsuccessful follow-up by the same GP were mainly (for 6 patients each): relapse, switch to methadone, no medical information, non-compliance with scheduled controls. Among the patients followed by the same GP, declaration of heroin and drug intake significantly decreased (p0.001), and social status (GAF scale) and TMSP evaluation significantly improved (p0.001). The social situation (housing condition and work) also improved significantly (p0.001). The rate of buprenorphine treatment was 84% with longer and less fractionated prescriptions. The HBV, HBC and HIV seroconversion rates were low in this high-risk population (2.7%, 4.1% and 0.8% respectively).This two-year follow-up of 909 opioid users showed that nearly 70% of the patient remained within the healthcare system, mainly with the same GP or more rarely with another practitioner. Among the 508 patients still followed by the same GP, maintenance treatment with high-dose buprenorphine was observed in more than 80% of the patients. These patients had a significantly improved social status, a significant decrease in drug intake and a significant improvement in their social adaptation and severity of drug abuse.

Since 1994-1995, rapid development of widely available substitution treatments has appeared to be a major healthcare step in heroin addiction. Currently approximately 60000 patients are taking daily maintenance doses of oral methadone and about 7200 are taking sublingual buprenorphine. In parallel with the expansion of these treatments, the number of lethal overdoses has fallen off regularly: 564 in 1994, 393 in 1996 and 143 in 1998 (-74.6% in 4 years).We searched for a correlation between the rise in the number of patients taking maintenance treatments and the decreased in recorded deaths due to heroin overdose. Other factors which may influence this decrease were also considered.A linear correlation was found between the increasing number of patients on maintenance treatment (high-dose buprenorphine or methadone) and the decrease in fatal heroin overdoses in France between 1994 and 1998. The importance of this correlation must be modulated by the presence of other events such as political, social, healthcare and behavioral events concerning drug users.

We report three personal cases of hydrocarbide aspiration pneumonia. High-viscosity non-volatile hydrocarbides (paraffin oil, for instance) cause often pseudotumoral exogenous fat-aspiration lung disease. Low-viscosity volatile hydrocarbides (petroleum, gasoline, white spirit, for instance) cause acute pseudo-infectious lung disease with dyspnea and fever which usually resolves within a few weeks but which may also be life-threatening. Purely symptomatic treatment has greatly progressed with advances in intensive ventilatory assistance. Gastric emptying with emetic agents or lavage procedures is dangerous and must be avoided except for exceptional cases. When required, the airways must be protected with tracheal intubation. Volatile hydrocarbides should be stored in protected areas in containers with safety stoppers which children cannot open.

The concept of addiction has gained recognition in French semantics, standing for a pathological condition that was formerly designated solely on the basis of specific drug abuse. We questioned 90 patients followed at there Parisian outpatient units about their understanding of the term "addiction". We also looked for signs that this term is used to federate notions since it is supposed to describe a general condition involving a large number of singular phenomena. One part of our questionnaire focused on treatment modes (several practitioners for several addictions, one institution for all addictions, specialized consultations with a practitioner other than the usual primary care physician). Our findings would illustrated areas where further details are needed in order to consider patient expectations when designing specialized care for outpatients or inpatients.

The aim of this study was to analyze the role of the imaginary and its link with reality among 30 subjects treated by methadone. The Rorschach test was proposed to 30 heroin addicts treated by methadone, over an average 7 months. The formal answers (used preferentially in the 30 results, though often inappropriately) and socializing landmarks involving considerable individual investment, we were able to identify two ways of working within the same protocol. The first relies most on conformity and adaptation and tries to put the imaginary aside. The second is a more projective, unorganized approach evidencing the influence of the imaginary. This specific imaginary activity could not be assimilated with the traditional "lack of fantasy" observed in heroin addicts. It would be interesting to examine the course of this approach over a longer period.

Early February 1999, the French Ministère de la Jeunesse et des Sports (Youth and Sports Ministry) sponsored three different studies, aiming to prevent harmful behavior in the area of sport practices among youth. Two years earlier, our health care team working with drug users published reports on the meaningfulness of intensive sports activities in the history of our patients. The present work was performed to highlight the midterm results of one of these studies, to better understand and quantify the importance of physical training in the history of a group of outpatients seen for addictive disorders and comorbid pathologies. For 20 consecutive weeks, 3,040 self-administered questionnaires were available for persons consulting 20 health centers, 2 self-help groups and a general practitioner network working in the field of alcohol or heroine abuse. One thousand one hundred and eleven questionnaires were filled out (36.1%) and returned by mail for complete analysis: 86% of the answering persons had practiced at least one sports activity or participated in physical training, 10.5% had participated in a national or international level competition, and 10.6% reported stress fractures. In the intensive sports group, 36% had used illicit drugs intravenously and 16.4% said they had already used doping substances. Only 28.4% said they experienced dependence during their period of intensive sports activities compared with 15.2% before this time, and a majority (56.4%) thereafter. Intensive sports or physical training should not be seen as a protective factor nor as a way of improving addictive behaviors. More studies are needed to evaluate individual vulnerability factors and specific harm of overtraining and to determine the exact periods when men and women participating in sports activities are likely to abuse drugs, especially at the end of their career.

To define the medical characteristics of intravascular drug users in Ho Chi Minh City, Vietnam, we examined 280 men, of whom 235 were infected with human immunodeficiency virus (HIV), being treated in a rehabilitation center. The patients used mainly opium, often in shooting galleries (50%). The prevalence of oral candidiasis (58%) and zoster infection (20%) was high in HIV-seropositive patients, whereas oral hairy leukoplasia and Kaposi's sarcoma were absent. The prevalence of acquired immunodeficiency syndrome was 24%. More than 80% of the patients had infections with hepatitis C virus, hepatitis B virus, cytomegalovirus, or human T cell lym- photropic virus type-1. The CD4 1 cell counts correlated well with viral load. Only HIV-1 subtype E was detected in the 30 patients tested. A cohort study of HIV-infected subjects in this population seems feasible, and would permit introduction of anti-retroviral therapy The large number of HIV-seronegative subjects sharing the same at-risk practices as the HIV-infected subjects raises the possibility of natural protection in this population.

Adequate dosage of sublingual buprenorphine is now recommended for substitution treatment of severe opioid dependance. We report two cases of acute discomfort, probably linked to withdrawal syndrome, after an IV injection of high doses of buprenorphine in opiate dependant patients. Data on the pharmacokinetics and neurobiochemical aspects of buprenorphine are compared with those of other opiates. A major issue of this work is a guideline for inducing substitution treatment with this "unique" partial agonist/antagonist of endorphinic receptors.

Emergencies during HIV infection consist mainly in opportunistic infections. They are varied and the physician should keep an "internist's eye" on the condition; they also require emergency complementary examinations for confirmation of diagnosis. If such diagnostic tests cannot be rapidly made, treatment should be started on the basis of presumption and frequency. In France, the most frequently observed opportunistic infections are: pneumocystosis, cerebral toxoplasmosis and candidiasis. Tuberculosis is a major concern of those responsible for public health care. Surgical complications following infections or opportunistic tumours, are rare and of poor prognosis. Iatrogenic complications (haematologic, cutaneous and infectious) are also reasons for emergency care.

In AIDS patients an acalculous cholecystitis may be responsible for abdominal pain subsiding after cholecystectomy. But the indications for cholecystectomy are not clear: cholecystitis is usually associated with diffuse cholangitis and this might cause the symptoms. Since 1985, 8 AIDS patients have undergone cholecystectomy for acute cholecystitis. Ultrasonography revealed a 5 to 12 mm thickening of the gallbladder wall in all of them and gallbladder stones in two; four patients had cholangitis. The decision to operate was based on persistent pain associated with fever, poor general condition and muscular rigidity at palpation. Four patients had septic shock at the time of surgery; one died in the immediate postoperative period. In all other patients pain and septic syndrome subsided. Two patients died of AIDS complications 20 days after surgery; the remaining five died of AIDS 6, 9, 10, 12 and 14 months respectively after surgery; in two of them cholestasis had reappeared due to cholangitis. To summarize, in the 8 AIDS patients studied cholecystectomy was performed for clinical deterioration. Gallbladder pathology was responsible for the abdominal pain and the febrile general condition which was relieved by cholecystectomy.

This multicenter retrospective study concerns 594 cases of HIV-1 positive patients. The majority were asymptomatic. Some had Aids-related complex and some had AIDS. They were all seen in seven hospitals of the western outskirts of Paris and in one Paris hospital between 1983 and 1988. There was a predominance of homosexuals and of cases of AIDS in the center of Paris. Intravenous (IV) drug users and asymptomatic cases were more numerous in the city outskirts, a reflection of the populations at risk around each hospital. The proportion of cases of AIDS was lower among IV drug users than among homosexuals or bisexuals probably due to the fact that the viral infection was discovered at an earlier stage in a population contaminated at a later date or to the tendency to ask for the test "systematically" in drug addicts. 22% of the cases were women with a sex ratio of 3.5. HIV infection was attributed to use of intravenous drugs in 51% and to heterosexual transmission in 18% of the women. But the incidence of heterosexual transmission increased significantly, essentially in women. Overall, the incidence of infection by the HIV 1 has decreased since 1986. A number of recent publications seem to indicate the same tendency. But this fundamental observation remains to be validated by further studies. The yearly incidence of AIDS increases. The 5 year calculated actuarial rate of probability of remaining asymptomatic decreased to 40% in 385 initially asymptomatic patients.

Sixteen patients with Churg-Strauss syndrome (CSS), a disorder characterized by hypereosinophilia and systemic vasculities which complicate preexisting asthma, were analyzed. The mean duration of asthma before CSS was 8 years; peripheral blood eosinophilia was always greater than 1,900/microliters and exceeded 5,000/microliters in 14 cases. The clinical manifestations were the following: 16 in generally poor condition with fever; 12 peripheral neuropathies; 11 cutaneous lesions; 9 pericardial or myocardial involvement; 9 digestive disorders; 9 muscular or articular diseases; 5 renal involvement, all associated with the vasculitis; 7 upper respiratory tract disorders. Chest radiographs showed pleuropulmonary or cardiac anomalies in 11 patients. The diagnosis was confirmed histologically in 11 cases, however, no clinical, biological or evolutive differences were observed between these patients and those with negative biopsies (5). Follow-up for 6.35 +/- 5.55 years was characterized by relapses always preceded by increased eosinophilia. Fourteen patients were successfully treated with corticosteroids, associated with cyclophosphamide in 7 of them. Five-year survival was 87%. Four deaths occurred, all CSS-associated, two because of a poorly adapted therapeutic regimen. The need for rapid and effective treatment must be stressed. The diagnosis can be made based on clinical manifestations alone before histological confirmation can be obtained.

We determined the relative value of the free erythrocyte protoporphyrin (FEP) assay compared to those of total iron-binding capacity (TIBC) and serum ferritin in the diagnosis of iron deficiency in a population of elderly anemic subjects. One hundred and three patients, 65 to 98 years old (mean +/- SD: 81.5 +/- 8.8), with hemoglobin levels of less than 110 milligrams (mean +/- SD: 97 +/- 12, range 53-109) were included in the study. In the patients with iron-deficiency anemia due solely to chronic bleeding, mean values for the three parameters were highly different from those in patients without chronic bleeding. In the patients with anemia due to an association of chronic bleeding and chronic inflammation, the mean FEP value was very significantly different (p less than 0.001) from that in the patients with chronic inflammation but without bleeding, whereas this was not the case for TIBC or serum ferritin. The sensitivity of FEP in the diagnosis of iron deficiency due to chronic bleeding in this population of anemic subjects was 60% (specificity 90%), compared to 13% (specificity 96%) for TIBC and 20% (specificity 100%) for serum ferritin. The FEP assay thus emerges as being highly suitable for the diagnosis of iron-deficiency anemia in the elderly subject, particularly when bone marrow is not examined.

In the first National Health and Nutrition Examination Survey (NHANES I) there were 3,479 persons aged 65-74 years corresponding to 12,773,000 in this age group in the total population. Presented here are major findings on the nutritional status of this age group in respect to 1) dietary intake (based on a 24-hour recall) and dietary frequency, 2) selected biochemical and hematological tests, 3) prevalences of clinical signs associated with deficiencies of nine essential nutrients, and 4) selected anthropometric measurements. These findings will be presented by sex, two racial groups (black and white), and two income groups (poverty index ratio (PIR) below and above unity). Some correlations between clinical signs and dietary intake comparing persons with signs and those without signs are shown. Some trends between dietary intake and biochemical values, on the one hand, and biochemical values and clinical signs, on the other hand, will be touched upon. The findings are discussed in relation to dietary adequacy and nutritional risk of the different subgroups. Some paradoxical results are discussed and the need for urgent research on the so-called secondary or conditioned deficiencies specifically in this age group are pointed out.

A histopathologic and immunopathologic study of changes in small vessels has been carried out on 168 amputated lower extremities. No difference was found in respect to the frequency of thrombotic or atheromatous lesions among the various clinical disease categories necessitating amputation. An increased frequency of inflammatory lesions of small vessels was found only in cases of osteomyelitis. The frequency of hemodynamic lesions was highest in nondiabetic subjects with arteriosclerosis, and second highest in diabetic subjects with arteriosclerosis, followed by thromboangiitis obliterans. Proliferative endothelial lesions were encountered most frequently in diabetes with arteriosclerosis, in osteogenic sarcoma, and in osteomyelitis. Such proliferative lesions were encountered in 80 per cent of diabetic subjects and in 20 per cent of nondiabetic individuals. Fluorescent insulin binding by small vessels was found in 70 per cent of diabetic subjects with proliferative vascular lesions and in only 30 per cent of diabetic individuals without this proliferative microangiopathy. Such insulin binding was observed in 54 per cent of diabetic subjects and in only about 15 per cent of nondiabetic patients. The binding of fluorescent rabbit antihuman globulin was observed in 56 per cent of diabetic subjects and in 22 per cent of nondiabetic patients. These findings are discussed in relation to the thesis that there may be diseases of immune origin primarily involving small peripheral vessels. The peripheral vascular disease of diabetes is particularly stressed here because it is probably the most common form of such disease of immune origin. Such pathologic processes in small vessels may secondarily involve large cognate system arteries, either by creating an increased peripheral resistance to the flow of blood or when lesions involve the vasa vasorum, there may be impairment of local nutrition. Either or both of these phenomena could intensify the development of arteriosclerosis of large trunk arteries. Although no attempt has been made here to justify or negate the existence of thromboangiitis obliterans as a disease entity, it has been pointed out that at least some cases with this diagnosis may have a similar immune origin.

The hour of day of primary ventricular tachycardia (VT) in the acute phase of myocardial infarction was studied in 63 consecutive patients without cardiac failure or antiarrhythmic therapy, admitted to hospital less than 6 hours after the onset of chest pain. There were 19 women and 44 men, with an average age of 63 years. The site of infarction was anterior in 23 cases, posterior in 34 cases and circumferential in 6 cases. The cardiac rhythm was analysed from the 6th hour following the onset of chest pain for 4 days, using a HP 98220 A computerised analyser CPK levels were measured daily. Ventricular tachycardia occurred in 73% of cases with no significant difference between daytime (18 patients) and night time (28 patients). The patients developing VT did not differ from the remainder with respect to age, sex, or site of ECG changes, but peak CPK levels were significantly higher than in patients without VT. The risk of VT decreased slowly as the interval from the onset of chest pain increased and fell practically to zero after the 40th hour. Diurnal and nocturnal VT were independent of age, sex or site of infarct. However, nocturnal VT correlated independently of the time of onset of chest pain to high values of CPK. There was no difference with respect to age, sex, location of infarct or incidence of ventricular tachycardia between infarcts with pain starting during the day, and infarcts with pain starting at night. However, when the pain started during the day, the peak CPK was significantly higher and there were significantly more attacks of nocturnal ventricular tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)