Search

International audience; The objective of this cross-sectional survey was to assess the prevalence of psychoactive substance use (PSU) in people attending 11 French Sexual Transmitted Infection Centers, and to specify their profiles (PSU and link with risky sexual behaviors) using the ascending hierarchical clustering method. Among the 5220 individuals who completed the survey, 55.6% were men and the median age was 24 years [IQR: 20-31]. Among the participants, 2751 (52.7%) reported PSU at least once in their life. Ascending hierarchical clustering identified seven distinct profiles of participants based on their PSU. This study shows a high prevalence of PSU and alcohol consumption in this young population. Moreover, subgroup analysis allowed identifying groups of psychoactive substance users who presented specific risks or vulnerabilities and who should be priority targets for interventions, particularly sexual minority groups.

Objectives Screening, brief intervention and referral to treatment (SBIRT) is an evidence-based practice used to identify, reduce and prevent problematic use and abuse of, and dependence on, tobacco, alcohol and psychoactive substances. To date, the pertinence of this practice among people living with HIV (PLHIV) is unknown. In this pilot study, we aimed to assess the acceptability of SBIRT in a cohort of HIV-infected out-patients who were asked about their consumption of alcohol, tobacco and psychoactive substances. Methods A monocentric study was performed at the University Hospital of Montpellier. In a 6-month period, 20 trained physicians screened for the consumption of alcohol [using the Alcohol Use Disorders Identification Test (AUDIT)], tobacco (using the Short Fagerstrom Test) and psychoactive substances [using the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) V3.0] via an auto-questionnaire and proposed a brief intervention to patients with misusage. Results One thousand and eighteen PLHIV completed the questionnaire, and 861 [84.6%; 95% confidence interval (CI) 82.2-86.7%] PLHIV returned it to the physician. Among the latter, 650 patients wished to discuss the answers with their physician (75.5%; 95% CI 72.5-78.3%), and brief interventions were realized in 405 patients (62.3%). Conclusions SBIRT is a simple screening and harm reduction tool that is well accepted by PLHIV in out-patient clinics. This method could be implemented in routine HIV care to screen and manage patients systematically for harmful substance use.

International audience

Despite satisfactory efficacy of WHO-recommended second-line antiretroviral treatment for patients with HIV in low-income countries, the need for simplified, low-cost, and less-toxic maintenance strategies remains high. We compared boosted protease inhibitor monotherapy with dual therapy with boosted protease inhibitor plus lamivudine in patients on second-line antiretrovial therapy (ART).We did a multicentre, randomised, parallel, open-label, superiority, trial in the HIV services of five hospitals in sub-Saharan Africa (Yaoundé, Cameroon; Dakar, Senegal; and Bobo Dioulasso, Burkina Faso). We recruited patients from the long-term, post-trial cohort of the ANRS 12169/2LADY study that compared the efficacy of three second-line combinations based on boosted protease inhibitors. Participants for our study were HIV-1 infected with multiple mutations including M184V, at first-line failure, aged 18 years and older, on boosted protease inhibitor plus two nucleoside reverse transcriptase inhibitors (NRTI) for at least 48 weeks with at least 48 weeks follow-up in the 2LADY trial, with two viral load measurements of less than 200 copies per mL in the previous 6 months, CD4 counts of more than 100 cells per μL, adherence of at least 90%, and no change to ART in the past 3 months. We randomly assigned participants (1:1) to receive either monotherapy with their boosted protease inhibitor (once-daily darunavir 800 mg [two 400 mg tablets] boosted with ritonavir 100 mg [one tablet] or coformulation of lopinavir 200 mg with ritonavir 50 mg [two tablets taken twice per day]) or to boosted protease inhibitor plus once-daily lamivudine 300 mg (one 300 mg tablet or two 150 mg tablets). Computer-generated randomisation was stratified by study site and viral load at screening (50 copies per mL, and 50-200 copies per mL), and concealed from study personnel throughout the inclusion period. After randomisation, treatment allocation was not masked from clinicians or patients]. Patients had follow-up visits at weeks 4 and 12, and every 3 months until 96 weeks; if viral load exceeded 500 copies per mL at any visit, NRTI (tenofovir and lamivudine) were reintroduced into treatment. The primary outcome was the proportion of participants who had treatment failure at 96 weeks in the intention-to-treat analysis, where treatment failure was defined as one of the following: a confirmed viral load of more than 500 copies per mL, reintroduction of NRTI, or interruption of boosted protease inhibitor. We designed the study to detect a difference of 12% between groups in the primary outcome, with an expected 20% of patients having treatment failure in the monotherapy group. This study is registered with ClinicalTrials.gov, number NCT01905059.Between March 5, 2014, and Jan 26, 2015, 265 participants were assigned to receive monotherapy (133) or boosted protease inhibitor plus lamivudine (132). At week 48, an independent data safety monitoring board reviewed data, and advised discontinuation of the monotherapy group because the number of failures had exceeded the expected 20%; therefore results here are for week 48. At this point, treatment failure occurred in four (3·0%; 95% CI 0·8-7·6) of 132 participants on dual therapy and 33 (24·8%; 17·7-33·0) of 133 participants on monotherapy (relative risk 8·2, 95% CI 3·0-22·5; odds ratio 10·6, 95% CI 3·6-42·1). The difference between groups (21·8%, 95% CI 13·9-29·7; p0·0001) showed superiority of dual therapy compared with monotherapy. We recorded 46 severe adverse events of grade 3 or 4 (29 in the monotherapy group, 17 in the boosted protease inhibitor plus lamivudine group); one event in the montherapy group (intoxication resulting from co-administration of ritonavir-boosted lopinavir with an ergotamine derivate) was deemed related to study drug. Two participants in the monotherapy group and one in the dual therapy group died, all from causes not related to study drugs or procedures (one from complications from gastric cancer surgery, one in a work accident, and one from a lung disease of unknown cause).After viral suppression with boosted protease inhibitor plus NRTI in second-line ART, maintenance therapy with boosted protease inhibitor plus lamivudine was associated with a high rate of success, despite the presence of M184V mutations at first-line treatment failure. Results indicated that boosted protease inhibitor monotherapy cannot be recommended for these patients.Agence National de Recherche sur le Sida et les hépatites and Janssen Pharmaceutica.

International audience; Direct-Acting Antivirals (DAAs) opened a new era in HCV treatment. We report the impact of HCV treatment in French HIV-HCV coinfected patients. METHODS: All HIV-HCV patients from the Dat'AIDS cohort followed between 2012 and 2015 were included. HCV status was defined yearly as naive, spontaneous cure, sustained virological response (SVR12), failure or reinfection. RESULTS: Among 32,945 HIV-infected patients, 15.2% were positive for anti-HCV antibodies. From 2012 to 2015, HCV incidence rate increased from 0.35%PY to 0.69%PY in MSM, while median incidence was 0.08%PY in other patients. Median reinfection rate was 2.56%PY in MSM and 0.22%PY in other patients. HCV treatment initiation rate rose from 8.2% in 2012 to 29.6% (48.0% in pre-treated patients vs 22.6% in naïve patients). SVR12 rate increased from 68.7% to 95.2%. By the end of 2015, 62.7% of the patients were cured either spontaneously or following SVR. CONCLUSIONS: HCV treatment dramatically increased in HIV-HCV patients in France from 2012 to 2015 resulting in HCV cure in nearly two-thirds of the patients in this cohort. Combined with a declining HCV prevalence, the prevalence of active HCV infection among HIV patients will drastically decrease in the forthcoming years.

Overexpression of the Fc receptor CD64 on neutrophils is associated with innate immune response and bacterial infections. During HIV infection a large set of immune disorders including T-lymphocyte over-activation, microbial translocation, impairment of neutrophil functions, and immunodeficiency may interplay with neutrophil CD64 expression.Associations of neutrophil CD64 expression with CD8Higher neutrophil CD64 expression was observed in HIV infected subjects compared to healthy controls (0.91 vs. 0.75, P 0.001). Among 115 HIV infected patients, nine (8.8%) had a CD64 expression over the clinical threshold as calculated against bead standard (i.e., 1.5). HIV viremic patients were more likely to have an index above 1.5 (OR: 6.68, P values: 0.01). A trend for correlation between CD64 expression and CD8 T cell activation was observed (P values: 0.08). Blood CD4HIV infection and HIV replication are associated with up-regulation of neutrophil CD64. CD64 overexpression above the clinical threshold was observed in a minor proportion of HIV infected individuals treated by antiretroviral therapy and may be a marker of neutrophil activation related to non-AIDS-linked comorbidities. © 2016 International Clinical Cytometry Society.

International audience; There is no consensus on a diagnostic strategy for osteomyelitis underlying pressure ulcers. We conducted a prospective study to assess the accuracy of multiple bone biopsies and imaging to diagnose pelvic osteomyelitis. Patients with clinically suspected osteomyelitis beneath pelvic pressure ulcers were enrolled. Bone magnetic resonance imaging (MRI) and surgical bone biopsies (three or more for microbiology and one for histology per ulcer) were performed. Bacterial osteomyelitis diagnosis relied upon the association of positive histology and microbiology (at least one positive culture for non-commensal microorganisms or three or more for commensal microorganisms of the skin). From 2011 to 2014, 34 patients with 44 pressure ulcers were included. Bacterial osteomyelitis was diagnosed for 28 (82.3%) patients and 35 (79.5%) ulcers according to the composite criterion. Discrepancy was observed between histology and microbiology for 5 (11.4%) ulcers. Most common isolates were Staphylococcus aureus (77.1%), Peptostreptococcus (48.6%) and Bacteroides (40%), cultured in three or more samples in 42.9% of ulcers for S. aureus and ≥20% for anaerobes. Only 2.8% of ulcers had three or more positive specimens with coagulase-negative staphylococci, group B Streptococcus, and nil with enterococci and Pseudomonas aeruginosa. Staphylococcus aureus, Proteus and group milleri Streptococcus were recovered from one sample in 22.8%, 11.4% and 11.4% of ulcers, respectively. Agreement was poor between biopsies and MRI (κ 0.2). Sensitivity of MRI was 94.3% and specificity was 22.2%. The diagnosis of pelvic osteomyelitis relies on multiple surgical bone biopsies with microbiological and histological analyses. At least three bone samples allows the detection of pathogens and exclusion of contaminants. MRI is not routinely useful for diagnosis.

Describe systemic antifungal therapy in non-neutropenic adult patients in intensive care unit (ICU).A prospective, observational study was conducted during the first half of 2010 in the 7 ICU in a hospital with medical consultant on antimicrobial therapy. All non-neutropenic consecutive adult patients receiving systemic antifungal therapy for documented or suspected invasive fungal infection (IFI) apart from aspergillosis were included.Out of 1502 patients admitted in ICU, 104 (7 %) underwent systemic antifungal therapy, including 30 (29 %) for a documented IFI and 74 (71 %) for a suspected IFI. Candida albicans was identified in 23 (77 %) of the IFI and 45/52 (86 %) of the broncho-pulmonary and/or urinary colonizations in suspected IFI. Echinocandin was significantly more prescribed in patients with a documented infection (19/30 patients) and fluconazole in patients with a suspected infection (48/74 patients). The first line therapy was primarily stopped after recovery (11/30 patients) or de-escalation (9/30 patients) in documented infections, and for lack of indication (34/74 patients) or due to recovery (21/74 patients) in suspected infections after on average of 7 days of treatment.For ICU non-neutropenic adult patients in our center, antifungal therapy is prescribed two times out of three for suspected, unproved infections, in most cases with fluconazole. Documented infections were more often treated by echinocandin with secondary de-escalation. An interventional prospective study to assess the role of antifungal pre-emptive or empirical therapy is necessary.

The aim of the study was to compare the metabolic and morphological effects of enfuvirtide plus an optimized background (OB) regimen vs. OB alone (control group) in treatment-experienced patients in the T-20 vs. Optimized Regimen Only (TORO) studies.Body composition and metabolic changes were investigated in patients over 48 weeks, based on fasting chemistries, body weight, and other anthropometric measurements. Dual-energy X-ray absorptiometry (DEXA) and computed tomography (CT) scans were performed in a patient subgroup (n=155) at baseline and at weeks 24 and 48.At week 48, mean changes from baseline were similar between treatment groups for glucose, insulin, C-peptide, total cholesterol, low-density lipoprotein (LDL) cholesterol, very low density lipoprotein (VLDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglyceride levels. The enfuvirtide group experienced a significant increase in body weight [mean change from baseline +0.99 kg; 95% confidence interval (CI) +0.54, +1.44] and, in those who had body scans, there was a significant increase in truncal fat (by DEXA: median change +419.4 g; 95% CI+71.3, +767.5) and total fat [visceral adipose tissue (VAT)+subcutaneous adipose tissue (SAT) by single-slice abdominal CT scan: median change +25.5 cm(2) ; 95% CI+8.9, +42.0] over 48 weeks; significant increases in these parameters were not seen in the control group. There was no significant change in truncal:peripheral fat ratio in either the enfuvirtide or the control group.The addition of enfuvirtide to an OB regimen does not appear to have unfavourable effects on fat distribution or metabolic parameters.

The authors had for objective to assess systemic antifungal treatment for candidemia in non-neutropenic patients, in intensive care units (ICU), and compare the results with French 2004 recommendations.A retrospective multicenter study (nine ICU in two teaching hospitals) was made.Thirty-eight non-neutropenic patients with at least one positive blood culture for Candida who had received systemic antifungal treatment were included between May 2004 and September 2007.Thirty-nine cases of candidemia were analyzed. The median age was 54.5 (21-80), the median SAPS II score at admission was 44 (20-79), the median duration of stay in ICU was 22.5 days (2-82), and the death rate was 45%. Candida albicans was identified in 69% of the cases. Eight percent of Candida sp. isolates were resistant or susceptible dose-dependent (S-DD) to fluconazole. Before identification, fluconazole, caspofungin, voriconazole, and amphotericin B were used in 74%, 15%, 5%, and 5% of cases respectively. After identification and antifungal susceptibility determination, fluconazole was used in 68% of cases, caspofungin in 24% of cases, any formulation of amphotericin B in 6% of cases, voriconazole in 3% of cases. The French recommendations were applied in 71% of cases before identification and in 68% of cases after identification and antifungal susceptibility determination.The main causes of non-compliance to recommendations were the use of fluconazole in patients previously exposed to azole agents, the use of caspofungin in hemodynamically unstable patients, and the absence of therapeutic desescalade.

Cryptococcosis is the most common life-threatening opportunistic fungal infection in patients with AIDS; meningitis and meningoencephalitis are the most frequent manifestations. Meningoradicular involvement is exceptional. We report a case of meningoradiculitis due to Cryptococcus appearing after several weeks of antiretroviral and antifungal treatments, managed by corticosteroids, and which was suggestive of immune reconstitution inflammatory syndrome (IRIS). ### Case report. A 32-year-old HIV-infected man presented with a 7-day history of intense headache and vomiting. On admission, he was afebrile and examination was normal (no radicular symptoms). Evaluation of CSF showed no white cells, a moderately elevated total protein (490 mg/L), and normal glucose levels (3 mmol/L). The intracranial pressure was 34 cm H2O. Smear and cultures for bacteria and acid-fast bacilli were negative. An India ink preparation of the CSF revealed encapsulated yeast-like fungi, and Cryptococcus neoformans variety grubii was isolated. The C neoformans antigen latex agglutination test showed elevated titers in both serum (1:16,000) and CSF (1:8,000). The CD4 cell count was 97/μL and viral load was 454 copies/mL. Treatment including IV liposomal amphotericin B (3 mg/kg per day) and flucytosine (100 mg/kg per day) was started, associated with external lumbar derivation for severe intracranial pressure. Highly active antiretroviral therapy was begun 2 weeks after antifungal treatment (abacavir/lamivudine with lopinavir/ritonavir). However, the patient’s consciousness level progressively deteriorated, the trachea was intubated, and he was transferred to the intensive …

The authors had for aim to assess the conformity of antibiotic prescription with guidelines, for the management of community-acquired pneumonia, in a French University Hospital.This prospective study included adults patients hospitalized for pneumonia over a period of six months. The attending physician estimated the severity of pneumonia. The adequacy to guidelines focused on: first antibiotic choice and prescription modality, antibiotic choice in case of treatment modification at 48 to 72 hours, and duration of antibiotherapy.A hundred and nine cases of pneumonia were included in 106 patients. The mean age was 66 years, the mortality rate was 17 %. Bacterial documentation was recorded in 40.4 % of cases. The first antibiotics used were in accordance with guidelines in 52.3 % of cases. The non conformity rate was minor in 55.8 % of cases. Antibiotherapies putting the patient at risk were used in less than 10 % of the cases. The rate of antibiotic modification at 48 to 72 hours was 46.8 %, primarily for bacteriological purposes (35.3 %) or initial treatment failure (27.4 %). The treatment duration was inappropriate in 52.7 % of cases and generally too long in case of non conformity.It seems important to support guideline information, training of prescribers, and to consult an antibiotic expert.

Misuse of high-dose buprenorphine (HDB), mainly by injection, is responsible of frequent infectious adverse events.This is a retrospective study of infectious complications occurring in patients using HDB by injection. Forty-two cases were identified (29 men and ten women) and the data were collected between March 1999 and December 2008.The infectious complications included cutaneous infections (27 cases), endocarditis (nine cases), osteoarticular infections (four spondylodiscitis and one sacroiliitis), and a vascular embolism with decrease in visual acuity.The results of HDB maintenance treatment must be improved, both from the point of view of substitution and to limit its misuse by intravenous route injection. Health professionals have to play an important role in drug addict patients' education and supervision, to prevent buprenorphine injection and related infectious complications.

Comparison of treatments initiated during invasive candidiasis in intensive care units with current French guidelines.Prospective, observational, French multicenter study (October 2005-May 2006).Selection of patients with Candida species identification and in vitro antifungal susceptibility determination. The empiric treatments instituted before the microbiologic documentation of infection and the curative treatments instituted after identification of the causative Candida and determination of its susceptibility were collected and compared with treatments proposed by the French clinical practice guidelines (2004) for the management of patients with invasive candidiasis.One hundred and eighty-six patients were studied. Invasive candidiasis was due to fluconazole-resistant or susceptible-dose dependent Candida in 18.3% of patients, without any significant influence of a previous treatment with azoles. Empiric and curative treatments were both in accordance with recommendations for 47% of patients. Recommendations were mainly not respected when proposed therapy was amphotericin B that disappeared from therapeutics used in ICU. Finally, 16.9% of episodes of invasive candidiasis, for which fluconazole was the recommended treatment, were due to fluconazole-resistant or susceptible-dose dependent Candida.The support of French ICU physicians to current French guidelines was observed in 47% of cases. The infrequent use of amphotericin B must be emphasized. The nonnegligible incidence of fluconazole-resistant or susceptible-dose dependent Candida sp., particularly in patients without any prior exposition to azole agents, and the inability to predict this resistance should lead to propose a revision of 2004 guidelines.

The aim of this work is to show to what extent a psychosocial evaluation can lead bring to comprehension of the subjectivity of Quality of Life (QoL) among HIV-infected patients. Evaluation of QoL makes it possible to understand the link between the therapeutic effectiveness and the subjective evaluation of the treatment, but also to estimate more precisely how people live and take their treatment in the context of HIV infection.This work confronts the variation of QoL with the variation of several social and psychosocial parameters identified as of the components of the system, which is the subjective evaluation, and more precisely to a specific side effect of Highly Active AntiRetroviral Therapies (HAART): lipodystrophy syndrome that consists in body fat redistribution. This side effect could consist in an accumulation of body fat, or a loss of body fat or a combination of both symptoms. The analysis was made on the data from APROCO-COPILOTE cohort composed of HIV-infected patients initiating HAART.Among a sample of 706 patients follow-up for three years and with available QoL data, we identified the variations of QoL according to the variation of this specific side effect and according to gender. Results show that lipodystrophy syndrome has a determinant impact on QoL different among male and female patients. Adjusted on clinical and socio-demographic characteristics, impaired women's QoL is associated with accumulation of body fat and impaired men's QoL is associated with loss of body fat.These results underline the role of body image on subjective evaluation of QoL. The analysis of empirical data made it possible to highlight the social implication of the evaluation of QoL from the role of the social support, patient-provider relationship and the social context.

The most frequent side-effects due to nevirapine (Viramune), the first non-nucleoside HIV reverse transcriptase inhibitor introduced for clinical use, are cutaneous hypersensitivity reactions. In non-serious cases, tolerance induction can be proposed.Describe the long-term safety and efficacy of tolerance induction to nevirapine.Six HIV-infected patients started a tolerance 1 to 2 months after an episode of nevirapine hypersensitivity. Increasing doses of nevirapine (2.5, 10, 25, 100, 250 and 750 microg and 2.5, 5, 10, 25, 50 and 100 mg) were given orally at half-hour intervals under strict medical surveillance and patients were followed up regularly.All but two of the patients tolerated this induction well. One had a mild and transient reaction on day 1; nevirapine was not stopped. One had a moderate to severe reaction one month later; nevirapine was stopped and he recovered fully. All other patients have been taking nevirapine for more than 3 months without any adverse reaction.Therefore, when no alternatives are available in severely ill and hypersensitive HIV-infected patients, tolerance induction is a possible therapeutic option.

To describe and analyze the clinical and biological manifestations of thrombotic microangiopathy (TMA) and evaluate the therapeutic strategies.A retrospective study was performed in 14 infectious diseases units of southern France. All HIV patients presenting TMA during the last decade were selected (n = 14).The principle signs observed, aside from defining TMA (association of microangiopathic hemolytic anemia, thrombocytopenia and renal failure), were diarrhea (n = 9) and a high level of lacticodehydrogenase (LDH). Patients were at an advanced stage of HIV infection (median of CD4+ cells counts = 70/mm3). Specific etiology was identified in 7 cases: bacterial infection (n = 5), CMV retinitis associated with Kaposi's sarcoma (n = 1) and intravenous drug use (n = 1). Various treatments were used: plasmatic exchange (5 cases), fresh frozen plasma (6 cases), steroid therapy (4 cases), acetyl salicylic acid (3 cases), adaptation of antiretroviral treatment (3 cases). The global prognostic was poor with 50% mortality within 2 months. A high level of LDH (2500 UI/L) was associated with premature death in 5 of the 6 cases observed.Our data confirm the severity of TMA in case of HIV infection. The common treatment remains the use of plasmatic exchange and fresh frozen plasma; an optimal antiretroviral therapy must be associated.

To compare the efficacy and safety of saquinavir soft gelatin capsules (SQV-SGC) and nelfinavir (NFV), with or without two concomitant nucleoside reverse transcriptase inhibitors (NRTIs), in an exploratory objective to identify populations most likely to benefit from quadruple therapy.Phase II/III, open-label, randomized, parallel-arm, multicenter trial.Enrollment included 157 protease inhibitor-naive adults (or = 13 years) with HIV-1 RNAor = 10,000 copies/ml; 132 participants completed 48 weeks of therapy.SQV-SGC 1200 mg, NFV 750 mg, SQV-SGC 800 mg plus NFV 750 mg, all with two NRTIs, and SQV-SGC 800 mg plus NFV 750 mg alone, all three times daily for 48 weeks.Proportion of participants with HIV-1 RNA50 copies/ ml (16 and 48 weeks); time to virologic relapse (48 weeks).Proportions of patients with HIV RNA50 copies/ml were not statistically significantly different between arms at 16 or 48 weeks, although trends favored the quadruple-therapy arm. In patients experiencing virologic relapse, time to relapse was statistically significantly longer in the quadruple-therapy arm than in the other three arms (p = .007). Quadruple therapy provided benefit in NRTI-experienced patients and those with viral loads above the median value at baseline. Adverse events were mainly mild gastrointestinal disorders in all treatment arms.Quadruple therapy, including SQV-SGC and NFV, gave a more durable response than triple therapy with either single protease inhibitor. Quadruple therapy might particularly benefit NRTI-experienced patients and those with high baseline viral loads.

Alterations of body fat distribution have been recently reported in HIV-infected patients. We aimed to investigate whether the hormones modulating adipose tissue metabolism could be implicated.We investigated twenty-eight HIV-infected patients who had developed abdominal fat, combined with peripheral lipodystrophy in 25 cases and 'buffalo hump' in 2 cases, but who had otherwise improved on antiretroviral therapies. Twelve patients with no change in body fat, matched for age, disease control and treatment, were studied as controls.Body composition was assessed by bioelectrical impedance analysis. Subcutaneous (SAT) and visceral (VAT) compartments of total abdominal adipose tissue (TAT) were measured by computed tomography. Resting metabolic rate (RMR) was assessed by indirect calorimetry. Endocrine investigations included plasma thyroid hormones, cortisol, testosterone, oestradiol and 24-hour urinary free cortisol (UFC) and catecholamines.Despite similar body mass index, the patients with body fat alterations showed significantly larger VAT and higher VAT:TAT ratio than controls (P = 0.002 and 0.0001, respectively). In these patients, RMR was significantly higher than estimated according to the Harris-Benedict formula (+ 19.7 +/- 11.6 %, P = 0.0001) and correlated with VAT (r = 0.58, P = 0.003) and 24-hour urinary output of catecholamines (r = 0.67, P = 0.002), that was significantly increased in comparison with controls (1737 +/- 1228 vs 476 +/- 292 nmol, P = 0.013). We also found a significant correlation between VAT and UFC (r = 0.41, P = 0.042) that was absent in controls, although levels of UFC were similar in the two groups.Our data suggest that body fat redistribution may involve cortisol and catecholamine actions. While high release of catecholamines may enhance RMR through increased lipolysis, cortisol may promote central fat storage. These effects might be related both to persistent hormonal responses to stress becoming inappropriate while disease control improved and to an increased sensitivity of visceral adipose tissue to cortisol in affected patients.

The pharmacokinetics of itraconazole formulated in a hydroxypropyl-beta-cyclodextrin oral solution was determined for two groups of human immunodeficiency virus (HIV)-infected adults with oral candidiasis (group A, 12 patients with CD4+ T-cell count of >200/mm3 and no AIDS, and group B, 11 patients with CD4+ T-cell count of 250 ng/ml) was reached at day 4. At day 14, Cmin values of itraconazole were 643 +/- 304 and 592 +/- 401 ng/ml for groups A and B, respectively, and Cmin values of hydroxyitraconazole were 1,411 +/- 594 and 1,389 +/- 804 ng/ml for groups A and B, respectively. In saliva, only unchanged itraconazole was detected, and mean concentrations were still high (>250 ng/ml) 4 h after the intake, which may contribute to the fast clinical response. In conclusion, the oral solution of itraconazole generates effective levels in plasma and saliva in HIV-infected patients; its relative bioavailability is not modified by the stage of HIV infection.

25 HIV-infected antiretroviral-naive adults were included in a 24-week study to evaluate the efficacy and the tolerability of a zidovudine/didanosine combination therapy in which didanosine was administered once daily (200 mg if weight60 kg, 300 mg if weight60 kg) and zidovudine twice daily (500 mg/day if weight90 kg, 600 mg/day if weight90 kg). 5 patients discontinued their treatment early: 3 had poor compliance and 2 presented adverse events. Evaluation of treatment efficacy was based on CD4+ T cell enumeration and HIV RNA level quantitation in plasma (NASBA). Baseline values were 278 CD4+/mm3 and 5.42 log RNA copies/ml. Mean changes from baseline were +102 CD4+/mm3 and -2.14 log RNA copies/ml at week 8 and +156 CD4+/mm3 and -2.07 log RNA copies/ml at week 24. HIV RNA in plasma was lower than the detection limit (2.60 log RNA copies/ml) in 55% of patients at week 8 and in 30% at week 24. No major adverse events such as neuropathy or pancreatitis were observed. Once-daily administration of didanosine in combination with twice-daily administration of zidovudine is a well tolerated regimen that appears to be as effective ad the conventional zidovudine/didanosine combination regimen.

The objective was to compare the efficacy and tolerance of monthly aerosolized pentamidine versus trimethoprim-sulfamethoxazole (TMP-SMX) to prevent the first episode of Pneumocystis carinii pneumonia (PCP) in human immunodeficiency virus (HIV)-infected patients. In an open, prospective, randomized multicentric clinical trial, HIV-infected patients (n = 214) with CD4 cell counts200/mm3 or 20% without a history of PCP or cerebral toxoplasmosis were randomized to receive for at least 2 years aerosolized pentamidine (300 mg monthly) or low-dose daily TMP-SMX (400-80 mg). The mean follow-up was 578 days. The two groups (except for gender) were homogeneous for age, risk group for HIV infection, initial CD4+ lymphocyte count, and mean follow-up. The PCP rate per year of observation using an intent-to-treat analysis was 3.1% and 1.3% in the groups treated with pentamidine and TMP-SMX, respectively (p0.05). Moderate or severe clinical and biological side effects were observed in five patients on pentamidine and 33 on TMP-SMX (p0.05). Nineteen episodes of cerebral toxoplasmosis were diagnosed during the study. The analysis showed no significant difference in time of development of toxoplasmosis, but only one patient was actually treated with TMP-SMX. Survival was not significantly different in the two groups. Low-dose daily TMP-SMX or monthly aerosolized pentamidine effectively prevented a first episode of PCP in HIV-infected patients, but aerosolized pentamidine was better tolerated. However, TMP-SMX is less costly and should have a preventive effect for toxoplasmosis.

Tumors usually spread by local invasion or by vascular or lymphatic metastases. We report six patients in whom tumor cells were shed into the common bile duct with resulting obstruction. The three men and three women had jaundice and upper abdominal discomfort. Jaundice was intermittent in four patients. Preoperative total serum bilirubin ranged from 2.5 to 16.1 mg/dl; alkaline phosphatase ranged from 221 to 605 IU/1. Ultrsasound showed a dilated gallbladder [GB] in five patients with dilated intrahepatic ducts in three and stones in only one. ERCP showed a single filling defect in two of three patients and multiple defects in one. PTC showed multiple defects in one patient. At operation a thick gelatinous tissue fragment or clot was seen in the common bile duct of each patient. Frozen section identified tumor tissue in all. The source was GB carcinoma [2], GB adenomyoma [1], hepatic metastases of colon cancer [2] and common bile duct cancer [1]. Treatment consisted of pancreaticoduodenectomy [2], including one for GB cancer, left hepatic lobectomy [1], choledochoduodenostomy [1], common duct exploration with T-tube insertion and cholecystectomy [1]. One patient with metastatic colon cancer and another with gallbladder cancer died within one year of operation. The other four are alive from 2 to 4 years later. Conclusion: Benign or malignant tumors within the hepatobiliary tree can shed tissue into the common bile duct which can cause biliary obstruction. Any tissue fragment found in the common bile duct should be evaluated by frozen section. Recognition of this mode of tumor spread is needed for appropriate therapy of the underlying benign or malignant tumor.

We describe the predictors of change in physical activity in a population-derived sample of residents of two New England communities. In 1986-1987 and again in 1990-1991, we assessed the self-reported physical activity of 1,081 survey respondents using a single question concerning the frequency of exercise-induced sweating. We measured and analyzed sociodemographic variables, cardiovascular disease risk factors, health knowledge and beliefs, social support variables, and exercise performance variables at baseline as potential predictors of physical activity change. We defined physical activity change in subjects as follows: maintainers (12.2%) persisted withor = 3 times per week of activity, adopters (16.0%) increased activity toor = 3 times per week, quitters (11.9%) decreased activity to3 times per week, and sedentary (59.9%) individuals persisted with3 times per week of activity. Using polychotomous multiple logistic regression analysis, we found that short-term success with exercise and weight loss, school children's recommendation of exercise, and work outside the home predicted adoption or maintenance of increased physical activity in women. For men, short-term success with exercise and weight loss and health beliefs regarding the role of exercise in preventing heart attacks and stroke were the major determinants of maintaining or adopting increased physical activity. This identification of the predictors of physical activity change provides the rationale for future sex-specific strategies aimed at increasing regular physical activity and long-term adherence to an active lifestyle.

This prospective study evaluated the in vitro susceptibility of Candida albicans isolates recovered from the oral cavity of AIDS/ARC patients before and during long-term therapy with fluconazole. Thirty adults (15 with ARC and 15 with AIDS) with a first episode of thrush candidiasis were given oral fluconazole (Triflucan 50 mg; one capsule daily) for at least three months. Fungal susceptibility testing was performed before treatment, after one month, and at last follow-up (range 3.5-12 months; mean 5.7 months). MICs were determined using the agar dilution method with casitone (Difco 259-01) as the test medium at pH 7.2-7.4. There were two initial clinical failures (one with high MICs before and under treatment and one with an intermediate MIC initially and a rise in MIC under fluconazole). Four patients developed a clinical relapse with no change in MICs (which were low or intermediate). In six patients, clinical symptoms resolved but carriage of C. albicans persisted (low MICs). In 18 patients, clinical resolution with eradication of C. albicans was achieved. These data suggest that (1) clinical failures may be associated with in vitro resistance; (2) relapses under fluconazole maintenance therapy may develop in patients with advanced HIV disease despite the lack of change in the susceptibility of strains.

In 5 acquired-immunodeficiency syndrome (AIDS) cases without peripheral neuropathy, we observed myogen clinical signs (diffuse amyotrophy of lower limbs or cramps) or an isolated increase in seric enzyme (LDH, CK). EMG abnormalities were observed in all cases: spontaneous activities (fibrillations and positive sharp waves) in 5 cases, myogenic signs in 2 case. Muscular biopsies were normal in 3 cases and showed myopathic changes in 1 case and polymyositis in another case. Antidystrophin and antilaminin antibodies reactions were altered in 1 case. The spontaneous activities together with these modifications could be in favour of a lesion at the membrane level.

The results of a study of cystic fibrosis patients with liver disease using computed tomography are reported. The findings are described, and a discussion of their significance and place in patient investigation is offered.

Three patients with idiopathic aneurysms of the superior vena cava, left innominate vein, and inferior vena cava are presented. The advantages of CT over other diagnostic modalities are discussed.

Thirty-two patients were treated by ofloxacin on bacteriological documented infections. They were Enterobacterias: n = 15 (MIC less than or equal to 0.06 to 0.5 microgram/ml); Pseudomonas aeruginosa and Acinetobacter: n = 1 (MIC 0.5 and 4 micrograms/ml); Staphylococcus: n = 6 (MIC less than or equal to 0.06 to 4 micrograms/ml); Pneumococcus: n = 1; Mycoplasma: n = 1; Chlamydia psittaci: n = 2; Legionella pneumophila: n = 1; Rickettsias: n = 4 (three mediterranean fevers one query fever). Ofloxacin was given orally from 400 to 800 mg per day (5 to 15 mg/kg/day). It was used alone 26 times and on 6 occasions it was associated with rifampin on 6 staphylococcal infections. On 19 cases it was used after failure or intolerance of initial therapy. Thirty times it was the first antibiotic substance used. Results were good mainly: 1) on nine pneumonitis (enterobacterias: 4; Pneumococcus: 1; Mycoplasma: 1; Chlamydia: 2; Legionella: 1) during a mean duration of twenty days; 2) urinary infections (n:7) provoked by E. coli and Enterobacter cloacae (mean duration: 20 days); 3) 4 osteo-articular-infections (mean duration: 77 days); 4) Rickettsial infections (n:4) during a mean duration of 11 days. Results are particularly noteworthy because patients treated had severe infections: 12 bacteremias, 1 endocarditis and 1 purulent meningitis. None severe adverse effect was observed.

A case of anomalous inferior vena cava with azygos continuation first diagnosed by computed tomography (CT) and later confirmed by venography is presented. In addition to identifying the dilated azygos vein in the chest, CT can determine the direction of flow in the vein by means of a bolus contrast medium injection. Once this is established, a search for the etiology of the dilated vein can be directed to the appropriate anatomic area.

Twenty nine patients with Rickettsiosis (Tick born fever, n: 22, Q fever, n: 7) has been treated with fluoroquinolones. These compounds was used alone n: 25 (Pefloxacin, n: 15; Ofloxacin, n: 10) or associated n: 4 (Pefloxacin + Rifampin). The general efficacy was excellent. Common Tick born fever and pulmonary forms of Q fever was fast cured. Severe Tick born fever (neurologic or polyvisceral forms, n: 5) and Q fever with long term hyperthermia, n: 4 cas always cured without complications but the time necessary to obtain apyrexia was often longer (6 cases).

A 4-3/12 old boy with a hypophosphoremic coma (serum phosphorus: 0.4 mg./dl.) is presented. The favoring conditions appear to be related to acute renal failure in polyuric phase with high phosphorus excretion, low phosphorus intake, rapid transit from a catabolic to an anabolic state with previous malnutrition and parenteral feeding, oral aluminum hydroxide gel administration and lung infectious disease. The clinical, biochemical data, evolution and physiologic mechanisms are commented, specially those of erythrocyte, leucocyte and platelet disfunction related to ATP, AMP and 2.3 DPG deficiency. Proteinuria and hematuria during phosphorus depletion are emphasized. The alarm symptoms and treatment are indicated.

A child without chronic stridor and tracheal narrowing was considered to have a primary tracheal abnormality. Computed tomography (CT) identified an aberrant left pulmonary artery originating from the right pulmonary as the cause of the tracheal abnormality. The advantages of CT over conventional studies are discussed.

Although pancreatic disease is suspected initially by historical or biochemical findings, the nature of the pathologic process in the past was frequently established only through invasive procedures. Inferences can be drawn from routine roentgenologic examinations, but visualization of the pancreas has only recently been achieved. Of the currently available noninvasive imaging procedures, computed tomography, in our opinion, is the screening procedure of choice. Care in the interpretation of pancreatic masses must be exercised since some of the findings can be attributed to anatomic variants, normal adjacent structures, or other neighboring pathologic processes.

The epidemiologic conditions and clinical characteristics of HIV infections in Languedoc-Roussillon, France, were studied in 355 HIV positive subjects followed at the Infectious Diseases Clinic in Montpellier through January 1988. 67.3% of the 52 AIDS patients were homosexuals and 13.5% were intravenous drug addicts. These rates were very similar to the French national rates of 61.9% for homosexuals and 11.8% for addicts. Among the 303 subjects who were HIV positive but had not developed AIDS, 43.5% were homosexuals and 38.2% were intravenous drug users. 49 of the 123 addicts studied were women, and almost 2/3 of the HIV positive women were addicts. The average age of HIV positive addicts was 25.8 years, significantly lower than the 34.4 years of the homosexuals. 18 women were infected by contact with HIV positive men, 9 of whom were addicts, 3 bisexual, 2 African, 3 with multiple partners, and 1 hemophiliac. 11 men were infected by contact with HIV positive women, 5 of whom were addicts, 4 African, and 2 with multiple partners. 303 of the subjects probably were infected within Languedoc-Roussillon. 100 of the subjects were not employed, of whom 60% were addicts. 38.3% of the homosexuals vs. 9.8% of the addicts had a history of or positive culture for syphilis. 33.3% of the addicts vs. 7.8% of the homosexuals had a history of hepatitis. Ages of the 52 AIDS patients ranged from 23 to 76 and averaged 39.2 years. The HIV positive subjects were 28.7 years on average. Among the notable observations were the increased proportion of intravenous drug users in the recently infected, which has led to a lowering of the average age and an increased proportion of women among patients. The increased representation of heterosexuals among the infected will lead to increased danger of infection for the general population.

Ultrasonically guided percutaneous biopsy and aspiration of solid and cystic structures in the abdomen, neck, and pericardial space are common practice. The technique may be utilized for biopsy of peripheral pulmonary masses in contact with the chest wall, in order to assure accurate placement of the needle in the center of the mass, reduce the risk of pneumothorax, and eliminate the exposure to radiation that occurs with fluoroscopic guidance. Four patients had successful biopsies in this manner, without complications. Histologic studies revelaed malignant neoplasms in three and lipoid pneumonia in one.

DURING the past 10 years aortocoronary bypass has been widely prescribed to treat angina pectoris. Dysfunction or closure of an aortocoronary-bypass graft is generally suggested by a patient's history, but few if any objective signs are derived from physical examination, electrocardiograms taken with patient at rest or under stress, or studies of regional myocardial perfusion with thallium–201.1 Definitive confirmation of graft closure or stenosis is obtained through postoperative selective angiography of the grafts in question. This invasive procedure is costly, requires hospitalization, and certainly carries some morbidity and mortality. A new technique, described by Lipton et al., 2 that uses computed . . .

Membranous laryngotracheobronchitis is a very serious infection which affects the larynx, trachea and bronchi, requiring aggressive therapeutic measures. It has been recently rediscovered as a cause of disease in children. However, it is a very unusual complication of measles. Two infants with measles and membranous laryngotracheobronchitis are reported.

A comparative study of two patients, one affected by haemorrhagic shock and encephalopathy (HSE) and the other by heatstroke is reported. Both presented shock, disseminated intravascular coagulation, neurological damage and hepatopathy. A lowered alpha 1-antitrypsin concentration as well as a slightly increased circulating immune complexes and complement consumption were observed in the HSE patient but not in the heatstroke one. In both, cultures for bacteria were negative, the viral serology was non-specific and hepatitis A and B studies were negative. HSE patient died. A possible relationship between HSE, heatstroke, malignant hyperthermia and halothane hepatitis is postulated. Fever, potentially hepatotoxic drugs or unknown agents (HSE) might trigger this clinical picture.

A review was made of the charts of 94 patients who underwent ultrasonography (US), computed tomography (CT), and gallium citrate Ga 67 (Gall) scan to rule out intra-abdominal abscesses. Of all the clinical and laboratory data, only the presence of pain and tenderness differentiated patients with and without abscesses. A review of radiologic data showed that CT was superior to US, and that US was superior to Gall scan with regard to sensitivity, specificity, accuracy, and positive and negative predictive values. When multiple radiologic tests were performed, results agreed in 72% of cases; therefore, the additional tests were essentially redundant. When radiologic test results disagreed, accuracy rates were CT, 0.86; US, 0.00; and Gall scan, 0.44. These findings suggest that, except to rule out pelvic abscesses in the presence of pelvic inflammatory disease, CT is usually the only special radiologic test that should be performed to localize a suspected intra-abdominal abscess.