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Purpose: Bereavement research has helped to improve end-of-life practices in the ICU. However, few studies have explored bereaved relatives experience of research participation in this context. We aimed to explore the experience of bereaved relatives' participation in the ARREVE study which included three telephone follow-up calls to complete several quantitative tools., Methods: Volunteer relatives who participated in the 12-month follow-up call completed a questionnaire about research participation that included ten open-ended questions so that respondents could use their own words and thoughts. These open-ended questions were analyzed using qualitative analysis that examines themes within the data., Results: 175/311 relatives completed the questionnaire. Three themes were derived from the thematic analysis: (1) struggling: reactivation of emotional distress associated with the ICU experience and the loss is frequent, specifically during the 1st follow-up call. (2) Resilience: as time goes by, research participation becomes increasingly positive. The calls are a help both in giving meaning to the relatives' experience and in accepting the loss. (3) Recognition: research calls can compensate for the absence of support during bereavement., Conclusion: Although some emotional difficulties must be acknowledged, bereavement research is overall associated with benefits, by facilitating emotional adjustments, meaning-making and resilience. Lack of support and social isolation during bereavement are frequent experiences, revealing that support strategies for bereaved relatives should be developed after the loss of a loved one in the ICU.

Correction to: Intensive Care Med (2017) DOI 10.1007/s00134-017-4891-0.

Purpose: The relative merits of immediate extubation versus terminal weaning for mechanical ventilation withdrawal are controversial, particularly regarding the experience of patients and relatives., Methods: This prospective observational multicentre study (ARREVE) was done in 43 French ICUs to compare terminal weaning and immediate extubation, as chosen by the ICU team. Terminal weaning was a gradual decrease in the amount of ventilatory assistance and immediate extubation was extubation without any previous decrease in ventilatory assistance. The primary outcome was posttraumatic stress symptoms (Impact of Event Scale Revised, IES-R) in relatives 3 months after the death. Secondary outcomes were complicated grief, anxiety, and depression symptoms in relatives; comfort of patients during the dying process; and job strain in staff., Results: We enrolled 212 (85.5%) relatives of 248 patients with terminal weaning and 190 relatives (90.5%) of 210 patients with immediate extubation. Immediate extubation was associated with airway obstruction and a higher mean Behavioural Pain Scale score compared to terminal weaning. In relatives, IES-R scores after 3 months were not significantly different between groups (31.9 ± 18.1 versus 30.5 ± 16.2, respectively; adjusted difference, -1.9; 95% confidence interval, -5.9 to 2.1; p = 0.36); neither were there any differences in complicated grief, anxiety, or depression scores. Assistant nurses had lower job strain scores in the immediate extubation group., Conclusions: Compared to terminal weaning, immediate extubation was not associated with differences in psychological welfare of relatives when each method constituted standard practice in the ICU where it was applied. Patients had more airway obstruction and gasps with immediate extubation., Trial Registration: ClinicalTrials.gov identifier: NCT01818895.

Because Q fever is mostly diagnosed serologically, localizing a persistent focus of Coxiella burnetii infection can be challenging. F-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) could be an interesting tool in this context.We performed a retrospective study on patients diagnosed with C burnetii infection, who had undergone F-FDG PET/CT between 2009 and 2015. When positive F-FDG PET/CT results were obtained, we tried to determine if it changed the previous diagnosis by discovering or confirming a suspected focus of C burnetii infection.One hundred sixty-seven patients benefited from F-FDG PET/CT. The most frequent clinical subgroup before F-FDG PET/CT was patients with no identified focus of infection, despite high IgG1 serological titers (34%). For 59% (n = 99) of patients, a hypermetabolic focus was identified. For 62 patients (62.6%), the positive F-FDG PET/CT allowed the diagnosis to be changed. For 24 of them, (38.7%), a previously unsuspected focus of infection was discovered. Forty-two (42%) positive patients had more than 1 hypermetabolic focus. We observed 21 valvular foci, 34 vascular foci, and a high proportion of osteoarticular localizations (n = 21). We also observed lymphadenitis (n = 27), bone marrow hypermetabolism (n = 11), and 9 pulmonary localizations.We confirmed thatF-FDG PET/CT is a central tool in the diagnosis of C burnetii focalized persistent infection. We proposed new diagnostic scores for 2 main clinical entities identified using F-FDG PET/CT: osteoarticular persistent infections and lymphadenitis.

Purpose: Terminal extubation (TE) and terminal weaning (TW) are the methods available for withdrawing mechanical ventilation. Perceptions of TE and TW by intensive care unit (ICU) staff may influence bedside practices and the feasibility of studies comparing these methods., Methods: From January to June 2013, 5 nurses and 5 physicians in each of 46 (out of 70, 65.7 %) French ICUs completed an anonymous self-questionnaire. Clusters of staff members defined by perceptions of TE and TW were identified by exploratory analysis. Denominators for computing percentages were total numbers of responses to each item; cases with missing data were excluded for the relevant item., Results: Of the 451 (98 %) participants (225 nurses and 226 physicians), 37 (8.4 %) had never or almost never performed TW and 138 (31.3 %) had never or almost never performed TE. A moral difference between TW and TE was perceived by 205 (45.8 %) participants. The exploratory analysis identified three clusters defined by personal beliefs about TW and TE: 21.2 % of participants preferred TW, 18.1 % preferred TE, and 60.7 % had no preference. A preference for TW seemed chiefly related to unfavorable perceptions or insufficient knowledge of TE. Staff members who preferred TE and those with no preference perceived TE as providing a more natural dying process with less ambiguity., Conclusion: Nearly two-fifths of ICU nurses and physicians in participating ICUs preferred TW or TE. This finding suggests both a need for shared decision-making and training before performing TE or TW and a high risk of poor compliance with randomly allocated TW or TE.

The emergence of bacterial resistance and the lack of new antibiotics in the pipeline represent a public health priority. Maximizing the quality of antibiotic prescriptions is therefore of major importance in terms of adequate preparation and administration modalities. Adequate preparation prevents the inactivation of antibiotics and is a prerequisite to maximizing their efficacy (taking into account the pharmacokinetic/pharmacodynamic relationship) and to minimizing their toxicity. Many antibiotic guidelines address the choice of drugs and treatment duration but none of them exclusively address preparation and administration modalities. These guidelines are based on the available literature and offer essential data for a proper antibiotic preparation and administration by physicians and nurses. They may lead to a better efficacy and to a reduced antibiotic resistance. Such guidelines also contribute to a proper use of drugs and improve the interaction between inpatient and outpatient care for a better overall management of patients., (Copyright © 2016. Published by Elsevier SAS.)

Objective: To compare the efficacy of assisted reproductive technology (ART) in women infected with human immunodeficiency virus type 1 (HIV-1) versus HIV-negative controls., Design: Retrospective case-control study., Setting: University hospital ART unit., Patient(s): Eighty-two women infected with HIV-1 and 82 women as seronegative controls., Intervention(s): Ovarian stimulation, oocytes retrieval, standard in vitro fertilization (IVF) or intracytoplasmic sperm injection, embryo transfer., Main Outcome Measure(s): Clinical pregnancies and live-birth rates., Result(s): After oocyte retrieval, all women infected with HIV-1 infected were matched 1:1 to HIV-negative controls according to the following criteria: date of ART attempt, age, parity, main cause of infertility, ART technique, and rank of attempt. Only the first IVF cycle during the study period was considered for each couple. We found no statistically significant differences between the two groups for ovarian stimulation data, fertilization rate, or average number of embryos transferred. The clinical pregnancy rate per transfer was statistically significantly lower for the cases compared with the controls (12% vs. 32%), as were the implantation rate (10% vs. 21%) and the live-birth rate (7% vs. 19%)., Conclusion(s): In one of the largest studies to pair six factors that influence the results of ART, HIV infection in women was associated with poorer outcomes after ART. These results suggest that women with controlled HIV-1-infection should be counseled not to delay ART in cases of self-insemination failure or other causes of infertility. Fertility preservation by vitrification of oocytes in women whose pregnancy should be delayed may be an important future consideration., (Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: Bare-metal stents are used to treat arterial stenotic lesions. Morbidity and mortality are less important compared with other techniques. Drug-eluting balloons are often used to treat stent stenosis. We reported the case of a bare-metal stent infection after drug-eluting balloon and a review on the subject., Material and Method: Two weeks after percutaneous transluminal angioplasty with paclitaxel-eluting balloon and a bare-metal stent, our patient presented an infection of the stent. Diagnosis was based on the clinical presentation, positron emission tomography findings and isolation of Propionibacterium granulosum in repeated blood cultures. Adapted antibiotic therapy was given for three months with removal of the surgical bare-stent. Antibiotic therapy was interrupted after a second positron emission tomography. A literature search (PubMed and Cochrane) was performed on the subject., Results: We found 49 cases of peripheral bare-metal stent infection including our patient. This is a rare but serious complication with a high morbidity (25% amputation rate) and mortality (30%). It seems to be underestimated. Treatment is based on surgical ablation of the bare-metal stent and intravenous antibiotics. The role of the paclitaxel-eluting balloon is not clearly established but some authors believe that it can produce a local immunosuppression., Conclusion: We report the first case of bare-metal stent infection after paclitaxel-eluting balloon. This complication is rare and difficult to diagnose. Manifestations are often limited to skin signs. Functional and vital prognosis is poor., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

It was demonstrated that combination antiretroviral therapy (cART) reduces the HIV-1 viral load (VL) in the blood and the seminal compartment. Some studies have reported that the seminal HIV-1 VL is undetectable in individuals with an undetectable blood plasma viral load (bpVL) under cART. However, some recent studies have demonstrated that seminal HIV-1 RNA may still be detected, and potentially infectious, even in the case of an undetectable bpVL. The aim of this retrospective study was to determine the detection rate of a seminal VL and whether shedding could be intermittent over a very short time. From January 2006 to December 2011, 88 HIV-1 infected men, enrolled in an Assisted Reproduction program, provided 306 semen samples, corresponding to 177 frozen sperm samples (two samples delivered at a one-hour interval (n = 129) or one sample (n = 48)). All enrolled men were under cART, with an undetectable bpVL for more than 6 months. HIV-1 RNA was quantified in seminal plasma using a Roche COBAS Ampliprep COBAS TaqMan HIV-1 test. Seminal HIV-1 RNA was detected in 23 samples (7.5%) from 17 patients (19.3%). This detection rate was stable over years. With regards to the freezing of two samples delivered at a one-hour interval, the proportion of discordance between the first and second samples was 9.3% (12/129). Our results confirm the intermittent shedding of HIV-1 in semen. While this finding has been shown by studies examining longer time intervals, to our knowledge, this has never been demonstrated over such a short time interval.

Background: Paradoxical tuberculosis immune reconstitution inflammatory syndrome (TB-IRIS) frequently follows the initiation of antiretroviral therapy (ART) in patients with tuberculosis (TB) and human immunodeficiency virus (HIV) co-infection. Treatment recommendations are nearly exclusively based on expert opinion., Objective: To assess the clinical outcomes of patients treated using various strategies for TB-IRIS., Methods: In a retrospective analysis of patients treated in Paris hospitals from 1996 to 2008, we describe TB-IRIS outcome, frequency of relapses and CD4 cell count changes after 12 months of ART for the following strategies: no treatment, interrupted ART and use of steroids., Result: Among 34 patients, TB-IRIS outcome was favourable in 10/10 with no treatment, 11/13 with ART interruption, 3/3 with ART interruption and simultaneous use of steroids and 8/8 with steroids alone. Relapses were observed in both the ART interruption (6/13, 46%) and steroids (4/8, 50%) groups, but were less frequent in the no-treatment group (1/10, 10%). Steroids were prescribed in 61% of the patients and had no significant side effects; steroid use was associated with a trend towards a lower median CD4 cell count at 12 months of ART compared to the others (230 vs. 322 cells/mm(3)), despite no baseline differences., Conclusion: TB-IRIS outcome was favourable regardless of the therapeutic strategies employed. Although steroids were widely used and well-tolerated, an initial wait-and-see attitude in the case of non-severe IRIS remains an interesting strategy to be evaluated.

Aims: Extracardiac complications of endocarditis influence diagnosis, therapeutic plans, and prognosis. The aim of this study was to assess how early combined cerebral and abdominal magnetic resonance imaging (MRI) affects the diagnosis and management of adults with endocarditis., Methods and Results: In a single-centre prospective study, 58 patients with endocarditis underwent systematic cerebral and abdominal MRI within 7 days following admission. Diagnostic classification (Duke's modified criteria) and therapeutic plans were established by two experts just before and after MRI and then compared. Endocarditis was initially classified as definite in 29 patients, possible in 27, and excluded in 2. MRI detected cerebral lesions in 47 patients (81%) (ischaemic lesions in 25, microbleeds in 32, and silent aneurysms in 6), and abdominal lesions in 20 patients (34%). Based solely on MRI results without taking microbleeds into account, experts upgraded endocarditis diagnostic classification in 8 out of 29 (28%) non-definite endocarditis cases either to definite in 6 or to possible in 2. This upgrading was exclusively due to cerebral MRI in four patients and to cerebral and/or abdominal MRI in four patients. Experts modified endocarditis therapeutic plans in 11 (19%) out of the 58 patients, based solely on cerebral MRI, including modification of surgical plans in six (10%) patients. Overall, early MRI led experts to modify classification and/or therapeutic plans in 16 (28%) patients., Conclusion: MRI identified cerebral and/or abdominal asymptomatic lesions in many patients with endocarditis, but more frequently cerebral. Both cerebral and abdominal MRI findings affected diagnosis, but only cerebral MRI affected clinical management plans. CLINICALTRIALS.GOV IDENTIFICATION NUMBER: NCT 00144885. IRB AUTHORIZATION NUMBER: 0511114 (Comité Protection des Personnes Paris-Ile de France 1).

Systemic lupus erythematosus (SLE) remains of unknown origin. Herpes viridae infections seem to play a role in the pathogenesis of this disease. We report a 31-year-old man who presented an acute cytomegalovirus (CMV) infection with persistent fever and myopericarditis as the presenting manifestation of SLE. This case report emphasizes a difficult differential diagnosis between SLE and an acute CMV infection and suggests a possible role of this virus in the pathogenesis of SLE., (Copyright © 2010 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

The case of a woman with native mitral valve endocarditis due to Haemophilus parainfluenzae (HPI) associated with a pelvic abscess and endometriosis is reported. Although HPI is an infrequent pathogen involved in endocarditis, association to a gynaecological infection has never been reported. Endometriosis could increase this risk.

HIV-infected patients with opportunistic infections receive therapeutic regimens that often contain numerous drugs and are then exposed to potential drug-to-drug interactions. We report here an unusual case of relapse of toxoplasmic encephalitis in an HIV-infected patient, possibly due to a drug-to-drug interaction between dapsone and minocycline.

Objective: The characteristics of patients with a suspected SARS hospitalized in a Paris hospital were studied to analyze the hypothetic differences between epidemiologic and clinical teams in the management of an epidemic emerging disease, and to gather experience for the management of the next outbreak., Study Design: All 90 patients hospitalized between March 16 and April 30, 2003, were included. Epidemiological and clinical data were shared with the French National Institute for Health. Cases were classified according to both the official definition ("possible", "probable", "excluded") and a local one, adapted from the official definition but including an additional level of suspicion ("equivocal"), intermediate between "possible" and "excluded"., Results: The initial assessment was different in 39% of the cases (n=35), according to epidemiological (n=24) or clinical (n=11) elements. The final assessment diverged in 54% of the cases (n=47). All patients were officially considered as "excluded" for epidemiologists, while 47 remained as "possible" or "equivocal" cases of SARS according to the clinicians., Conclusion: The risk assessment was different in almost 40% of the cases, with no impact on epidemic diffusion or hospital-borne exposure as no probable case of SARS was diagnosed among these patients or their households. The confrontation of these different but complementary points of view will thus enrich the interdisciplinary management of eventual future outbreaks.

Various emerging diseases have been reported in recent years as epidemiologic monitoring improves. These infections can compromise the pregnancy, through adverse maternal outcomes, as well as the outcome for the child following transmission. We report a review of the literature concerning the most quoted emergent virus (H5N1, SARS Coronavirus, Chikungunya, West Nile virus), and relate the perinatal management.

Objective: To describe the implementation and initial results of a specific educational and counseling intervention to examine and improve adherence to antiretroviral therapy (ARV) in HIV-infected patients., Method: Four patient profiles were defined: 1) discontinuation and 2) failure: patients with virological failure (defined as two consecutive viral loads>200 copies/mL) at ARV discontinuation or under treatment, both seen after the fact; 3) preparation: naive patients seen before starting treatment, and 4) reinforcement: patients in treatment seen for counseling to prevent virological failure. A clinical psychologist, nurse and hospital pharmacist jointly conducted the session. Data collected include standardized information about the characteristics of HIV infection and ARV regimens, and demographic, behavioral, social and cultural indicators. CD4 cell counts and HIV viral loads were recorded at D0, M1, M3, M9 and M12. The effectiveness of the adherence intervention was defined separately for each patient profile based on some combination of taking or restarting an ARV regimen, virological response, and M12 follow-up., Results: The study included 139 patients between November 1998 and April 2000. The intervention was defined as effective in 50% and 40% of the discontinuation (n=26) and failure (n=61) patients respectively, 84% of those with preparation profile (n=37) and 93% (14/15) of reinforcement patients. Only undetectable HIV viral load at M3 was significantly associated with the effectiveness of the adherence intervention for all 4 profiles. The preventive interventions (preparation and reinforcement) were less effective in patients from outside Europe (p=0.013)., Conclusion: The adherence intervention was more effective in preventing virological failure than in restoring ARV effectiveness among patients who had already experienced virological failure. It should therefore be proposed primarily before starting ARV, to prevent failure in treatment-naive patients, especially those from outside Europe.

Introduction: Tuberculosis can be responsible for myocardial damage, the frequency of which is probably underestimated because of the difficulty in its diagnosis. We studied the contribution of cardiac magnetic resonance imaging (MRI) in three patients., Observations: Three patients were treated for disseminated tuberculosis. They had moderate cardiac abnormalities (tachycardia, dyspnoea on effort). The electrocardiogram was normal in 2 patients and the echocardiography showed localized hyperkinesias. Cardiac MRI revealed intra-myocardial nodular gadolinium enhancement and hyperkinesias. The clinical outcome in the 3 patients was favourable following anti-tuberculosis therapy; one patient was also administered corticosteroids., Discussion: Cardiac MRI is a non-invasive examination that brought important arguments for the diagnosis of tubercular myocarditis in the 3 patients.

Immune reconstitution inflammatory syndrome (IRIS) occurred in 16 of 37 antiretroviral-naive patients who were treated subsequently for tuberculosis and human immunodeficiency virus (HIV) type 1 infection. IRIS was related to increases in the CD4 cell percentage and in the ratio of CD4 cells to CD8 cells after 1 month of antiretroviral therapy and to dissemination of tuberculosis. These results have implications for the diagnosis of IRIS and the understanding of its pathogenesis.

To reduce the number of daily pills for improving adherence to antiretrovirals, 17 protease inhibitor-treated patients receiving toxoplasmic encephalitis (TE) standard maintenance therapy were instead given cotrimoxazole 960 mg twice daily. After a median follow-up of 31 months, one relapsed after three months, TE relapse incidence = 2.1 cases per 100 patient-years (95% confidence interval, 0.05-11.3). This strategy could be useful for patients awaiting immune reconstitution which allows the interruption of TE maintenance therapy.

To describe the rate of response to an antibiotic-lock technique (ALT) in the treatment of venous access port (VAP)--related bacteremia and to analyze the role of the reservoir in the persistence of infection, we reported the data from 12 human immunodeficiency virus--infected and 8 oncologic patients with VAP-related bacteremia. The ALT consisted of intracatheter delivery of antibiotics and was associated with a systemic antibiotic infusion. We monitored clinical manifestations and performed qualitative and quantitative blood cultures during and at the end of the treatment. Four patients had catheters removed before antibiotic treatment. Of the 16 patients who were treated with the ALT, 5 (31%) were cured, as determined by negative cultures of blood and of samples from the catheter; 2 (12.5%) were cured but had recurrent infection with another microorganism; and 9 (56%) had persistent positive cultures of blood and of samples from the tip, reservoir, or both of the VAP. Limited efficacy of the ALT might be explained by the presence of deposits of fibrin that include clusters of bacteria inside the reservoir of the port.

Background: Restoration of immunocompetence in HIV-infected patients after antiretroviral treatment can have unexpected effects., Case Reports: An unusual course of treated tuberculosis was observed in four HIV-infected patients soon after initiation of antiretroviral therapy. These patients developed fever and enlarged necrotic adenopathies despite an efficacious antituberculous therapy. They were in the initial stage of their antituberculous therapy that had been initiated a mean 12 days prior to initiation of antiretroviral therapy. The antiretroviral therapy led to an undetectable HIV load within 2 months., Discussion: These unusual features, which also occurred with an increase in CD4 cell counts, could be related to the immunological restoration and to the reappearance of delayed type hypersensitivity. The onset of antiretroviral therapy could thus be delayed by several weeks in HIV-infected patients treated for active tuberculosis and who have never received antiretroviral therapy.

From March to July 1996, 61 patients with CD4<50/mm(3)began a therapy with protease inhibitors. Increase and maintenance of CD4>100/mm(3) was observed in 39/61 patients with a protective effect for occurrence of AIDS or death. This immunological response was correlated with the duration of the virological response. However, 38% of patients with long-term immunological response never had a undetectable viral load.

FAILURES OF ANTIBIOTIC TREATMENT: The number of failures after treatment of acute middle ear infections with the 2 main antibiotics prescribed (amoxicillin and the combination amoxicillin-clavulanic acid) is on the rise. These failures appear to be related to increased resistance of the 2 principal pathogens, pneumococci and Hemophilus influenzae. A NEW FORMULATION: In order to reduce the rate of failure, it has been necessary to both increase the dose of penicillin to overcome the reduced susceptibility of pneumococci to penicillin and to prescribe a beta-lactam because of the frequent isolation of beta-lactamase producing Hemophilus influenzae. A new formulation has been developed where the amoxicillin-clavulanic acid dose is 14 to 1. This allows a daily dose of 80 mg/kg for amoxicillin and 6.4 mg/kg for clavulanic acid. In one open multicentric study including 51 pediatric patients aged 3 to 48 months with acute middle ear infections, it was demonstrated that this new formulation can be very effective in eradicating the causal agents of acute middle ear infections, including pneumococci and penicillin-resistant Hemophilus. RECOMMENDATIONS FOR GOOD EFFICACY: Amoxicillin must always be prescribed, either alone or in combination with clavulanic acid, at the dose of 45 to 50 mg/kg b.i.d. the amoxicillin-clavulanic acid combination should be preferred for children under 2 years due to the risk of beta-lactamase producing Hemophilus.

The accumulation of infected clots under the silicone septum of the reservoir of venous access ports (VAPs) has been reported. We analyzed the relationship between these deposits and the occurrence of VAP-related bloodstream infections (VAP-BSIs) by (1) evaluating the accuracy of paired quantitative blood cultures for diagnosing VAP-BSI before the removal of the device and (2) assessing the accuracy of cultures of the tip and septum (i.e., the internal lumen of the VAP) for diagnosing VAP-BSI after removal of the device. Over a 16-month period, all VAPs removed were prospectively investigated. Before VAP removal, paired quantitative blood cultures were 77% sensitive and 100% specific and had a positive predictive value of 100% and a negative predictive value of 98% for diagnosing VAP-BSI. After VAP removal, tip culture was only 46% sensitive, whereas septum culture was 93.3% sensitive for confirming the diagnosis of VAP-BSI. Thus infected deposits that accumulate under the VAP septum are the source of VAP-BSI.

We report the cases of three patients treated for infective endocarditis (IE) for whom corticosteroids were added to the antibiotic treatment. They all had clinical and biological evidence of immune-mediated glomerulonephritis. The microorganisms responsible for IE were Coxiella burnetii, Streptococcus bovis, and Cardiobacterium hominis. Median duration of IE before antimicrobial therapy was 7 months. In all patients, renal function deteriorated despite appropriate antimicrobial treatment for a mean duration of 16 days, but it improved after addition of corticosteroid therapy. All patients were cured of IE. A literature review revealed four additional cases of IE-related glomerulonephritis in which adjunctive immunosuppressive therapy was considered to be effective. Although corticosteroid therapy is generally not recommended for IE, it should be considered for patients whose renal dysfunction secondary to glomerulonephritis does not improve with appropriate antimicrobial treatment, especially if the duration of the illness is long.

Objective: To determine more precisely the clinical and biological characteristics of AIDS-related cholangitis, and to investigate prognostic variables of this disease., Design: Retrospective clinical and prognostic study., Setting: Biliary unit, Bicêtre Hospital, France., Patients: HIV-positive patients (n = 52) referred to the unit between December 1986 and June 1993 for biliary symptoms leading to the suspicion of AIDS-related cholangitis, (42 men; 10 women; mean age, 37 +/- 8 years)., Intervention: Endoscopic retrograde cholangiopancreatography (ERCP) was performed in order to determine the cause of the biliary symptoms., Main Outcome Measure: Clinical features and evolution of the cholangitis., Results: Among the 52 patients, 45 met the ERCP criteria of AIDS-related cholangitis (36 men; nine women). The diagnosis of cholangitis was strongly suggested by abdominal ultrasonography in 47% of the cases. ERCP showed papillary stenosis, diffuse cholangitis, extrahepatic cholangitis alone, and intrahepatic cholangitis alone in 60, 67, 7 and 27%, respectively. Endoscopic sphincterotomy was performed in 28 patients. Pain was relieved by sphincterotomy in nine patients, but the other clinical or biological features were not influenced. One-year and 2-year survival rates were 41 +/- 7% and 8 +/- 4%, respectively. Multidimensional analysis using a Cox model showed that a lymphocyte count > 500 x 10(6)/l was the only independent predictive factor of better survival., Conclusion: AIDS-related cholangitis is a disease which leads preferentially to papillary stenosis or diffuse abnormalities of the biliary tract. Prognostic factors depend on the stage of the HIV infection. Another diagnosis of cholestasis was found in approximately 15% of the patients who showed biliary symptoms.

Objectives: Determine the clinical features and outcome of acute pneumonia due to Streptococcus pneumoniae in HIV infected patients compared with non-HIV infected patients., Methods: From January 1986 to February 1992, we observed 33 episodes of pneumococcal pneumonia in 27 HIV-infected patients. Most of the patients were drug addicts (16/27), and/or originated from Central Africa or Haiti (10/27). In 9/27 (33%) patients, HIV infection was previously unknown. Eleven of the 27 patients were at the CDC stages II-III and CD4 cell count was greater than 200/mm3 and CD8 cell count was greater than 1000/mm3 in 12/23 patients and 10/20 patients respectively., Results: In 10/33 episodes, respiratory symptoms were severe: bilateral pneumonia (n = 2) and/or hypoxaemia (n = 9). In 22/33 episodes, hospitalization occurred less than 24 h after the onset of symptoms and in 9/33 episodes, the initial chest X-ray was normal. Streptococcus pneumoniae was isolated in 16/33 episodes, from blood (n = 10), bronchoalveolar lavage (n = 3) or sputum (n = 3). Penicillin G or amoxicillin was used and allowed a favorable and quick response in all episodes. Recurrence occurred in 5/18 (27%) followed patients. These recurrences were not favoured by a low CD4 cell count since it was more than 200/mm3 in these five patients. However, the mean count of CD8 cells was higher in patients with recurrence than in patients without recurrence, 1990/mm3 versus 995/mm3 (p = 0.03)., Conclusion: CD8 hyperlymphocytosis could increase the risk of recurrence and would help identify a subgroup with higher risk of pneumococcal pneumonia among HIV infected persons.

Objectives: To evaluate the respective diagnostic value of flexible rectosigmoidoscopy and colonoscopy in the cytomegalovirus colitis., Methods: Twenty-four patients with AIDS were studied retrospectively. The entry criteria were: flexible rectosigmoidoscopy or colonoscopy, with 2 rectal and 2 caecal biopsies, presenting cytomegalovirus inclusions bodies linked to an inflammation at least on one colonic biopsy., Results: Twenty-four patients had 29 colonoscopies. In 16 cases colonoscopy was performed to the caecum. The endoscopic findings of the 16 full colonoscopies were: 7 right colitis, 5 diffuse colitis, 2 bisegmentary colitis, 1 proctitis and 1 non endoscopic lesion. The histologic findings of the 16 full colonoscopies were: 5 cytomegalovirus inclusions on rectal biopsies and 16 on caecal biopsies. For the 13 incomplete colonoscopies, 11 had inclusions on rectal biopsies. So the flexible rectosigmoidoscopy was not sufficient to find inclusions 13 times out of 29., Conclusion: Our study indicates that in the cytomegalovirus colitis, inclusions predominate in the caecum, isolated right colitis exists and extra-colonic cytomegalovirus disease is not always found. For these reasons full colonoscopy is necessary for diagnosis in patients with normal flexible rectosigmoidoscopy.

Purpose: To evaluate the incidence and the prognosis of retinal detachment in CMV retinitis in AIDS. To test intravitreal injections of ganciclovir into the vitreal cavity filled with silicone., Methods: Among 136 eyes with CMV retinitis, 15 (11%) had retinal detachment. Ten eyes underwent intraocular surgery with injection of silicone oil, one extraocular surgery and four eyes were not operated. Later, four eyes filled with silicone received intravitreal injections of ganciclovir., Results: At 2 months, the retina was flat in all the operated eyes, with a visual acuity improved or stabilized in 8 cases (73%). Conversely, visual acuity was lost in all the unoperated eyes. The 14 intravitreal injections of ganciclovir performed in four eyes (which received 2, 3, 3 or 6 injections, respectively) were well tolerated., Conclusion: Surgery of retinal detachment in CMV retinitis usually allows the conservation of ambulatory visual acuity. Its indications must be discussed together with the patient, the ophthalmologist and the physician. Intravitreal injections of ganciclovir in vitreal cavity filled with silicone oil are possible.

Objectives: The aim of the study was to assess the incidence and aetiology of fever of unknown origin in human immunodeficiency virus (HIV)-infected patients, and to evaluate the usefulness of the main diagnostic procedures., Design: A retrospective study., Setting and Subjects: We reviewed the records of 270 HIV-infected patients who were hospitalized for the first time in a department of infectious and tropical diseases during the 27 month study period., Main Outcome Measures: Fifty-seven patients (21%) had a history of fever of unknown origin., Results: The aetiology was found in 49 cases (86%). The major cause of the fever was mycobacteriosis: atypical mycobacteria in 10 cases, Mycobacterium tuberculosis in 10, mycobacteria of unspecified type in two, and BCG strain in one. A liver biopsy and a thoracic CT scan greatly contributed to the diagnosis of mycobacterial infection. Seventeen patients were given empiric antimycobacterial therapy as a therapeutic test, of whom seven had a favourable response. The other main causes of fever were cytomegalovirus infection in five patients, leishmaniasis in four, and lymphoma in four., Conclusions: Fever of unknown origin is a frequent occurrence in the course of HIV infection, and mycobacterial infection should be considered as a first-line diagnosis in such cases. The place of empiric antimycobacterial therapy in the diagnostic strategy requires further evaluation, but appears to be an alternative to multiple investigative procedures.

Setting: Tuberculosis may be diagnosed too late, especially in HIV-infected patients, with consequences on bacillus transmission and survival. Empiric antibuberculosis treatment (EATT) may be started before diagnosis of tuberculosis is confirmed. As rifampicin is a broad spectrum antibiotic, EATT including rifampicin may be effective in infections other than tuberculosis, leading to misdiagnosis., Objective: To define the efficiency criteria of EATT with or without rifampicin., Design: Between 1988 and 1991, 20 febrile patients with suspected tuberculosis (including 15 who were HIV-positive) were started on EATT in the absence of bacteriological or histological proof of tuberculosis. 10 patients (50%) received a 4-drug non-specific EATT including rifampicin, isoniazid, pyrazinamide and ethambutol, and 10 (50%), received a 3-drug specific EATT without rifampicin., Results: In 10 patients (50%), the diagnosis of tuberculosis was confirmed by positive cultures within a mean of 32 days (15-57 days) after the beginning of EATT (group TB 1). Of the 10 patients whose cultures remained negative, 4 (20%) became afebrile and showed improvement under EATT (group TB 2), and 6 (30%) remained febrile and did not improve (group No TB). Patients from groups TB 1 and TB 2 became afebrile within a mean of 11 days (1-54 days). This delay was not different between patients receiving specific or non-specific EATT. In patients receiving specific EATT, rifampicin was added to the initial 3-drug treatment after resolution of fever., Conclusion: EATT appears to be a useful method for rapid presumptive diagnosis and treatment of tuberculosis.

Relapse of brain toxoplasmosis in AIDS patients continue to occur despite maintenance therapy. The characteristics of 15 patients who experienced a relapse were reviewed. Mean delay of relapse was 7 months (2-20). Maintenance therapy for the 2 months prior to the relapse was pyrimethamine alone (n = 4), pyrimethamine plus dapsone (n = 3), pyrimethamine plus spiramycine (n = 1), pyrimethamine plus clindamycine (n = 4), pyrimethamine plus sulfadiazine (n = 1) and no treatment (n = 2). Strict compliance was ascertained for only 5 patients. Compared with the first episode of brain toxoplasmosis, all 15 patients had new neurological signs, and new lesions of the brain were detected by CT scan in 67% patients. This study showed that poor compliance to maintenance therapy is a major factor of relapse, and the less favourable response to acute therapy could be due to progression of immunodeficiency.

We report two cases of penicillin G-resistant pneumococcal meningitis in adults, with clinical and bacteriological failure of amoxicillin and negative or incomplete response to third generation cephalosporins. Meningitis occurred in a man treated for myeloma and in an elderly woman under prolonged intermittent amoxicillin therapy for chronic otitis. Such situations are known as exposing to pneumococcal meningitis and to resistance of the strain involved to penicillin G. Both patients were cured by vancomycin in continuous infusion associated with rifampicin or fosfomycin. Contrary to third generation cephalosporins, which have higher minimal inhibitory concentrations, vancomycin and rifampicin are still fully active against penicillin G-resistant pneumococcal strains. Thus, vancomycin administered in continuous infusion and associated with rifampicin and fosfomycin deserves to be tried as first-line treatment of pneumococcal meningitis in patients at risk of resistance to penicillin G.

To assess the clinical presentation and outcome of infectious sinusitis in HIV-infected patients, we analyzed in a retrospective study, the records of HIV-infected patients hospitalized from June 1986 to November 1989. Twenty-eight episodes of infectious sinusitis, defined by radiological signs, were recorded in 20 HIV-infected patients. Clinical presentation suggestive of acute sinusitis was inconstant and in 6 episodes a persistent fever was the only symptom. Concomitant pneumonia was detected in 8 episodes. Bacteria were isolated in 8 episodes, and in 4 of them, Haemophilus influenzae was identified. Clinical relapses occurred in 8/20 patients, requiring a surgical drainage in 3 cases. The frequency of relapses and the possibility of chronicity justify a more prolonged and aggressive therapy in infectious sinusitis occurring in HIV-infected patients.

Prevalence of aspergillosis in patients infected with the human immunodeficiency virus (HIV) is unknown. Mycologic findings in bronchopulmonary specimens from 614 HIV-positive patients sent to a parasitology laboratory between June 1, 1989 and May 31, 1991 were analyzed retrospectively; medical records of Aspergillus sp--positive patients were studied to evaluate the potential pathogenic role of this organism. Prevalence of Aspergillus sp. was 2.7% in bronchoalveolar lavage (BAL) specimens, (21/757), 15.1% in sputum specimens (3/53), 12.6% in bronchial aspirates (11/87), 7% in protected brush specimens (2/28), and 16.6% in lung biopsy specimens (4/24). A total of 20 patients (rate = 3.14%) had lung specimens positive for Aspergillus sp. (A. fumigatus 95% and A. niger 5%). Among them, 66% had a single positive specimen (14.3% with a positive smear) and 33% had several positive specimens (mean 4.9 +/- 3.3). Four patients (20%) with a more than 20-month history of AIDS and less than 36 CD4+ cells per microliter had documented pulmonary aspergillosis; three of these patients also had a current or past history of pulmonary mycobacterial infection. Rate of recovery of Aspergillus sp. in LAB specimens was low. The other specimens were harvested because of clinically suggestive manifestations. However, in 20% of patients with positive specimens. A. fumigatus was the cause of patent infection; these patients had severe AIDS-related immunodeficiency.

So far, no ideal study providing an exhaustive knowledge of acute pharyngitis epidemiology has been carried out. What is available now is a number of investigations, all with deficiencies, which concern the duration of the disease (there may be seasonal variations), its limits in space and, above all, the number of pathogens sought for. A well-organized investigation span over at least one year, involve a fairly wide range of age-groups and be repeated in several countries. Bacterial epidemiology is dominated by beta-haemolytic streptococci group A, but other streptococcal groups, notably group C, have been incriminated. Other responsible bacteria, such as Haemophilus spp., Staphylococcus spp. and Corynebacterium spp., are extremely rare but most probable. Mycoplasma pneumoniae and perhaps Chlamydia pneumoniae are probably found more frequently. Rheumatic fever--which had virtually disappeared in medically advanced countries due to a higher level of life and to the general use of penicillin therapy--has reappeared in recent years, as shown by a few North-American epidemics. Such epidemics have come on time to remind us that we should be vigilant and continue, as in the past, to treat all streptococcal foci systematically, in order to prevent the occurrence of rheumatic fever.

Acute rheumatic fever is characterized by non suppurative inflammatory lesions involving the heart, joints, subcutaneous tissues and central nervous system. It is a complication of group A streptococcal upper respiratory tract infection. The pathogenic mechanisms remain unknown although there is a general agreement as to an immunological hypothesis. Pharyngitis must be treated, even if streptococcal origin is not proved. Penicillin remains the first choice antibiotic. Epidemiological studies of all group A streptococcal serotypes isolated should be performed.

Amphotericin B (AMB), either alone or incorporated into small unilamellar vesicles of pure dipalmitoylphosphatidyl choline (DPPC SUV-AMB), was administered intravenously to male Sprague-Dawley rats once daily for 5 days. Either 1.5 or 3.5 mg of AMB or DPPC SUV-AMB per kg was given, since these concentrations corresponded, respectively, to the lowest nephrotoxic dose and the sublethal dose of AMB in our model. Tubular functions were evaluated daily, and AMB concentrations in plasma, urine, and tissues were measured by high-performance liquid chromatography. AMB at both doses induced tubular toxicity, hyposthenuria being the earliest symptom. DPPC SUV-AMB at 1.5 mg/kg/day was atoxic, but the tubular alterations induced by 3.5 mg of DPPC SUV-AMB per kg were similar to those observed with 3.5 mg of AMB per kg, except that the ability to concentrate urine was partly restored 72 h after the last infusion. Incorporating AMB into DPPC SUV did not influence the pharmacokinetics of the drug. Using this lipidic AMB formulation, we thus observed a beneficial effect toward limiting the renal tubular toxicity of repeated low doses of AMB but, unexpectedly, not that of high doses. These results indicate that tubular renal functions and electrolyte serum values should be closely monitored in patients treated with AMB liposomal formulations, especially high-dose regimens.