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The pathophysiological link between adiposity and blood pressure is not completely understood, and evidence suggests an influence of sex and genetic determinants. We aimed to identify the relationship between adiposity and blood pressure, independent of a robust set of lifestyle and metabolic factors, and to examine the modulating role of sex and Angiotensin-Converting Enzyme (ACE) insertion/deletion (I/D) polymorphisms. In the Relationship Between Insulin Sensitivity and Cardiovascular Disease (RISC) study cohort, 1211 normotensive individuals, aged 30 to 60 years and followed-up after 3.3 years, were characterized for lifestyle and metabolic factors, body composition, and ACE genotype. Body mass index (BMI) and waist circumference (WC) were independently associated with mean arterial pressure, with a stronger relationship in women than men (BMI: r =0.40 versus 0.30; WC: r =0.40 versus 0.30, both P ID and II ACE genotypes in both sexes ( P ACE genotype only in women ( P =0.03). A 5 cm larger WC at baseline increased the risk of developing hypertension at follow-up only in women (odds ratio, 1.56 [95% CI, 1.15–2.10], P =0.004) and in II genotype carriers (odds ratio, 1.87 [95% CI, 1.09–3.20], P =0.023). The hypertensive effect of adiposity is more pronounced in women and in people carrying the II variant of the ACE genotype, a marker of salt sensitivity.

Objective Microprolactinomas are currently treated with dopamine agonists. Outcome information on microprolactinoma patients treated by surgery is limited. This study reports the first large series of consecutive non-invasive microprolactinoma patients treated by pituitary surgery and evaluates the efficiency and safety of this treatment. Design Follow-up of a cohort of consecutive patients treated by surgery. Methods Between January 2008 and October 2020, 114 adult patients with pure microprolactinomas were operated on in a single tertiary expert neurosurgical department, using an endoscopic endonasal transsphenoidal approach. Eligible patients presented with a microprolactinoma with no obvious cavernous invasion on MRI. Prolactin was assayed before and after surgery. Disease-free survival was modeled using Kaplan–Meier representation. A cox regression model was used to predict remission. Results Median follow-up was 18.2 months (range: 2.8–155). In this cohort, 14/114 (12%) patients were not cured by surgery, including ten early surgical failures and four late relapses occurring 37.4 months (33–41.8) after surgery. From Kaplan–Meier estimates, 1-year and 5-year disease free survival was 90.9% (95% CI: 85.6–96.4%) and 81% (95% CI: 71.2–92.1%) respectively. The preoperative prolactinemia was the only significant preoperative predictive factor for remission (P < 0.05). No severe complication was reported, with no anterior pituitary deficiency after surgery, one diabetes insipidus, and one postoperative cerebrospinal fluid leakage properly treated by muscle plasty. Conclusions In well-selected microprolactinoma patients, pituitary surgery performed by an expert neurosurgical team is a valid first-line alternative treatment to dopamine agonists.

The affiliation details for Geltrude Mingrone are corrected below.

Prevalence of postpartum depression (PPD) ranges from 10 to 15 % of parturients. The impact of the PPD is major on the maternal bond and the health of both mother and child. Its physiopathological mechanisms appear to differ from other types of depression. Today, pharmacotherapy is based on nonspecific treatment, and recent therapeutic advances in this field require a comprehensive approach of the implication of the GABAergic system in the development of PPD. Neurosteroid levels during pregnancy and after parturition and the GABA-A-r modulation are thought to be involved in PPD.To evaluate if the GABAergic approach is relevant in postpartum depression management.We conducted a systematic review of literature based on the MEDLINE database with the following Medical Subject Headings (MeSH): "postpartum depression", "GABA", "ganaxolone", "brexanolone", "allopregnanolone", prior to September 2019. We selected articles in English: preclinical and clinical studies, literature review, observational and therapeutic studies.Preclinical models (mouse and rat) show changes in GABAergic inhibition in the peripartum period and correlation between allopregnanolone and GABA-A-r plasticity. This plasticity in the peripartum period maintains levels of inhibition adapted despite increased neurosteroid levels. KO models for the GABA-A-r δ subunit develop depression and anxiety symptoms in the postpartum period, and a change in the expression of the gene coding for the GABA-R alpha-4 subunit was found. Artificial inhibition of progesterone metabolism during post-partum increased depression symptoms. GABAergic fluctuation seems to be interrelated with other systems such as those of oxytocins. A synthetic neurosteroid (SGE-516) was tested on mouse models of PPD, KO for δ-GABA-A-r or KCC2, and showed decreased depressive symptoms and better mothering. Clinical studies confirm neurosteroid fluctuation and changes in the GABAergic system during the peripartum period. Allopregnanolone is the neurosteroid the most studied in PPD, and it is elevated in the brain during the pregnancy. Studies disagree on the presence of significant differences in allopregnanolone plasma levels during pregnancy or postpartum between women with PPD or not. Women with a history of PPD have greater susceptibility to neurosteroid withdrawal. Imagery and genetical data also show a link between allopregnanolone and PPD. The GABA-A-r may not recover in time following a reduced number during pregnancy, and this mismatch between neurosteroid levels and their receptor may trigger PPD. Several randomized controlled trials investigated brexanolone administrated IV, a synthetic formulation of allopregnanolone, and demonstrated a rapid and well tolerated reduction in depressive symptoms. In March 2019 brexanolone obtained FDA approval in PPD indication under the name Zulresso. However, there are differences in the time of beginning of PPD, which could constitute different subgroups of this disease, and which physiopathology could respond to different mechanisms. Prenatal depression does not respond to a GABAergic approach, but women without any risk factor or previous mood disorder developing PPD in the weeks following childbirth could be particularly responsive to this kind of treatment.Disability to modulate GABA-A-r expression during pregnancy and restore its previous state after parturition appears to trigger PPD. The GABAergic system is a promising pharmacotherapy target. From preclinical to clinical studies for about twenty years the GABAergic system has been incriminated and targeted in this challenging mental disease.

Assessing disease activity in patients suffering from autoimmune diseases is complex. Symptoms are multiple, often subjective and there are no reliable biomarkers. Many activity scores have been implemented to compare treatment efficacy in clinical trials. Their use in clinical practice is largely unknown. We performed a practical survey to analyze the use of activity scores in clinical practice to consider treatment response and to assess the determinants of their use.A sample of French internists answered a questionnaire about activity scores of systemic lupus erythematosus, Sjögren's syndrome, autoimmune myositis and necrotizing vasculitis of small vessels. The frequency of use of these tools, the causes of their non-use, and the general opinion of practitioners about the place of theses scores in current practice were described.The form was completed by 92 internists. Seventy percent of them supported the use of activity scores in consultations, but actually used them in less than 25% of patient visits. The reasons for the low use of these scores are mainly the ignorance of their existence (42%) and their length or complexity (28%).The discrepancy between the ratio of practitioners who believe that scores have a place in daily practice and their actual use shows that the current scores do not meet the needs. The implementation of easily usable activity scores in inflammatory diseases remains a challenge for the internists.

With approximately 67 million individuals affected worldwide, autism spectrum disorder (ASD) is the fastest growing neurodevelopmental disorder (United Nations, 2011), with a prevalence estimated to be 1/100. In France ASD affects approximately 600,000 individuals (from childhood to adulthood, half of whom are also mentally retarded), who thus have a major handicap in communication and in adapting to daily life, which leads autism to be recognized as a national public health priority. ASD is a neurodevelopmental disorder that affects several domains (i.e., socio-emotional, language, sensori-motor, executive functioning). These disorders are expressed early in life with an age of onset around 18 months. Despite evidence suggesting a strong genetic link with ASD, the genetic determinant remains unclear. The clinical picture is characterized by impairments in social interaction and communication and the presence of restrictive and repetitive behaviors (DSM-5, ICD-10). However, in addition to these two main dimensions there is significant comorbidity between ASD and other neurodevelopmental disorders such as attention deficit hyperactivity disorder or with genetic and medical conditions. One of the diagnostic features of ASD is its early emergence: symptoms must begin in early childhood for a diagnosis to be given. Due to brain plasticity, early interventions are essential to facilitate clinical improvement. Therefore, general practitioners and pediatricians are on the front line to detect early signs of ASD and to guide both medical explorations and early rehabilitation.

The aims of the present study were to estimate the prevalence of renal impairment (RI) among HIV-infected adult patients and to investigate the associated factors.A cross-sectional survey was conducted in a French hospital-based cohort. Clearance of creatinine (CC) was calculated using the Cockcroft-Gault formula. Four stages of RI were defined: mild (60-90 mL/min), moderate (30-60), severe (15-30) and end stage (15). Logistic regression models were used to investigate factors associated with RI.The male/female ratio of the 2588 patients enrolled was 3:1 and the median age was 42 years. At the time of assessment of CC, the median CD4 count was 430 cells/microL and HIV plasma viral load (VL) was50 copies/mL in 60%. The overall prevalence of RI was 39.0%: 34.2% mild, 4.4% moderate, 0.3% severe and 0.2% end-stage. Mild RI was associated with female gender [odds ratio (OR)=3.3: 95% CI 2.6-4.3)], age50 years (OR=9.8: 7.4-13.0) and 40-50 years (OR=1.9: 1.5-2.4), body mass index (BMI)22 kg/m(2) (OR=3.3: 2.7-4.3) and tenofovir exposure (OR=1.4: 1.0-1.9 for1 year and OR=1.5: 1.2-2.0 for1 year). Advanced RI (CC60 mL/min) was associated with age50 years (OR=5.6: 2.9-10.9) and 40-50 years (OR=2.2: 1.1-1.4), BMI22 kg/m(2) (OR=1.5: 1.0-2.4), hypertension (OR=2.5: 1.4-2.5) and indinavir (IDV) exposure1 year (OR=2.3: 1.5-3.6).This survey confirms the high prevalence of RI in HIV-infected patients and indicates the importance of the investigation of renal function especially in women, older patients, those with a low BMI or treated with tenofovir or IDV.

Background More than 10 years after the introduction of combination antiretroviral therapy (cART), we examined the trend in the proportion of deaths caused by end-stage liver disease (ESLD) in HIV-infected adults in France between 1995 and 2005. Design and methods In 2005, 34 departments prospectively recorded all deaths in HIV-infected patients who were followed in those departments (around 24 000). Results were compared with those of four previous cross-sectional surveys conducted since 1995 using the same methodology. Results Among 287 reported deaths in 2005, 100 (35%) were related to AIDS, and 48 (17%) to ESLD. Three out of four patients who died from ESLD-related causes had chronic hepatitis C. Excessive alcohol consumption was reported in approximately half of the patients (48%). At death, 62% of patients had undetectable HIV viral load and the median CD4 count was 237 cells/μL. From 1995 to 2005, the proportion of deaths caused by ESLD increased from 2 to 17% (P

Orbital tumors are a rather frequent pathology. Their diagnosis and treatment may be difficult. They can be benign or malignant. All the tissues of the orbit can give rise to a tumor, resulting in their large number. Among the benign tumors, we have meningiomas and cavernous hemangiomas, and for the malignant tumors, lymphomas, metastasis, ENT tumors and lacrimal gland tumors in the adult. Usually the signs are nonspecific, with proptosis, oculomotor disturbance, inflammatory signs, pain and sometimes a mass. Imaging (CT, MRI and color Doppler ultrasound) shows the tumor, its location, extent and possible metastases. Biopsy and anatomic and cytopathologic examination confirm the type of benign or malignant tumor. Based on these three elements: clinical appearance, imaging and histology, the tumor will be treated, usually by a surgical approach according to the recommendations of a multidisciplinary tumor conference. Radiation therapy and chemotherapy may supplement the treatment.

Background After cardiac surgery adequate postoperative analgesia is necessary. We assessed analgesia using intrathecal morphine and clonidine. Methods In a double-blind randomized study, 45 patients having coronary artery bypass graft surgery were allocated randomly to receive i.v. patient-controlled analgesia (PCA) morphine (bolus, 1 mg; lock-out interval, 7 min) (control group), either alone or combined with intrathecal morphine 4 μg kg −1 or with both intrathecal morphine 4 μg kg −1 and clonidine 1 μg kg −1 . Intrathecal injections were performed before the induction of general anaesthesia. Pain was measured after surgery using a visual analogue scale (VAS). We recorded i.v. PCA morphine consumption during the 24 h after operation. Results Morphine dosage [median (25th–75th percentiles)] was less in the first 24 h in the patients who were given intrathecal morphine + clonidine [7 (0–37) mg] than in other patients [40.5 (15–61.5) mg in the intrathecal morphine group and 37 (30.5–51) mg in the i.v. morphine group]. VAS scores were lower after intrathecal morphine + clonidine compared with the control group. Time to extubation was less after intrathecal morphine + clonidine compared with the i.v. morphine group [225 (195–330) vs 330 (300–360) min, P Conclusion Intrathecal morphine and clonidine provide effective analgesia after coronary artery bypass graft surgery and allow earlier extubation.

We assessed the prognostic role of plasma levels of beta2-microglobulin, TNF-alpha, sTNFR-II, and IFN-gamma on the progression to AIDS in patients mostly treated with combination antiretroviral therapies. HIV-1-infected patients with advanced HIV disease (baseline CD4+ cell count between 50 and 250 x 10(6)/L) were included in a prospective cohort followed up for 36 months. In the 113 patients included, 22 first AIDS-defining events were reported. Cumulative probability of AIDS was 12% at M12, 18% at M24, and 20% at M36. Using a Cox model, the baseline level of sTNFR-II (hazard ratio of 3.75 for sTNFR-IIor =10 ng/ml vs10 ng/ml, P = 0.01) was associated with progression to AIDS. sTNFR-II remained a prognostic factor before and after the introduction of combinations of antiretrovirals. Whether or not this marker is of value in patients exclusively treated with highly active antiretroviral therapy needs to be assessed in specific studies.

Object. The aim of this study was to reassess whether middle cerebral artery blood flow velocity (MCAv) variations measured by transcranial Doppler ultrasonography during acute PaCO2 manipulation adequately reflect cerebral blood flow (CBF) changes in patients with severe closed head injury. Methods. The study was performed by comparing MCAv variations to changes in CBF as assessed by measurements of the difference in the arteriovenous content in oxygen (AVDO2). The authors initiated 35 CO2 challenges in 12 patients with severe closed head injury during the acute stage. By simultaneous recording of systemic and cerebral hemodynamic parameters, 105 AVDO2 measurements were obtained. Patients were stratified into two groups, “high” and “low,” with respect to whether their resting values of MCAv were greater than 100 cm/second during moderate hyperventilation. Four patients displayed an elevated MCAv, which was related to vasospasm in three cases and to hyperemia in one case. The PaCO2 and intracranial pressure levels were not different between the two groups. The slope of the regression line between 1 divided by the change in (Δ)AVDO2 and ΔMCAv was not different from identity in the low group (1/ΔAVDO2 = 1.08 × ΔMCAv − 0.07, r = 0.93, p < 0.001) and significantly differed (p < 0.05) from the slope of the high group (1/ΔAVDO2 = 1.46 × ΔMCAv − 0.4, r = 0.83, p < 0.001). Conclusions. In patients with severe closed head injury, MCAv variations adequately reflect CBF changes as assessed by AVDO2 measurements in the absence of a baseline increase in MCAv. These observations indicate that both moderate variations in PaCO2 and variations in cerebral perfusion pressure do not act noticeably on the diameter of the MCA. The divergence from the expected relationship in the high group seems to be due to the heterogeneity of CO2-induced changes in cerebrovascular resistance between differing arterial territories.

alpha 2-Adrenergic agonists induce cerebral vasoconstriction, reduce intracranial pressure (ICP) in experimental animals and may be useful in the hemodynamic management of head-injured patients. We studied the effects of the alpha 2 agonist clonidine on the cerebral circulation in 12 head-injured patients (Glasgow Coma Scale score8). Middle cerebral artery flow velocity (MCAV), ICP, mean arterial pressure (MAP), and cerebral perfusion pressure (CPP), were continuously recorded before (T0), at the end (T1), and 30 min after (T2) a 10-min intravenous (i.v.) infusion of 2.5 micrograms/kg clonidine. The cerebral arteriovenous oxygen content difference (AVDO2) and Paco2 were sequentially obtained. ICP, Paco2, AVDO2, and MCAV did not change after clonidine administration. In contrast, MAP and CPP decreased (P0.05 and P0.05, respectively, at T1 and T2). Three subjects displayed a transient increase in ICP (10 mm Hg) at T1; this increase was concomitant with the decrease in MAP. Clonidine administered as an i.v. infusion may induce a critical but transient increase in ICP in some severely head-injured patients. This effect may result from cerebral autoregulatory vasodilation and increased cerebral blood volume as a response to the hypotensive effects of clonidine.

Sympathetic nervous system stimulation, which releases noradrenaline, influences the nociceptor activity which develops after tissue injury. The alpha 2-adrenergic agonist, clonidine, produces analgesia through a central mechanism but also inhibits noradrenaline release at terminal nerve fibre endings. Clonidine may induce analgesia when administered at peripheral sites. This study assesses the potential analgesic effect of clonidine after intra-articular administration. Forty ASA I-III patients, scheduled for arthroscopic knee surgery under general anaesthesia were allocated randomly in 4 groups of 10 patients each, at the end of the surgical procedure. In the control group (group 1), the patients received 20 ml of intra-articular isotonic saline. In group 2, the patients received 150 micrograms of clonidine diluted in 20 ml of isotonic saline injected into the knee joint. In group 3, the patients were given 20 ml of intra-articular isotonic saline and clonidine 150 micrograms was injected subcutaneously. In group 4, morphine 1 mg, diluted in 20 ml of isotonic saline, was injected into the knee joint. Postoperative pain was assessed in a double-blind fashion using a visual analogue scale (VAS) at 1, 2, 3, 6 and 24 h after the end of surgery. VAS scores were significantly lower in groups 2 and 4, compared to groups 1 and 3, at 1 and 2 h after surgery. The delay between intra-articular injection and further postoperative analgesic administration was significantly longer (P < 0.05) in group 2 (533 +/- 488 min) compared to groups 1 and 3 (70 +/- 30 min and 132 +/- 90 min, respectively). The difference was not significant between group 4 (300 +/- 419 min) and the other groups. We conclude that a low dose of intra-articular clonidine produces analgesia unrelated to vascular uptake of the drug. This study further supports a peripheral analgesic effect of clonidine.

Teenagers and adults with intellectual disabilities are nowadays "over-handicapped", often due to lack of care in self-sufficiency and continued learning, two essential domains for living in a community. Their cognitive limits, particularly on the executive functions, could be an obstacle to their involvement in the daily life activities, through their difficulties to plan, anticipate, shift and maintain information in working memory. These high level mental functions can be taught with the CRT program (Cognitive Remediation Therapy - Wykes and Reader 2005) developed in other pathologies and providing an adaptation regarding the developmental level of the person.Firstly, it is essential to determine cognitive developmental levels of the teenager or the adult, using standard tools, such as Wechsler scales. Secondly, functional and/or adaptative levels have to be assessed using specific tools, such as the Vineland Adaptative Behavior Scale 2nd Edition (VABS-II, Sparrow et al., 2005) and the Functional Intervention Scale (EFI, Willaye et al., 2005). Finally, in order to clearly distinguish what are the preserved and impaired cognitive domains, standard tools assessing executive functions such as the Wisconsin Card Sorting Test, the Tower of London, Stroop Test and BADS are used if possible for the patient. The setting of cognitive remediation programs, previously developed for schizophrenic patients, requires adaptation for teenagers and adults with intellectual disabilities, taking into account the limitation of their cognitive abilities. In this paper, we will show that the CRT method for cognitive remediation is particularly relevant for subjects with intellectual disabilities. This method is hence focused on strategies and exercises to improve working memory, categorization and moreover executive functions. Of course this method might need adaptations, with examples based on simplification of the different tasks, notably for verbal materials, and with variations of the media used. These sessions will be part of a wider individualized caring project, allowing the person to transfer the cognitive acquisitions to his/her daily life.The use of cognitive programs adapted to people with intellectual disabilities can provide benefits in the development of autonomy and daily life activities, leading to a better quality of life and self-esteem.

Causes of acquired thrombotic thrombocytopenic purpura (TTP) are multiple and rarely iatrogenic.A 40-year-old, HIV and hepatitis C virus co-infected woman was treated with interferon and ribavirine and developed a TTP confirmed by the presence of anti-ADAMTS 13 antibodies. The outcome was favourable when treatment was discontinued and rituximab infusion administered.The occurrence of anemia and thrombocytopenia in patients treated with interferon and ribavirine is not always related to direct toxicities of these treatments. The ADAMS 13 testing may help the clinician to diagnose iatrogenic acquired TTP.

BackgroundOpen inguinal hernia repair is associated with moderate postoperative pain, but optimal analgesia remains controversial. The aim of this systematic review was to evaluate the available literature on the management of pain after open hernia surgery.MethodsRandomized studies, in English, published between January 1966 and March 2009, assessing analgesic and anaesthetic interventions in adult open hernia surgery, and reporting pain scores, were retrieved from the Embase and MEDLINE databases. In addition to published evidence, clinical practice was taken into account to ensure that the recommendations had clinical validity.ResultsOf the 334 randomized studies identified, 79 were included. Quantitative analysis suggested that regional anaesthesia was superior to general anaesthesia for reducing postoperative pain. Spinal anaesthesia was associated with a higher incidence of urinary retention and increased time to home-readiness compared with regional anaesthesia.ConclusionField block with, or without wound infiltration, either as a sole anaesthetic/analgesic technique or as an adjunct to general anaesthesia, is recommended to reduce postoperative pain. Continuous local anaesthetic infusion of a surgical wound provides a longer duration of analgesia. Conventional non-steroidal anti-inflammatory drugs or cyclo-oxygenase 2-selective inhibitors in combination with paracetamol, administered in time to provide sufficient analgesia in the early recovery phase, are optimal. In addition, weak opioids are recommended for moderate pain, and strong opioids for severe pain, on request.

Extradural clonidine produces analgesia, with sedation, hypotension and bradycardia, in postoperative patients. This study assessed if oral yohimbine would reverse these side effects. We studied 30 ASA I-II patients undergoing orthopaedic surgery. After operation they were allocated randomly to three groups to receive placebo, extradural clonidine 450 micrograms or extradural clonidine 450 micrograms plus oral yohimbine 16 mg. Pain score was measured on a visual analogue scale (VAS); sedation was assessed on a simple scale graded from 0 (awake and alert) to 3 (deeply sedated, awakening after tactile stimulations) and heart rate and arterial pressure were monitored for 5 h. Yohimbine reversed the sedation induced by extradural clonidine, but also shortened the duration of analgesia (31 (SD 15) min, 186 (72) min and 126 (52) min in the placebo, extradural clonidine and extradural clonidine+yohimbine groups, respectively) (P0.05), and did not reduce the hypotension and bradycardia related to clonidine administration. These results suggest that alpha 2 adrenoceptors are mediators of the sedation induced by clonidine and that the haemodynamic effects are not related to stimulation of supraspinal alpha 2 receptors.

Autism spectrum disorders are a class of conditions categorized by communication problems, ritualistic behaviors, and deficits in social behaviors. This class of disorders merges a heterogeneous group of neurodevelopmental disorders regarding some phenotypic and probably physiopathological aspects. Genetic basis is well admitted, however, considering phenotypic and genotypic heterogeneity, correspondences between genotype and phenotype have yet to be established.To better identify such correspondences, genetic models have to be identified and phenotypic markers have to be characterized. Recent insights show that a variety of genetic mechanisms may be involved in autism spectrum disorders, i.e. single gene disorders, copy number variations and polygenic mechanisms. These current genetic models are described. Regarding clinical aspects, several approaches can be used in genetic studies. Nosographical approach, especially with the concept of autism spectrum disorders, merges a large group of disorders with clinical heterogeneity and may fail to identify clear genotype/phenotype correlations. Dimensional approach referred in genetic studies to the notion of "Broad Autism Phenotype" related to a constellation of language, personality, and social-behavioral features present in relatives that mirror the symptom domains of autism, but are much milder in expression. Studies of this broad autism phenotype may provide a potentially important complementary approach for detecting the genes involved in these domains. However, control population used in those studies need to be well characterized too. Identification of endophenotypes seems to offer more promising results. Endophenotypes, which are supposed to be more proximal markers of gene action in the same biological pathway, linking genes and complex clinical symptoms, are thought to be less genetically complex than the broader disease phenotype, indexing a limited aspect of genetic risk for the disorder as a whole. However, strategies useful to characterize such phenotypic markers (for example, electrophysiological markers) have to take into account that autism is an early neurodevelopmental disorder occurring during childhood when brain development and maturation are in process.Recent genetic results have improved our knowledge in genetic basis in autism. Nevertheless, correspondences with phenotypic markers remain challenging according to phenotypic and genotypic heterogeneity.

Summary Background Lung deposition is crucial for asthma treatment. However, there is no study comparing the potential role of lung co-deposition of combination therapy (inhaled corticosteroid and long-acting β2 agonist) in the same inhaler. In moderate to severe asthmatics, an extra-fine hydrofluoroalkane combination of beclomethasone dipropionate and formoterol given via a single pressurised metered-dose inhaler (pMDI) was compared with beclomethasone dipropionate chlorofluorocarbon (CFC) pMDI and formoterol dry powder inhaler (DPI) given via separate inhalers. Methods In a double-blind, double-dummy, 24-week randomised clinical trial, 645 patients with moderate to severe asthma uncontrolled by regular treatment with inhaled corticosteroids received regular treatment with extra-fine fixed combination beclomethasone dipropionate 200μg/formoterol 12μg bid, or beclomethasone dipropionate (500μg bid) via CFC pMDI and formoterol (12μg bid) via DPI, or beclomethasone dipropionate (500μg bid) via CFC pMDI. The primary outcome was morning peak expiratory flow (PEF). Secondary outcomes included lung function measured at clinic, asthma symptoms and control, exacerbations. Results Beclomethasone dipropionate/formoterol combination via single inhaler or via separate inhalers improved morning PEF. However, the combination via single inhaler was more effective than given via separate inhalers for asthma control. Both combination treatments were superior to beclomethasone dipropionate alone in improving lung function and asthma control. All treatments were well tolerated. Interpretation In patients with moderate to severe asthma, beclomethasone dipropionate/formoterol in a single inhaler was as effective as beclomethasone dipropionate plus formoterol and superior to beclomethasone dipropionate alone in improving lung function. For the first time with a single inhaler, beclomethasone dipropionate/formoterol was significantly superior to separate components for asthma control. This trial is registered with ClinicalTrials.gov , number NCT00476268 .

Twenty patients were randomly anaesthetized with either thiopental 5 mg/kg followed by a 15 mg/kg/h continuous infusion, or propofol 2.5 mg/kg followed by a 9 mg/kg/h continuous infusion, paralysed with vecuronium 0.1 mg/kg, intubated and ventilated with nitrous oxide 50% in oxygen. Fifteen minutes after induction, fentanyl 5 micrograms/kg was injected. Inspiratory tracheal pressure (PT), gas flow (V) and volume (V) were continuously measured while the lungs were inflated with a constant inspiratory flow ventilator. Respiratory compliance (Crs) and resistance (Rrs) were calculated from the regression of PT on V. In both groups Crs decreased following anaesthesia. Fentanyl injection elicited an increase in Rrs (from 1.04 +/- 0.70 to 1.63 +/- 0.92 kPa x l-1 x s) and a further decrease in Crs (from 0.55 +/- 0.30 to 0.42 +/- 0.10 l x kPa-1) in the thiopental group but not in the propofol group (Rrs: 1.26 +/- 0.69 to 1.08 +/- 0.44 kPa x l-1 x s, Crs: 0.49 +/- 0.11 to 0.48 +/- 0.13 l x kPa-1). These results suggest that the dose of propofol administered in this study may prevent fentanyl-induced bronchoconstriction.

Sore throat and dysphonia are a significant source of postoperative discomfort for patients scheduled for breast surgery who have been intubated for general anaesthesia. The aim of this study was to compare the incidence of postoperative pharyngo-laryngeal pain and dysphonia in the use of the laryngeal mask airway (LMA) or tracheal intubation in these patients. In a prospective, double-blind, randomised clinical trial we studied 53 women undergoing elective breast surgery to test the hypothesis that the use of the LMA could reduce the incidence of pharyngo-laryngeal morbidity compared with tracheal intubation. Postoperative sore throat and hoarseness were assessed at 6 and 24h by a standardised interview. The incidence of postoperative sore throat was significantly higher in the case of tracheal intubation at 6h (74% vs. 27%, p=0.0003) and at 24h (27% vs. 0%, p=0.004). The incidence of hoarseness was significantly higher in the tracheal intubation group than in the LMA group at 6h after surgery (40% vs. 15%, p=0.04), but not at 24h. Compared with tracheal intubation, the use of the LMA is associated with a lower incidence of postoperative sore throat and hoarseness and may contribute for improving patient comfort after breast surgery.

The treatment of pressure ulcers complicated by osteitis in patients with paraplegia is often complex. Surgical debridement of a pressure ulcer and infected bone often creates a large wound that is left to heal by either secondary intention or covered with a flap (immediately or later). Topical negative pressure (TNP) therapy, delivered using the Vacuum Assisted Closure device (KCI International, the Netherlands), is a non-invasive technique for healing by negative pressure. We report its use in the treatment of large wounds following segmentary resection of osteitis of the lower limbs in two paraplegic patients.

To provide up-to-date and covariate-specific estimates on tobacco smoking prevalence in a representative cohort of French human immunodeficiency virus (HIV) 1 infected patients in 2002.We conducted a cross-sectional analysis of the Aquitaine Cohort of HIV-infected patients. A logistic regression model was used to estimate associations between regular tobacco smoking and sex, age, HIV transmission categories, duration and immuno-virological status of HIV infection and duration of antiretroviral therapy. Smoking prevalence estimates were compared with the general French population values after stratification on age and sex.Among 2036 patients included in the analysis, 51% were regular smokers (95%CI 49-53). Smoking prevalence was significantly higher with younger age (OR 1.7 among thoseor = 45 years of age), among injecting drug users (OR 4.3), among those whose infection was not controlled (OR 1.2) and those whose HIV infection had been diagnosed foror = 5 years (OR 1.5). The main difference with the general population was the peak smoking prevalence among HIV-positive patients infected through injecting drug use.HIV-infected patients are highly exposed to tobacco smoking, which is implicated in multiple conditions occurring in the course of HIV infection. Adapted smoking cessation programmes should become one of the priorities of the medical care of HIV-infected individuals.

Postobstructive pulmonary oedema is a complication after extubation that occurs rarely . It can be associated with haemoptysis. We report two cases of haemoptysis occuring in ASA 1 otherwise healthy patients who underwent uncomplicated anaesthesia. Understanding of the mechanism and prompt treatment lead to rapid recovery of this dramatic complication.

Autoimmune hepatitis (AIH) is a chronic inflammatory hepatic disorder, characterized by hypergammaglobulinemia and autoantibodies. In some cases, AIH can be associated with another liver disease; such as the hepatitis C-AIH overlap syndrome, which diagnosis and treatment may be delicate.We report a type 1 AIH case in a HIV-HCV co-infected woman. AIH remission and HCV eradication were obtained with prednisone and interferon plus ribavirine. AIH relapse appeared with corticosteroid withdrawal and a new remission was obtained with immunosuppressive treatment associating prednisone and azathioprine, without opportunistic infection.This case illustrates diagnostic and therapeutic difficulties of hepatitis C-AIH overlap syndromes in an HIV-infected patient. To our knowledge, it is the first AIH case report in a HIV-HCV co-infected patient.

Patent blue V dye is used to localize the sentinel lymph node during breast and uterine oncological surgery. The case of a grade III anaphylactic reaction related to patent blue dye paracervical injection is described in a 34-year-old woman scheduled for hysterectomy. This complication needs to be rapidly diagnosed to apply adapted supportive treatment.

To analyse the causes of death among HIV-infected adults in France in the year 2000.Based on data from a national survey, our study describes and analyses the causes and characteristics of patients with immunological and virological response (CD4200/mm3, ARN-HIV500 copies/mL), who died during antiretroviral treatment.Among a total of 964 deaths registered, data on 864 cases were available for analysis. One hundred forty-nine patients (17%)were immunovirological responders. The underlying causes of death were non AIDS-defining malignancies for 36 (24%), mainly due to lung cancer (16 cases), hepatocarcinoma (7) and ano-rectal carcinoma (3), AIDS for 22 (15%), mainly due to Non Hodgkin Lymphoma (10 cases) and uterine cancer (3), cardiovascular diseases for 22 (15%), post hepatitis C hepatic failure for 16 (11%), suicide for 16 (11%), and bacterial infections for 14(9%). When comparing characteristics of death in the 149 responders versus the 715 other patients, the responders were significantly more frequently: co-infected by HCV+ (45 vs. 33%), injected drug addicts (40 vs. 27%),alcoholics (38 vs. 28 %), and dyslipidemics (19 vs. 11%). In 2000,around 20% of registered deaths of HIV patients in France had occurred among good immunovirological responders.To further reduce mortality among such efficiently treated patients, attention must be focused on treatable conditions such as hepatitis C, dyslipidemia and on the prevention of malignancies such as lung cancer and cervical or ano-rectal carcinoma.

Addiction behaviours in the anaesthetist population have been recognized as a significant health-related issue and its scope is a matter of concern.A national survey conducted among French anaesthetists consisted of a questionnaire designed to elicit information related to demographics, and work conditions, as well as substance consumption status. The study investigated the following: tobacco, alcohol, tranquillizers-hypnotics, and other agents such as cannabis, cocaine, opiates and anaesthetic agents. Respondents were classified in two categories: (no use and use)-(abuse and dependence). An univariate and multivariate analysis were performed to determine risk factors associated with drug abuse and dependence.3,476 physicians responded to the questionnaire (38.0% response rate); 22.7% were daily tobacco smokers; 10.9% were abuser or dependent to one or more substances other than tobacco i.e. alcohol (59.0%), tranquillizers and hypnotics (41.0%), cannabis (6.3%), opiates (5.5%), and stimulants (1.9%). Sleep disturbances and negative perception of work environment were more frequently reported among addicted anaesthetists.In French anaesthetists, addiction is mainly related to alcohol consumption but includes a broad spectrum of substances. Addicted subjects report issues around work environment that may have contributed to the development of their pathology.

Portal vein thrombosis (PVT) seems rare among HIV infected patients. Even though, the report of such cases is of great interest because it may help to determine the factors of occurrence. We describe cases of PVT in 4 HIV-infected men, aged 32 - 64. Two of them were co-infected with hepatitis C virus (HCV). The four patients had a history of disseminated mycobacterial infection (one case of tuberculosis, 3 cases of mycobacterium avium complex infection) with abdominal lymphadenitis. Despite HAART, their immunodeficiency was profound (CD4: 65 to 216/mm(3)). At the time of diagnosis, two patients were treated with protease-inhibitor containing regimen: indinavir (one case), ritonavir-saquinavir (one case). PVT was revealed by haematemesis (one case), abdominal pain (ome case), anasarca (2 cases). In three patients, the diagnosis of PVT was confirmed by imagery (echo-doppler or angio- RMI), and for the last patient, PVT was found during the transjugular intrahepatic portosystemic shunt setup. A low level of C protein was diagnosed in one case. Cirrhosis was not found in HIV-HCV co-infected patients. Two patients died early after diagnosis, one patient died 3 years after the onset of symptoms. Various factors may cause the development of a PVT in HIV infected patient. Serious immunodeficiency, opportunistic infections such as tuberculosis and mycobacterium avium complex related infection with abdominal lymphadenitis can further the development of PVT. Protease-inhibitor might have facilitated the process. Due to the severe prognosis of advanced cases, early evocation of diagnosis is needed.

To describe efficacy and safety in clinical practice of pegylated interferon plus ribavirin (INFpeg-Riba) in the treatment of hepatitis C viral infection (HCV) in HIV infected patients.Monocentric retrospective study with inclusion of all patients who received at least once INFpeg-Riba before April 1st 2003. All patients were followed up to six months after the end of HCV therapy.Thirty two HIV-positive patients (23 men and 9 women) with chronic hepatitis C treated by INFpeg-Riba were included. The mean age was 43 years. Fourteen patients carried HCV genotype 2 or 3 (43 %) and 18 patients carried genotype 1 or 4 (57%). The Metavir score of fibrosis showed fibrosis F1 (N =3), F2 (N =14), F3 (N =7) and F4 - cirrhosis (N =8). Twenty six patients (81%) were naive for anti hepatitis C drugs. Thirty one per cent of patients were at AIDS stage and 84% were receiving antiretroviral drugs. The mean CD4 cell count was 469 /ml and the plasma RNA HIV was less than 50 copies /ml in 57% of the cases. Adverse events leading to reduction of dose of drugs occurred in 40% and adverse events leading to discontinuation treatment occurred in 12%. A decline of CD4 cell count200 CD4/ml was observed in 15%. Clearance of HCV-RNA in end of treatment was seen in 46 % and sustained virological response in 34 %. The main predictors of sustained virological response were HCV genotype 2 or 3 (P =0.04) and plasma HIV RNA less than 50 copies/ml (P =0.001). The predictive value of good virological response of a CD4 cell count350/ml before treatment was very near the statistical significancy (p =0.07).The efficacy of pegylated interferon plus ribavirin in HIV-HCV co-infected patients is disappointing mainly due to a poor tolerance. In addition to HCV genotype, plasma HIV RNA level and CD4 cell count were essential to predict INFpeg-Riba response and should be taken into account in the process leading to the initiation of such therapy in HIV-HCV co-infected patients.

Symptomatic lactic acidosis requiring intensive care is a rare and severe adverse event related to the mitochondrial toxicity of the nucleoside analog reverse transcriptase inhibitors (NRTIs).We retrospectively investigated the clinical and biological features of HIV-infected patients who developed severe lactic acidosis syndrome at the University teaching hospital of Bordeaux and the regional community hospital, during 1996-2000.Nine patients were identified (incidence: 0,9/1000 NRTI treated patient-years), 4 men and 5 women with a median age of 36 years. They had a moderate immunodeficiency (median CD4+ T lymphocyte counts: 197/mm(3)) and only one of them presented a virological failure. The causes of hospital admission were abdominal pain (n = 6), dyspnea (n = 6), asthenia (n = 5), jaundice (n = 4), and vomiting (n = 2). Hepatomegaly was present in 6 patients. Lactic acidosis was found in all cases: median pH: 7.28, bicarbonate: 12 mmol/l, anion gap: 27 mEq/l, plasma lactic acid: 13 mmol/l. Cytolysis (n = 8), cholestasis (n = 6), hepatic failure (n = 4), rhabdomyolysis (n = 4) and pancreatitis (n = 2), were also present. Despite medical intensive care, seven patients died. The only two post-mortem examinations revealed severe hepatic steatosis. Median duration of NRTI therapy was 4 years. At presentation, five patients were receiving lamivudine, five didanosine, four stavudine and three zidovudine. Six patients were coinfected by HCV and/or HBV, four had chronic renal failure and five an immediately preceding infectious disease.The prognosis of lactic acidosis is severe. Nucleosid-analog therapy needs clinical and biological monitoring, specially in patients with comorbidities.

The commercial introduction of atypical antipsychotics (AAP) constitutes a considerable step forward in the sense that it has led to a world-wide reappraisal of the established treatment strategies for people with psychoses (including schizophrenia and affective psychoses). They have allowed refinements in the pharmacologic management of psychoses but they have a higher acquisition cost than conventional neuroleptics. The cost of the newer AAP had a substantial effect on medical resources: the AAP account for only 43.2% of neuroleptic prescriptions, but 76.1% of medical costs associated with neuroleptic drugs, and in terms of treatment costs, a reduction (50%) was found with risperidone compared with olanzapine for a same number of treated patients. The aim of this paper was to examine the use of these drugs, to compare them and to assess their impact within the context of psychiatric hospital practice, by means of analysis of prescribing practices for amisulpride, clozapine, olanzapine and risperidone for all treated patients. We conducted an observational, naturalistic study at Charles Perrens psychiatric Hospital in Bordeaux (France) that reproduced the clinical conditions in which these new drugs are used. Four photographies of all the medical prescriptions concerning atypical antipsychotic drugs were done between October 1999 (four months after the introduction in France of the olanzapine, the last of the new antipsychotics) and June 2001 (n=682 prescriptions). The total amount of these prescriptions corresponded to 527 patients. Treatment groups were compared - first overall and after by considering 2 groups: psychotic and non-psychotic patients - through descriptive analyses of sociodemographic characteristics of patients, diagnosis, percentages of patients receiving concomitant psychotropic medication and/or receiving treatment-emergent side effects and mean dosages of AAP therapy according to concomitant medication. In the same way, we compared the four AAP through their prescribing practices'evolution during the four survey.AAP drugs account for 43.2% of prescriptions (and conventional neuroleptics 56.8% of them). We recorded a significant increase between the four surveys (p0.02): 36.6% at the beginning to 47.8% at the end of the study. From the 682 collected prescriptions, 72 (10.6%) included clozapine, 130 (19.1%) amisulpride, 229 (33.6%) olanzapine and 251 (36.8%) risperidone. Sixty five percent of AAP prescriptions involved psychotic patients. A relative stability in characteristics of AAP prescriptions during the four surveys was found. So, no significant differences were observed between amisulpride, olanzapine, risperidone, in terms of age, sex, sociodemographic characteristics, unlike clozapine. However, there were statistical differences between all the AAP in the concurrent use of other neuroleptic agents (p0.02), hypnotic drugs (p0.006), mood stabilizer drugs (p0.03), and anticholinergic drugs (p0.007). Statistically, the mean dosage of amisulpride increased when a mood stabilizer drug was coprescribed (p0.0007), but it decreased with an antidepressant drug (p0.004) or an hypnotic drug (p0.02); clozapine 's one decreased every time an antidepressant drug was coprescribed (p0.02); with olanzapine, there was a significant increase every time an other neuroleptic agent (p0.03) or an anticholinergic drug (p0.006) was associated; then for risperidone, the mean dosage increased with the coprescription of an other neuroleptic agent (p0.00002), an anticholinergic (p0.00003) or an adrenolytic drug (p0.04). The pattern of prescribing practices that emerges from our four surveys suggests that these new AAP are significantly more and more often associated with a stabilizer mood drug (p0.009) (particularly the olanzapine) or/and an anxiolytic drug (p0.05) (like the amisulpride in particular). Considering the four AAP globally, but more with the risperidone, the association with a neurovegetative corrector agent decreased (p0.004) during the four surveys. Then, concerning the psychoticng the four surveys. Then, concerning the psychotic patients, the AAP were significantly more often associated with other neuroleptic agents (p0.03), the amisulpride in particular, with anticholinergic drugs (p0.00005), but significantly less with mood stabilizer drugs (p0.00003) principally the amisulpride and the risperidone, with antidepressant drugs (p0.02) particularly the risperidone. This kind of survey, however it is too much rare, is very important because it shows the clinical conditions in which these new drugs are really used. The results show that AAP appear to be the replacements of the older neuroleptics used in the treatment of psychoses, including particularly schizophrenia, but also in the treatment of mood disorders, and they reflect actual clinical practices. Other surveys must be achieved to see if our study confirms the general trend concerning the use of these drugs and so as to reassess these prescribing practices.

This study presents a tool including survey questionnaires and a specific data-processing software for the data processing, allowing health care providers to assess the quality of postoperative pain management in surgical wards.Descriptive study.A committee including anesthesiologists, nurses and epidemiologists had elaborated and tested three survey questionnaires to assess patients, nurses and medical staff satisfaction respectively. Specific data processing software was issued out of the final questionnaires. It allowed a quick analysis of items possibly, explaining inadequate postoperative pain management. After this adjustment, this tool was used in three different surgical wards, named A, B, C.The rate of answer (of investigated persons) being over 50%, data resulting from the survey performed in the surgical wards A and B were considered valid. The items which could explain insufficient pain relief were classified into 4 levels: patients assertion (ex: more than 50% of patients experienced persistent postoperative pain); practices evaluation (ex: 42 to 72% health care providers declared being aware of analgesic procedures); behavior's evaluation (ex: 19 to 34% of health care providers considered persistent postoperative pain to be useful for monitoring); and surgical wards potential (ex: 21 to 61% of health care providers took a specific course on pain management). Pros and cons of this tool were carefully examined and subsequent strategies defined.This survey's device should allow health care providers to assess the quality of postoperative pain management in surgical wards. Its validation is currently developed to improve its use, and keep the most performing indicators, showing an adequate postoperative pain management.

We assessed the correlations between some plasma markers of immune activation (soluble receptors of interleukin 2 (sIL2-R) and TNFap75 (sTNFII-R) and usual markers of HIV infection in patients treated with protease-inhibitors (PI). Forty-six PI-naive HIV-1-infected adults were included in a 1-year prospective cohort from the initiation of a P1-containing regimen (M0). Measurements of CD4+cell count, plasma HIV-RNA, sIL2-R and sTNFII-R were performed at M0, M6, and M12. The evolution of sIL2-R from baseline to M12 was significantly different between immunological responders (IR) (CD4+count above 200/mm3 for subject having less than 200 CD4 +/mm3 at inclusion, or increase of at least 50 CD4+/mm3 for others) (58 UI/ml) and non-IR (+28 UI/ml) (P =0.01). The evolution of sTNFII-R between M0 and M12 was significantly different between virological responders (VR) (plasma HIV-1 RNA less than 500 copies/ml at M12) (-2.5 ng/ml) and non-VR (+0.2 ng/ml) (P = 0.02). Our study shows significative correlations between the evolutions of soluble interleukin-2 and TNFR-II receptors and those of CD4+T-lymphocytes or HIV-RNA responses in patients under HAART.

Although several reports of sarcoidosis have been reported in hepatitis C virus (HCV)-infected patients treated with interferon-alpha, this association has never been described in nontreated HCV patients. We report two cases of sarcoidosis associated with chronic hepatitis C infection. The patients developed multivisceral sarcoidosis (cutaneous, lungs, nodes) at two and at least six years after the presumed date of infection. One patient obtained remission of sarcoidosis with corticosteroid treatment but the other remained corticodependent. The levels of hepatic enzymes were not significantly modified throughout the course of corticosteroid therapy. In conclusion, these case reports suggest that HCV itself could induce a granulomatous reaction in chronic HCV-infected patients through the stimulation of the cellular immune system. It could be of interest to test for HCV infection all patients diagnosed with sarcoidosis and to watch over every treated or nontreated hepatitis C infected patient for the development of granulomatous lesions.

The demand for organ transplantation exceeds organ donation in France and refusal to organ donation remains close to 30%. This study analysed risk factors associated with refusal of organ donation.Retrospective study.All potential organ donors registered by the French transplantation agency between 1996 and 1999 were included, excepted those with a contraindication to organ procurement or a logistic problem: 5,911 donors were included.Data analysed were those collected routinely on the French database. A logistic model was used to identify statistically significant factors and a stepwise procedure was performed to identify independent factors linked with refusal.In univariate analysis, age60 years and age13 years, stroke, lack of suicide, localisation in an university hospital and in others regions than the Centre-East of France were associated with a higher refusal rate. Year of harvesting, low level of organ procurement activity were not associated with refusal. In multivariate analysis, factors independently associated with refusal were age60 years [Odds-Ratio (OR) = 1.2)] or age13 years (OR = 1.5), stroke (OR = 1.2), meningitis and cranial tumour (OR = 1.4), suicide (OR = 0.5) and others French regions than Centre-East.The risk factors described should be taking into account when family's members are approached for donation. They represent the interactions between the history of the donors, harvesting organisation, and sociocultural factors.

A retrospective study was set up to investigate active pathologic processes associated with sarcoidosis diagnosed in 32 patients.Eighteen patients had two identified granulomatous localizations (56%) and 14 patients had three localizations or more (27%). Comorbidity was noticed in nine patients (28% of cases). Sarcoidosis was associated with an infectious disease five times (hepatitis C virus [HCV] infection three times, including one case after recombinant interferon alpha therapy, and HIV and HCV co-infection two times). The association of sarcoidosis with a chronic immunologic inflammatory disease was noticed four times (lupus erythematosus two times, myasthenia and primary biliary cirrhosis). Finally, in two cases sarcoidosis was associated with a neoplasia (non-Hodgkin's lymphoma in a co-infected HIV-HCV patient, ovarian cystadenocarcinoma in another patient). Sarcoidosis preceded or revealed the comorbidity four times.

We report a retrospective study of 115 hospitalized non-immunocompromised adults with proved or presumed diagnosis of cytomegalovirus infection. Clinical symptoms were fever (95%), constitutive symptoms (80%), joint and muscle pain (41%), shivering (32%), abdominal pain (26%), non-productive cough (20%), cutaneous eruption (20%), and diarrhea (10%). Examination found hepatomegaly (25%), splenomegaly (23%), cutaneous rash (20%), adenopathy (19%), pharyngitis (9%), jaundice (3%) or signs of meningeal irritation (1%). Seventeen patients had a gastrointestinal form (hepatitis, jaundice, colitis, antral gastritis or cholecystitis), eight had a pattern of hemopathy, two interstitial pneumonitis, two pericarditis, two immune thrombocytopenic purpura, two a polymyalgia rheumatica-like pattern, one thrombotic thrombocytopenic purpura, one cutaneous vasculitis and one meningoencephalitis. Sixty-four percent of the patients had atypical lymphocytosis. Hepatocellular injury occurred in 90% of the patients. Nineteen of the patients had biological immune abnormalities. Cytomegalovirus infection should be mainly suspected in any patient with persistent fever, isolated or associated with signs of poor specificity, or in some patients with visceral manifestations of initially unknown origin.

To determine the effect of epidural analgesia (EA) on the duration of labour and the mode of delivery.A Medline computerised literature research was conducted from 1989 to 2000 including all the prospective studies comparing EA and systemic analgesia during labour.EA prolongs the first and second stages of labour and increases the rate of instrumental delivery, without neonatal side effects. EA is not responsible for dystocia and caesarean section rate is not increased by this mode of analgesia. The effect of combined spinal-epidural analgesia is comparable to the one of EA on the length of labour and the mode of delivery. Ropivacaine does not appear to be different from bupivacaine in that setting. The benefit of ambulation remains controversial since it does not reduce the incidence of instrumental delivery, compared to conventional EA with similarly diluted local anaesthetic solutions.Pain relief provided by EA combined to modification of obstetric management (amniotomy, oxytocin) does not impair the rate of caesarean section and dystocia.

In order to determine prognostic factors associated with treatment failure (TF) in advanced HIV-infected patients treated with a regimen including indinavir, a prospective cohort study of 80 patients was set up between 1 March and 31 December 1996. TF time was calculated using the Kaplan-Meier method, from treatment induction to the first of the following events: treatment modification for adverse event or lack of significant virological and/or immunological response, AIDS-defining diagnosis or death. Date of point was 31 December 1998. Multivariate analysis was performed using a Cox model. At baseline, 60% of the patients were AIDS-free, median viral load and CD4+ count were respectively 4.8 log/ml and 79/microl. After a median follow-up of 26 months, 70% of the patients experienced a TF in a median time of 8 months. Seventy-two per cent presented an hyperbilirubinaemia (2 mg/dl). In multivariate analysis, initial AIDS stage (hazard ratios [HR]=1.94, P=0.04) and digestive intolerance (HR=2.32, P=0.003) were predictive of TF. Conversely, hyperbilirubinaemia was associated with a better outcome (HR=0.35, P0.0001). These 2 latter parameters very likely reflected patients' treatment compliance.

Cytomegalovirus (CMV) infection in non-immunocompromised adults can sometimes induce hematological and immunological disorders that may mislead diagnosis.Case reports of hospitalized non-immunocompromised adults with positive serology for CMV including the presence of immunoglobulin M or seroconversion were assessed in a retrospective study (1981-1998). We focused on clinical and biological abnormalities showing the role of CMV in disruption of functioning of hematological and immunological systems.Among 115 patients, lymphoma-like syndrome with large adenopathies and/or splenomegaly was diagnosed in eight patients, uncovering underlying CMV infection. Lymphoma was accompanied by hematoma in two patients. Three patients presented leg purpura (with thrombotic thrombocytopenic purpura in one case), one patient had cutaneous vasculitis and on other a Still's disease. Blood abnormalities were mononucleosis (64%), anemia (20%), and thrombopenia (25%) often of peripheral or hemolytic origin or due to hypersplenia. Electrophoresis of serum proteins showed an increase in immune globulins in 56% of the cases and monoclonal abnormality in nine cases. Immunological assessment was conducted in 18 patients. At least one abnormality was depicted in ten patients, consisting of either antinuclear, anti-platelet or anti smooth muscle antibodies, cryoglobulinemia, rheumatoid factor, or reduced complement fixation.Testing for CMV infection can be of value in case of blood or immunological disorders associated with clinical or biological signs. Although hematological disorders occur early, they are rarely severe. Immunological disorders are rarely symptomatic, but often raise issues regarding the potential genesis of immune diseases in at-risk patients.

The aim of this study was to search for potential diagnostic, therapeutic and prognosis differences between a series of 49 adenocarcinomas of the cervix and a matched series of epidermoid carcinomas.Forty-nine adenocarcinomas were treated between 1978 and 1992 and retrospectively compared to a series of 98 paired epidermoid carcinomas.The adenocarcinoma incidence is 5.4%. There was no significant difference for age distribution, parity, or hormonal status. There was also no significant difference for clinical features. Stage I appeared more frequently in the adenocarcinoma group (stage I: 69.4%, stage II: 14.3%, stage III: 14.3%, stage IV: 2%). Stage I are also more frequently found in the adenocarcinoma group (69.4% versus 42. 9%, p0,05). Combined radio-surgical treatment was proposed more often for the adenocarcinoma group (respectively radio-surgery combination 73%, radiotherapy alone 18%, surgery 9%); in the epidermoid carcinoma group, combined radio-surgical treatment and radiotherapy were the usual treatment (46%); surgery alone appeared in third rank place (8%). Adenocarcinoma pelvic recurrences appeared more frequently (28.6% for adenocarcinoma group versus 13.3% for epidermoid group p0.05), while distant recurrence was the same (12. 2% for adenocarcinoma group versus 11.2% for epidermoid group, p0. 05). Five years overall survival rate was worse for the adenocarcinoma group (52% versus 63.7%, p0.05) but the difference was not significant for the disease free survival rate. Only for stage Ib, there are also more pelvic recurrences (35.4% versus 13.1%, p0.05), more distant recurrences (9.6% versus 2.6%, p0.05), and lower overall survival for adenocarcinomas (58.7% versus 88.5%, p0. 01).The incidence of adenocarcinomas is slightly increasing (absolute value in our experience) and the low stages seem to be more frequent in our experience probably by staging inaccuracy. Adenocarcinoma prognosis seems to be worse because of its poor radio-sensitivity. It seems necessary to optimize clinical staging and therapeutic protocols excluding radiotherapeutic approach, including surgical purposes or radio-surgical associations if unfavorable histological features or tumoral enlargement (T3 cm) are found.

Clonidine or epinephrine are frequently combined to epidural local anesthetics to strengthen sensory block and prolong analgesia. Both drugs impair the hemodynamic profile of central neural blockade but the effects of their combination on arterial pressure and heart rate are not known and were examined in this double-blind prospective randomised study. Forty four patients scheduled for lumbar disc surgery were allocated to two groups. Epidural anesthesia was obtained by administration of 150 micrograms clonidine in 15 ml bupivacaine 0.25% solution without (group C) or with (group C + E) 37.5 micrograms epinephrine. Systolic, mean, diastolic arterial pressure and heart rate were measured throughout the study. Combined epidural and general anesthesia induced a significant decrease in arterial pressure and heart rate in both groups. SAP and MAP decreased significantly less in the patients receiving epinephrine. Low dose epidural epinephrine decreases arterial pressure instability during combined epidural and general anesthesia.

We report a series of seven patients who had scleroderma renal crisis. Their primary clinical and laboratory features along with the details of their management were compared with those of similar cases from the literature. The seven patients died within one to four months of the diagnosis with a pattern of acute renal failure, left ventricular failure and malignant hypertension. Histopathologic examination was performed in four of the patients, in two of whom it revealed thickening of the wall of the interlobular arteries related to the scleroderma, and in the other two patients nonspecific lesions of malignant hypertension. This histopathologic particularity led us to propose, on the basis of multiple renal biopsies performed in patients with scleroderma, a lesion chronology of the kidney in patients with scleroderma. Nevertheless, the triggering factors and pathophysiologic mechanisms of scleroderma renal crisis remain unclear and its prognosis is severe. Early treatment with angiotensin-converting enzyme inhibitors and other vasodilatators administered intravenously can prevent death and dialysis.

Squamous cell carcinomas of the oral cavity were treated in 157 patients by surgery as first-line (104) or salvage (53) treatment. Postoperative irradiation delivered either for locally advanced tumors (stade III-IV) or for unfavorable histological data (nodal or surgical margins involvement). The retrospective study with a mean time of follow-up of 2.5 years shows a loco-regional control rate of 75% statistically influenced by histological nodal status (p0.01). Cumulative and cause specific survival rates at 5 years are 41.1% and 57.2% respectively. T stage was found to be a prognostic factor of survival (p0.01) as bone involvement (p0.05). Surgical margins are influent on local control and survival only in absence of radiation.

The potential risks of spinal lidocaine have generated interest in an alternative local anesthetic solution. Features of anesthetic block were therefore assessed in a double-blind randomized prospective study following administration of spinal bupivacaine in small doses.Ninety patients scheduled for lower limb saphenous vein stripping were randomized to receive a 4-mL hyperbaric solution containing 4, 6, or 8 mg bupivacaine in the subarachnoid space. Sensory and motor block and hemodynamic changes were assessed at regular intervals. Patients were also questioned regarding transient radicular irritation symptoms.The mean duration of sensory block increased with increasing dose (duration at L2: 56 +/- 27, 71 +/- 29, 79 +/- 25 minutes in groups 4, 6, and 8 mg, respectively, P.05). Motor block was also dose dependent. The incidence of grade 3 motor block increased from 0%, to 21%, and to 53%. No patient had symptoms of transient radicular irritation. Arterial pressure and heart rate were stable throughout the study.Hyperbaric bupivacaine 6-8 mg provides a suitable alternative to spinal lidocaine for surgical procedures of short duration.

To study the relationship between sedation and respiration under N2O, we performed polysomnographic recordings in 15 healthy men with documented normal breathing patterns during sleep. In a first study in five subjects, we found that 50% N2O in O2 compared to 50% O2 increased sleep latency to stage 2 (59 +/- 12 vs. 17 +/- 3 min), total sleep duration (59 +/- 12 vs. 26 +/- 11 min), depth of sleep and respiratory events during sleep (18 +/- 5 vs. 1 +/- 1/h of sleep). In a second study, ten subjects were exposed to N2O (30 and 50%) in O2 during two consecutive experimental periods. Eight subjects had EEG features of physiological sleep, but nevertheless exhibited a total of 181 respiratory events. Respiratory disturbance index (RDI) during sleep was similar under 30 and 50% N2O (25 +/- 7 and 25 +/- 5/h of sleep, respectively). Obstructive events predominated, except in three subjects during N2O 30% and one during N2O 50% exposure. We conclude that N2O can induce central and obstructive sleep apneas.