Effectiveness and safety of saquinavir/ritonavir in HIV-infected pregnant women: INEMA cohort.

OBJECTIVE: The authors had for aim to describe the effectiveness and the safety of a saquinavir/ritonavir (SQV/r) regimen, 1000/100mg twice daily, in HIV-infected pregnant patients. PATIENTS AND METHOD: We made a prospective and observational study of HIV positive female patients beginning or going on SQV/r antiretroviral treatment (ART) during pregnancy. RESULTS: Sixty-two patients were enrolled from July 2007 to June 2009 in 10 infectious diseases units in France. Thirty-six women (group 1) were ART naive on inclusion, 20 (group 2) had been previously treated and then switched to SQV/r, six (group 3) were treated with SQV/r before pregnancy. 58 patients delivered while on SQV/r regimen after a median pregnancy duration of 39 WA. Eighty percent had a viral load below 50 copies/mL and 93% below 400 copies/mL: respectively 77% and 93.5% in group 1, 83% and 89% in group 2, 83% and 100% in group 3. The median SQV minimum concentrations (C(min)) measured at the third trimester and at delivery were adequate, respectively 0.91 mg/L and 0.86 mg/L. Most women (52%) had a vaginal delivery; 12 (21%) had an elective caesarean section, for obstetrics factors in eight cases. None of the newborns were HIV-infected at 6 months of age (n = 59, one death at day 3). Only one severe adverse event occurred due to saquinavir (maternal grade 3 hepatotoxicity). CONCLUSION: SQV/r 1000/100mg twice daily seems to be effective and safe in HIV-infected pregnant women with adequate saquinavir C(min).

[Acute chest syndrome of adults suffering from sickle cell disease]. / Le syndrome thoracique aigu de l'adulte drépanocytaire.

UNLABELLED: Sickle cell disease is a common but often poorly understood by chest physicians. The acute chest syndrome represents its main respiratory complication. STATE OF ART: Sickle cell disease is an autosomal recessive disorder inducing, in certain circumstances, sickling of red cells. Natives from western or central Africa and from the Caribbean islands are mainly affected. Acute chest syndrome is defined by the association of chest pain or fever and recent radiographic infiltrates, in patients suffering from sickle cell disease. Determination of etiology, infection, fat embolism or hypoventilation, is difficult, as a self-perpetuating vicious circle is ongoing. Support, largely undervalued, is based on etiological treatment and measures to avoid worsening linked to complications, especially microcirculatory disease. CONCLUSIONS: Acute chest syndrome is a severe respiratory complication of sickle cell disease. Therapeutic measures are simple but undervalued.

[Incidence, risk factors and skin manifestations of post-thrombotic syndrome: a four-year follow-up of patients included in the EDITH study]. / Incidence, facteurs de risque et signes cutanés de la maladie post-thrombotique : suivi à quatre ans des patients inclus dans l'étude EDITH.

PURPOSE: Despite appropriate therapy 10 to 100% of patients with deep vein thrombosis (DVT) of the lower limbs will develop post-thrombotic syndrome (PTS). The aim of this study was to evaluate the incidence of PTS in the EDITH cohort and to estimate the association between initial patients' characteristics and the risk of development of PTS. METHODS: One hundred and eighty patients included in the EDITH study for a first event of DVT of the lower limbs without clinical signs of venous insufficiency were recalled 4 years after their initial thrombotic event. PTS was diagnosed according to the Villalta score. RESULTS: Ninety-five patients (45 men, mean age 50.7 ± 16.9 years) were evaluated for PTS. Among them, 28.4% (95% CI 19.3-37.5) developed PTS but none had severe PTS. The most frequent clinical signs of PTS were varicose veins (59%), corona phlebectatica (48%), swelling leg (30%) and pigmented dermatitis (26%). No single risk factor was associated with PTS development (age, sex, BMI thrombophilia, etiology, localization, recurrence, symptomatic DVT and familial history of DVT). CONCLUSION: PTS is a frequent disease. However, lack of uniformity of diagnosis criteria in the different studies does not make possible the estimation of PTS risk factors.

Inherited thrombophilias and unexplained pregnancy loss: an incident case-control study.

BACKGROUND: Despite an initial impressive impact, a critical appraisal of the link between pregnancy loss and inherited thrombophilias is currently growing. Furthermore, little is known about the paternal thrombophilic phenotype and pregnancy loss. OBJECTIVE: We sought an association between unexplained pregnancy loss and parental factor V Leiden (FVL) and Prothrombin G20210A (PTG) mutations. METHODS: Design - Incident case-control study. Setting- University Hospital of Brest (France). Patients - Women and their partners from the West Brittany area, consecutively referred for unexplained pregnancy losses (two or more consecutive losses at or before 21 weeks of gestation, or at least one later loss). Controls - Women and their partners with no history of pregnancy loss and at least one normal pregnancy, from the same geographic area, recruited using electoral lists. Statistical analysis - Comparison of FVL and PTG allele frequency between cases and controls using the chi-square test. Separate analyses were performed according to the type of pregnancy loss (early recurrent or later loss). RESULTS: 311 women (mean age: 32.8) and 284 of their partners were enrolled as cases while 599 women (mean age: 34.3) and 297 of their partners were recruited as controls. The prevalence of female, male or couple thrombophilic mutations was not statistically different between cases and controls whatever the definition of pregnancy loss retained. CONCLUSIONS: Presently, there is no clinical indication to routinely test for FVL and likely PTG mutations in women with early recurrent pregnancy loss. Moreover, our results did not reveal that paternal thrombophilic polymorphism should be further explored.

[A bilateral diaphragmatic paralysis due to Parsonage and Turner syndrome--its evolution over eight years]. / Paralysie diaphragmatique bilatérale imputable à un syndrome de Parsonage-Turner. Evolution à huit ans.

The diaphragmatic paralysis is a rare disease whose causes and evolving forms are numerous. We report the development to eight years of paralysis diaphragmatic bilateral attributed to a Parsonage-Turner syndrome: the lack of recovery is proved by respiratory functional follow-up. The therapeutic possibilities, limited, are discussed.

Strong evidence that skewed X-chromosome inactivation is not associated with recurrent pregnancy loss: an incident paired case control study.

BACKGROUND: Previous studies have reported conflicting results regarding recurrent pregnancy loss and skewed X-chromosome inactivation. Hence, we sought an association by carrying out a specifically designed incident paired case-control study with required statistical power. METHODS: Design incident 1:3 matched case-control study, from 2003 to 2007. SETTING: University Hospital of Brest. PATIENTS: Women, from the Brittany area, consecutively referred for at least two unexplained consecutive spontaneous abortions. CONTROLS: Women from the same geographic area, with no history of pregnancy loss and at least one normal pregnancy, recruited using electoral lists and then paired with cases, with respect to age, to within 1 year. INTERVENTION: Assessment of skewed X-chromosome inactivation. STATISTICAL ANALYSIS: Comparison of the ratio of >90% skewed X-chromosome inactivation by conditional logistic regression. RESULTS: Five hundred and forty-three controls (mean age: 34.3 years) were paired within 1 year to 200 cases. The cases (mean age: 33.6 years) had experienced between 2 and 14 consecutive losses (median 3). The rate of >90% skewed X-chromosome inactivation was not statistically different (P = 0.33, odds ratio: 0.58, 95% confidence interval: 0.19-1.77) between cases and paired controls, 2.27% versus 4.1%, respectively. CONCLUSIONS: We conclude that there is no association between skewed X-chromosome inactivation and recurrent pregnancy loss, defined as two or more unexplained consecutive spontaneous abortions.

[Bullous pemphigoid sparing acquired lymphedema]. / Une pemphigoïde bulleuse épargnant un lymphoedème acquis.

BACKGROUND: Bullous pemphigoid is an autoimmune disease, common in the elderly and generally of symmetrical and systemic localization. We report a case with sparing of the lower limb and acquired lymphedema secondary to lymph node surgery. CASE REPORT: A 74-year-old woman was hospitalized for a bullous eruption. The left lower limb was completely spared and was unaffected by pruritus. Acquired lymphedema was seen in this limb secondary to lymph node surgery. Standard histopathology tests confirmed the diagnosis of bullous pemphigoid with subepidermal blistering, while a direct immunofluorescence antibody test showed linear binding of IgG and C3 throughout the basement membrane. Western blotting revealed anti-BPAg2 antibodies. Skin biopsy on the lymphedema spared by the disease revealed no inflammatory infiltrate in the dermis. However, linear binding of anti-IgG and anti-C3 autoantibodies was observed. DISCUSSION: Other cases of localized bullous pemphigoid appearing on body areas treated by UV or radiotherapy have been reported. Cases of bullous pemphigoid with predilection for areas of lymphedema have also been previously described: the hypothesis has been advanced of reduced lymphatic flow, with increased antigen-antibody contact enabling better binding. Our case is original and, given the protective nature of this lymphedema, suggests two hypotheses. There could be deterioration of local cellular immunity, with decreased activation of T lymphocytes. They could also be impairment of nervous conduction, as suggested by the absence of pruritus, with partial or total inhibition of neurogenic inflammation.

Chlamydia pneumoniae IgG serological status and venous thromboembolism: a cross-sectional hospital based study.

OBJECTIVE: To search for a link between Chlamydia pneumoniae serological status and venous thromboembolic disease. METHODS: From March 1992 to October 1999, we conducted a cross-sectional hospital-based study of consecutive unselected outpatients referred to us for clinical suspicion of venous thromboembolism. We compared the Chlamydia pneumoniae serological status with respectively, the venous thromboembolism, the deep vein thrombosis and the proximal deep vein thrombosis status. RESULTS: Among 1193 patients registered for suspected venous thromboembolism, 1010 samples were available (499 negative and 511 positive patients for venous thromboembolism). Seventy-nine patients were Chlamydia pneumoniae positive. Our work failed to demonstrate any clear association between Chlamydia pneumoniae and venous thromboembolism status. Nevertheless, we identified a statistical difference regarding Chlamydia pneumoniae seropositivity and proximal vein thrombosis status (adjusted odds ratio of 1.70, CI95%: 1.05 to 2.77). CONCLUSION: The presence of Chlamydia pneumoniae antibodies might be a minor risk factor for venous thrombosis.

[Antiretroviral therapy and cardiovascular risk]. / Traitement antirétroviral et risque cardio-vasculaire.

Current antiretroviral therapy protocols enable long-term survival of HIV-infected patients, decreasing the risk of infectious complications. Three classes of anti-HIV treatments are available. With longer survival, unusual cardiovascular complications related to iatrogenic biological anomalies (dyslipidemia and impaired glucose tolerance) have appeared among this young population which is exposed to usual risk factors of atherosclerosis. Antiretroviral therapies are suspected to cause these complications, inducing maturity-onset diabetes in 4 to 20% of patients, impaired glucose tolerance in 15 to 60%, hypertriglyceridemia in 15 to 74% depending on the survey, and hypercholesterolemia in 20 to 60%, especially in case of associated lipodystrophia. A lipid battery including total cholesterol, HDL, and triglycerides, and 12-h fasting blood glucose should be obtained before initiating antiretroviral therapy. Any anomalous finding should be followed carefully with regular surveillance every 3 to 6 months and search for other causes of secondary dyslipidemia. In the event of casual and persisting elevation of LDL-cholesterol levels, a statin treatment can be introduced. For secondary prevention, irrespective of the context, recommendations currently merge with the consensus applying to the general population. These patients require careful surveillance of cardiovascular risk factors and a specific care in addition to treatment of their immunodeficiency.

[Acute colonic pseudo-obstruction (Ogilvie's syndrome) in pneumococcal meningo-encephalitis treated with neostigmine]. / Syndrome d'Ogilvie traité par néostigmine, lors d'une méningo-encéphalite à Streptococcus pneumoniae.

We report the case of a 71-year-old man with acute colonic pseudo-obstruction that complicates a pneumococcal meningo-encephalitis. After 48 h of conservative management with nothing by mouth, nasogastric suction, fluid and electrolyte correction, withdrawal of any anticholinergic agents, a pharmacological approach with 2 mg of neostigmine was successful in intensive care unit. This treatment was effective in over 80% of patients of recent reports. Neostigmine might be considered as first-line therapy in patients who do not have major contraindications to its use, because of less frequent iatrogenic risk than colonoscopic decompression or surgery.

A cross sectional study of antiphospholipid-protein antibodies in patients with venous thromboembolism.

OBJECTIVE: To look for an association between venous thromboembolism (VTE) and antiphospholipid antibodies (aPL) in patients without Systemic Lupus Erythematosus (SLE) when implementing, beside conventional assays, new tests for aPL screening directed towards purified proteic targets. METHODS: We conducted a cross-sectional, hospital-based study of consecutive unselected outpatients. We compared VTE+ patients to VTE- among 398 consecutive unselected outpatients referred for clinical suspicion of VTE. To detect aPL, the following ELISAs were performed: 1) a conventional standardized ELISA 2) an improved APA assay, 3) an anti-Beta2GPI ELISA, 4) an anti-Annexin V ELISA, 5) an anti-Prothrombin ELISA. We sought an association between VTE and aPL through a quantitative (t-test) and a qualitative comparison (chi-square test, according to the cut-off values set as the 95th percentile of aPL distribution). First we conducted an analysis of all patients. Then we stratified them into 2 subgroups, with or without a wellknown risk factor for VTE (prolonged immobilization >72h, surgery or trauma within the past three months, current malignancy). RESULTS: 61% of patients were classified as VTE-positive. Before stratification, we did not find any significant association between the VTE status and aPL. However, after stratification, in the subgroup without risk factors for VTE, the frequency of positive values as regards the anti Prothrombin antibodies detection was significantly higher in VTE+ patients (p = 0,04). CONCLUSION: The presence of anti Prothrombin antibodies might be an independent risk factor of VTE. However systematic screening for aPL in non SLE patients referred for VTE suspicion at the time of the thrombo-embolic event has little clinical relevance.

[Teaching ethics in French medical schools: evolution or revolution ?]. / Enseignement de l'éthique dans les UFR médicales françaises: évolution ou révolution?

Ethics was introduced as subject matter in French medical schools only recently despite a rich historical context where scientific legitimacy, humanistic exigencies and anglo-saxon influence have all played a role. Ten years after the thesis presented by Bastian in 1986, a survey of French medical schools shows that ethics has become an integral part of the curriculum. Ethics has tended to become a discipline on its own, separate from law and deontology. However, the lack of specific courses on concentration in the first years of the curriculum show that there is much room for growth in the discipline of medical ethics.

Assessment of activated protein C resistance using a new and rapid venom-based test: STA Staclot APC-R.

Activated protein C (APC) resistance is related to a single point mutation in the factor V gene (FV:Q506) and appears to be the most common inherited risk factor for venous thromboembolism. A reliable screening test is therefore useful. We aimed to evaluate a new APC resistance test, on the basis of the procoagulant activity present in one snake venom of a crotalidae family: STA Staclot APC-R. We studied 36 consecutive patients with an acute deep venous thrombosis (DVT) confirmed by compression ultrasonography and carrying the FV:Q506 allele, assessed by DNA analysis, 103 of their family members and 35 consecutive patients with a proven DVT but who did not carry the FV:Q506 allele. Blood samples were collected within 24 h of admission for the DVT cases and on the day of medical registration for the family members. Tests were performed blind. The STA Staclot APC-R test, using a cut-off value of 0.80, had an overall sensitivity of 100% (95% CI, 95-100) and a specificity of 98.8% (95% CI, 92.0-99.6). An acute thrombosis process did not influence the performance of the test. We conclude that this test is easy and rapid to perform in every day practice and fulfills the criteria for a screening test.

Interaction of Neisseria meningitidis with a polarized monolayer of epithelial cells.

An important step in the pathogenesis of Neisseria meningitidis is the crossing of two cellular barriers, one in the nasopharynx and one in the brain. To approach the mechanisms by which this bacterium can achieve these goals, we studied the interactions between N. meningitidis and a monolayer of polarized tight junction-forming T84 cells grown on filter units. A capsulated, piliated, Opa-, and Opc- N. meningitidis strain is shown to be capable of adhering to and crossing this monolayer several orders of magnitude more efficiently than an isogenic nonpiliated derivative. This bacterial interaction does not affect the barrier function of tight junctions, as assessed by (i) the absence of modification of the transepithelial resistance, (ii) the lack of increase of [3H]inulin penetration across the monolayer, and (iii) the absence of delocalization of ZO-1, a tight junction protein. Electron microscopy studies and confocal examinations demonstrated that N. meningitidis (i) induces cytoskeletal rearrangements with actin polymerization beneath adherent bacteria, (ii) is intimately attached to the apical membrane of the cells, and (iii) can be internalized inside cells. Immunofluorescent staining with antipilus antibodies showed evidence that meningococcal piliation was dramatically reduced at later time points of bacterial cell interaction compared to the early phase of this interaction. In addition, adhesive bacteria recovered from an infected monolayer are piliated, capsulated, Opa-, and Opc-, a phenotype similar to that of the parental strain. Taken together, these data demonstrate that following pilus-mediated adhesion, N. meningitidis is involved in an intimate attachment which requires a bacterial component different from Opa and Opc and that meningococci cross a monolayer of tight-junction-forming epithelial cells by using a transcellular pathway rather than a paracellular route.

Outer ear temperature and time of death.

From a research sample of 138 corpses, divided into four subgroups of ambient storage temperature (0-5 degrees C, 6-10 degrees C, 11-15 degrees C and 16-23 degrees C) four linear regression formulae of actual versus estimated post-mortem interval were obtained ('interval' formulae) using a single outer ear temperature measurement on both sides. This method showed the best correlation coefficient among five other methods previously proposed for time of death determination (rectal temperature, vitreous K+, CSF K+, blood log NA+/K+ and log Cl-), however its results were less accurate than those obtained with a multivariate equation combining several of the above mentioned methods. Eventually an equation expressing time of death (TOD) as a function of outer ear temperature (OE T degrees) and ambient temperature was also established from the whole research sample ('global' formulae). On a different sample of 141 corpses the regression formulae ('interval' and 'global') for the outer ear temperature were compared to three methods based on a single rectal temperature measurement ('rule of thumb' 1 and 2, Henssge nomogram) and therefore useful at the scene; the results of all methods were compared within the four subgroups of ambient temperature as well as in three subgroups of different post-mortem interval lengths (< 7 h, < 10 h, < 15 h). In all cases the outer ear temperature formulae provided better results than the rectal temperature methods (especially Henssge nomogram and rule of thumb 1). Moreover they did not show any post-mortem plateau which was present in almost 30% of cases when rectal temperature was measured in corpses kept at ambient temperature above 15 degrees C. Our results show that outer ear temperature measurement is the method which provides the best simplicity/quality ratio and should therefore be proposed for use at the scene when conditions are similar to those of our experiment (within buildings). A software equipped thermometer is required in order to use in each case the appropriate formula and confidence interval.

Infections associated with totally implantable venous access devices (TIVAD) in human immunodeficiency virus-infected patients.

We report on a retrospective study evaluating infectious morbidity associated with totally implantable venous access devices (TIVAD) (Port-A-Cath) in HIV-infected patients. This study of 84 consecutive HIV-infected patients requiring 89 TIVAD between January 1990 and October 1993 was performed in the Department of Infectious Diseases Hôpital de l'Institut Pasteur, Paris, France. The total number of catheter days was 11,595. Eighteen of 89 patients with TIVAD (20%) were infected, causing 25 infectious events (25/89: 28%) among 17 different patients (17/84: 20%). The infection rate was 0.22 per 100 catheter days. Mean onset of infection was 82 days. Twenty microorganisms were isolated: Staphylococcus aureus in eight cases (40%), coagulase-negative Staphylococcus in six cases (30%), Streptococcus D faecalis in one case; Gram-negative bacilli were found in five cases (25%). All patients received an intravenous antibiotherapy combined with a local lock treatment in eight cases. Nine TIVAD removals were performed. One death was related to the TIVAD infection. No additional predisposing factor for infection was identified other than the implied condition of the HIV infection. The population and material in this study were homogeneous. The TIVAD infection rate was comparable to other published reports. Prospective evaluation comparing tunneled catheter and TIVAD in HIV-infected patients is needed.

The Neisseria meningitidis haemoglobin receptor: its role in iron utilization and virulence.

The Neisseria meningitidis haemoglobin receptor gene, hmbR, was cloned by complementation in a porphyrin-requiring Escherichia coli mutant. hmbR encodes an 89.5 kDa outer membrane protein which shares amino acid homology with the TonB-dependent receptors of Gram-negative bacteria. HmbR had the highest similarity to Neisseria transferrin and lactoferrin receptors. The utilization of haemoglobin as an iron source required internalization of the haemin moiety by the cell. The mechanism of haemin internalization via the haemoglobin receptor was TonB-dependent in E. coli. A N. meningitidis hmbR mutant was unable to use haemoglobin but could still use haemin as a sole iron source. The existence of a second N. meningitidis receptor gene, specific for haemin, was shown by the isolation of cosmids which did not hybridize with the hmbR probe, but which were able to complement an E. coli hemA aroB mutant on haemin-supplemented plates. The N. meningitidis hmbR mutant was attenuated in an infant rat model for meningococcal infection, indicating that haemoglobin utilization is important for N. meningitidis virulence.