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Objectives Isoniazid-monoresistant tuberculosis (HR-TB) is the most prevalent form of drug-resistant TB worldwide and in France and is associated with poorer treatment outcomes compared with drug-susceptible TB (DS-TB). The objective of this study was to determine the characteristics of HR-TB patients in France and to compare outcomes and safety of treatment for HR-TB and DS-TB. Methods We performed a case-control multicenter study to identify risk factors associated with HR-TB and compare treatment outcomes and safety between HR-TB patients and DS-TB patients. Results Characteristics of 99 HR-TB patients diagnosed and treated in the university hospitals of Paris, Lille, Caen and Strasbourg were compared with 99 DS-TB patients. Female sex (OR = 2.2; 1.0–4.7), birth in the West-Pacific World Health Organization region (OR = 4.6; 1.1–18.7) and resistance to streptomycin (OR = 77.5; 10.1–594.4) were found to be independently associated with HR-TB. Rates of treatment success did not differ significantly between HR-TB and DS-TB. Conclusions Factors associated with HR-TB are not significant enough to efficiently screen TB patients at risk of HR-TB. The systematic implementation of rapid molecular testing on clinical samples remains the only effective way to make the early diagnosis of HR-TB and adapt treatment.

Although the COVID-19 pandemic has left no country untouched there has been limited research to understand clinical and immunological responses in African populations. Here we characterise patients hospitalised with suspected (PCR-negative/IgG-positive) or confirmed (PCR-positive) COVID-19, and healthy community controls (PCR-negative/IgG-negative). PCR-positive COVID-19 participants were more likely to receive dexamethasone and a beta-lactam antibiotic, and survive to hospital discharge than PCR-negative/IgG-positive and PCR-negative/IgG-negative participants. PCR-negative/IgG-positive participants exhibited a nasal and systemic cytokine signature analogous to PCR-positive COVID-19 participants, predominated by chemokines and neutrophils and distinct from PCR-negative/IgG-negative participants. PCR-negative/IgG-positive participants had increased propensity for Staphylococcus aureus and Streptococcus pneumoniae colonisation. PCR-negative/IgG-positive individuals with high COVID-19 clinical suspicion had inflammatory profiles analogous to PCR-confirmed disease and potentially represent a target population for COVID-19 treatment strategies., Clinical management of COVID-19 in resource-poor settings has distinct challenges and detailed patient characterisation is needed. Here, the authors describe the clinical and immunological profiles of patients at a hospital in Malawi with confirmed and suspected COVID-19.

Urinary tract infections (UTI) are the second cause of community-acquired bacterial infections in the elderly. Distinguishing symptomatic UTI from asymptomatic bacteriuria is problematic, as older adults are less likely to present with localized urinary symptoms. We evaluated characteristics of patients presenting UTI among elderly with sepsis. Moreover, we aimed to evaluate the sensibility and specificity of urine dipstick tests in the diagnosis of UTI in geriatric population.We led a prospective, monocentric, observational study between April 2017 and January 2018. We included patients hospitalized in geriatric wards, who were prescribed urine culture for UTI symptoms or/and infection without primary sites for which a urine culture was prescribed. Dipstick urinalyses were performed for all patients. Clinical and biological characteristics of all patients were compared according to the final diagnosis of UTI. Moreover, results of dipstick tests were evaluated for the diagnosis of UTI in this population.Among 165 patients, 67 (40.6 %) had a UTI and 98 (59.4 %) had another diagnosis. These two groups were comparable for age and daily-living activities. In the UTI group, the proportion of women was higher than in the other group (P0.05), and mean MMSE score was lower (P0.05). Positive urine dipstick test for leukocytes and/or nitrites had high sensitivity (92 %), but low specificity (50 %). Negative predictive value of this test was high (91 %).For suspicion of UTI among elderly, few criteria are specific. Negative dipstick tests can suggest an absence of UTI due to its high negative predictive value.

IF 11.855; International audience; BackgroundOutcome of intermediate risk rectal cancer may be improved by the addition of oxaliplatin during 5-fluoruracil concomitant neoadjuvant chemoradiotherapy. The purpose of this study is to analyze the main clinical results of the ACCORD12 trial (NCT00227747) in rectal cancer after 5 years of follow-up.Patients and methodsInclusion criteria were as follows: rectal adenocarcinoma accessible to digital examination staged T3-T4 Nx M0 (or T2 Nx distal anterior rectum). Two neoadjuvant chemoradiotherapy regimens were randomized: CAP45 (RT 45 Gy + capecitabine) and CAPOX50 (RT 50 Gy + capecitabine and oxaliplatin). Main end point was sterilization of the operative specimen. Acute and late toxicities were prospectively analyzed with dedicated questionnaires.ResultsBetween November 2005 and July 2008, 598 patients were included in the trial. After a median follow-up of 60.2 months, there was no difference between treatment arms in multivariate analysis either for disease-free survival or overall survival (OS) [P = 0.9, hazard ratio (HR)=1.02; 95% confidence interval (CI), 0.76–1.36 and P = 0.3, HR = 0.87; 95% CI, 0.66–1.15, respectively]. There was also no difference of local control in univariate analysis (P = 0.7, HR = 0.92; 95% CI, 0.51–1.66). Late toxicities were acceptable with 1.6% G3 anal incontinence, and

International audience; The main objective of this study was to assess the diagnostic performance of a set of three Mucorales quantitative PCR assays in a retrospective multicentre study. Mucormycosis cases were recorded thanks to the French prospective surveillance programme (RESSIF network). The day of sampling of the first histological or mycological positive specimen was defined as day 0 (D0). Detection of circulating DNA was performed on frozen serum samples collected from D-30 to D30, using quantitative PCR assays targeting Rhizomucor, Lichtheimia, Mucor/Rhizopus. Forty-four patients diagnosed with probable (n = 19) or proven (n = 25) mucormycosis were included. Thirty-six of the 44 patients (81%) had at least one PCR-positive serum. The first PCR-positive sample was observed 9 days (range 0-28 days) before diagnosis was made using mycological criteria and at least 2 days (range 0-24 days) before imaging. The identifications provided with the quantitative PCR assays were all concordant with culture and/or PCR-based identification of the causal species. Survival rate at D84 was significantly higher for patients with an initially positive PCR that became negative after treatment initiation than for patients whose PCR remained positive (48% and 4%, respectively; p \textless10(-6)). The median time for complete negativity of PCR was 7 days (range 3-19 days) after initiation of l-AmB treatment. Despite some limitations due to the retrospective design of the study, we showed that Mucorales quantitative PCR could not only confirm the mucormycosis diagnosis when other mycological arguments were present but could also anticipate this diagnosis. Quantification of DNA loads may also be a useful adjunct to treatment monitoring.

International audience; This study investigated the long-term outcome of patients with tuberculosis (TB) as a complication of tumour necrosis factor (TNF)-alpha blocker therapy. All TB cases (n = 21) complicating TNF-alpha blocker therapy from French university hospitals were collated between January 2000 and September 2002. Outcome was assessed via a postal questionnaire during September 2005. The mortality rate after 4 years was 4.8%, and one patient had relapsed and six (29%) patients had recommenced TNF-alpha antagonist treatment, after appropriate anti-TB therapy, without reactivation. These data support the concept that TNF-alpha antagonists can be restarted in TB patients provided that adequate anti-TB treatment has been completed.

International audience; BACKGROUND:Metastatic colorectal cancer (mCRC) frequently occurs in elderly patients. However, data from a geriatric tailored randomized trial about tolerance to and the efficacy of doublet chemotherapy (CT) with irinotecan in the elderly are lacking. The benefit of first-line CT intensification remains an issue in elderly patients.PATIENTS AND METHODS:Elderly patients (75+) with previously untreated mCRC were randomly assigned in a 2 × 2 factorial design (four arms) to receive 5-FU (5-fluorouracil)-based CT, either alone (FU: LV5FU2 or simplified LV5FU2) or in combination with irinotecan [IRI: LV5FU2-irinotecan or simplified LV5FU2-irinotecan (FOLFIRI)]. The CLASSIC arm was defined as LV5FU2 or LV5FU2-irinotecan and the SIMPLIFIED arm as simplified LV5FU2 or FOLFIRI. The primary end point was progression-free survival (PFS). Secondary end points were overall survival (OS), safety and objective response rate (ORR).RESULTS:From June 2003 to May 2010, 71 patients were randomly assigned to LV5FU2, 71 to simplified LV5FU2, 70 to LV5FU2-irinotecan and 70 to FOLFIRI. The median age was 80 years (range 75-92 years). No significant difference was observed for the median PFS: FU 5.2 months versus IRI 7.3 months, hazard ratio (HR) = 0.84 (0.66-1.07), P = 0.15 and CLASSIC 6.5 months versus SIMPLIFIED 6.0 months, HR = 0.85 (0.67-1.09), P = 0.19. The ORR was superior in IRI (P = 0.0003): FU 21.1% versus IRI 41.7% and in CLASSIC (P = 0.04): CLASSIC 37.1% versus SIMPLIFIED 25.6%. Median OS was 14.2 months in FU versus 13.3 months in IRI, HR = 0.96 (0.75-1.24) and 15.2 months in CLASSIC versus 11.4 months in SIMPLIFIED, HR = 0.71 (0.55-0.92). More patients presented grade 3-4 toxicities in IRI (52.2% versus 76.3%).CONCLUSION:In this elderly population, adding irinotecan to an infusional 5-FU-based CT did not significantly increase either PFS or OS. Classic LV5FU2 was associated with an improved OS compared with simplified LV5FU2.CLINICALTRIALSGOV:NCT00303771.

Background/Aims: To determine patterns of loss of abilities in instrumental activities of daily living (IADL) in community-dwelling women with Alzheimer’s disease (AD). Methods: Sixteen French university hospitals included 471 consecutive women with mild to moderately severe AD (Mini-Mental State Examination scores between 10 and 26) from April 2000 to June 2002 in the noninterventional REAL cohort. At inclusion, 6 and 12 months, IADL were assessed with the Lawton scale. Patterns of loss of abilities in the 8 IADL of the Lawton scale were described using Lawton binary grading. Results: At inclusion, 56.7% of the patients shared the same pattern of loss of abilities and 84.3% had this pattern or variants of it. Frequencies of the 8 incapacities were: 80.7% to do the grocery shopping, 76.0% to take medication, 72.2% to prepare meals, 41.4% to travel on public transportation even when assisted, 40.6% to manage purchases, 30.1% to launder small items, 14.2% to participate in some housekeeping tasks and 11.0% to answer the telephone. Conclusion: In this study including 471 community-dwelling women with AD of the French REAL cohort, the loss of the 8 IADL, assessed with the Lawton binary grading, was homogeneous for more than four fifths of the patients.

Objectives To compare the coverage for the third dose and the compliance to two hepatitis B vaccination schedules: 0,1,4 versus 0,1,6 months, in commercial sex workers (CSW) in Belgium; to compare the immunogenicity of the actually administered schedules. Methods In seven health centres in Belgium, hepatitis B vaccination was offered free of charge to CSW. In a randomised, prospective study a commercialised hepatitis B vaccine (Engerix-B™ 20 mcgr) was offered according to one of both schedules. After complete vaccination, bleeding was performed to assess immunogenicity. Results Between June 2003 and September 2004, 615 non-immune CSW were enrolled, of whom 52% in the 0,1,4 month schedule (n = 322). Coverage of the third dose was 57% overall, 59% (0,1,4) and 54% (0,1,6), respectively. Age, the health centre and drug use significantly influenced the compliance and the coverage of dose 3, whereas the planned vaccination did not. When comparing the immunogenicity results as a function of the actually administered vaccination schedule, immune responses did not significantly differ between CSW receiving the third dose 4–6 months and those receiving it at least 6 months after the first dose. In total, 19 persons (8%) were not protected after a full vaccination course (anti-HBs Conclusions In this highly mobile at-risk population, a 0,1,4 month schedule is more easy to offer and confers equal protection within a shorter period of time. We therefore propose this 0,1,4 month schedule to vaccinate CSW in the future.

MR-guided HIFU ablation is a promising technique for the non-invasive treatment of breast cancer. A phase I study was performed to assess the safety and treatment accuracy and precision of MR-HIFU ablation in breast cancer patients (n=10) using a newly developed MR-HIFU platform dedicated to applications in the breast. In this paper a technical analysis of the performance of the dedicated breast MR-HIFU system during breast tumors ablation is described. The main points of investigation were the spatial targeting accuracy and precision of the system and the performance of real-time respiration-corrected MR thermometry.The mean targeting accuracy was in the range of 2.4-2.6 mm, whereas the mean targeting precision was in the range of 1.5-1.8 mm. To correct for respiration-induced magnetic field fluctuations during MR temperature mapping a look-up-table (LUT)-based correction method was used. An optimized procedural sedation protocol in combination with the LUT-based correction method allowed for precise MR thermometry during the ablation procedure (temperature standard deviation3 °C). No unwanted heating in the near field (i.e. skin) nor in the far field (pectoral muscle) was detected.The newly developed dedicated breast MR-HIFU system allows for safe, accurate and precise ablation of breast tumors.

Summary. In industrialized countries, transmission of hepatitis C occurs primarily through injecting drug use. Transmission of hepatitis C in injecting drug users is mainly associated with the sharing of contaminated syringes/needles, although evidence for risk of hepatitis C infection through sharing of other injecting paraphernalia is increasing. In this paper, the independent effects of sharing paraphernalia other than syringes/needles have been estimated. The prevalence and force of infection were modelled using three serological data sets from drug users in three centres in Belgium as a function of the sharing behaviour. It was found that sharing of materials other than syringes/needles indeed seemed to contribute substantially to the spread of hepatitis C among injecting drug users.

Of 176 invasive Streptococcus pneumoniae isolates from children in Malawi, common serotypes were 1 (23%), 6A/B (18%), 14 (6%), and 23F (6%). Coverage with the 7-valent pneumococcal conjugate vaccine (PCV) was 39%; PCV10 and PCV13 increased coverage to 66% and 88%, respectively. We found chloramphenicol resistance in 27% of isolates and penicillin nonsusceptibility in 10% (by using meningitis breakpoints); all were ceftriaxone susceptible.

International audience; We report 3 consecutive episodes of invasive aspergillosis in a single hematopoietic stem cell transplant patient successively attributed to TR(34) /L98H azole-resistant Aspergillus fumigatus and to a first occurrence of invasive Emericella sublata infection. This case illustrates potential selection of resistant molds during antifungal therapy in hematological patient.

We report a case of a 71-year-old woman with carcinoid heart disease admitted in ICU after tricuspid valve replacement. She quickly developed a acute heart right failure. Optimal medical treatment failed and we implanted ventricular assistance. After 10 days of support, patient improved and the right ventricle recovered. Temporary devices can provide a successful bridge to cardiac recovery. However, the risk of infection that is a major prognosis factor should be carefully considered particularly when temporary assistance implanted on immunosuppressed patients.

Objectives. Our aim was to look at the clinical features and long-term follow-up of seven patients without coronary artery disease, who had a history of life-threatening ventricular arrhythmias due to coronary spasm. Background. Arrhythmic cardiac arrest due to isolated coronary spasm is rare, and there is limited information on the patients affected by this entity alone. Methods. The seven patients were recruited retrospectively from a cohort of survivors of cardiac arrest. None had a history of angina pectoris, structural heart disease or significantly narrowed coronary segments. All had a positive ergonovine provocation test result. Results. The patients’ mean age was 44 years; three were male and four female. All were habitual cigarette smokers. No arrhythmias were induced on programmed ventricular stimulation; corrected QT interval (QTc) and corrected JT interval (JTc) dispersion were within normal ranges. After the ergonovine provocation test, treatment with calcium channel blocking agents (diltiazem, verapamil, nifedipine or amlodipine) was initiated at a dose determined by titration until a negative test result was obtained. At a mean follow-up interval of 58 months for the total group, six patients remained free of symptoms, whereas the one patient who did not stop smoking had a new cardiac arrest despite treatment for coronary spasm. Conclusions. A favorable long-term outcome may be expected in survivors of cardiac arrest due to coronary spasm, in the absence of significant coronary artery disease. Calcium channel blockers are the most appropriate therapy in these patients. These observations provide further evidence for the role of silent ischemia in cardiovascular death.

We have analyzed the relationship between the prevalence of diabetes mellitus (type 2) and socio-economic status of patients. The cross-sectional study included 79,855 patients registered in Belgium capitation-fee primary health care centers. The adjusted prevalence for age and gender was 6.3%, significantly higher than the estimated 4.7% in the general population. The gap is mainly explained by the lower socio-economic status of the patients we take care of. Inside our population we found a 1.8 times higher risk to be affected by diabetes mellitus for patients with lower socio-economic status (95% confidence interval: 1.6-1.9). This higher risk is found for all age groups except for the elderly. Studies should be designed to investigate how that social inequality for health also concern quality of care and therapeutical outcomes.

Many techniques of thermotherapy have emerged over the last several years in the field of oncology using different types of physical agents, including ultrasound. Only ultrasound can target deep seated lesions non-invasively without need for percutaneous probe insertion. Depending on their utilization, it is possible to select either thermal effects, in a continuous mode, at low temperature (allowing thermo-induced biological effects) or at high temperature (allowing thermoablation), or mechanical effects, in a pulsed mode, at low energy level (allowing biological effects) or at high energy levels (histotripsy). Thermoablation by focused ultrasound is now developing fast for applications in many organs. It gained a well defined role for the treatment of prostatic cancer and uterine leiomyoma but needs to be better evaluated in other organs such as the breast. Treatment of abdominal tumors must still be considered as experimental as long as problems related to acoustic interfaces (produced by ribs and gas) and movement correction are not resolved. Biological applications of focused ultrasound are currently being explored and have a great long term potential.

Objectives: To evaluate the role of a cytopathologist expert in interpreting difficult pancreatic endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in terms of impact on diagnostic yield and therapy in current clinical practice. Methods: Retrospective study of 106 EUS-FNA performed between January 2002 and September 2004. Forty-seven cases of difficult interpretation by the local cytopathologist were mailed to an expert cytopathologist. The final diagnosis was established by histology obtained by either surgery (n = 30), non-equivocal FNA (n = 40) or core (n = 8) biopsies, or by a mean follow-up of 14 months (n = 28). Results: EUS-FNA involved 68 solid lesions (SL). Specimens collected were adequate in 63%. The overall sensitivity of EUS-FNA for the diagnosis of malignancy of SL was 88% versus 72% for local cytopathologist and 89% for expert. EUS-FNA with the reevaluation by expert of 39 SL gave a therapeutic impact in 47% of SL. Thirty-eight cystic lesions (CL) were evaluated. Specimens collected were adequate for cytology in 84% of cases and for biochemistry in 79%. The sensitivity of imaging + EUS-FNA ± biochemistry for the diagnosis of a surgical CL was 58% with a therapeutic impact in 39.5%. Conclusion: Pancreatic EUS-FNA is an easy technique for experienced endosonographers, which can be safely performed on an outpatient basis. The possibility of mailing difficult cases to an expert cytopathologist increases the diagnostic yield. In these circumstances, EUS-FNA has a therapeutic impact in current practice in nearly one out of two pancreatic lesions.

Background and Purpose— Recent studies have shown that the brain ischemic area defined by the map of decreased apparent diffusion coefficient (ADC) obtained by diffusion-weighted imaging (DWI) during the first hours of ischemic stroke includes a significant part of ischemic penumbra. We hypothesize that the misjudgment of the final infarct size by ADC mapping may be related to a restricted ability of DWI to capture variations in the intensity of cellular suffering. In an attempt to characterize metabolically the hypoperfused brain parenchyma, we studied the relationship between ADC values and brain metabolic parameters measured by proton MR spectroscopic imaging (SI). Methods— Six patients with hyperacute ischemic stroke were explored within the first 7 hours after onset with the use of a MR protocol including T2*-weighted MRI, DWI, SI, perfusion-weighted imaging, and MR angiography. Results— This study demonstrates, for the first time, a wide gradient of ischemia-related metabolic anomalies within the abnormal area delineated by DWI during hyperacute ischemic stroke. In the narrow range of decreased mean ADC values (0.60 to 0.40×10 −9 m 2 · s −1 ), a 33% decrease in mean ADC is associated with a 122% increase in lactate/ N -acetyl aspartate ratio. Mean ADC values never fall below 0.40×10 −9 m 2 · s −1 within the severely affected ischemic tissue, while SI still detects a large metabolic heterogeneity inside areas showing similar decreased mean ADC values close to this threshold. Conclusions— Our results indicate that the region of very low mean ADC values observed during hyperacute ischemic stroke contains areas of various tissue damage intensity characterized by SI in relation to different stages of cellular metabolic injury. This observation may explain why ADC mapping does not reliably predict final infarct size.

We report the case of a patient who co-ingested a tricyclic antidepressant (amitriptyline), benzodiazepines (alprazolam and lormetazepam) and a neuroleptic drug (prothipendyl). Major neurologic and cardiac symptoms occurred including a prolonged cardiac arrest. The cardiopulmonary resuscitation phase was complicated by a haematoma of the liver treated by a left hepatectomy. The clinical features and management of this combined intoxication are discussed.

Background —The exercise treadmill test (ETT) and Tl201 single proton emission computed tomography (SPECT) are of short- to medium-term prognostic value in coronary heart disease. We assessed the long-term prognostic value of these tests in a large population of patients with low- to intermediate risk of cardiac events. Methods and Results —One thousand one hundred thirty-seven patients (857 men, age 55±9 years) referred for typical (62.1%) or atypical (22.4%) chest pain, or suspected silent ischemia (15.5%), were followed up for 72±18 months. Overall mortality was higher after strongly positive (ST depression >2 mm, or >1 mm for a workload ≤75 W) (2.36%/y) or nondiagnostic ETT (1.63%/y) than after normal (0.85%/y) or positive ETT (1.37%/y) ( P =0.002), and after abnormal SPECT than after normal SPECT (1.60%/y versus 0.68%/y, P =0.001). The major cardiac event rate (cardiac death or myocardial infarction [MI]) was 0.88%, 1.59%, 2.10%, and 2.13%/y after negative, positive, strongly positive, and nondiagnostic ETT, respectively ( P =0.003), and 0.56%, 1.43%, and 2.05%/y in patients with 0, 1 to 2, and ≥3 abnormal segments on SPECT, respectively ( P P Conclusions —The incremental predictive value of SPECT is maintained over 6 years and is particularly relevant after positive, strongly positive, and nondiagnostic ETT.

OBJECTIVE: We evaluated the prognostic value of an exercise stress test and thallium-201 scintigraphy for the prediction of cardiac events in selected high-risk NIDDM patients. RESEARCH DESIGN AND METHODS: NIDDM patients (n = 158, 105 men, aged 63 +/- 9 years) with two or more of the following criteria were prospectively included: age > or = 65 years, active smoking, hypertension > 160/95 mmHg, hypercholesterolemia (cholesterol > 5.70 mmol/l or LDL > 3.10 mmol/l), peripheral artery disease, abnormal rest electrocardiogram, or microalbuminuria (20-200 micrograms/min). An exercise-stress scintigraphy was performed in 77 patients able to exercise, while a dipyridamole scintigraphy was performed in 80 patients unable to exercise. Follow-up was 23 +/- 17 months. Major end points were cardiac deaths or nonfatal myocardial infarction. RESULTS: The annual event rate was 7.31% (deaths: 8, myocardial infarction: 14). Independent predictors of events were as follows: an age > 60 (P = 0.02), an abnormal rest electrocardiogram (P = 0.02), microalbuminuria (P = 0.001), the inability to exercise (P = 0.009), and the presence of more than two defects on scintigraphy (P = 0.001). A cardiac death occurred in 1.3% of patients able to exercise versus 8.8% of patients unable to exercise (odds ratio = 6.8, P = 0.001). Among patients unable to exercise, large perfusion defects corresponded to an annual mortality rate of 22.3%. Conversely, the negative predictive value of a normal scintigraphy for the occurrence of death was 97%. CONCLUSIONS: Inability to exercise and large perfusion defects on thallium-201 scan are major predictors of future death and myocardial infarction in high-risk NIDDM patients.

The hobo transposon is responsible for one of the three hybrid dysgenic systems that have been described in Drosophila melanogaster. Most studies on the hobo dysgenic system have been carried out using the PM system as a reference. However, these two systems differ significantly. In particular, several studies have failed to find any correlation between the molecular structures of hobo elements, the instability of the transposon and the incidence of gonadal dysgenic (GD) sterility. On the other hand, no study of the ability of females to permit hobo activity in their progeny when they are crossed with males harboring active hobo elements (permissivity) has yet been reported. In order to investigate the parameters involved in hobo permissivity, four E strains were studied with regard to the molecular nature of their hobo sequences and the GD sterility induced by a controlled source of hobo transposase. We show that hobo permissivity varies both within and between E strains. Moreover, permissivity decreases with age in E females. Our results are discussed with respect to similar phenomena that have been described in relation to the reactivity of the IR dysgenic system.

Identify factors predicting favorable outcome after medical management of valve ring abscesses in order to propose a surveillance schedule for conservative treatment.A multicentric study conducted from July 1989 to February 1996 included 28 patients (mean age 64 +/- 16 years, range 26-83) hospitalized for active endocarditis and valve ring abscesses diagnosed at transthoracic or transesophageal echography. Conservative medical therapy was given because of a decision of the medico-surgical team (n = 9), high surgical risk (n = 12), or patient refusal of surgery (n = 7). Outcome was favourable in 18 patients (Group I) and unfavorable in 10 (Group II) due to death (n = 9) or subsequent surgery (n = 1). Univariate and multivariate analysis were used to determine differences between the groups in terms of clinical and laboratory data.Mean follow-up in Group I was 33 +/- 18 months and 15 +/- 10 months in Group II. Univariate analysis showed significant differences between Group I and II respectively for age (59 +/- 18 yr vs 72 +/- 10, p = 0.04), delay to apyrexia after antibiotics (4.3 +/- 2.8 vs 8.3 +/- 2.4 days, p0.0008), heart failure (5% vs 70%, p = 0.003), grade III or IV valvular regurgitation (5% vs 60%, p0.04), and mean surface area of the abscess (1.5 +/- 1.2 vs 5.4 +/- 6.4 cm2, p0.03). Independent factors at multivariate analysis were by decreasing order: lack of heart failure at admission, delay to apyrexia, abscess surface area, and age. Outcome was favorable (mean follow-up 33 +/- 10 months) in all patients with an abscess surface area1.5 cm2, no signs of heart failure, no grade III or IV valvular regurgitation, apyrexia after less than 8 days on antibiotics and no staphylococcus positive blood culture.Medical management of valve ring abscesses may be indicated in selected patients in care units with rigorous surveillance facilities. Further studies are needed to precisely identify surveillance and treatment criteria.

Endoscopic sphincterotomy (ES) is a minimally invasive technique which is the standard of reference in many clinical situations (e.g distal choledocolithiasis, recurrent lithiasis or bile duct stenosis). Complication are rare but are often misdiagnosed although radiological aspects are demonstrative. The purpose of this study is to illustrate the patterns of the complications. Ten patients have been treated for the last four years in our institution for ES complications. There were eight cases of pancreatitis, three of which had associated perforation, one arterioportal fistula, and one isolated perforation. Diagnosis was reached with CT in all but one case. Two patients have been successfully treated with percutaneous treatment (one embolization with Gianturco coils, and one drainage). Two patients died, one of necrotizing pancreatitis and the second of decubitus complication. The other patient were followed with CT. We give exemples of different observations and discuss their follow up. The severity and extent of post ES pancreatitis were readily assessed by CT and response to therapy monitored by serial examinations. Severity of disease, evaluated according to the length of hospitalization, correlated well with the presence and degree of pancreatic necrosis. CT also highlights perforations including minimal effusions. In our study differential diagnosis between post ES pancreatitis and perforation is not significant regarding the initial conservative therapy in both situations. CT scan helps us to opt for a surgical decision or for a percutaneous drainage. It also permits to follow the evolution of the lesions. In our cases involving perforations, we noted a spontaneous complete resolution of gas effusion on control and we also observed that pancreatitis evolution was similar to standard pancreatitis evolution. In a life threatening post ES hemobilia, not responding to standard medical treatment, angiography is the diagnostic exam of choice before embolization which is regarded as the best initial treatment of vascular lesions. We conclude that CT is the exam of choice in the initial diagnosis and follow up post ES complications.

The study of mitral flow and pulmonary venous flow by Doppler provides a non-invasive method of assessing diastolic function. But there are difficulties in differentiating normal pattern from "pseudo-normal" (Appleton Type II) (E/A Mitral1). Phonocardiography enables the recording of early (B3) and late (B4) diastolic gallops. The apexogramme enables calculation of the a/H and D/H ratios (amplitude of the "D" wave resulting from rapid early diastolic filling to the total amplitude of the apexogramme). These two techniques record pulsatile phenomena ("pulse waves") arising from variations in intra-left ventricular pressure. They may complete the interpretation of Doppler recordings of velocities of blood flow ("flow waves"). To evaluate the value of each technique, the authors studied left ventricular diastolic function by Doppler phonocardiography and apexography in 60 subjects (38 patients of which 30 with ischaemic heart disease, and 22 healthy subjects). The results showed that increase in velocity and deceleration slope of the Doppler mitral E wave was associated with the presence of a B3 and correlated (r = 0.60; p = 0.0001) with the D/H ratio of the apexogramme. On the other hand, the absence of correlation between the mitral A wave velocity and a B4 associated with an increased a/H ratio enables the differentiation of normal Doppler mitral flow (absence of B4, Doppler a/H ratio12%) from pseudo-normal appearances (B4, a/H ratio12%). Therefore, the evaluation of diastolic function by Doppler mitral and pulmonary venous flow analysis may be usefully completed by phonocardiography and apexography.

The authors report the results of a multicenter study which recensed 59 cases (46 men, 13 women, average age 59.8 +/- 14 years) of valve ring abscesses defined by echocardiographic criteria alone (20 cases) or by echocardiographic and/or operative criteria (39 cases). The site of abscess was aortic (53 cases), mitral (5 cases) and tricuspid (1 case). The abscess complicated a prosthetic valve in 34 cases, occurred with a non-pathological valve in 11 cases or a pathological valve in 14 cases. Taking the 39 operated patients as a reference, the diagnostic sensitivity of transthoracic echocardiography was 25% and that of transoesophageal echocardiography: 88%. Bacterial vegetations were diagnosed with a sensitivity of 55% for transthoracic and 88% for transoesophageal echocardiography. The mediocre results of transthoracic echocardiography make transoesophageal echocardiography mandatory when there is a clinical suspicion of abscess: transoesophageal echocardiography should be systematic in prosthetic valve endocarditis and widely employed in native aortic valve endocarditis. The clinical outcome of these cases was: 39 cases were operated: global mortality of 23%, and 18 cases were treated medically, surgery having been declined for various reasons: old age (2 patients), operative risk (1 patient), patient refusal (4 patients), general condition considered to be too good to justify surgery (11 cases, including 6 sterilised abscesses diagnosed some time after the acute infectious phase). The outcome of these 18 patients, who form the biggest non-operated series of valve ring abscesses to date, was studied in detail: 4 died (18% mortality), 1 was operated secondarily for progressive valve dehiscence and 13 had a favourable outcome with an average follow-up period of 2 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Thirty-two patients with advanced non-small cell lung carcinoma (NSCLC) received a chronomodulated 5-day venous infusion of 5-fluorouracil (5 FU) (700 mg/m2/day), folinic acid (F) (300 mg/m2/day), and carboplatin (C) (40, 50, or 55 mg/m2/day), as first chemotherapy. Courses were repeated every 21 days (after a 16-day interval). In total, 158 courses (median: 4, range: 1 through 16; 81 and 58 courses at, respectively, a 40 and 50 to 55 mg/m2 daily dosage of C) were delivered using a multichannel programmable in-time pump (Intelliject, Aguettant) connected to a double lumen implanted venous side-port. The administration was allowed in fully ambulatory convenience. Overall tolerance was excellent. Grade 3 of 4 hematologic toxicity was encountered in 4.6% of courses for thrombopenia and in 7.0% of courses for neutropenia. Nausea or vomiting (grade 3 or 4) occurred in 7.8% of courses. Mucositis, diarrhea, alopecia, or skin grade 3 or 4 toxicity were observed in less than 3% of courses. Treatment delay was needed in only 7.8% of courses and dose reductions were needed in 4.6% of courses for 5 FU and in 6.5% of courses for C. This good tolerance allowed a sustained quality of life and prompted further trials aiming to define the place of this protocol in the multidisciplinary treatment approach of NSCLC.

Eight cases of pneumatosis cystoides intestinalis (PCI) affecting the descending colon at first misdiagnosed in seven of them, are reported. The mechanism of cyst formation remains unclear but certain specific endoscopic and X-ray findings should help in differentiating PCI from other intramural tumors, i.e. polyposis. Diagnostic investigations and management approaches are described. No treatment is necessary in most instances because of the benign nature of PCI.

This study was designed to assess the prognostic value of thallium-201 single-photon emission computed tomographic (thallium SPECT) perfusion imaging in patients evaluated for stable angina pectoris and to examine the relation, if any, between the presence and extent of myocardial defect and future fatal or nonfatal cardiovascular events (revascularization, secondary myocardial infarction).Compared with planar scintigraphy, thallium SPECT enables better evaluation of the extent of myocardial perfusion defect. However, its prognostic value has not yet been studied in a large population of patients.Between 1987 and 1989 we studied 3,193 patients. After exclusion of patients with unstable angina, myocardial infarction during the previous month or earlier revascularization, 1,926 patients were followed up for 33 +/- 10 (mean +/- SD) months after stress thallium SPECT imaging (performed after exercise in 1,121 patients or during dipyridamole infusion in 805 patients). Thallium SPECT imaging of the left ventricle was divided into six segments.After normal thallium SPECT imaging (715 patients), the annual total and cardiovascular mortality rates were, respectively, 0.42%/year and 0.10%/year and were significantly higher after abnormal thallium SPECT imaging (respectively, 2.1%, relative risk 5, p = 0.012; 1.5%, relative risk 15, p0.0001 [log-rank test]). There was a significant relation between the number of abnormal segments and cardiovascular mortality during follow-up (p0.02) or the occurrence of nonfatal events (p0.001). The extent of defect on the initial scan provided the best SPECT variable for long-term prognosis. Thallium SPECT imaging provided additive prognostic information compared with other clinical variables (gender, previous myocardial infarction) and exercise electrocardiogram.In patients with stable angina, normal thallium SPECT imaging indicates a low risk patient, and the extent of myocardial defect is an important prognostic predictive factor.

One of the main advantages of Doppler echocardiography is the possibility of non-invasive measurement of blood flow at each valvular orifice. This method enables quantification of valvular regurgitation, the measurement of Qp/Qs in cardiac disease with atrial or ventricular shunts, and the interpretation of gradients and functional surface areas in valvular stenosis or prosthesis with respect to the underlying haemodynamics. In each of these application, the measurement of pulmonary blood flow is valuable as the reference blood flow, and even indispensible in cases of shunts. The authors' objective was to study the feasibility and accuracy of pulmonary flow measurement in 100 consecutive patients (40 women and 60 men, average age 56.7 +/- 17.5 years) with cardiac disease (82%) or healthy hearts (18%). A grading from A to D was accorded depending on the technical difficulty of the examination, each grade having three degrees: 1) difficulty of recording and poor quality Doppler spectrum, 2) difficulty of measuring orifice diameter by 2D echocardiography, 3) necessity of analysis of color coded anterograde flow to measure the pulmonary valvular orifice. Grade A was distributed to easily recordable measurements with no difficulty; grade B for measurements with one difficulty; grade C for measurements with 2 difficulties and grade D for investigations judged to be impossible or unreliable (3/3 criteria). The feasibility of measurement of the cardiac output at the pulmonary orifice was 88% (A:55%, B:25%, C:8%). The correlation between the pulmonary flow and reference measurements at the aortic and/or mitral valve and/or mitral annulus was 0.96. The average difference between the pulmonary and reference flow was 51 +/- 273 cc/min.(ABSTRACT TRUNCATED AT 250 WORDS)

Non-invasive quantification of mitral regurgitation remains a clinical problem. The aim of this study was to assess a new methodology of Doppler echocardiographic assessment of the mitral regurgitant fraction. The study included 60 patients (average age 61 years) in sinus rhythm with mitral regurgitation. The cardiac output was measured by Doppler echocardiography at four sites: the aortic, pulmonary and mitral rings and at the tips of the mitral leaflets by a method previously validated and published. Using the average of the aortic and pulmonary cardiac outputs on the hand and the mitral cardiac output on the other, it was possible to calculate the regurgitant fraction: (mean mitral flow-mean aortic/pulmonary flow)/mean mitral flow. This was correlated with the Sellers angiographic grades of regurgitation. The results confirm this validated procedure: the correlation of aortic and pulmonary flows was good: r = 0.94. This also held true for mitral flow at the two sites: r = 0.96. The correlation between the Doppler echocardiographic regurgitant fraction and the angiographic estimation of the severity of mitral regurgitation was good: r = 0.89. There was a statistically significant difference between the Doppler echocardiographic regurgitant fractions corresponding to Sellers Grades I, II and III mitral regurgitation (p = 0.0001). This study shows that Doppler echocardiographic measurements of blood flow at different orifices of the heart applied to the quantification of mitral regurgitation is a reliable method, the use of which, with strict methodological criteria, may be proposed in everyday clinical practice.

Acute hepatitis related to psychotropic drugs has been rarely reported with anxiolytic treatments. Alpidem (Ananxyl) is a new imidazopyridine derivative with anxiolytic properties which was launched in October 1991. Several cases of acute hepatitis, some severe, were described with this drug and its liver toxicity was questioned. Results of a study monitoring drug side-effects caused this drug to be withdrawn from the market for one year. We report four cases of acute hepatitis and discuss the role of alpidem. All but one case were presented as severe acute hepatitis with hepatic failure. One patient ran a fulminant course and died despite liver transplantation. The mechanism of liver toxicity remains unclear.

Surgical treatment of rectocele causing outlet blockage is still a subject of controversy. A retrospective study of eight rectocele repairs endorectally using a surgical stapling device done over a two years period was performed. The most common indication was constipation. All patients underwent in the preoperative period complete physiologic examination including defecography, anorectal manometry, electromyography and colonic transit studies. All patients underwent colonoscopy to exclude an obvious physical disorder. There was no postoperative morbidity and the mean hospital stay was four days. Good functional results were obtained in seven patients with a one year follow-up. Endorectal resection using a stapling device is both a simple and effective technique to treat rectocele associated with difficulty in evacuation.

Fainting (short loss of consciousness) is a frequent reason for a consultation in a general practitioner's or cardiologist's office. Four main causes are recognized commonly: cardial with auriculo-ventricular block and arrhythmias, vascular in particular vaso-vagal syncopes, neurologic and other causes. In 38 to 47% of the patients no etiology is found: these are syncopal attacks of unknown origin. The first diagnostic step comprises noninvasive investigations. A 24-hour recording of the ECG or a 'long strip' improve the diagnostic rate by 10%. They are particularly useful for sick sinus syndromes. The head-up tilt-test has been developed recently. It is very useful for detection of vagovasal syncope and permits to understand the pathophysiology and the therapeutic consequences of these disorders. This test plays a particular role for the diagnosis of syncopes of unknown causes and shows in 24 to 75% of the cases pathologic results. Patients at high risk for ventricular arrhythmia can be recognized by ECG with high amplification. Doppler investigation of the neck vessels, however, seems to be of low diagnostic value in syncopes. Invasive measures are the last line resort. Electrophysiologic studies provide criteria that are well defined. They are useful for detection of ventricular dysrhythmias and conduction disorders. This latter approach is reserved to patients with negative noninvasive tests and in particular with cardiopathy. The approach to syncope and the power of noninvasive and invasive tests is thus well established. However, in a certain number of patients the cause for fainting is not disclosed. Fortunately mortality is low in this particular group.

Two hundred and seventy patients, under 71 years of age and suffering from a less than 4 h infarction diagnosed according to clinical and electrocardiographic criteria, were included: two 90-patient groups were randomized and then treated with either anistreplase (30 mg iv over 5 min) or alteplase (10 mg bolus injection + 5000 IU heparin bolus injection, followed by 90 mg alteplase over 3 h), and compared with a consecutive control series of 90 patients treated with streptokinase (1.5 million U over 1 h). Intravenous heparin and aspirin (250 mg day-1) were then prescribed routinely. The three groups were comparable as regards age (55.2 +/- 10 years), male/female ratio (10.4), the site of the infarction (42% anterior, 55% inferior) and initial clinical seriousness (Killip I = 90%, II = 8%, III = 2%). The patients were thrombolysed in 17 community hospitals, and then referred to a university hospital with catheterization facilities. An efficacy score was determined, based on four parameters: two obtained from coronary angiography and left ventriculography performed on day 6 +/- 2 (N = 252) (asynergic score and patency of the infarct-related artery), one from Tl-tomography performed at rest (infarct size) and one from radionuclide angiography (global left ventricular ejection fraction) performed between day 15 and day 21 (N = 242). The score (range: 0-24 per patient) was 17.8 +/- 6.4 for alteplase, 17.7 +/- 6.0 for anistreplase and 18.1 +/- 6.0 for streptokinase respectively (NS).(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of 6 months of treatment with indapamide (IND, 2.5 mg/day) on regression of left ventricular hypertrophy (LVH), an independent predictor of poor prognosis in hypertension, was compared by echocardiography to that of nifedipine (NFD, 40 mg/day), enalapril (ENL, 20 mg/day), atenolol (ATL, 100 mg/day), and hydrochlorothiazide (HCTZ, 25 mg/day) in four parallel double-blind studies in 151 hypertensive patients with a diastolic blood pressure between 95 and 120 mm Hg and a raised left ventricular mass index (LVMI) (mg/m2) (Devereux). Patients were randomized to IND or comparator following a 2-week washout (1 month in the IND vs. ATL study). Respective baseline and 6-month LVMI values (mg/m2) were: IND (n = 20) vs. HCTZ (n = 20): 151.4 +/- 6.3 and 125.70 +/- 4.6 (p0.001) vs. 141.3 +/- 6.6 and 135.6 +/- 8.3 (p = N.S.); IND (n = 22) vs NFD (n = 19): 144.1 +/- 5.3 and 125.1 +/- 4.3 (p0.001) vs. 170.4 +/- 6.6 and 148.2 +/- 6.2 (p0.001); IND (n = 9) vs. ENL (n = 9): 155.1 +/- 6.3 and 143.4 +/- 5.2 (p0.001) vs. 142.0 +/- 6.7 and 130.0 +/- 5.9 (p0.001); IND (n = 17) vs. ATL (n = 12): 146.2 +/- 5.1 and 130.8 +/- 6.5 (p0.001) vs. 156.7 +/- 8.4 and 142.9 +/- 10.3 (p0.01). All drugs significantly reduced diastolic blood pressure, and all except HCTZ induced a significant and similar reduction in left ventricular mass.

The aim of this study was evaluation of mid-term results, with a mean follow-up of 23 months (range: 6 months to 6 years), in 449 patients undergoing 500 consecutive angioplasty procedures before 1989. All of these 449 patients underwent primary angioplasty, and not dilatation after restenosis. Data processing of information, based upon a questionnaire filled out by the patient's own cardiologist, enabled 100 per cent follow-up. In these patients with a mean age of 56 (range: 32-83), angioplasty was single in 93 per cent of cases. The indication was unstable angina (45%), following a myocardial infarction (44%) or, more rarely, stable angina (10%). The anterior interventricular was dilated more often than the right coronary and circumflex (56%, 31% and 22% respectively). The cardiac survival rate of 41 months was 94.3 per cent, 78 per cent of patients not having experienced any serious coronary events at the time of last available information. 65 (sixty five) per cent of patients were asymptomatic and the Thallium stress test was normal in 67 per cent of them. Angina recurred in 17 per cent of patients, twice as often in women (p0.02). 14 (fourteen) per cent had undergone a bypass procedure and 14 per cent had been redilated. Comparisons by the Kaplan-Meier method showed less good results after the age of 57: higher mortality (p0.01), more frequent recurrences of angina (p0.05), more frequent aorto-coronary bypasses (p0.001). Aorto-coronary bypasses were commoner after dilatation of the anterior interventricular (p0.005), after multiple dilatations (p0.03) or after unstable angina (p0.05).

In order to realize the future Hermes and Columbus space-flights, European Space Agency decided to build up a european astronaut corps. Space-flights and training constraints require a strict initial selection among candidates. This paper describes space-flights psychological constraints, the aims of a psychiatric exam and its position in astronaut selection procedures as a whole. This paper also describes means and results of that selection among the candidates seen in Paris (France) in 1991.

The measurement of cardiac output at the extremity of the mitral cusps, by Doppler-echocardiography, is of fundamental value, in particular for the evaluation of valve regurgitation. However, it comes up against a theoretical difficulty resulting from constant variation in the surface area of this orifice during diastole. After reviewing the main measurement methods available in the literature, a simplified method based upon the diameter of the ring and calculation of a mean diastolic intercusp distance by TM is suggested. Evaluation of this technique in 101 patients free of valve of leak showed its feasibility to be close to 100% and the correlation with aortic (r = 0.90), pulmonary (r = 0.91) and mitral ring (r = 0.88) outputs was entirely satisfactory. Our method would thus seem to be a good compromise between digitalised integration methods for the measurement of mitral surface area--optimal but complex--and the aim of simplification compatible with routine clinical use.

Fifteen patients with an ostium secundum type atrial septal defect, aged between 5 and 68 (mean = 31) underwent Doppler-echocardiographic evaluation of the ratio of pulmonary and systemic flow rates. Systemic flow was evaluated at the aortic orifice, as well as at the mitral ring and at the extremities of the mitral cusps, based upon the measurement of valve diameters by 2D or TM echocardiography, pulsed Doppler velocity curve and hear rate. Pulmonary flow was measured by the same technique at the site of insertion of the pulmonary cusps. The values obtained were compared with cardiac catheterisation findings, the reference method being an oxymetric measurement of the shunt ratio. Feasibility of the Doppler investigation was 100 per cent. Correlation between the two techniques was r = 0.85 when the Doppler measurement was at the aorta, r = 0.81 for the mitral ring and r = 0.71 at the extremity of the mitral cusps. Doppler-echocardiography thus appears to be a reliable and reproducible method for the evaluation of left-right shunts, confirming data from the literature.

Measurement by Doppler-echocardiography of blood flow rates has the advantage over techniques for the measurement of cardiac output of determining the latter for each valve orifice, and of opening up an approach to the quantification of aortic and mitral regurgitation. This prospective study involving 103 subjects free of any valve leak showed the absence of an significant difference between aortic, pulmonary and mitral ring flow rates in a given individual. Correlations between results obtained at the three measurement sites were: r = 0.92 between aorta and pulmonary artery, r = 0.90 between aorta and mitral ring and r = 0.90 between pulmonary artery and mitral ring. These results support the validation of this technique and would justify its use in the evaluation, quantification and monitoring of mitral and aortic valve leaks.

The authors report on a 3-year experience of interventions by a psychomotrician in the waiting-room of a mother-child protection (PMI) centre in order to recognize and prevent mother-infant interaction difficulties. The main mission of the psychomotrician was to help mothers to discover the competences and the desire of communication of their infants. This experience appears to be positive, allowing the improvement of some mother-infant difficulties, and a better acceptance by the mothers of a child psychiatric consultation when it appears to be necessary.

The combination of left bundle-branch block with right ventricular hypertrophy is said to be exceptional. Faced with this possibility, many authors consider a diagnosis of right ventricular hypertrophy as impossible. The two cases reported were found in a total of approximately 10,000 vectorcardiograms. Starting in 1950, Laham drew attention to the special morphology of precordial left bundle-branch block when there is right ventricular hypertrophy. In 1971, Chou and Helm suggested vectorcardiographic criteria for right ventricular hypertrophy in the case of left bundle-branch block--right posterior shift of the QRS loop and clockwise rotation on the horizontal plane. These criteria are satisfied in the first case, i.e. partial atrioventricular canal, but not in the second, i.e. ostium secundum defect. In both cases, the appearance of the left bundle-branch block is very atypical.

Plasma tocopherol, plasma total lipid levels and tocopherol-lipid ratio were measured every 6 h during 48 h in 12 critically ill patients and compared with those of a control group. The patients were divided into two groups. Group I comprised 6 critically ill patients with ARDS and group II comprised 6 severely ill patients without ARDS. The means for all observations of plasma tocopherol, total lipid levels and tocopherol-lipid ratio in groups I and II were significantly depressed relative to a control group (p less than 0.0001). The difference in the average tocopherol-lipid ratio between the three groups (p less than 0.0001) and between the groups I and II was statistically significant (p less than 0.0001). Our results indicated: (1) a decrease of vitamin E concentrations in the critically ill patients, particularly in ARDS patients; (2) the importance of the relationship between plasma tocopherol and plasma lipids levels in evaluating the deficiency in vitamin E which was evident in ARDS patients.