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J Robert

Publications and source records attributed to J Robert.

At least 91 records · Page 5Linked to original sources

High ethanol intake and malnutrition in alcoholic cerebellar shrinkage.

To determine the influence of chronic ethanol intake and nutritional status on cerebellar shrinkage in alcoholism, we studied 12 undernourished patients with acute Wernicke's encephalopathy (WE), 12 undernourished and 24 well-nourished asymptomatic chronic alcoholics, and 24 age-matched well-nourished controls, using morphometric analysis of MRI scans with volumetry of the cerebellum. Alcoholics reported a mean daily intake of ethanol of 177+/-8 g over a period of 27+/-1 years. Most undernourished alcoholics and half of the well-nourished alcoholics, compared to one-tenth of the controls, showed a significant reduction in cerebellar volume (p< or =0.01, both). Alcoholics with cerebellar shrinkage (n=33) were older (p=0.05) and tended to report greater daily ethanol intake than alcoholics without cerebellar shrinkage (n=15), although not significantly so (p=0.09). Cerebellar volume correlated negatively with age in controls and asymptomatic alcoholics (r> or =0.52, p< or =0.01, both), with a significantly greater shrinkage for age in the latter (p=0.003). Logistic regression analysis showed that malnutrition (OR 6.6 [95%CI 1.7-25.6], p=0.005) and a daily ethanol intake of more than 140 g over ten years (OR 6.1 [95%CI 1.8-20.5], p=0.003) were independently associated with the development of cerebellar shrinkage.

Adult↗

B-cell development in the amphibian Xenopus.

The amphibian Xenopus and mammals have similar organization and usage of their immunoglobulin gene loci with combinatorial joining of V, D and J elements. The differences in B-cell development between mammals and this amphibian are due to major differences in developmental kinetics, cell number and lymphoid organ architecture. Unlike mammals, the immune system of Xenopus develops early under pressure to develop quickly and to produce a heterogeneous repertoire before lymphocyte numbers reach 5,000, thereby imposing a limitation on clonal amplification. In addition, it is submitted to metamorphosis. Thus, during the early antigen-independent period, several features of B-cell development related to immune diversification are under strict genetically preprogramed control: 1) D reading frames contribute complementary determining region 3 with features that occur in mammals by somatic selection, 2) the temporal stepwise utilization of V(H) genes in Xenopus occur in families probably because of structural DNA features rather than their position in the locus. Larval and adult immune responses differ in heterogeneity. Larval rearrangements lack N diversity. During the course of immune responses, somatic mutants are generated at the same rate as in other vertebrates but are not optimally selected, probably due to the simpler organization of the lymphoid organs, with neither lymph nodes nor germinal centers resulting in poor affinity maturation. Switch from IgM to other isotypes is mediated by loop-excision deletion of the IgM constant region gene via switch regions which, unlike their mammalian counterpart, are A-T rich and reveal conserved microsites for the breakpoints.

Amino Acid Sequence↗

Activities of several antimicrobials against Mycobacterium ulcerans infection in mice.

Mycobacterium ulcerans inoculated into the footpads of mice at 6 x 10(3) CFU was shown to have a generation time of 6.5 days when estimated from weekly changes in microscopic counts of acid-fast bacilli (AFB) and 7.5 days when calculated from actual CFU enumerated on Lowenstein-Jensen egg medium incubated at 32 degrees C. Footpads became swollen at week 10 (W10) after infection, and all infected control mice were dead at W15 after infection. Daily (5 days/week) treatment with 100 mg of clarithromycin (CLR)/kg of body weight beginning the day after infection prevented swelling of footpads at W10. When initiation of treatment was delayed until obvious footpad swelling was observed, there was a reduction in both the increase in AFB counts and deterioration of swollen footpads and also a prolonged survival of the mice to W18. Mice infected in the hind footpads with 5 x 10(5) CFU of M. ulcerans were divided into an untreated control group and six treatment groups that received one of the following therapies for 8 weeks: 100 mg of CLR/kg, 25 mg of minocycline (MIN)/kg, 50 mg of sparfloxacin (SPX)/kg, 10 mg of rifampin (RIF)/kg, 10 mg of rifabutin (RBT)/kg, or 100 mg of amikacin (AMK)/kg. After completion of therapy, treated animals were observed for an additional 17 weeks. All control mice and mice treated with CLR, MIN, or SPX exhibited swollen footpads during the observation period. In contrast, of those animals treated with RIF, RBT, or AMK, none had footpad swelling and all inoculated cultures done after the W17 observation remained negative. These results suggest that RIF, RBT, and AMK may be effective in the treatment of human infection with M. ulcerans.

Animals↗

High-dose albuterol by metered-dose inhaler plus a spacer device versus nebulization in preschool children with recurrent wheezing: A double-blind, randomized equivalence trial.

UNLABELLED: Inhaled albuterol is the most frequently used bronchodilator for acute wheezing, and nebulization is the standard mode of delivery in hospital setting. However, recent guidelines consider spacer devices as an easier to use, and cost-saving alternative and recommend the high-dose metered-dose inhaler bronchodilator. OBJECTIVE: To demonstrate clinical equivalence between a spacer device and a nebulizer for albuterol administration. DESIGN: Randomized, double-blind, parallel group equivalence trial. SETTING: Pediatric emergency wards at 2 tertiary teaching hospitals. PATIENTS: Sixty-four 12- to 60-month-old children with acute recurrent wheezing (32 per group). INTERVENTIONS: Albuterol was administered through the spacer device (50 microg/kg) or through the nebulizer (150 microg/kg) and repeated 3 times at 20-minute intervals. Parents completed a questionnaire. OUTCOME MEASURES: Pulmonary index, hospitalization, ease of use, acceptability, and pulse oximetry saturation. RESULTS: The 90% confidence interval of the difference between treatment groups for the median absolute changes in pulmonary index values between T0 and T60 was [-1; +1] and was included in the equivalence interval [-1.5; +1.5]. Clinical improvement increased with time. Less than 10% of the children (3 in each group) required hospitalization (2 in each group attributable to treatment failure). Parents considered administration of albuterol using the spacer device easier (94%) and better accepted by their children (62%). CONCLUSIONS: The efficacy of albuterol administered using the spacer device was equivalent to that of the nebulizer. Given its high tolerance, repeated 50-microg/kg doses of albuterol administered through the spacer device should be considered in hospital emergency departments as first-line therapy for wheezing.

Acute Disease↗

Risk and aggressiveness of breast cancer in relation to plasma organochlorine concentrations.

Several organochlorines identified as "hormone mimics" were proposed as possible risk factors for breast cancer. We conducted a case-control study to assess breast cancer risk and disease aggressiveness in relation to plasma concentrations of several organochlorine compounds. Plasma lipid concentrations of 11 chlorinated pesticides and 14 polychlorinated biphenyl congeners were measured in 315 women newly diagnosed with breast cancer, 219 hospital-based controls, and 307 population controls from the Quebec City area (Canada). Concentrations of hormonally active organochlorines or their surrogates were compared between cases and controls as well as between groups of cases defined according to tumor size and axillary-lymph-node involvement. We found similar levels of organochlorines in cases and controls and no relationship between the relative risk of breast cancer and organochlorine exposure. However, the probability of lymph-node invasion among cases increased with exposure to 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene [p,p'-DDE; odds ratio, 2.54; 95% confidence interval (CI), 1.20-5.35; between the highest and the lowest tertiles]. Furthermore, p,p'-DDE exposure was associated with a dose-related increased relative risk of exhibiting both lymph-node involvement and a large tumor. Indeed odds ratio raised to 2.33 (95% CI, 0.94-5.77) for the second tertile relative to the first tertile and reached 3.51 (95% CI, 1.41-8.73) for the third tertile relative to the first tertile. Similar associations were noted with beta-hexachlorocyclohexane, oxychlordane, and transnonachlor. We conclude that exposure to persistent, hormonally active organochlorines during adulthood is not associated with breast cancer risk. The possibility that some organochlorines and especially p,p'-DDE may increase breast cancer aggressiveness deserves further attention.

Adult↗

Twenty-five years of tuberculosis in a French university hospital: a laboratory perspective.

OBJECTIVE: To determine the impact of recent changes in the epidemiology of tuberculosis in France and other industrialised countries on the primary trends of tuberculosis case rates in a French university hospital. DESIGN: Descriptive study of all 4549 culture-positive tuberculosis cases hospitalised at Pitié-Salpêtrière Hospital between 1972 and 1996. RESULTS: From 1972, there was a decline of 5% per year in the tuberculosis case rate, which levelled off in 1983. The proportion of tuberculosis patients who were human immunodeficiency virus (HIV) positive increased from 2% in 1983 to 28% in 1990, and thereafter remained stable. The proportion of foreign-born tuberculosis patients also increased, from 40% in 1972 to 55% in 1985. These two changes affected drug resistance patterns. Drug resistance was more common among foreign-born than among French-born patients, whether previously treated or not. Resistance to rifampicin and multidrug resistance among previously untreated patients was highly related to HIV co-infection. Extrapulmonary sites of tuberculosis were more often smear-positive in HIV-positive than in non-HIV-positive patients (22.8% vs 12.6%), and bacteraemia was diagnosed almost exclusively in HIV-positive patients. CONCLUSION: The changes in clinical and bacteriological tuberculosis patterns at the hospital level over the last 25 years have paralleled those observed at national and international level in industrialised countries, including a slowing in the decrease in the case rate, due in part to the HIV epidemic, a higher proportion of foreign-born patients and an increase in drug resistance.

AIDS-Related Opportunistic Infections↗

Heart mitochondrial respiratory chain complexes are functionally unaffected in heavy ethanol drinkers without cardiomyopathy.

BACKGROUND: Harmful effects of chronic ethanol intake on liver mitochondria have been clearly demonstrated; however, mitochondria from skeletal muscle are preserved, and the effect of ethanol on heart mitochondria remains controversial. We assessed individual enzyme activity of mitochondrial respiratory chain (MRC) complexes and membrane oxidative damage of heart mitochondria in active ethanol drinkers before the development of dilated cardiomyopathy. PATIENTS AND METHODS: Heart samples were obtained from otherwise healthy organ donor individuals with a sudden death of traumatic or neurological cause in whom hearts could not be used because of absence of matched receptors or size inadequacy. Detailed history of alcohol intake was achieved from the relatives. Citrate synthase activity was spectrophotometrically assayed, as well as absolute (nmol x min(-1) x mg protein(-1)) and relative (corrected by citrate synthase) activities of complex I, II, III, and IV of the MRC. Oxidative damage of myocardium membranes was assessed measuring the degree of lipid peroxidation by fluorescence using cis-parinaric acid as probe. RESULTS: We included 10 ethanol drinkers (age 53 +/- 13 years, 100% males, mean lifetime intake of 15.6 +/- 7.9 kg ethanol kg body weight(-1)) and 12 controls (age 60 +/- 10 years, 75% males). Mitochondrial content did not differ between the two groups. Absolute enzyme activities for ethanol drinkers and controls were, respectively, 145 +/- 75 and 130 +/- 50 for complex I (p = NS); 399 +/- 193 and 376 +/- 100 for complex II (p = NS); 719 +/- 288 and 714 +/- 308 for complex III (p = NS); and 475 +/- 139 and 570 +/- 160 for complex IV (p = NS). After correcting such activities by citrate synthase activity, we failed again to demonstrate differences between ethanol drinkers and controls. Lipid peroxidation of myocardium membranes was similar in both groups. CONCLUSIONS: Chronic ethanol drinkers without cardiomyopathy exhibit normal MRC activity in the heart and do not show increased oxidative damage in myocardial membranes.

Adult↗

Surveillance of Mycobacterium tuberculosis drug resistance in France, 1995-1997. AZAY Mycobacteria Study Group.

OBJECTIVE: To measure the rate of primary and secondary drug resistance of Mycobacterium tuberculosis on an ongoing basis. DESIGN: Data on all culture-positive tuberculosis were collected prospectively from 1995 through 1997 from a microbiological laboratory network of 19 university hospitals throughout France, and submitted quarterly to the National Reference Centre for Surveillance of Mycobacterial Diseases. RESULTS: A total of 2998 patients were included in the study. Among the 2333 (78%) previously untreated patients, 8.6% had isolates resistant to any drug, 4.8% to streptomycin (SM) alone, 1.2% to isoniazid (INH) alone, 1.8% to SM + INH, and 0.3% to INH + rifampicin (RMP) or multidrug resistance (MDR). Foreign birth was independently associated with a higher risk of primary resistance to any drug (odds ratio [OR] 1.5). Among the 268 (9%) previously treated patients, 20.9% had isolates resistant to any drug, 6.3% to SM alone, 3.4% to INH alone, 4.1% to SM + INH, and 3.7% to INH + RMP. Foreign birth (OR = 2.3), and human immunodeficiency virus positive status (OR = 4.4) were independently associated with a higher risk of secondary resistance to any drug. CONCLUSION: During the last 30 years there has been no increase in resistance to any drug among previously untreated patients. As expected, secondary resistance was highly associated with foreign birth. MDR-TB remains a rare event in France.

AIDS-Related Opportunistic Infections↗

[Bacteremia and meningitis caused by Yersinia spp].

Yersinia spp infection in human people are increasing attention last thirty years. We have reviewed the bacteremia in our hospital last five years. Three episodes were Yersinia spp bacteremia. Presence of disease or predisponent therapy were present in most of episodes. All patients were more than seventy years old. The septic metastasis were present in all the cases: one with meningitis, other with liver abscess and one with septic arthritis. We have documented a good clinical evolution, though the mortality in different reports is around 50%. The election therapy for all episodes were cephalosporins, and in two cases we added quinolones.

Aged↗

Tamoxifen and mammographic breast densities.

The extent of breast tissue density on mammograms is one of the strongest risk factors for breast cancer. The aim of this analysis was to evaluate whether tamoxifen can affect mammographic breast density. Subjects were participants in the National Surgical Adjuvant Breast Project Breast Cancer Prevention Trial (BCPT), recruited and followed at the Breast Center of Saint-Sacrement Hospital in Quebec City, Canada. The Breast Cancer Prevention Trial is a double-blind trial in which women at high risk of breast cancer were randomized to receive either 20 mg tamoxifen per day or placebo. Mammograms were taken before treatment began and yearly thereafter. For the purpose of this analysis, Wolfe's parenchymal pattern and the percentage of the breast showing tissue densities were assessed by review of pre- and posttreatment mammograms without knowledge of treatment assignment. Among the 69 women included in this analysis, 36 received tamoxifen and 33 received placebo for an average of 3.3 and 3.5 years, respectively. Among women receiving tamoxifen, 16 of 36 (44.4%) changed to a parenchymal pattern of lower density compared with 5 of 33 (15.2%) women receiving placebo (P = 0.010). Moreover, in the tamoxifen-treated group, the difference in the percentage of the breast showing tissue densities between the pre- and posttreatment mammograms reached -9.4% on average compared with a reduction of -3.6% in the placebo group (P = 0.010). Our data show that tamoxifen can reduce high-risk mammographic features. Breast densities should be evaluated as possible early markers of the preventive effect of selective estrogen receptor modulators.

Adult↗

Early prediction in acute pancreatitis: the contribution of amylase and lipase levels in peritoneal fluid.

CONTEXT: Predicting the severity of acute pancreatitis early in the course of the disease is still difficult. OBJECTIVE: The value of amylase and lipase levels in serum and peritoneal fluid might be of value in predicting the course of acute pancreatitis. DESIGN: Prospective study. PATIENTS: One-hundred and sixty-seven patients with acute pancreatitis as confirmed by computed tomography scan within 24 hours of admission were studied. MAIN OUTCOME MEASURES: Each patient was given an enzymatic score which reflected the predominance of serum or peritoneal levels of amylase and/or lipase. Enzymatic score was 0 if neither enzyme was predominant in the peritoneal fluid, 1 if amylase or lipase alone were predominant and 2 if both enzymes were predominant. The predictive value of the enzymatic score or computed tomography scan for a severe attack was determined. RESULTS: One-hundred and thirty-three attacks were graded as mild (79.6%) and 34 were considered as severe (20.4%). The frequency of severe acute pancreatitis significantly increased as the enzymatic score increased (5.4%, 12.5%, and 31.7% in 0, 1, and 2 enzymatic score patients, respectively; P<0.001). An enzymatic score greater than 0 predicted a severe outcome in 32 of 34 patients (sensitivity 94.1%, specificity 26.3%), whereas an enzymatic score of 2 predicted a severe attack in 26 of 34 patients (sensitivity 76.5%, specificity 57.9%). Edema on computed tomography scan was found in 97 of 129 mild attacks (specificity 75.2%) and necrosis in 25 of 33 severe attacks (sensitivity 75.8%), whereas all patients with severe attacks exhibited extrapancreatic acute fluid collection (sensitivity 100%, specificity 34.9%). CONCLUSIONS: Peritoneal dialysis is less predictive and more cumbersome than a computed tomography scan in the early prediction of acute pancreatitis.

Acute Disease↗

Cell surface expression of the endoplasmic reticular heat shock protein gp96 is phylogenetically conserved.

In mammals, the heat shock protein gp96 complexed to antigenic peptides elicits T cell adaptive immunity. By itself, however, gp96 can evoke responses that are characteristic of innate immunity. Interestingly, this protein, which resides in the endoplasmic reticulum, is expressed on the surface of certain mouse tumor cells. Given that heat shock proteins are highly conserved, we investigated whether the cell surface expression of gp96 is also evolutionarily conserved. Our data reveal that gp96, most likely containing the endoplasmic reticulum retention motif (KDEL), is expressed on the surface of three different Xenopus lymphoid tumor cell lines, each derived from a different spontaneously arising thymic tumor. Levels of expression differ among the tumor lines tested, with more immunogenic tumors expressing greater amounts of surface gp96. Moreover, a high level of gp96 surface expression is detectable on a subset of Xenopus normal nontransformed splenic lymphocytes (mainly surface IgM+ B cells) but not on other normal cells, including macrophages and nucleated erythrocytes. Surface expression of a gp96 protein homologue occurs also on some, but not all, T and B cell clones derived from peripheral blood cells of the channel catfish, as well as on lymphocyte-like cells, but not on erythrocytes from the hagfish, a primitive agnathan vertebrate lacking markers of an adaptive immune system. gp96 is actively directed to and retained on the plasma membrane of Xenopus lymphocytes and tumor cells and hagfish lymphocyte-like cells by a process that requires vesicular transport. This selective surface expression of gp96 on some immune cells from different vertebrate classes is consistent with an ancestral immunological role of gp96 as danger-signaling molecule.

Animals↗

[Experience of surgical treatment for primary lung cancer in Geneva 1977-1996].

INTRODUCTION: In Switzerland, primary lung carcinoma is the leading cause of cancer death among males and the third cause of cancer death after carcinomas of the breast and colon in females. Surgical resection is the only potentially curative treatment but only in 20-25% of the patients. METHODS: Between January 1, 1977 and December 31, 1996, 1079 consecutive patients (877 males, 202 females) underwent surgery for primary lung carcinoma at the University Hospital of Geneva. RESULTS: Lobectomy was performed in the majority of patients (n = 558, 51.7%), followed by pneumonectomy (n = 319, 29.6%), exploratory thoracotomy (n = 73, 6.8%), segmentectomy (n = 68, 6.3%), and bilobectomy (n = 61, 5.6%). Most tumours were squamous cell carcinomas (n = 613, 57%) and adenocarcinomas (n = 327, 30.3%). Small cell lung carcinomas were diagnosed in 33 patients (3%). The overall operative mortality rate was 6.6%. However, over the period studied, the operative mortality decreased from 9% in 1977-1980 to 4% in 1993-1996. Survival according to the new staging system was 61% at 5 years in stage IA, 43% in stage IB, 37% in stage IIA, 19% in stage IIB, 14% in stage IIIA, 0% in stage IIIB, and 4% in stage IV. CONCLUSIONS: In future, improvement in long-term survival will require earlier detection of lung carcinomas and better adjuvant and neoadjuvant therapies for advanced tumours.

Adenocarcinoma↗

Interferon-alpha may exacerbate cryoblobulinemia-related ischemic manifestations: an adverse effect potentially related to its anti-angiogenic activity.

The discovery of the strong association between hepatitis C virus (HCV) infection and the development of mixed cryoglobulinemia has motivated active testing of antiviral-directed alternative therapies. Several trials have demonstrated that classic cryoglobulinemia-associated manifestations improve with interferon-alpha (IFNalpha) treatment. Herein we report on 3 HCV-infected patients with severe cryoglobulinemia-related ischemic manifestations who were closely followed up during IFNalpha therapy. Clinical evaluations with special attention to ischemic lesions, liver function tests, and cryocrit determinations were serially performed. In addition to prednisone and immunosuppressive agents, the patients received IFNalpha at 3 x 10(6) units, 3 times per week for 2 months, 3 months, and 4 months, respectively. In all 3 patients, systemic features improved, liver function results returned to normal, and cryocrit values decreased. However, ischemic lesions became less vascularized and ischemia progressed, leading to transmetatarsal and subcondylar amputation, respectively, in 2 of the patients and fingertip necrosis and ulcer enlargement in the third. Skin biopsies performed before IFNalpha therapy and after 2 months of IFNalpha therapy in the third patient showed a significant decrease in subepidermal microvessels. When IFNalpha was discontinued, the lesions finally healed. Cryoglobulinemia-related ischemic lesions may worsen during IFNalpha treatment, presumably through a decrease in inflammation-induced angiogenesis. The anti-angiogenic activity of IFNalpha may delay the appropriate healing of ischemic lesions.

Cryoglobulinemia↗

7Li double quantum filtered NMR and multinuclear relaxation rates of clay suspensions: the effect of clay concentration and nonionic surfactants

7Li double quantum NMR spectra were used to investigate ordering process of synthetic Li+-saponites dispersed in water. Synthetic clays suspended in aqueous solutions of poly(ethylene glycol) monoalkyl ethers were also studied by 7Li, 23Na, and 13C NMR techniques. The strongest surfactant-Li+-saponite interaction occurs with the lowest charged clay. Laponite interacts more strongly with organic molecules than does a similarly charged saponite. The number of oxyethylene units rather than the chain length seems to govern the solid-surfactant interaction. Copyright 1999 Academic Press.

Journal Article↗