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Showing papers by "University of Paris published in 2002"


Journal ArticleDOI
TL;DR: An anatomical parcellation of the spatially normalized single-subject high-resolution T1 volume provided by the Montreal Neurological Institute was performed and it is believed that this tool is an improvement for the macroscopical labeling of activated area compared to labeling assessed using the Talairach atlas brain.

13,678 citations


Journal ArticleDOI
TL;DR: Used in conjunction with other clinical information, rapid measurement of B-type natriuretic peptide is useful in establishing or excluding the diagnosis of congestive heart failure in patients with acute dyspnea.
Abstract: Background B-type natriuretic peptide is released from the cardiac ventricles in response to increased wall tension. Methods We conducted a prospective study of 1586 patients who came to the emergency department with acute dyspnea and whose B-type natriuretic peptide was measured with a bedside assay. The clinical diagnosis of congestive heart failure was adjudicated by two independent cardiologists, who were blinded to the results of the B-type natriuretic peptide assay. Results The final diagnosis was dyspnea due to congestive heart failure in 744 patients (47 percent), dyspnea due to noncardiac causes in 72 patients with a history of left ventricular dysfunction (5 percent), and no finding of congestive heart failure in 770 patients (49 percent). B-type natriuretic peptide levels by themselves were more accurate than any historical or physical findings or laboratory values in identifying congestive heart failure as the cause of dyspnea. The diagnostic accuracy of B-type natriuretic peptide at a cutoff ...

3,130 citations


Journal ArticleDOI
TL;DR: In patients with invasive aspergillosis,Initial therapy with voriconazole led to better responses and improved survival and resulted in fewer severe side effects than the standard approach of initial therapy with amphotericin B.
Abstract: Background Voriconazole is a broad-spectrum triazole that is active against aspergillus species. We conducted a randomized trial to compare voriconazole with amphotericin B for primary therapy of invasive aspergillosis. Methods In this randomized, unblinded trial, patients received either intravenous voriconazole (two doses of 6 mg per kilogram of body weight on day 1, then 4 mg per kilogram twice daily for at least seven days) followed by 200 mg orally twice daily or intravenous amphotericin B deoxycholate (1 to 1.5 mg per kilogram per day). Other licensed antifungal treatments were allowed if the initial therapy failed or if the patient had an intolerance to the first drug used. A complete or partial response was considered to be a successful outcome. Results A total of 144 patients in the voriconazole group and 133 patients in the amphotericin B group with definite or probable aspergillosis received at least one dose of treatment. In most of the patients, the underlying condition was allogeneic hematop...

3,003 citations


Journal ArticleDOI
TL;DR: The primary effect of low RWC on Apot is most probably caused by limited RuBP synthesis, as a result of decreased ATP synthesis, either through inhibition of Coupling Factor activity or amount due to increased ion concentration.
Abstract: Summary Experimental studies on CO2 assimilation of mesophytic C3 plants in relation to relative water content (RWC) are discussed. Decreasing RWC slows the actual rate of photosynthetic CO2 assimilation (A) and decreases the potential rate (Apot). Generally, as RWC falls from c. 100 to c. 75%, the stomatal conductance (gs) decreases, and with it A. However, there are two general types of relation of Apot to RWC, which are called Type 1 and Type 2. Type 1 has two main phases. As RWC decreases from 100 to c. 75%, Apot is unaffected, but decreasing stomatal conductance (gs) results in smaller A, and lower CO2 concentration inside the leaf (Ci) and in the chloroplast (Cc), the latter falling possibly to the compensation point. Down-regulation of electron transport occurs by energy quenching mechanisms, and changes in carbohydrate and nitrogen metabolism are considered acclimatory, caused by low Ci and reversible by elevated CO2. Below 75% RWC, there is metabolic inhibition of Apot, inhibition of A then being partly (but progressively less) reversible by elevated CO2; gs regulates A progressively less, and Ci and CO2 compensation point, Γ rise. It is suggested that this is the true stress phase, where the decrease in Apot is caused by decreased ATP synthesis and a consequent decreased synthesis of RuBP. In the Type 2 response, Apot decreases progressively at RWC 100 to 75%, with A being progressively less restored to the unstressed value by elevated CO2. Decreased gs leads to a lower Ci and Cc but they probably do not reach compensation point: gs becomes progressively less important and metabolic limitations more important as RWC falls. The primary effect of low RWC on Apot is most probably caused by limited RuBP synthesis, as a result of decreased ATP synthesis, either through inhibition of Coupling Factor activity or amount due to increased ion concentration. Carbohydrate synthesis and accumulation decrease. Type 2 response is considered equivalent to Type 1 at RWC below c. 75%, with Apot inhibited by limited ATP and RuBP synthesis, respiratory metabolism dominates and Ci and Γ rise. The importance of inhibited ATP synthesis as a primary cause of decreasing Apot is discussed. Factors determining the Type 1 and Type 2 responses are unknown. Electron transport is maintained (but down-regulated) in Types 1 and 2 over a wide range of RWC, and a large reduced/oxidized adenylate ratio results. Metabolic imbalance results in amino acid accumulation and decreased and altered protein synthesis. These conditions profoundly affect cell functions and ultimately cause cell death. Type 1 and 2 responses may reflect differences in gs and in sensitivity of metabolism to decreasing RWC.

1,791 citations


Journal ArticleDOI
TL;DR: In this paper, the authors investigated the distribution of well being among world citizens during the last two centuries and found that inequality of world distribution of income worsened from the beginning of the 19th century to World War II and after that seems to have stabilized or to have grown more slowly.
Abstract: This paper investigates the distribution of well being among world citizens during the last two centuries. The estimates show that inequality of world distribution of income worsened from the beginning of the 19th century to World War II and after that seems to have stabilized or to have grown more slowly. In the early 19th century most inequality was due to differences within countries; later, it was due to differences between countries. Inequality in longevity, also increased during the 19th century, but then was reversed in the second half of the 20th century, perhaps mitigating the failure of income inequality to improve in the last decades. (JEL D31, F0, N0, O0)

1,186 citations


Journal ArticleDOI
01 Jun 2002-Chest
TL;DR: In this article, the authors identified and critically reviewed the published peer-reviewed, English-language studies investigating predictive factors of fluid responsiveness in ICU patients and compared responder and nonresponder patients' characteristics before volume expansion.

1,144 citations


Journal ArticleDOI
TL;DR: PEG-interferon and ribavirin combination significantly reduces the rate of fibrosis progression in patients with hepatitis C.

1,127 citations


Journal ArticleDOI
15 Nov 2002-Science
TL;DR: A spontaneous, rhythmic activity initiated in the subiculum of slices from patients with temporal lobe epilepsy was described, similar to interictal discharges of patient electroencephalograms.
Abstract: The origin and mechanisms of human interictal epileptic discharges remain unclear. Here, we describe a spontaneous, rhythmic activity initiated in the subiculum of slices from patients with temporal lobe epilepsy. Synchronous events were similar to interictal discharges of patient electroencephalograms. They were suppressed by antagonists of either glutamatergic or γ-aminobutyric acid (GABA)–ergic signaling. The network of neurons discharging during population events comprises both subicular interneurons and a subgroup of pyramidal cells. In these pyramidal cells, GABAergic synaptic events reversed at depolarized potentials. Depolarizing GABAergic responses in neurons downstream to the sclerotic CA1 region contribute to human interictal activity.

930 citations


Journal ArticleDOI
TL;DR: Control of glutathione concentration and redox state is due to a complex interplay between biosynthesis, utilization, degradation, oxidation/reduction, and transport, and all these factors must be considered in order to evaluate the significance of glutATHione as a signalling component during development, abiotic stress, or pathogen attack.
Abstract: Glutathione has numerous roles in cellular defence and in sulphur metabolism. These functions depend or impact on the concentration and/or redox state of leaf glutathione pools. Effective function requires homeostatic control of concentration and redox state, with departures from homeostasis acting as signals that trigger adaptive responses. Intercellular and intracellular glutathione pools are linked by transport across membranes. It is shown that glutathione can cross the chloroplast envelope at rates similar to the speed of biosynthesis. Control of glutathione concentration and redox state is therefore due to a complex interplay between biosynthesis, utilization, degradation, oxidation/reduction, and transport. All these factors must be considered in order to evaluate the significance of glutathione as a signalling component during development, abiotic stress, or pathogen attack.

840 citations


Journal ArticleDOI
TL;DR: The extended follow-up of Syst-Eur patients reinforces the evidence that blood pressure–lowering therapy initiated with a long-acting dihydropyridine protects against dementia in older patients with systolic hypertension.
Abstract: Background After the double-blind, placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial ended in February 1997, randomized patients were offered active study medication for a further period of observation. Objective To refine the estimates of the long-term effects of antihypertensive therapy on the incidence of dementia. Methods Eligible patients had no dementia and were at least 60 years old. Their systolic blood pressure at entry was 160 to 219 mm Hg, with diastolic blood pressure below 95 mm Hg. Antihypertensive therapy was started immediately after randomization in the active treatment group, but only after termination of the double-blind trial in the control patients. Treatment consisted of nitrendipine (10-40 mg/d), with the possible addition of enalapril maleate (5-20 mg/d), hydrochlorothiazide (12.5-25 mg/d), or both add-on drugs. Results Median follow-up increased from 2.0 years in the double-blind trial to 3.9 years overall. The incidence of dementia doubled from 32 to 64 cases, 41 of whom had Alzheimer disease. Throughout follow-up, systolic/diastolic blood pressure was 7.0/3.2 mm Hg higher in the 1417 control patients than in the 1485 subjects randomized to active treatment. At the last examination, the blood pressure difference was still 4.2/2.9 mm Hg; 48.1%, 26.4%, and 11.4% of the control patients were taking nitrendipine, enalapril, and/or hydrochlorothiazide, whereas in the active treatment group these proportions were 70.2%, 35.4%, and 18.4%, respectively. Compared with the controls, long-term antihypertensive therapy reduced the risk of dementia by 55%, from 7.4 to 3.3 cases per 1000 patient-years (43 vs 21 cases, P P Conclusion The extended follow-up of Syst-Eur patients reinforces the evidence that blood pressure–lowering therapy initiated with a long-acting dihydropyridine protects against dementia in older patients with systolic hypertension.

810 citations


Journal ArticleDOI
TL;DR: The predominant mechanism for resistance to β-lactam antibiotics in gram-negative bacteria is the synthesis of β- lactamase, which has implications for drug resistance and drug discovery.
Abstract: The predominant mechanism for resistance to β-lactam antibiotics in gram-negative bacteria is the synthesis of β-lactamase. To meet this challenge, β-lactams with greater β-lactamase stability, including cephalosporins, carbapenems, and monobactams, were introduced in the 1980s. Resistance

Journal ArticleDOI
Bernard Aubert, A. Bazan, A. Boucham, D. Boutigny  +816 moreInstitutions (68)
TL;DR: BABAR as discussed by the authors is a detector for the SLAC PEP-II asymmetric e+e-B Factory operating at the upsilon 4S resonance, which allows comprehensive studies of CP-violation in B-meson decays.
Abstract: BABAR, the detector for the SLAC PEP-II asymmetric e+e- B Factory operating at the upsilon 4S resonance, was designed to allow comprehensive studies of CP-violation in B-meson decays. Charged particle tracks are measured in a multi-layer silicon vertex tracker surrounded by a cylindrical wire drift chamber. Electromagentic showers from electrons and photons are detected in an array of CsI crystals located just inside the solenoidal coil of a superconducting magnet. Muons and neutral hadrons are identified by arrays of resistive plate chambers inserted into gaps in the steel flux return of the magnet. Charged hadrons are identified by dE/dx measurements in the tracking detectors and in a ring-imaging Cherenkov detector surrounding the drift chamber. The trigger, data acquisition and data-monitoring systems, VME- and network-based, are controlled by custom-designed online software. Details of the layout and performance of the detector components and their associated electronics and software are presented.

Proceedings ArticleDOI
10 Jul 2002
TL;DR: In this article, the Buchberger criteria were replaced by an optimal criteria and the resulting algorithm (called F5) was shown to generate no useless critical pairs if the input is a regular sequence.
Abstract: This paper introduces a new efficient algorithm for computing Grobner bases. We replace the Buchberger criteria by an optimal criteria. We give a proof that the resulting algorithm (called F5) generates no useless critical pairs if the input is a regular sequence. This a new result by itself but a first implementation of the algorithm F5 shows that it is also very efficient in practice: for instance previously untractable problems can be solved (cyclic 10). In practice for most examples there is no reduction to zero. We illustrate this algorithm by one detailed example.

Journal ArticleDOI
10 Jul 2002-JAMA
TL;DR: Because of increased awareness of the activity and toxicity of current drugs, the threshold for initiation of therapy has shifted to a later time in the course of HIV disease, however, the optimal time to initiate therapy remains imprecisely defined.
Abstract: ObjectiveNew information warrants updated recommendations for the 4 central issues in antiretroviral therapy: when to start, what drugs to start with, when to change, and what to change to. These updated recommendations are intended to guide practicing physicians actively involved in human immunodeficiency virus (HIV)– and acquired immunodeficiency syndrome (AIDS)–related care.ParticipantsIn 1995, physicians with specific expertise in HIV-related basic science and clinical research, antiretroviral therapy, and HIV patient care were invited by the International AIDS Society-USA to serve on a volunteer panel. In 1999, others were invited to broaden international representation. The 17-member panel met regularly in closed meetings between its last report in 2000 and April 2002 to review current data. The effort was sponsored and funded by the International AIDS Society-USA, a not-for-profit physician education organization.Evidence and Consensus ProcessThe full panel was convened in late 2000 and assigned 7 section committees. A section writer and 3 to 5 section committee members (each panel member served on numerous sections) identified relevant evidence and prepared draft recommendations. Basic science, clinical research, and epidemiologic data from the published literature and abstracts from recent (within 2 years) scientific conferences were considered by strength of evidence. Extrapolations from basic science data and expert opinion of the panel members were included as evidence. Draft sections were combined and circulated to the entire panel and discussed in a series of full-panel conference calls until consensus was reached. Final recommendations represent full consensus agreement of the panel.ConclusionsBecause of increased awareness of the activity and toxicity of current drugs, the threshold for initiation of therapy has shifted to a later time in the course of HIV disease. However, the optimal time to initiate therapy remains imprecisely defined. Availability of new drugs has broadened options for therapy initiation and management of treatment failure, which remains a difficult challenge.

Journal ArticleDOI
TL;DR: Specific consensus-based recommendations were made regarding the definition, diagnostic criteria, pathogenic factors, medical treatment, and prognostic indicators for mucous membrane pemphigoid.
Abstract: OBJECTIVE: We aimed to develop consensus-based recommendations for streamlining medical communication among various health care professionals, to improve accuracy of diagnosis and treatment, and to facilitate future investigations for mucous membrane pemphigoid. PARTICIPANTS: Because of the highly specific nature of this group of diseases, the 26 invited participants included either international scholars in the field of mucous membrane pemphigoid or experts in cutaneous pharmacology representing the 3 medical disciplines ophthalmology, oral medicine, and dermatology. EVIDENCE: The first author (L.S.C.) conducted a literature search. Based on the information obtained, international experts who had contributed to the literature in the clinical care, diagnosis, and laboratory investigation for mucous membrane pemphigoid were invited to participate in a consensus meeting aimed at developing a consensus statement. CONSENSUS PROCESS: A consensus meeting was convened and conducted on May 10, 1999, in Chicago, Ill, to discuss the relevant issues. The first author drafted the statement based on the consensus developed at the meeting and the participants' written comments. The draft was submitted to all participants for 3 separate rounds of review, and disagreements were reconciled based on literature evidence. The third and final statement incorporated all relevant evidence obtained in the literature search and the consensus developed by the participants. The final statement was approved and endorsed by all 26 participants. CONCLUSIONS: Specific consensus-based recommendations were made regarding the definition, diagnostic criteria, pathogenic factors, medical treatment, and prognostic indicators for mucous membrane pemphigoid. A system of standard reporting for these patients was proposed to facilitate a uniform data collection.

Journal ArticleDOI
TL;DR: A graph of 909 genetically or biochemically established interactions among 491 yeast genes is created, showing a deviation from randomness probably reflects functional constraints that include biosynthetic cost, response delay and differentiative and homeostatic regulation.
Abstract: Interpretation of high-throughput biological data requires a knowledge of the design principles underlying the networks that sustain cellular functions. Of particular importance is the genetic network, a set of genes that interact through directed transcriptional regulation. Genes that exert a regulatory role encode dedicated transcription factors (hereafter referred to as regulating proteins) that can bind to specific DNA control regions of regulated genes to activate or inhibit their transcription. Regulated genes may themselves act in a regulatory manner, in which case they participate in a causal pathway. Looping pathways form feedback circuits. Because a gene can have several connections, circuits and pathways may crosslink and thus represent connected components. We have created a graph of 909 genetically or biochemically established interactions among 491 yeast genes. The number of regulating proteins per regulated gene has a narrow distribution with an exponential decay. The number of regulated genes per regulating protein has a broader distribution with a decay resembling a power law. Assuming in computer-generated graphs that gene connections fulfill these distributions but are otherwise random, the local clustering of connections and the number of short feedback circuits are largely underestimated. This deviation from randomness probably reflects functional constraints that include biosynthetic cost, response delay and differentiative and homeostatic regulation.

Journal ArticleDOI
TL;DR: The sources of the acquired carbapenemase genes remain unknown, as does the relative importance of the spread of epidemic strains as opposed to thespread of plasmid- or integron-borne genes.

Journal ArticleDOI
TL;DR: It is suggested that consumption of a diet enriched in n-3 PUFA and inhibition of COX-2 by NSAIDs may confer cardioprotective effects and provide a significant mechanism for the prevention and treatment of human cancers.

Journal ArticleDOI
01 Jul 2002-Diabetes
TL;DR: In this article, the longitudinal changes in insulin sensitivity during pregnancy were correlated with changes in placental hormones, cortisol, leptin, and tumor necrosis factor (TNF)-alpha.
Abstract: Historically, insulin resistance during pregnancy has been ascribed to increased production of placental hormones and cortisol. The purpose of this study was to test this hypothesis by correlating the longitudinal changes in insulin sensitivity during pregnancy with changes in placental hormones, cortisol, leptin, and tumor necrosis factor (TNF)-alpha. Insulin resistance was assessed in 15 women (5 with gestational diabetes mellitus [GDM] and 10 with normal glucose tolerance) using the euglycemic-hyperinsulinemic clamp procedure, before pregnancy (pregravid) and during early (12-14 weeks) and late (34-36 weeks) gestation. Body composition, plasma TNF-alpha, leptin, cortisol, and reproductive hormones (human chorionic gonadotropin, estradiol, progesterone, human placental lactogen, and prolactin) were measured in conjunction with the clamps. Placental TNF-alpha was measured in vitro using dually perfused human placental cotyledon from five additional subjects. Compared with pregravid, insulin resistance was evident during late pregnancy in all women (12.4 +/- 1.2 vs. 8.1 +/- 0.8 10(-2) mg. kg(-1) fat-free mass. min(-1). microU(-1). ml(-1)). TNF-alpha, leptin, cortisol, all reproductive hormones, and fat mass were increased in late pregnancy (P < 0.001). In vitro, most of the placental TNF-alpha (94%) was released into the maternal circulation; 6% was released to the fetal side. During late pregnancy, TNF-alpha was inversely correlated with insulin sensitivity (r = -0.69, P < 0.006). Furthermore, among all of the hormonal changes measured in this study, the change in TNF-alpha from pregravid to late pregnancy was the only significant predictor of the change in insulin sensitivity (r = -0.60, P < 0.02). The placental reproductive hormones and cortisol did not correlate with insulin sensitivity in late pregnancy. Multivariate stepwise regression analysis revealed that TNF-alpha was the most significant independent predictor of insulin sensitivity (r = -0.67, P < 0.0001), even after adjustment for fat mass by covariance (r = 0.46, P < 0.01). These observations challenge the view that the classical reproductive hormones are the primary mediators of change in insulin sensitivity during gestation and provide the basis for including TNF-alpha in a new paradigm to explain insulin resistance in pregnancy.

Journal ArticleDOI
TL;DR: Increased IL-6 production by sc adipose cells might participate to the insulin-resistant state observed in human obesity, suggesting that locally secreted IL- 6 could act on adipocytes by an autocrine/paracrine mechanism.
Abstract: Obesity and type 2 diabetes are associated with insulin resistance, the mechanisms of which remain poorly understood. A significant correlation between circulating IL-6 level and insulin sensitivity has recently been found in humans. Because adipose tissue could be a significant source of IL-6, we analyzed the relationship between the levels of adipose tissue IL-6 and insulin action in vivo, during a hyperinsulinemic normoglycemic clamp, and in vitro by measuring glucose transport in adipocytes from 12 obese subjects with (n = 7) or without (n = 5) diabetes. We observed an inverse correlation between adipose tissue IL-6 content and maximal insulin-responsiveness measured in vivo (P < 0.02) and in vitro (P < 0.02). Conversely, there was no significant correlation between these two later parameters and adipose tissue leptin or tumor necrosis factor-alpha protein contents. Furthermore, we showed, for the first time, the presence of immunoreactive IL-6 receptors in the plasma membrane of human abdominal sc adipocytes. This suggests that locally secreted IL-6 could act on adipocytes by an autocrine/paracrine mechanism. In conclusion, increased IL-6 production by sc adipose cells might participate to the insulin-resistant state observed in human obesity.

Journal ArticleDOI
TL;DR: It is, therefore, essential to know the nature of the main polyphenols ingested, their dietary origin, the amounts consumed in different diets, their bioavailability and the factors controlling theirBioavailability.

Journal ArticleDOI
TL;DR: In this article, a comparison between the different studies of hydrogen adsorption in carbon nanotubes is presented, where the authors consider the possibility of controlling tube diameters and lengths that will enable to optimize nanotube structure for a maximal hydrogen adorption.

Journal ArticleDOI
TL;DR: It is argued that this new level of complexity, implying that there may be no such thing as a ‘bona fide’ genetic death program in the authors' cells, might be better understood when considered in an evolutionary context.
Abstract: On the origin, evolution, and nature of programmed cell death: a timeline of four billion years

Journal ArticleDOI
TL;DR: This article is an extended review of nanocapsule technologies and their applications for the treatment of various diseases (including cancer and infections).
Abstract: Nanocapsules are submicroscopic colloidal drug carrier systems composed of an oily or an aqueous core surrounded by a thin polymer membrane. Two technologies can be used to obtain such nanocapsules: the interfacial polymerization of a monomer or the interfacial nanodeposition of a preformed polymer. This article is an extended review of these nanocapsule technologies and their applications for the treatment of various diseases (including cancer and infections).

Journal ArticleDOI
TL;DR: Misuse of pressurized metered-dose inhalers, which is mainly due to poor coordination, is frequent and associated with poorer asthma control in inhaled corticosteroid-treated asthmatics, highlighting the importance of evaluating inhalation technique and providing appropriate education in all patients.
Abstract: This study assessed whether the improper use of pressurized metered-dose inhalers (pMDIs) is associated with decreased asthma control in asthmatics treated by inhaled corticosteroids (ICS). General practitioners (GPs) included consecutive asthmatic outpatients treated by pMDI-administered ICS and on-demand, short-acting beta2-agonists. They measured an asthma instability score (AIS) based on daytime and nocturnal symptoms, exercise-induced dyspnoea, beta2-agonist usage, emergency-care visits and global perception of asthma control within the preceding month; the inhalation technique of the patient also was assessed. GPs (n=915) included 4,078 adult asthmatics; 3,955 questionnaires were evaluable. pMDI was misused by 71% of patients, of which 47% was due to poor coordination. Asthma was less stable in pMDI misusers than in good users (AIS: 3.93 versus 2.86, p<0.001). Among misusers, asthma was less stable in poor coordinators (AIS: 4.38 versus 3.56 in good coordinators, p<0.001). To conclude, misuse of pressurized metered-dose inhalers, which is mainly due to poor coordination, is frequent and associated with poorer asthma control in inhaled corticosteroid-treated asthmatics. This study highlights the importance of evaluating inhalation technique and providing appropriate education in all patients, especially before increasing inhaled corticosteroid dosage or adding other agents. The use of devices which alleviate coordination problems should be reinforced in pressurized metered-dose inhaler misusers.

Journal ArticleDOI
TL;DR: The results of this randomized, multicenter trial do not support the adjunctive use of MTX to control disease activity or to decrease the cumulative dose and toxicity of CS in patients with GCA.
Abstract: Objective To evaluate treatment with methotrexate (MTX) in patients with newly diagnosed giant cell arteritis (GCA) to determine if MTX reduces GCA relapses and cumulative corticosteroid (CS) requirements and diminishes disease- and treatment-related morbidity. Methods This was a multicenter, randomized, double-blind study. Over 4 years, 16 centers from the International Network for the Study of Systemic Vasculitides enrolled patients with unequivocal GCA. The initial treatment was 1 mg/kg/day (≤60 mg every day) prednisone, plus either 0.15 mg/kg/week MTX (increased to 0.25 mg/kg/week, for a maximum weekly dosage of 15 mg) or placebo. Two physicians, both blinded to treatment allocation, evaluated each patient at every trial visit. One physician was responsible for providing global medical care. The other assessed GCA status according to a standard protocol. Treatment failure was defined as 2 distinct relapses or persistence of disease activity after the first relapse, in spite of increased CS therapy. Results Ninety-eight patients were enrolled. No significant differences between treatment groups were noted with regard to age, frequency of positive findings on temporal artery biopsy (placebo 87%, MTX 79%), or comorbidities at the time of enrollment. The median dosage of MTX was 15 mg/week. The incidence of treatment failure was comparable between groups after 12 months: 57.5% in the MTX group failed treatment (95% confidence interval [95% CI] 41.6–73.4%) compared with 77.3% in the placebo group (95% CI 61.9–92.8%) (P = 0.26). In a Cox regression analysis, MTX was not associated with a reduced risk of treatment failure (relative risk 0.72; 95% CI 0.41–1.28). There were no significant differences between groups with regard to abnormal elevations of the erythrocyte sedimentation rate following initial remissions, serious morbidity due to GCA, cumulative CS dose, or treatment toxicity. In the MTX group, there were fewer cases of GCA relapse heralded by symptoms of isolated polymyalgia rheumatica (1 case versus 5 in the placebo group; P = 0.05). Conclusion The results of this randomized, multicenter trial do not support the adjunctive use of MTX to control disease activity or to decrease the cumulative dose and toxicity of CS in patients with GCA.

Journal ArticleDOI
TL;DR: In the present script, a four-parameter family of Boussinesq systems are derived from the two-dimensional Euler equations for free-surface flow and criteria are formulated to help decide which of these equations one might choose in a given modeling situation.
Abstract: Considered herein are a number of variants of the classical Boussinesq system and their higher-order generalizations Such equations were first derived by Boussinesq to describe the two-way propagation of small-amplitude, long wavelength, gravity waves on the surface of water in a canal These systems arise also when modeling the propagation of long-crested waves on large lakes or the ocean and in other contexts Depending on the modeling of dispersion, the resulting system may or may not have a linearization about the rest state which is well posed Even when well posed, the linearized system may exhibit a lack of conservation of energy that is at odds with its status as an approximation to the Euler equations In the present script, we derive a four-parameter family of Boussinesq systems from the two-dimensional Euler equations for free-surface flow and formulate criteria to help decide which of these equations one might choose in a given modeling situation The analysis of the systems according to these criteria is initiated

Journal ArticleDOI
TL;DR: Clinical presentation of HSPN in adults is severe and its outcome relatively poor, worse than in children, andMultivariate analysis demonstrated that renal function impairment and proteinuria level at presentation and, on renal biopsy, the degree of interstitial fibrosis, percentage of sclerotic glomeruli, and presence ofglomeruli with fibrinoid necrosis were associated with a poor renal prognosis.
Abstract: Henoch-Schonlein Purpura nephritis (HSPN) has been extensively studied in children but, its natural history in adults is much less known. A cohort of 250 adults suffering HSP was retrospectively analyzed for a median follow-up period of 14.8 yr. All patients had biopsies consistent with HSP (predominant IgA mesangial deposits) associated with purpura, bowel angina, and/or abdominal pain. At presentation, palpable purpura was present in 96% of patients, and arthritis was reported in 61%, and gastrointestinal involvement in 48%. Thirty-two percent of the patients showed renal insufficiency (Creatinine clearance [CrCl] <50 ml/min), usually associated with proteinuria (99%) and/or hematuria (93%). Endocapillary glomerulonephritis was the most frequent lesion on renal biopsy (61%). At the end of follow-up, patient survival was only 74%. The first cause of death was carcinoma (most of them of respiratory or digestive tract). Regarding renal function, 11% of patients reached end-stage renal failure, 13% exhibited severe renal failure (CrCl <30 ml/min), and 14% moderate renal insufficiency (CrCl <50 ml/min). Clinical remission defined as the absence of proteinuria, hematuria, and a normal renal function was achieved in only 20%. This is a retrospective study; therefore, it is not possible to demonstrate any steroid and/or cyclophosphamide efficacy in diminishing the incidence of renal insufficiency. Multivariate analysis demonstrated that renal function impairment and proteinuria level at presentation and, on renal biopsy, the degree of interstitial fibrosis, percentage of sclerotic glomeruli, and presence of glomeruli with fibrinoid necrosis were associated with a poor renal prognosis. The data indicate that clinical presentation of HSPN in adults is severe and its outcome relatively poor, worse than in children. Identification of clinical and histologic prognostic factors may permit the design of appropriate therapeutic prospective studies.

Journal ArticleDOI
TL;DR: Application of recruiting maneuvers improves oxygenation only in patients with early ARDS who do not have impairment of chest wall mechanics and with a large potential for recruitment, as indicated by low values of EstL.
Abstract: Background: A lung-protective ventilatory strategy with low tidal volume (VT) has been proposed for use in acute respiratory distress syndrome (ARDS). Alveolar derecruitment may occur during the use of a lung-protective ventilatory strategy and may be prevented by recruiting maneuvers. This study examined the hypothesis that the effectiveness of a recruiting maneuver to improve oxygenation in patients with ARDS would be influenced by the elastic properties of the lung and chest wall. Methods: Twenty-two patients with ARDS were studied during use of the ARDSNet lung-protective ventilatory strategy: VT was set at 6 ml/kg predicted body weight and positive end-expiratory pressure (PEEP) and inspiratory oxygen fraction (FIO2) were set to obtain an arterial oxygen saturation of 90 ‐95% and/or an arterial oxygen partial pressure (PaO2 )o f 60 ‐ 80 mmHg (baseline). Measurements of PaO2/FIO2, static volume‐ pressure curve, recruited volume (vertical shift of the volumepressure curve), and chest wall and lung elastance (EstW and EstL: esophageal pressure) were obtained on zero end-expiratory pressure, at baseline, and at 2 and 20 min after application of a recruiting maneuver (40 cm H2O of continuous positive airway pressure for 40 s). Cardiac output (transesophageal Doppler) and mean arterial pressure were measured immediately before, during, and immediately after the recruiting maneuver. Patients were classified a priori as responders and nonresponders on the basis of the occurrence or nonoccurrence of a 50% increase in PaO2/FIO2 after the recruiting maneuver. Results: Recruiting maneuvers increased PaO2/FIO2 by 20 3% in nonresponders (n 11) and by 175 23% (n 11; mean standard deviation) in responders. On zero end-expiratory pressure, EstL (28.4 2.2 vs. 24.2 2.9 cm H2O/l) and EstW (10.4 1.8 vs. 5.6 0.8 cm H2O/l) were higher in nonresponders than in responders (P < 0.01). Nonresponders had been ventilated for a longer period of time than responders (7 1 vs. 1 0.3 days; P < 0.001). Cardiac output and mean arterial pressure decreased by 31 2 and 19 3% in nonresponders and by 2 1 and 2 1% in responders (P < 0.01). Conclusions: Application of recruiting maneuvers improves oxygenation only in patients with early ARDS who do not have impairment of chest wall mechanics and with a large potential for recruitment, as indicated by low values of EstL. TRADITIONAL respiratory support for the acute respiratory distress syndrome (ARDS) involves the use of relatively large (10 –15 ml/kg) tidal volumes (VT) to minimize atelectasis and positive end-expiratory pressure (PEEP) to improve arterial oxygenation by means of low inspiratory oxygen fractions (FIO2). 1 More recently, lungprotective ventilatory strategies have been proposed 2 that are based on the large body of animal data indicating that mechanical ventilation with high VT is associated with pulmonary injury indistinguishable from ARDS. 3 Cycling end-expiratory collapse with tidal inflation may exacerbate this process. 4 Three recent randomized controlled trials supported these experimental findings, showing that a lung-protective ventilatory strategies based on low VT is able to decrease markers of pulmonary and systemic inflammation 5 and decrease mortality among patients with ARDS. 6,7

Journal ArticleDOI
12 Apr 2002-AIDS
TL;DR: There are several reasons to highlight HBV in HIV positive individuals, and a few reports have devoted particular attention to hepatitis B, which is currently an important cause of morbidity and mortality among HIV-infected patients in the western world.
Abstract: Liver disease caused by chronic hepatitis B virus (HBV) infection is currently an important cause of morbidity and mortality among HIV-infected patients in the western world where classical opportunistic complications of severe immunodeficiency have declined dramatically as a result of the widespread use of potent antiretroviral therapies. Over the past few years several consensus reports have addressed the issue of viral hepatitis and HIV co-infection. However as a result of the larger impact of hepatitis C virus (HCV) they have focused mainly on HIV and HCV co-infection whereas only a few reports have devoted particular attention to hepatitis B. There are several reasons to highlight HBV in HIV positive individuals. (excerpt)