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J P Boissel

Publications and source records attributed to J P Boissel.

At least 19 recordsLinked to original sources
PubMed2006

A multiscale mathematical model of avascular tumor growth to investigate the therapeutic benefit of anti-invasive agents.

With the aim of inhibiting cancer growth and reducing the risk of metastasis, pharmaceutical companies in the early 1990s developed anti-metastatic agents called inhibitors of metalloproteinases (MMPi). Despite the promising results obtained in pre-clinical studies, results of Phase III trials have been somewhat disappointing for late stage cancer patients. With the aim of mathematically investigating this therapeutic failure, we developed a mechanistically based model which integrates cell cycle regulation and macroscopic tumor dynamics. By simulating the model, we evaluated the efficacy of MMPi therapy. Simulation results predict the lack of efficacy of MMPi in advanced cancer patients. The theoretical model may aid in evaluating the efficacy of anti-metastatic therapies, thus benefiting the design of prospective clinical trials.

Antineoplastic Agents↗
PubMed2006

Low protein diets for chronic kidney disease in non diabetic adults.

BACKGROUND: For more than fifty years, low protein diets have been proposed to patients with kidney failure. However, the effects of these diets in preventing severe renal failure and the need for maintenance dialysis have not been resolved. OBJECTIVES: To determine the efficacy of low protein diets in delaying the need to start maintenance dialysis. SEARCH STRATEGY: Cochrane Renal Group trials register, the Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE. Congress abstracts (American Society of Nephrology since 1990, European Dialysis Transplant Association since 1985, International Society of Nephrology since 1987). Direct contacts with investigators. Date of most recent search: December 2004. SELECTION CRITERIA: Randomised trials comparing two different levels of protein intake in adult patients suffering from moderate to severe renal failure, followed for at least one year. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected studies and extracted data. Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) for dichotomous outcomes with 95% confidence intervals (CI). Collection of the number of "renal deaths" defined as the need for starting dialysis, the death of a patient or a kidney transplant during the trial. MAIN RESULTS: Eight trials were identified from over 40 studies. A total of 1524 patients were analysed, 763 had received reduced protein intake and 761 a higher protein intake. Two hundred and fifty one renal deaths were recorded, 103 in the low protein diet and 148 in the higher protein diet group (RR 0.69, 95% CI 0.56 to 0.86, P = 0.0007). To avoid one renal death, 2 to 56 patients need to be treated with a low protein diet during one year. AUTHORS' CONCLUSIONS: Reducing protein intake in patients with chronic kidney disease reduces the occurrence of renal death by 31% as compared with higher or unrestricted protein intake. The optimal level of protein intake cannot be confirmed from these studies.

Adult↗
PubMed2005

Phosphodiesterase III inhibitors for heart failure.

BACKGROUND: In the treatment of chronic heart failure, vasodilating agents, ACE inhibitors and beta-blockers have shown an increase of life expectancy. Another strategy is to increase the inotropic state of the myocardium : phosphodiesterase inhibitors (PDIs) act by increasing intra-cellular cyclic AMP, thereby increasing the concentration of intracellular calcium, and lead to a positive inotropic effect. OBJECTIVES: This overview on summarised data aims to review the data from all randomised controlled trials of PDIs III versus placebo in symptomatic patients with chronic heart failure. The primary endpoint is total mortality. Secondary endpoints are considered such as cause-specific mortality, worsening of heart failure (requiring intervention), myocardial infarction, arrhythmias and vertigos. We also examine whether the therapeutic effect is consistent in the subgroups based on the use of concomitant vasodilators, the severity of heart failure, and the type of PDI derivative and/or molecule. This overview updates our previous meta-analysis published in 1994. SEARCH STRATEGY: Randomised trials of PDIs versus placebo in heart failure were searched using MEDLINE (1966 to 2004 January), EMBASE (1980 to 2003 December), Cochrane CENTRAL trials (The Cochrane Library Issue 1, 2004) and McMaster CVD trials registries, and through an exhaustive handsearching of international abstracting publications (abstracts published in the last 22 years in the "European Heart Journal", the "Journal of the American College of Cardiology" and "Circulation"). SELECTION CRITERIA: All randomised controlled trials of PDIs versus placebo with a follow-up duration of more than three months. DATA COLLECTION AND ANALYSIS: 21 trials (8408 patients) were eligible for inclusion in the review. 4 specific PDI derivatives and 8 molecules of PDIs have been considered. MAIN RESULTS: As compared with placebo, treatment with PDIs was found to be associated with a significant 17% increased mortality rate (The relative risk was 1.17 (95% confidence interval 1.06 to 1.30; p<0.001). In addition, PDIs significantly increase cardiac death, sudden death, arrhythmias and vertigos. Considering mortality from all causes, the deleterious effect of PDIs appears homogeneous whatever the concomitant use (or non-use) of vasodilating agents, the severity of heart failure, the derivative or the molecule of PDI used. AUTHORS' CONCLUSIONS: Our results confirm that PDIs are responsible for an increase in mortality rate compared with placebo in patients suffering from chronic heart failure. Currently available results do not support the hypothesis that the increased mortality rate is due to additional vasodilator treatment. Consequently, the chronic use of PDIs should be avoided in heart failure patients.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2003

Level of evidence as a future gold standard for the content quality of health resources on the internet.

OBJECTIVE: An assessment of the quality of health information on the Internet is an absolute necessity. In this study 'sensitive' information was defined as information found in documents published on the Internet, which could be used in a medical decision. For sensitive information, the main criterion chosen for the quality of the information was an indication of the level of evidence. A survey was conducted using the CISMeF health catalogue to assess how often a score of the level of evidence is mentioned in the information accessible on the Internet in French-language health resources. METHODS: Since 1999, members of the CISMeF team have systematically been searching for all documents containing 'sensitive' information and verifying whether the level of evidence was explicitly indicated as a score at least once in the document. RESULTS: As of June 2001, 10,190 resources were included in CISMeF; including 2964 textual 'sensitive' resources (29.1%). Out of all these resources, only 4.7% (95% confidence interval: 4.0 - 5.5%) indicated the level of evidence. A statistically significant difference in the prevalence of indicating the level of evidence according to resource types (e.g., 18.1% for guidelines compared to 0.0% for teaching material), year of publication (almost three times greater in 1997-2001 compared with 1990-1996) and publishers was observed. CONCLUSION: As the number of people accessing the growing amount of information on the Internet is increasing daily, publishers have an ethical obligation to inform their readers about the validity of 'sensitive' information their sites contain. However, the vast majority of the French language Internet resources that were surveyed do not mention a score of the level of evidence for their sensitive information.

Consensus↗
PubMed2002

Terbinafine in fungal infections of the nails: a meta-analysis of randomized clinical trials.

BACKGROUND: Historically, there has been a general resistance to treating onychomycosis on the basis that such treatments were protracted and of uncertain outcome. However, modern treatments act more promptly and reliably. OBJECTIVES: To carry out a meta-analysis to evaluate the efficacy and safety of terbinafine in comparison with placebo, itraconazole and griseofulvin. METHODS: The analysis used data from published trials, supplemented where necessary by reference to the original trial reports. RESULTS: Three trials were included in which terbinafine was compared with placebo. From four trials comparing terbinafine with itraconazole, a statistically significant advantage in favour of terbinafine was observed for negative culture and microscopy at the end of the trials. Furthermore, both patients and physicians reported terbinafine to be better tolerated than itraconazole. From two trials comparing terbinafine with griseofulvin, a significantly higher rate of negative microscopy and culture was observed with terbinafine. CONCLUSIONS: A significant advantage in favour of treatment with terbinafine was observed.

Antifungal Agents↗
PubMed2002

Persistent asthma: disease control, resource utilisation and direct costs.

Despite evidence that adverse outcomes are less frequent when asthma management is optimised, the link between the level of control, disease severity and medical resource utilisation (MRU) is poorly documented. This relationship was investigated in a group of patients suffering from persistent asthma (Global Initiative for Asthma (GINA) > or = 2) in France. In 1998 a computerised family practice database was used to identify asthma patients aged 17-50 yrs. Information from the database was complemented by a patient survey to retrospectively assess the level of asthma control and hospital contacts. Costs of MRU over a 12-month study period were related to demographics, medical history, asthma control, and doses of inhaled corticosteroids prescribed during the prestudy period. A review of the computerised medical database identified 1,038 adult patients with persistent asthma, who completed the survey questionnaire. Over a 12-month period, the mean cost of MRU was 549.8 euros for well-controlled patients, 746.3 euros per patient with moderate control, and 1,451.3 euros per patient with poor control. Costs also increased significantly with age, access to free asthma care, comorbid conditions, asthma symptoms in the past year and whether inhaled corticosteroids had been prescribed before the study period. In patients with persistent asthma, large differences were observed in the use of medical resources according to control and severity. Therefore, if patients appropriately use prescribed control therapy, their use of medical resources may be reduced.

Adolescent↗
PubMed2001

Human cationic amino acid transporter hCAT-3 is preferentially expressed in peripheral tissues.

At least five distinct carrier proteins form the family of mammalian cationic amino acid transporters (CATs). We have cloned a cDNA containing the complete coding region of human CAT-3. hCAT-3 is glycosylated and localized to the plasma membrane. Transport studies in Xenopus laevis oocytes revealed that hCAT-3 is selective for cationic L-amino acids and exhibits a maximal transport activity similar to other CAT proteins. The apparent substrate affinity and sensitivity to trans-stimulation of hCAT-3 resembles most closely hCAT-2B. This is in contrast to rat and murine CAT-3 proteins that have been reported to display a very low activity and to be inhibited by neutral and anionic L-amino acids as well as D-arginine (Hosokawa, H., et al. (1997) J. Biol. Chem. 272, 8717-8722; Ito, K., and Groudine, M. (1997) J. Biol. Chem. 272, 26780-26786). Also, in adult rat and mouse, CAT-3 has been found exclusively in central neurons. Human CAT-3 expression is not restricted to the brain, in fact, by far the highest expression was found in thymus. Also in other peripheral tissues, hCAT-3 expression was equal to or higher than in most brain regions, suggesting that hCAT-3 is not a neuron-specific transporter.

Amino Acid Sequence↗
PubMed2001

Efficacy of pneumococcal polysaccharide vaccine in immunocompetent adults: a meta-analysis of randomized trials.

The use of pneumococcal polysaccharide vaccine (PPV) is low in some countries, maybe because of doubts regarding its efficacy. This meta-analysis aims at combining evidence from randomized trials of PPV assessing its efficacy in preventing Streptococcus pneumoniae related diseases in immunocompetent adults. In the fourteen trials totalling 48,837 patients retrieved, PPV prevents definite pneumococcal pneumonia by 71%, presumptive pneumococcal pneumonia by 40%, and mortality due to pneumonia by 32%, but not all-cause pneumonia or death. No preventive effect was seen in the subgroup of patients aged 55 years or more, possibly due to a lack of statistical power.

Adult↗
PubMed2001

A score for predicting risk of death from cardiovascular disease in adults with raised blood pressure, based on individual patient data from randomised controlled trials.

OBJECTIVE: To create a risk score for death from cardiovascular disease that can be easily used. DESIGN: Data from eight randomised controlled trials of antihypertensive treatment. SETTING: Europe and North America. PARTICIPANTS: 47 088 men and women from trials that had differing age ranges and differing eligibility criteria for blood pressure. MAIN OTUCOME MEASURE: 1639 deaths from cardiovascular causes during a mean 5.2 years of follow up. RESULTS: Baseline factors were related to risk of death from cardiovascular disease using a multivariate Cox model, adjusting for trial and treatment group (active versus control). A risk score was developed from 11 factors: age, sex, systolic blood pressure, serum total cholesterol concentration, height, serum creatinine concentration, cigarette smoking, diabetes, left ventricular hypertrophy, history of stroke, and history of myocardial infarction. The risk score is an integer, with points added for each factor according to its association with risk. Smoking contributed more in women and in younger age groups. In women total cholesterol concentration mattered less than in men, whereas diabetes had more of an effect. Antihypertensive treatment reduced the score. The five year risk of death from cardiovascular disease for scores of 10, 20, 30, 40, 50, and 60 was 0.1%, 0.3%, 0.8%, 2.3%, 6.1%, and 15.6%, respectively. Age and sex distributions of the score from the two UK trials enabled individual risk assessment to be age and sex specific. Risk prediction models are also presented for fatal coronary heart disease, fatal stroke, and all cause mortality. CONCLUSION: The risk score is an objective aid to assessing an individual's risk of cardiovascular disease, including stroke and coronary heart disease. It is useful for physicians when determining an individual's need for antihypertensive treatment and other management strategies for cardiovascular risk.

Adult↗
PubMed2001

Impact of osmolality on burning sensations during and immediately after intramuscular injection of 0.5 ml of vaccine suspensions in healthy adults.

A randomised placebo controlled double-blind cross-over trial was performed on twenty healthy adults to assess the effect of osmolality (300,600,850 and 1100 mOsm) on local tolerance of an intramuscular injection (0.5 ml) of five suspensions containing the same components as the excipients of a combined Diphtheria-Tetanus-acellular Pertussis-inactivated Poliomyelitis-Haemophilus influenzae type b paediatric vaccine (DtacP-IPV-Hib, PENTAVAC). The results did not show any dose-effect relationship between burning or pain sensations and the different osmolalities tested. Although mild and not clinically relevant, these sensations seemed to occur more frequently following injection of an isotonic saline solution (P<0.05). Thus, the osmolality of vaccine like suspensions does not appear to be a potential cause of local pain or burning sensation after their administration.

Adolescent↗
PubMed2001

Comparison of 3 and 6 months of oral anticoagulant therapy after a first episode of proximal deep vein thrombosis or pulmonary embolism and comparison of 6 and 12 weeks of therapy after isolated calf deep vein thrombosis.

BACKGROUND: The optimal duration of oral anticoagulant therapy after a first episode of venous thromboembolism remains controversial. METHODS AND RESULTS: We performed an open-label, randomized trial comparing a short oral anticoagulant course (3 months for proximal deep vein thrombosis [P-DVT] and/or pulmonary embolism [PE]; 6 weeks for isolated calf DVT [C-DVT]) with a long course of therapy (6 months for P-DVT/PE; 12 weeks for C-DVT). The outcome events were recurrences and major, minor, or fatal bleeding complications. A total of 736 patients were enrolled. There were 23 recurrences of venous thromboembolism in the short treatment group (6.4%) and 26 in the long treatment group (7.4%); the 2 treatment regimens had an equivalent effect. For the hemorrhage end point, the difference between the short and the long treatment groups was not significant: 15.5% versus 18.4% for all events (P=0.302), 1.7% versus 2.8% (P=0.291) for major events, and 13.9% versus 15.3% for minor bleeding. Subgroup analysis demonstrated that the rate of recurrence was lower for C-DVT than for P-DVT or PE. CONCLUSIONS: After isolated C-DVT, 6 weeks of oral anticoagulation is sufficient. For P-DVT or PE, we demonstrated an equivalence between 3 and 6 months of anticoagulant therapy. For patients with temporary risk factors who have a low risk of recurrence, 3 months of treatment seems to be sufficient. For patients with idiopathic venous thromboembolism or permanent risk factors who have a high risk of recurrence, other trials are necessary to assess prolonged therapy beyond 6 months.

Administration, Oral↗
PubMed2001

Level of control and hospital contacts in persistent asthma.

The purpose of this study was to estimate relationships between asthma control and hospital contacts (visits to emergency rooms and hospitalizations) in a group of patients suffering from persistent asthma, after adjustment for prior use of inhaled corticosteroids. A computerized family practice database was used to identify patients (aged 6-50 years) with persistent asthma who received asthma therapy from January 1995. The database provided information on patient demographics and drug therapy. Asthma control was estimated by a survey of patients at the end of a 12-month study period. Frequency of hospital contacts during the study period was related to demographics, asthma control, and prescribed doses of inhaled corticosteroids during a prestudy period. Review of computerized medical files of 497 family practice physicians identified 1,966 patients with persistent asthma who met the study criteria. Of these patients, 1,251 completed the survey (63.6%). Asthma control was assessed in 1,130 patients; it was moderate or poor in 42% of the cases. During the 12-month study period, 14.8% of patients reported at least one hospital contact. The level of asthma control was significantly (p < 0.001) associated with hospital contacts. The odds ratio (OR) for hospital contact for good and poor asthma control was 0.5 (95% confidence interval [CI] 0.2-0.7) and 2.2 (95% CI 1.2-4.4), respectively. Asthma control was related to hospital contacts independently of use of inhaled corticosteroids before the study period. Overall, control of asthma was not optimal in this population. The occurrence of hospital contacts was closely related with the level of control. This association was independent of the dose of inhaled corticosteroids prescribed before the study, suggesting that in asthma, hospital contacts are primarily related to the level of control experienced by the patients.

Adolescent↗
PubMed2001

Involvement of PKC and NF-kappaB in nitric oxide induced apoptosis in human coronary artery smooth muscle cells.

Apoptosis of vascular smooth muscle cells is critically involved in progression of atherosclerosis and may prevent intimal hyperplasia in restenosis and vascular remodeling. Nitric oxide (NO) is known to induce apoptosis, but the signaling pathways still remain unclear. We investigated p53 accumulation, protein kinase C (PKC) activation and nuclear transcription factor (NF-kappaB) binding activity as possible signaling mechanisms of NO-induced apoptosis. Apoptosis was induced dose-dependently with the NO-donors sodiumnitroprusside (SNP: 232+/-48%) and SIN-1 (241+/-90% of actinomycin D induced apoptosis; means +/- SEM, *p< or =0.05 vs. control) in HSMC. Inhibition of PKC significantly attenuated NO-induced apoptosis. Staurosporine reduced SIN-1/SNP-mediated DNA fragmentation by 55.3+/-13.8% and 38.3+/-13.9% respectively. Comparable results were obtained for calphostin C. However, NO-mediated induction of apoptosis was not preceded by p53 accumulation. SNP decreased NF-kappaB binding activity in HSMC. These results suggest that induction of apoptosis by exogenous NO in HSMC is not dependent on p53 accumulation but involves protein kinase C signaling and regulation of NF-kappaB binding activity. This opens a new therapeutical approach in preventing restenosis after angioplasty.

Apoptosis↗
PubMed2001

[Antihypertensive therapy and improved life expectancy without cerebrovascular accident or coronary artery disease].

The absolute benefit from antihypertensive therapy increases with the baseline risk. However, age is a major determinant of cardiovascular risk, so it is important to express therapeutic efficacy with indices for which age is not a confounder. With this aim we explored the expected gain in life expectancy without cardiovascular events according to age at the initiation of the treatment. The treatment effect estimated from the INDANA meta-analysis, was applied to the cardiovascular risk of a French hypertensive population, simulated from national vital statistics. The gain in life expectancy was estimated from the area between survival curves without events. The treatment effect varied according three different hypotheses: increasing, decreasing or constant effect. When assuming a constant treatment effect, our results show a 29 month gain without stroke for a man who began his treatment at 40 years, and 15 months if hypertension is screened and treatment initiated at 75 years. The gains without coronary heart disease are respectively of 11 and 6 months. The variation of treatment effect over time could have a major impact on the treatment benefit. The gain in life expectancy without events is a relevant decision tool, completing usefully the absolute benefit, since it takes into account the influence of age.

Adult↗
PubMed2000

Postmenopause hormone treatment in women with NIDDM or impaired glucose tolerance: the MEDIA randomized clinical trial.

OBJECTIVE: To assess the biological safety of four hormone replacement treatment (HRT) combinations in women with non insulin dependent diabetes mellitus (NIDDM) or impaired glucose tolerance (IGT). SUBJECTS AND METHODS: Randomized, double-blind, placebo-controlled trial to analyze the variation of fibrinogen, factor VII, PAI1, and TG blood levels in women (n=99), with NIDDM or IGT, receiving a 3-month course of either oral oestradiol (1 or 2 mg) combined with Chlormadinone Acetate 5 mg, or transdermal oestradiol 50 microg/24 h in association with Norethisterone Acetate (11.2 or 22.4 mg), or placebo. Follow-up lasted 3 months. RESULTS: Ninety nine patients, mean age 56 years (SD 5), mean diabetes duration 7 years (S.D. 7), mean glycated hemoglobin (7.3%) were enrolled. There was no significant difference between the groups for any of the primary hemostasis criteria (n=77). Triglycerides (TG) variation significantly differed between groups, P=0.01, from -21% in the large patch group, to +22% in the placebo group (n=82). Treatment administration routes did not significantly differ for any of the criteria. There was a significant difference in the total cholesterol variation between groups, from +8.7% in the placebo group to -10.8% in the oral 1 mg group (P=0.001). CONCLUSION: The treatments had no highly deleterious effect in these patients with NIDDM or with IGT. Long-term trials can be performed with such patients, and an hormone treatment can be prescribed to relieve symptoms. Since these patients had a well-controlled NIDDM, results might be different in less well-controlled diabetes. The data do not support the hypothesis of an impaired oestrogen effect in patients with NIDDM.

Biomarkers↗
PubMed2000

Oral Beraprost sodium, a prostaglandin I(2) analogue, for intermittent claudication: a double-blind, randomized, multicenter controlled trial. Beraprost et Claudication Intermittente (BERCI) Research Group.

BACKGROUND: Beraprost sodium (BPS) is a new stable, orally active prostaglandin I(2) analogue with antiplatelet and vasodilating properties. We report the results of a phase III clinical trial of BPS in patients with intermittent claudication. METHODS AND RESULTS: Patients (n=549) with a pain-free walking distance of between 50 and 300 m were entered into a 4-week single-blind placebo run-in phase. Patients whose pain-free walking distance had changed by <25% were then randomized to receive either BPS (40 microg TID, n=209) or placebo (n=213) in a double-blind manner for 6 months. Pain-free and maximum walking distances were measured on the occasion of treadmill exercise tests performed at baseline and 1.5, 3, 4.5, and 6 months after randomization. Success was defined as an improvement of >50% in pain-free walking distance at month 6 and in > or =1 earlier treadmill exercise test in the absence of critical cardiovascular events. Success was observed more frequently in the BPS group (43.5%) than in the placebo group (33.3%, P=0.036). Pain-free walking distances increased by 81.5% and 52.5%, respectively, in the BPS and placebo groups (P=0.001) and maximum walking distances by 60.1% and 35.0%, respectively (P=0.004). The incidence of critical cardiovascular events was 4.8% in the BPS group and 8.9% in the placebo group. CONCLUSIONS: These results show that BPS is an effective symptomatic treatment of patients with intermittent claudication. The beneficial effects of BPS on critical cardiovascular events should be confirmed in appropriate clinical trials.

Administration, Oral↗