PubMed Health⌕ Search

Biomedical subjects

H Laurent

Publications and source records attributed to H Laurent.

At least 19 recordsLinked to original sources
PubMed2006

Myasthenia gravis exacerbation or unmasking associated with telithromycin treatment.

Telithromycin, a new ketolide antibiotic, has been implicated in the exacerbation or unmasking of myasthenia gravis. This retrospective study presents two clinical reports and summarizes eight other suspected cases notified to the French pharmacovigilance system, highlighting a potentially life-threatening risk of telithromycin treatment in myasthenic patients. An important common feature was that, in seven cases, symptomatology occurred within 2 hours of first telithromycin intake--notably in cases of severe exacerbation.

Adult↗
PubMed2001

[Inaugural symptoms of Horton's disease in a series of 260 patients].

PURPOSE: Horton disease or 'giant cell arteritis' is a known entity in its typical form; the difficulty in diagnosis is due to the atypical signs and symptoms. METHODS: We review 260 medical files presenting Horton disease between 1979 and 1999 in five different departments: three internal medicine departments, one rheumatology department and one geriatric department. RESULTS: The study shows a female domination with a mean age of 75 years. Temporal artery biopsy was done on all patients. Ten patients presented a vascular manifestation. The neurological manifestation was the first symptom in four patients. Five patients had cutaneous symptomatology, with positive temporal artery in three cases. Renal manifestation was present in two patients. Two symptoms are important to discuss because of their frequency: the cough and the peripheral arthritis. We found nine observations with arthritis affecting large joints and responding to nonsteroidal antiinflammatories with positive temporal artery biopsy in seven patients, and 21 observations manifesting by cough without radiological signs; in 57% of cases the temporal artery biopsy was positive, and the cough regressed with corticoids. CONCLUSION: These atypical symptoms have to be known to make a diagnosis and to begin a corticotherapy as soon as possible.

Age Distribution↗
PubMed2000

The type IV phosphodiesterase specific inhibitor mesopram inhibits experimental autoimmune encephalomyelitis in rodents.

Experimental autoimmune encephalomyelitis (EAE) is an autoimmune disease with pathological features reminiscent of those seen in multiple sclerosis and thus serves as an animal model for this disease. Inhibition of type IV phosphodiesterase (PDE IV) in animals with this disease has been shown to result in amelioration of disease symptoms. Here we describe the immunomodulatory activity of the novel potent and selective PDE IV inhibitor mesopram. In vitro, mesopram selectively inhibits the activity of type 1 helper T (Th1) cells without affecting cytokine production or proliferation of type 2 helper T (Th2) cells. Administration of mesopram to rodents inhibits EAE in various models. Clinically, EAE is completely suppressed by mesopram in Lewis rats. This is accompanied by a reduction of inflammatory lesions in spinal cord and brain. RT-PCR analysis revealed a marked reduction in the expression of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) in the brains of these animals. Furthermore, the ex vivo production of Th1 cytokines by activated spleen cells derived from mesopram-treated animals is significantly reduced compared to vehicle-treated controls. Amelioration of the clinical symptoms is also observed during chronic EAE in mesopram-treated SJL mice as well as in relapsing-remitting EAE in SWXJ mice using a therapeutic treatment regimen. These data demonstrate the anti-inflammatory activity of mesopram and provide a rationale for its clinical development.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2000

Search for isovector giant monopole resonances via the Pb(3He,tp) reaction

The (nat)Pb(3He,tp) reaction at E(3He) = 177 MeV was studied to identify 2Planck's over 2piomega isovector monopole strength in Bi isotopes. Monopole strength was found in the region -45<Q<-30 MeV in the coincidence data. The cross section is compared with distorted-wave Born approximation calculations for non-spin-flip and spin-flip isovector monopole resonances. The observed spin-flip and non-spin-flip monopole strengths in the proton-decay channel amount to 20% of the respective non-energy-weighted sum rule.

Journal Article↗
PubMed1998

Prodrugs of gestodene for matrix-type transdermal drug delivery systems.

PURPOSE: The aim of this study was to enhance the transdermal absorption of the highly active progestin gestodene from matrix type transdermal delivery systems (TDDS) by formation of prodrugs with improved matrix solubility. METHODS: Gestodene esters were synthesized via acylation of the drug with the respective carboxylic anhydrides. Subsequently TDDS were produced using the solvent cast method. Selected formulations were examined with in vitro diffusion experiments using skin of nude mice. RESULTS: One prodrug, gestodene caproate proved to be an oil at ambient temperature and showed a very high solubilty of over 10.5% in the TDDS matrix. Within in vitro penetration studies using those systems the prodrug exhibited a significantly higher transdermal penetration rate than gestodene from reference systems. Furthermore, the prodrug was hydrolyzed to the parent drug to a high extent during the passage of the skin. CONCLUSIONS: Designing prodrugs to the requirements of matrix TDDS is an efficient way of enhancing the transdermal drug flux rate.

Acylation↗
PubMed1994

Silica dust exposure and lung cancer.

OBJECTIVE: The study evaluated the possibility of a direct association between silica dust exposure and lung cancer. METHODS: Mortality and morbidity among 1026 granite workers was followed in 1940-1989. Regional census data for 1970-1985 and lung cancer incidence data were also linked. The cytotoxicity of different granite fractions and their capacity to induce reactive oxygen species (ROS) in human leukocytes was studied in vitro. RESULTS: Excess lung cancer mortality was found during several follow-up periods. The rate ratios were 1.6-3.8 for different latency periods. Lung cancer risk increased with the length of exposure and latency. Lung cancer morbidity in 1953-1987 showed an excess for the red and grey granite areas, the rate ratio being 2.5 for > or = 20-year latency. Only one lung cancer case came from the black granite area. The cancer cases from the grey area had a shorter latency than those from the red area. The mineral composition differed for each area. The strongest ROS-inducing activity of grey and red granite was seen in the quartz-containing fractions. In the cytotoxicity tests the quartz-containing fractions of the grey and red granite also caused the strongest lactic dehydrogenase (LDH) release. However, plagioclase, the main constituent of black granite (60%), had approximately the same ability to induce ROS as the quartz-containing fractions of red and grey granite. CONCLUSIONS: The cancer morbidity and mortality figures of the three different granite areas, combined with the found differences in biological activity of granite dusts and a hypothesis that there is a cancer-inducing mechanism for ROS, point to a direct role for quartz in cancer induction.

Adult↗
PubMed1991

Aldosterone antagonists. 4. Synthesis and activities of steroidal 6,6-ethylene-15,16-methylene 17-spirolactones.

Several steroidal 6,6-ethylene-15,16-methylene 17-spirolactones were synthesized to find new progestogens that exhibit both progestational and antimineralocorticoidal activities. The influence of substituents in the 10- and 13-position of the steroidal framework on both properties was investigated. It was found that only compound 12, carrying methyl groups at the 10- and 13-positions, possesses high progestational and antimineralocorticoidal activity.

Adrenalectomy↗
PubMed1990

Aldosterone antagonists. 3. Synthesis and activities of steroidal 7 alpha-(alkoxycarbonyl)-15,16-methylene spirolactones.

Several A- and D-ring substituted steroidal 7 alpha-alkoxycarbonyl spirolactones were synthesized with the purpose of increasing the aldosterone antagonistic potency and reducing the endocrinological side effects relative to the standard drug spironolactone. It was found that the 15 beta,16 beta-methylene derivative 17 exhibited a 2-fold higher aldosterone antagonistic activity compared to either spironolactone or the 15,16-unsubstituted derivative 29 while showing remarkably reduced antiandrogenicity.

Animals↗
PubMed1987

[Distribution of HLA-DR antigens in unrelated giant cell arteritis].

HLA-DR antigen distribution was determined by lymphotoxicity on total lymphocytes for locus A.B.C. antigens numbering 14,28 and 7 respectively, and by a search on B lymphocytes for the 12 antigens of locus DR. The normal population included 124 subjects typed for HLA-A.B.C. and 200 subjects typed for HLA-DR. The frequency of alleles was compared to that of the different groups of patients. Significant variations were evaluated by the X2 test, using Woolf's method; the P value obtained was multiplied by the number of antigens looked for (P corrected, or pc). No deviation in frequency was found with the HLA-A.B.C. antigens. Only the DR 4 antigen, present in 23% of the normal population, was increased in proportions that depended on clinical classification: 39.4% (Pc = 0.05) in all patients with giant cell arteritis: 27% (NS) in the 37 polymyalgia rheumatica patients with negative biopsy of the temporal artery; 46.8% (P 0.05) in the 62 patients with Horton's disease presenting either as clinical and histological temporal arteritis (26 cases; DR 4 = 38.5%; NS), or as clinical and/or histological temporal arteritis associated with polymyalgia rheumatica (36 cases; DR 4 = 52.8%; Pc less than 0.005). The frequency of DR 4 antigen in Horton's disease with typical temporal artery biopsy (37 cases) was 46% (Pc = 0.05).

Aged↗
PubMed1987

Aldosterone antagonists. 2. New 7 alpha-(acetylthio)-15,16-methylene spirolactones.

Some 15,16-methylene derivatives of the aldosterone antagonist spironolactone were synthesized with the purpose of increasing the antialdosterone potency and reducing the endocrinological effects of this standard compound. By introduction of a 1,2-double bond and a 15 beta,16 beta-methylene ring in the spironolactone molecule both goals were achieved. In animal studies mespirenone exhibited a threefold-greater antialdosterone potency and less than 10% of the antiandrogenic activity of spironolactone.

Animals↗
PubMed1987

(Z)-17 beta-hydroxy-17 alpha-(2-[125I]iodovinyl)-4-estren-3-one: a new specific gamma-emitting ligand for determination of progesterone receptor.

An iodine-125 labeled ligand for progesterone receptor determination was synthesized: (Z)-17 beta-hydroxy-17 alpha-(2-[125I]iodovinyl)-4-estren-3-one ([125I]SH-D 510). The ligand is stable chemically as well as under the conditions of a receptor assay. The relative binding affinity of the nonradioactive compound towards human uterine progesterone receptor was 7.0 for the Z-isomer (promegestone (R5020) 1.0) and 0.95 for the E-isomer. 4 S and 8 S receptor forms were obtained on sucrose density gradient analysis. Progesterone receptors were assayed in 103 human mammary tumour cytosols, using either [3H]promegestone or [125I]SH-D 510. The coefficient of correlation was r = 0.951.

Animals↗
PubMed1986

Mespirenone and other 15,16-methylene-17-spirolactones, a new type of steroidal aldosterone antagonists.

The ability of a series of 15,16-methylene-spirolactones in comparison to known antimineralocorticoids to inhibit the renal actions of aldosterone was tested in adrenalectomized, glucocorticoid-treated rats. The standard procedure involved continuous i.v. infusion with an isotonic solution of low sodium content (0.05% NaCl + 5.2% glucose, 3 ml/rat/h) supplemented with d-aldosterone [1 micrograms/(kg X h)] resulting in a long-lasting reduction of renal sodium excretion, increase of renal potassium excretion and hence decrease of the urinary Na/K-ratio. In some experiments sodium input was increased (0.2% NaCl + 4.3% glucose or 0.9% NaCl, respectively). The test drugs either were administered orally 1 h before start of the infusion or were added to the infused solution. With the exception of two steroids which could only be tested at single doses, all compounds were administered at three doses ranging from 2.2 to 40 mg/kg (p.o.) or from 0.83 to 6.7 mg/kg/h (i.v.). Spironolactone or spirorenone (oral administration) and potassium canrenoate (i.v. infusion) served as reference compounds. The antimineralocorticoid activity of the steroids was judged by the increase in the aldosterone-lowered Na/K-ratio in urine which was collected at hourly intervals for 15 or 21 h, respectively. Adrenalectomized, glucocorticoid-treated rats receiving an i.v. infusion without aldosterone were used as controls. To obtain preliminary information on potential antiandrogenic and progestogenic (side-)effects, binding of the test-compounds to androgen receptors (rat prostate cytosol) and progestogen receptors (rabbit uterus cytosol) was measured in vitro using 3H-dihydrotestosterone (DHT) and 3H-progesterone (prog.) as tracer and unlabelled DHT and prog. as references. All steroids tested exhibited antimineralocorticoid activity. For compounds tested at three doses levels the potency relative to the standard used was evaluated using regression analysis based on the Na/K-ratio or the log (Na X 100)/K-ratio. The relative potency of the other compounds was estimated by comparing the biological effect of single doses of test drug and standard drug, respectively, using nonparametric statistical tests.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗