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J Honorato

Publications and source records attributed to J Honorato.

At least 19 recordsLinked to original sources
PubMed2007

Detection and incidence of drug-induced agranulocytosis in hospital: a prospective analysis from laboratory signals.

AIMS: Our objectives were to assess the detection and incidence of drug-induced agranulocytosis in two university hospitals using hematology laboratory data. METHODS: A prospective study was undertaken at Toulouse University Hospital (France) and Navarra University Hospital (Spain) for 1 year (from 1 May 2004 to 30 April 2005). Using a computerized process and hematology laboratory data, all neutrophil counts with a value less than 500/mm(3) were registered, allowing identification of inpatients suffering from agranulocytosis during the period of the study. Medical records of all selected patients were then consulted. Cytostatic drugs were excluded from this study. RESULTS: During the period of the study, 225,659 neutrophil counts were performed in both hospitals, of which 2,835 (1.26%) had a neutrophil count less than 500/mm(3), corresponding to 739 patients. Seventeen patients were excluded because of lack of data, and 20 cases of infants younger than 3 months were excluded. Among the remaining patients (n = 702), 23 cases of drug-induced agranulocytosis (excluding cytostatic drugs) were suspected. All cases were classified as "serious" since they led to death in 2 cases, hospitalization or prolongation of hospitalization in 19 cases and threatening of vital prognosis in 2 cases. Withdrawal of suspected drugs was done in all cases with regression of neutropenia in 21 cases. According to hospitalization data, the annual incidence of drug-induced agranulocytosis was 1.62 (1.0-2.6) per 10,000 inpatients in Toulouse University hospital (based on 534 cases) and 3.24 (0.9-8.3) per 10,000 inpatients in Navarra University Hospital (based on 168 cases). The involved drugs were mainly antibacterial (30.4%), immunosuppressive (17.4%), antithyroid (13.0%), antiplatelet (8.7%) and nonsteroidal anti-inflammatory (8.7%) ones. Only seven cases from Toulouse University Hospital were spontaneously reported by physicians during the same period. Thus, the underreporting coefficient (U) was 2.71 (63.2%) in France. CONCLUSION: Our survey allowed us to identify the suspected drug-induced agranulocytosis through a prospective study in a large sample of inpatients using only laboratory data analysis. We also note an important underreporting rate of this serious adverse drug reaction (ADR) to the official French pharmacovigilance system. Laboratory data analysis could be used for identifying serious ADRs.

Adult↗
PubMed2006

[Albuminuria and cardiovascular risk: basal results of the KORAL-CARDIO study].

BACKGROUND AND OBJECTIVES: Albuminuria is a marker of higher cardiovascular and renal risk in hypertension; it also indicates the need of a tighter control of blood pressure with drugs blocking the renin-angiotensin system. The objective of the KORAL-CARDIO study was to assess the clinical picture and management of patients with hypertension and cardiac disease and albuminuria not previously treated with angiotensin inhibitors. METHODS: A total of 2711 hypertensive patients (44% female) with ischemic or hypertensive cardiopathy or atrial fibrillation and with a positive screening test for albuminuria was included. Type 2 diabetes was also present in 42%. RESULTS: Macroalbuminuria was present in 7.2% of non diabetic and 12.7% of diabetic patients, respectively. Associated complications were: 25% and 35% body mass index over 30 kg/m2; 22% and 39% ischemic heart disease; 4% and 8% stroke; 19% and 22% atrial fibrillation; 42% and 53% high cholesterol levels; 8% and 8% grade 3 hypertension, for non-diabetics and diabetics respectively. Antihypertensive monotherapy was used in 66% of non-diabetics and in 63% of diabetics; only 7% of patients in both groups were treated with triple antihypertensive therapy. CONCLUSIONS: Cardiovascular complications are very frequently associated to albuminuria in patients with hypertension and heart disease not previously treated with angiotensin inhibitors. Blood pressure control was clearly inadequate in this group.

Aged↗
PubMed2005

Antimicrobial therapy for pulmonary pathogenic colonisation and infection by Pseudomonas aeruginosa in cystic fibrosis patients.

Pseudomonas aeruginosa colonisation has a negative effect on pulmonary function in cystic fibrosis patients. The organism can only be eradicated in the early stage of colonisation, while reduction of bacterial density is desirable during chronic colonisation or exacerbations. Monthly, or at least 3-monthly, microbiological culture is advisable for patients without previous evidence of P. aeruginosa colonisation. Cultures should be performed at least every 2-3 months in patients with well-established colonisation, and always during exacerbations or hospitalisations. Treatment of patients following the first isolation of P. aeruginosa, but with no clinical signs of colonisation, should be with oral ciprofloxacin (15-20 mg/kg twice-daily for 3-4 weeks) plus inhaled tobramycin or colistin (intravenous treatment with or without inhaled treatment can be used as an alternative), while patients with acute infection should be treated for 14-21 days with high doses of two intravenous antimicrobial agents, with or without an inhaled treatment during or at the end of the intravenous treatment. Maintenance treatment after development of chronic P. aeruginosa infection/colonisation (pathogenic colonisation) in stable patients (aged>6 years) should be with inhaled tobramycin (300 mg twice-daily) in 28-day cycles (on-off) or, as an alternative, colistin (1-3 million units twice-daily). Colistin is also a possible choice for patients aged<6 years. Treatment can be completed with oral ciprofloxacin (3-4 weeks every 3-4 months) for patients with mild pulmonary symptoms, or intravenously (every 3-4 months) for those with severe symptoms or isolates with ciprofloxacin resistance. Moderate and serious exacerbations can be treated with intravenous ceftazidime (50-70 mg/kg three-times-daily) or cefepime (50 mg/kg three-times-daily) plus tobramycin (5-10 mg/kg every 24 h) or amikacin (20-30 mg/kg every 24 h) for 2-3 weeks. Oral ciprofloxacin is recommended for patients with mild pulmonary disease. If multiresistant P. aeruginosa is isolated, antimicrobial agents that retain activity are recommended and epidemiological control measures should be established.

Amikacin↗
PubMed2001

[Prevalence of osteoporosis assessed by densitometry in the Spanish female population].

BACKGROUND: Osteoporotic fractures represent an important clinic and socioeconomic problem. Although it is well known the incidence of fractures in Spain, we do not know how many persons are at risk. The World Health Organization (WHO) has approved a densitometric criteria to define osteopenia (OSPE) and osteoporosis (OSP). The aim of this study has been to evaluate the prevalence of OSP and OSPE in women of the Spanish population. SUBJECTS AND METHOD: With the data of a study of bone mass in the Spanish population, stratified according to age, using dual-energy X-ray absortiometry (DXA) with a QDR/1000 Hologic device and according the WHO criteria, we have calculated the prevalence of OSP and OSPE in normal Spanish women at the lumbar spine (LS) and/or femoral neck (FN). RESULTS: The prevalence of osteoporosis at LS is: 0.34% in the group aged 20-44 years; 4.31% in the group aged 45-49 years; up to 9.09% in the group aged 50-59 years; 24.29% in the 60-69 years, and 40.0% in the group aged 70-79 years. The overall prevalence of osteoporosis is 11.13%, confidence interval (CI) 95% from 9.4 to 12.8%. The prevalence of osteoporosis at FN is: 0.17% in the group aged 20-44 years, 0% in the 45-49 years, up to 1.3% in the 50-59 years, 5.71% in the 60-69 years and 24.24% in the group aged 70-79 years. The overall prevalence of osteoporosis is 4,29% (CI 95% 3.2-5.4%). The prevalence in female older than 50 years was 22.8% at LS and 9.1% at FN. 12.73% of Spanish women population has osteoporosis at LS or FN, which represent about 1,974,400 women; 2.68% of total population has osteoporosis in both sites. CONCLUSIONS: Even we do not include in this study women with established osteoporosis (with fractures), the number of Spanish women with osteoporosis is very high.

Absorptiometry, Photon↗
PubMed2001

A sensitive method for the determination of gemfibrozil in human plasma samples by RP-LC.

A sensitive high-performance liquid chromatographic assay for the quantitative determination of gemfibrozil is described in this work. Ibuprofen was used as internal standard. The assay involved a single cyclohexane extraction and LC analysis with fluorescence detection. Chromatography was performed at 40 degrees C on a Hypersil ODS column. The mobile phase was a mixture of a solution of phosphoric acid 0.4% and acetonitrile (45:55). The method was validated. The detection limit of this method was 0.025 microg ml(-1); only 0.5 ml of the plasma sample was required for the determination. The calibration graph was linear from 0.05 to 0.5 microg ml(-1) and required a cubic equation from 0.5 to 30 microg ml(-1). Intra and inter-day precision (C.V.) did no exceed 15%. Mean recoveries were of 90.15+/-6.9% (C.V.'s<8%) for gemfibrozil and 93.10% for ibuprofen Applicability of the method was demonstrated by a pharmacokinetic study in normal volunteers who received gemfibrozil by oral route.

Area Under Curve↗
PubMed1999

Enantiomeric separation of tramadol and its active metabolite in human plasma by chiral high-performance liquid chromatography: application to pharmacokinetic studies.

A sensitive and stereoselective high-performance liquid chromatographic assay for the quantitative determination of the analgesic tramadol and O-demethyltramadol, an active metabolite, is described in this work. Ketamine was used as internal standard. The assay involved a single tert-butymethylether extraction and liquid chromatography analysis with fluorescence detection. Chromatography was performed at 20 degrees C on a Chiracel OD-R column containing cellulose tris-(3,5-dimethylphenylcarbamate) as stationary phase, preceded by an achiral end-capped C18 column. The mobile phase was a mixture of phosphate buffer (containing sodium perchlorate (0.2 M) and triethylamine (0.09 M) adjusted to pH 6) and acetonitrile (80:20). The method developed was validated. The limit of quantitation of each enantiomer of tramadol and its active metabolite by this method was 0.5 ng/mL; only 0.5 mL of the plasma sample was required for the determination. The calibration curve was linear from 0.5 to 750 ng/mL for tramadol enantiomers, and from 0.5 to 500 ng/mL for O-demethyltramadol enantiomers. Intra and interday precision [coefficient of variation (CV)] did not exceed 10%. Mean recoveries of 95.95 and 97.87% for (+)R,R- and (-)S,S-tramadol and 97.70 and 98.79% for (+)R,R- and (-)S,S-O-demethyltramadol with CVs < 2.15% were obtained. Applicability of the method was demonstrated by a pharmacokinetic study in normal volunteers who received 100 mg of tramadol by the intravenous route.

Analgesics, Opioid↗
PubMed1999

Rapid liquid chromatographic assay for the determination of acetaminophen in plasma after propacetamol administration: application to pharmacokinetic studies.

A simple method for the rapid estimation of acetaminophen in plasma is described here. p-Propionamidophenol was used as internal standard. The assay involved a single ethyl acetate extraction and liquid chromatographic analysis at a wavelength of 242 nm using a reversed-phase encapped column, with a mobile phase of acetonitrile and 0.005 M potassium dihydrogen phosphate adjusted at pH 3.00. The limit of quantitation of acetaminophen by this method was 0.05 microg ml(-1), only 0.1 ml of the plasma sample was required for the determination. The calibration graph was linear from 0.05 to 100 microg ml(-1). Intra and inter-day precision (CV) did not exceed 8.93%. Mean recoveries of 90.31% with a CV of 1.38% were obtained. Applicability of the method was demonstrated by a pharmacokinetic study in normal volunteers who received 2 mg propacetamol.

Acetaminophen↗
PubMed1997

Continuous intragastric pH monitoring in the evaluation of ebrotidine, cimetidine and placebo on gastric acidity in healthy volunteers.

This study was conducted to determine the efficacy and tolerance of ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene)amino]-4-thiazolyl) methyl]thio]ethyl]amino]methylene]-4-bromo-benzenesulfonamide, CAS 100981-43.9, FI-3542), a new H2-receptor antagonist, on reducing gastric acidity after a single 800 mg dose, compared with cimetidine 800 mg once daily and placebo by means of a continuous intragastric pH monitoring. A total of 30 healthy volunteers were allocated to receive in a double blind, parallel design the study medication. Clinical observations, physical examinations and visual analogue scales (VAS) were performed during the study to assess the tolerability of the three treatments. Ebrotidine and cimetidine caused a greater and longer-lasting gastric acid inhibition than placebo. With ebrotidine, significantly (p < 0.05) higher median pH values (and interquartile range, IQR) were reached in the post-administration (2.61, IQR 2.02-3.93), postprandial (3.38, IQR 2.82-3.91) and nocturnal (2.83, IQR 1.69-3.77) periods than with placebo: 1.82 (IQR, 1.66-2.09), 2.81 (IQR, 2.02-3.28), and 1.89 (IQR, 1.44-2.13), respectively. Cimetidine showed significant differences compared to placebo in the post-administration (2.36, IQR 1.89-3.46) and nocturnal (2.46, IQR 1.88-4.33) periods. No statistical differences were observed between the active treatments. Ebrotidine caused a significantly higher percentage of time above pH 2.0 in the post-administration and nocturnal periods compared to placebo (p < 0.05), and above pH 3.0 in the post-administration, postprandial and nocturnal periods. No serious adverse effects, or disturbances in the VAS or in the vital signs were reported, and all medications were well tolerated. It is concluded that a single dose of ebrotidine 800 mg is as effective as cimetidine 800 mg in reducing total and nocturnal intragastric acidity. The study also confirms the excellent safety profile of the new drug.

Adult↗
PubMed1997

[Clinical pharmacology and indications of meropenem in severe pediatric infection].

The choice of an antibiotic for the treatment of a serious paediatric infection is generally a difficult problem. The arrival of Carbapenem resulted an important advance in the field of medicine due to its broad-spectrum, low incidence of resistances and good safety profile. Among Carbapenems, Meropenem introduction represents a progress because of its pharmacokinetics characteristics and blood-brain barrier penetration. Meropenem dosage depends on the patient weight, and the way of administration is potentially easier. Meropenem has been compared with the most used paediatric antimicrobial in controlled and randomised clinical trials, showing a high efficacy in the treatment of several infections (respiratory, urinary, intraabdominal, dermatological, septicemia) and in neutropenic and cystic fibrosis patients aged between one month and twelve years old. Meropenem is specially useful in the bacterial meningitis treatment because it penetrates into the cerebrospinal fluid of patients with inflamed meninges and reaches therapeutic concentrations, and because appearance of seizures is low. Adverse reactions produced by Meropenem show a poor incidence and its severity is usually mild. With regard to this characteristics, it can be concluded that Meropenem is an antimicrobial which efficacy and safety profiles guarantee its use in the treatment of severe paediatric infections.

Bacterial Infections↗
PubMed1995

Cimetidine does not alter sparfloxacin pharmacokinetics.

The interaction between cimetidine and sparfloxacin was studied in 10 healthy volunteers who received a single oral dose of 400 mg sparfloxacin on the third day of an 8 day cimetidine (400 mg t.i.d.) or placebo randomly assigned treatment. No statistically significant differences were observed in the pharmacokinetic parameters (Cmax-AUC-T1/2-urinary excretion and metabolic ratio) of sparfloxacin following the 2 treatment. Cimetidine does not affect absorption, metabolism or urinary excretion of sparfloxacin; consequently, patients exposed to this drug combination are not at risk.

Adult↗
PubMed1990

[Buspirone: a new non-benzodiazepine anxiolytic drug].

Buspirone is a new drug with ansiolitic properties which chemical structure and mechanism of action is different from the classical drugs traditionally used for this symptom. Its farmacokinetic characteristics make it a convenient drug to be used for oral administration. Buspirone's double-blind controlled clinical studies contrasted with benzodiazepines have shown that buspirone has an ansiolitic effect close to them but without sedation or relaxation. Other secondary effects appear with a smaller incidence with buspirone. These properties make buspirone very efficient in anxiety treatment.

Adult↗
PubMed1989

[Clinical experience with a new fluoroquinolone: ciprofloxacin].

Twenty one adult patients, both males and females, with 32 bacterial infections of several localizations and moderate to severe prognosis were treated with ciprofloxacin (200 mg every 12 hours), initially intravenously and then with 500 mg every 12 hours orally during 25 +/- 11 days. At the end of the evolution period it was found that 28 infections (87.5%) were cured in 24 of the 28 patients (85.7%), in three patients there was a definite clinical improvement and the treatment failed in the remaining patient. Adverse reactions were suspected in 2 patients, but their relation with the administration of ciprofloxacin was considered to be remote. In 3 patients mild leukopenia without clinical relevance was detected.

Adult↗
PubMed1986

201Tl myocardial imaging in a cardiac rejection episode.

Serial myocardial imaging using thallium Tl 201 was performed in the early follow-up of two patients with orthotopic cardiac transplantation. In one patient, non-homogeneous uptake, small defects and an irregular myocardial edge were observed during a moderately acute rejection crisis revealed by endomyocardial biopsy. The abnormal gammagraphic findings and histological changes were coincident and exhibited a parallel reversal. We emphasize the connection between these two events. The mechanisms which could explain these phenomena are discussed.

Acute Disease↗