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Biomedical subjects

M I Lucena

Publications and source records attributed to M I Lucena.

At least 55 records · Page 3Linked to original sources

Endogenous digoxin-like substance in liver failure.

Digoxin-like immunoreactive substance (DLIS) has been detected in several patient populations that were not receiving digoxin. We therefore studied the sensitivity of EMIT Convenience Pack Digoxin immunoassay to interference by DLIS in patients with liver failure. Serum digoxin was measured in cirrhotic patients with moderate to severe liver failure (Child-Pugh B or C grade), patients with mild liver disease (chronic hepatitis) and matched control patients without liver disease. Excluded were patients taking or who had ever received any cardiac glycoside in the past. Blood samples were obtained by venipuncture and assayed in duplicate. Twenty-two out of 30 cirrhotic patients (73%) showed false-positive results, vs. one of 6 patients (16.7%) with mild liver disease, and 1 of 10 (10%) controls. The serum DLIS level was negatively correlated with prothrombin activity (r = -0.55, p < 0.00011). Digoxin levels must be interpreted carefully in patients with moderate to severe liver failure.

Chronic Disease↗

Short-term effect of various doses of cyclosporin A on plasma lipoproteins and its distribution in blood: an experimental study.

Hyperlipidaemia commonly develops in both transplant recipients and experimental animals receiving cyclosporin A (CsA). However, the threshold of CsA induced-changes on lipoproteins and the role of parenteral vehicle (cremophor) has not been defined. Male Wistar rats were classified into five groups of six animals each and received CsA in cremophor vehicle at doses of 5, 10 or 20 mg kg-1 d-1, s.c., vehicle alone or saline for 7 d. Blood was obtained 24 h after the last dose and plasma was analysed. Plasma very low density lipoprotein (VLDL), low density lipoprotein (LDL), and high density lipoprotein subfractions (HDL-2, HDL-3) were isolated by sequential ultracentrifugation and their content of cholesterol, triglyceride and phospholipid was determined. Whole blood and trough plasma CsA levels were measured by monoclonal radioimmunoassay. Plasma lipids did not differ significantly among the five groups. At a dose of 20 mg kg-1 d-1 of CsA VLDL cholesterol rose significantly (P < 0.05). Administration of either CsA or cremophor vehicle increased HDL-2 phospholipids (P < 0.05) and decreased HDL-3 cholesterol. There was not a linear relationship between whole blood and plasma CsA levels and increasing CsA doses. Short-term treatment with low doses of CsA have little influence on lipid profile in the rat. Changes on lipoprotein composition can be attributed mainly to cremophor vehicle, conceivably due to its ethanol content.

Animals↗

[Evaluation of the incidence of nephrotoxicity associated with the use of aminoglycosides in patients with extrahepatic biliary obstruction].

In the present publication we discuss nephrotoxicity (NT) incidence by reviewing all the clinical histories of one year (May 1989-May 1990) with diagnosis of obstructive jaundice or cholangitis. Of a total of 90 patients. 53 were treated with aminoglycosides and 37 received other antibiotics. Nephrotoxicity developed in nine patients of the group that received aminoglycosides (17%), versus only three patients (8%) in the other group. Both groups were comparable regarding sex, age and liver and renal basal functions. Analysis of the variables that could be associated with a higher incidence in the nephrotoxicity group that received aminoglycosides showed that there were no differences regarding age, sex, dosage, duration of treatment, plasmatic levels of aminoglycosides and liver and renal basal functions. Only simultaneous administration o furosemide was significantly associated with the development of nephrotoxicity. Results of this study underline the need of a prospective follow-up of patients with biliary obstruction during treatment with aminoglycosides. Meanwhile the evidence available allows us to recommend the monitoring of renal function in this type of patients.

Aged↗

[Knowledge and attitudes of ambulatory patients regarding various aspects of pharmacologic treatment].

Recognizing the patients believes and attitudes towards their disease and treatment as well as facilitating basic information are essential for a satisfactory compliance. In this respect, and in order to know the state of things, personal interviews were carried out following a pre-established protocol and evaluating the degree of acceptance of information oriented to the outpatient. Two hundred and seven questionnaires were collected. Populations mean age was 50 years, 60% were women and there was a high percentage of illiterate patients or with only primary school level (69.8%), with a medium-low social status (98%). In general, they were aware of the indication of treatment (80%) although 56% of patients did not know the consequences of a poor control of their disease. Seventy eight percent wished to receive more information and 147 (96%) patients preferred the physician as the provider of it. The opinion regarding the information leaflets oriented towards the outpatient was unanimously favorable being the most interesting aspects those regarding the instructions on the use of drugs and adverse effects. The educational level was the factor influencing most significantly the patient's attitude. We conclude saying that in order to carry out a pharmacological treatment educational program it is necessary to evaluate the knowledge, needs and attitudes of the population towards whom it is directed.

Ambulatory Care↗

Enhanced gentamicin nephrotoxicity after experimental biliary obstruction in rats.

To explore whether bile duct ligation increased the risk for gentamicin nephrotoxicity, male Wistar rats were subjected to bile duct ligation or sham surgery and given either gentamicin 20 mg/kg or saline twice daily intraperitoneally for 8 days. Bile duct ligated and gentamicin injected rats elicited a decline in renal function and tubular cell necrosis after 8 days of treatment whereas equal dosage regimen in sham operated rats exhibited no evidence of renal dysfunction. In addition, though serum and kidney gentamicin levels were higher in bile duct ligated rats (1.84 +/- 0.11 micrograms/ml versus 0.20 +/- 0.03 microgram/ml, and 1453 +/- 164 micrograms/g versus 698 +/- 138 micrograms/g of cortex, respectively, P less than 0.05). The data indicate that complete biliary obstruction enhances renal sensitivity to gentamicin.

Animals↗

Bronchodilator effect and serum theophylline level after combined treatment with fenoterol and theophylline in reversible chronic airflow obstruction.

Sustained-release theophylline 10.1 mg/kg b.d. was given with placebo of fenoterol 2.5 mg t.d.s. to 12 patients with chronic airway obstruction. Fenoterol did not significantly affect the steady state serum theophylline trough level (11.84 micrograms/ml for fenoterol vs 11.10 micrograms/ml for placebo). Addition of fenoterol produced no further increase in spirometric function nor in clinical status.

Adult↗

Haemodynamic and endocrine effects of digitoxin in healthy volunteers.

A study was conducted to evaluate the effects of a single oral dose of digitoxin on the circulatory function and the renin-angiotensin-aldosterone system. Seven doses of digitoxin and 6 of a placebo were given at random to 13 healthy volunteers, all of whom remained at rest, without smoking, throughout the study. Blood samples were taken initially after 1 h at rest, and at 1, 2 and 24 h after receiving the dose. Concentrations of serum digitoxin, aldosterone, angiotensin II (A II) as well as plasma renin activity (PRA) were determined by radioimmunoassay (RIA). In all subjects the blood pressure did not change throughout the study. Digitoxin decreased the heart rate significantly during the first and second hours, while in the placebo group the heart rate remained unchanged during the same period. The placebo had no detectable effect on PRA, A II and aldosterone. Digitoxin decreased PRA and A II levels, reaching its maximum effect 2 h after the administration. There was no correlation between the serum digitoxin concentration and PRA, A II or the aldosterone values. Digitoxin reached its maximum effect upon these parameters faster than what is generally accepted.

Adult↗

Digitoxin elimination in healthy subjects taking ampicillin.

The present study was carried out to evaluate the changes in digitoxin kinetics during ampicillin administration. Subjects were informed of the nature of the study and the treatment was applied to those who gave their written consent. Six healthy volunteers received a single oral dose of 1.0 mg of digitoxin. Three days later, they were given orally ampicillin trihydrate, 500 mg four times daily, for five consecutive days. Blood samples were taken at 24, 36, 48, 60, 72, 96, 120, 144, 168 and 192 hours after digitoxin. Compliance with ampicillin regimen was verified by fluorimetric measurement of serum ampicillin. Concentrations of serum digitoxin were determined by radioimmunoassay. The mean digitoxin elimination half-life changed from 162.8 +/- 12.9 h before to 181.3 +/- 10.1 h (mean +/- s.e. mean) after ampicillin. These differences were not significant. No consistent evidence of a kinetic interaction between digitoxin and the broad-spectrum antibiotic ampicillin was found.

Adult↗

Serum protein binding of tolbutamide in patients treated with antiepileptic drugs.

The possible development of a displacement interaction involving tolbutamide, in epileptic patients, has been explored by studying the serum protein binding of this drug in vitro in 199 samples of sera from patients treated with antiepileptic agents included in a programme of therapeutic drug monitoring. 82 of the samples were from patients receiving a single drug, 86 from patients treated with 2 drugs, and 31 from patients treated with 3 drugs. The free fraction of tolbutamide was higher in serum from patients treated with antiepileptic drugs than in serum from untreated 'normal' volunteers. The increase was more marked the greater the number of antiepileptic drugs administered. Valproate appeared to be the most powerful displacing agent.

Adolescent↗

[Acute hepatitis due to ticlopidine. A report of 12 cases and review of the literature].

OBJECTIVE: To analyze the characteristics of hepatotoxicity due to ticlopidine. PATIENTS AND METHODS: We describe all the case of hepatotoxicity attributed to ticlopidine and reported to the Register of drug associated hepatopathies. We also obtained data from MEDLINE and the Spanish Medical Index regarding cases reported during the period 1982 2001. RESULTS: We reported twelve cases of hepatopathy related to the use of ticlopidine. These made up 5% of all the cases notified to the Register. Eighty three percent of the patients were male, and of an average age of 68 years. Sixty six percent required hospital admission. The latent period varied between 2 and 13 weeks. The liver lesion was of cholestatic type in 75% of the cases, hepatocellular in 16.6% and mixed in 8.3%. Twenty five percent of the patients had received sub therapeutic doses. CONCLUSIONS: Ticlopidine is often related to hepatotoxicity. This seems to be due to an idiosyncratic mechanism and is mainly cholestatic. The use of lower dosage than that recommended means that the desired therapeutic effect is not attained but does not protect against the development of hepatotoxicity. Doctors who use this drug should be aware of this so as to establish the true risk benefit relation.

Aged↗