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T Buclin

Publications and source records attributed to T Buclin.

At least 73 records · Page 4Linked to original sources
PubMed1997

Pharmacokinetic-pharmacodynamic profile of angiotensin II receptor antagonists.

The pharmacokinetic and pharmacodynamic properties of nonpeptide angiotensin antagonists in humans are reviewed in this paper. Representatives of this new therapeutic class share common features: lipophilia, intermediate bioavailability, high affinity for plasma proteins and liver metabolism; some have active metabolites. Angiotensin II antagonists block the blood pressure response to exogenous angiotensin II in healthy volunteers, decrease baseline blood pressure in both normal and hypertensive patients, produce a marked rise in plasma renin activity and endogenous angiotensin II and increase renal blood flow without altering glomerular filtration rate. These effects are dose-dependent, but their time course varies between the drugs owing to pharmacokinetic and pharmacodynamic differences. Additionally, the extent of blood pressure reduction is dependent on physiological factors such as sodium and water balance. The characterisation of their pharmacokinetic-pharmacodynamic relationships deserves further refinement for designing optimal therapeutic regimens and proposing dosage adaptations in specific conditions.

Angiotensin II↗
PubMed1995

Influence of perinatal, developmental and environmental factors on cognitive abilities of preterm children without major impairments at 5 years.

The relative role of perinatal factors (birthweight, gestational age, gender, asphyxia, mechanical ventilation and cerebral lesions), developmental factors (neuromotor development during the first 18 months of life) and environmental factors (socio-economic status and bilingualism) on cognitive abilities was evaluated in a cohort of preterm children who had been prospectively examined for haemorrhage (PVH) and periventricular leucomalacia (PVL) and followed-up to 5 years of age. Standardized neurological examinations and development assessment including tests of cognitive function were carried out. Major impairments could be ascribed to the presence of large PVL changes. Among the 226 children without major impairment, the overall incidence of neuropsychological anomalies (neuromotor, language, visual, auditory and behaviour anomalies) was 46.5% and did not differ within ultrasound groups (normal scans, PVH and small PVL). However, children with small changes of PVL presented more abnormal neuromotor development within the first 18 months of life and had more complex neuropsychological anomalies at 5 years. The multiple regression analysis (General Intellectual Index (GII) predicted = 113.7 - coefficient x social class - 8.5 x bilingualism - 5.5 x dystonia + 1.4 x gestational age + 8 x mechanical ventilation) showed that socioeconomic status was the most important factor affecting the General Intellectual Index (GII). The contribution of sex and cerebral lesions was not significant. As children grew-up, environmental factors seemed to overcome perinatal factors.

Asphyxia Neonatorum↗
PubMed1995

Whole-blood pharmacokinetics and metabolic effects of the topical carbonic anhydrase inhibitor dorzolamide.

Following a single-dose, open-label, pilot pharmacokinetic study in six subjects, the systemic pharmacokinetics and metabolic effects of dorzolamide after topical ocular administration were investigated in a double-blind, randomised, placebo-controlled study in 12 healthy volunteers. The subjects received a controlled diet on the 5 days before treatment initiation and throughout the study. For 14 days, a bilateral q.i.d. regimen of 3% dorzolamide, consisting of approximately 7.7 micrograms per day (21.3 mumol) dorzolamide hydrochloride, or placebo was given. Blood and urine electrolytes and acid-base profiles were measured 1 day prior to treatment and on days 1, 7 and 14 of treatment, and 24-h urine samples were collected daily. Topically applied dorzolamide was slowly taken up in erythrocytes and eliminated with a half life of approximately 120 days. Compared to the pre-study values, no significant treatment effect was observed in either the daily profiles or the 14-day cumulative sodium, potassium and citrate excretions. Two other volunteers given acetazolamide (125 mg q.i.d.) and assessed with the identical set of observations demonstrated marked metabolic changes. In spite of the prolonged and marked inhibition of carbonic anhydrase in red blood cells by dorzolamide, clinically significant metabolic and renal effects were not observed. The ocular tolerability profile was acceptable to all subjects.

Administration, Topical↗
PubMed1995

Inhibition of Na(+)-K(+)-ATPase by digoxin and its relation with energy expenditure and nutrient oxidation rate.

This study investigates the effects of digoxin, an inhibitor of the Na+ pump (Na(+)-K(+)-ATPase), on resting metabolic rate (RMR), respiratory quotient (RQ), and nutrient oxidation rate. Twelve healthy male subjects followed a double-blind protocol design and received either 1 mg/day digoxin or a placebo 2 days before indirect calorimetry measurements. Digoxin induced a 0.22 +/- 0.07 kJ/min or 3.8 +/- 1.5% (mean +/- SE, P = 0.01) decrease in RMR and a 0.40 +/- 0.13 kJ/min (P = 0.01) decrease in fat oxidation rate, whereas carbohydrate and protein oxidation rates did not change significantly. A dose-response relationship between serum digoxin and RQ was observed. These results suggest that digoxin reduces not only RMR but also fat oxidation rate by mechanisms that remain to be elucidated. Because a linkage and an association between genes coding the Na(+)-K(+)-ATPase and the RQ have been previously observed, the present demonstration of an effect of Na(+)-K(+)-ATPase inhibition on fat oxidation rate strengthens the concept that the activity of this enzyme may play a role in body weight regulation.

Adult↗
PubMed1995

Radiolabeled chimeric anti-CEA monoclonal antibody compared with the original mouse monoclonal antibody for surgically treated colorectal carcinoma.

UNLABELLED: Biodistribution and tumor uptake of a chimeric human-mouse monoclonal antibody (MAb) and the original mouse MAb have been comparatively studied. METHODS: Eighteen patients with suspected colorectal cancer scheduled for surgery underwent immunoscintigraphy with 123I-labeled chimeric anti-CEA MAb. Iodine-125 and 131I trace-labeled chimeric and original mouse MAb were simultaneously injected for biodistribution studies. RESULTS: Similar serum kinetics and a low immunogenicity were observed for both antibodies. Mean binding capacity to CEA measured in PBS after radiolabeling was identical for both MAbs and it was slightly decreased when measured in serum 1-4 hr after injection. Radiochromatograms of patients sera showed immune complex formation related to the amount of circulating CEA. Postoperative ex vivo radioactivity counting in tissue samples revealed similar antibody distributions with notably similar antibody uptakes in tumors. High tumor uptakes (between 0.02 to 0.06% injected dose per g) were observed in 3 of 13 patients operated for primary or metastatic colorectal cancer. CONCLUSION: In this dual-label technique, the radioiodinated anti-CEA IgG4 chimeric MAb and the original mouse IgG1 MAb were shown to have very similar behavior in colorectal cancer patients.

Adult↗
PubMed1994

Fractional excretion of trace lithium and uric acid in acute renal failure.

The early distinction between prerenal azotemia, characterized by an avid proximal tubular sodium reabsorption, and ATN, in which proximal tubule function is depressed, remains an important but difficult clinical task. Indices of acute renal failure based on urinary sodium excretion may be helpful but have several limitations, among which is the use of diuretics. The effectiveness of the fractional excretion of uric acid (FEUA) and that of endogenous lithium (FELi) in the diagnosis of acute renal failure has been evaluated in an unselected group of 46 patients, 28 with prerenal azotemia and 18 with ATN. In the entire group, FELi concurred with the clinical diagnosis in 78% of the patients, whereas the fractional excretion of sodium (FENa) and FEUA were in agreement in only 63 and 50%, respectively. FELi was more sensitive to identify hemodynamic renal failure, because 93% of prerenal failure patients had a low FELi, contrasting with a low FEUA in only 68% and a low FENa in 75%. The major reason for the discrepancy between FENa and FELi was the administration of diuretics. In both acute renal failure groups, FENa was higher in the subgroups receiving diuretics. In contrast, diuretic therapy had no effect on FELi in either group. These results suggest that FELi is more accurate than either FENa or FEUA for distinguishing prerenal azotemia from ATN. The superiority of FELi appears especially relevant in patients treated with the usual diuretics.

Acute Kidney Injury↗
PubMed1993

Renal effects of nimesulide in furosemide-treated subjects.

In clinical settings where effective plasma volume is decreased, nonsteroidal anti-inflammatory drugs (NSAIDs) may induce acute renal failure. We have evaluated the effects of single and repeated doses of nimesulide on renal haemodynamics and electrolyte excretion in 8 healthy volunteers during a prolonged course of furosemide (frusemide). Under these study conditions, renal prostaglandin synthesis is expected to be elevated, with renal function being dependent upon increased levels of prostaglandins. Nimesulide induced an acute but transient decrease in indices of renal haemodynamics. Furosemide-induced increases in plasma renin activity and aldosterone levels were blunted, and urinary excretion of prostaglandin E2 was markedly reduced by nimesulide. The magnitude and time course of the natriuretic, kaliuretic and diuretic effects of furosemide were attenuated by nimesulide. Although the transient nature of the observed renal haemodynamic changes suggests that the risk of developing acute renal failure is small, the rise should be taken into account in patients with renal dysfunction. Sodium and potassium retention, and the blunting of the diuretic-induced electrolyte excretion, could be of clinical relevance. Nimesulide appears, therefore, to share the prostaglandin-dependent renal effects of other NSAIDs.

Adult↗
PubMed1992

[Acquired factor V inhibitor treated with intravenous immunoglobulins].

We report the appearance of a factor V inhibitor in an 82-year-old female patient following abdominal surgery. This anomaly was totally corrected following 9-day treatment with i.v. immunoglobulins (0.4 g/kg/day), which allowed a needed further surgical intervention to be performed without hemorrhagic diathesis. The activity of this inhibitor was partly reversed by the in vitro addition of immunoglobulins, suggesting a concentration-effect relationship. This finding supports the hypothesis that anti-idiotypic antibodies could play a role in the therapeutic effect of immunoglobulins in such situations.

Aged↗
PubMed1992

The effect of a low dose of quinidine on the disposition of flecainide in healthy volunteers.

We have studied the effects of quinidine on ECG intervals and on the pharmacokinetics of flecainide and its two metabolites in 6 healthy men in an open randomized crossover study. Flecainide acetate (150 mg) was given as a constant rate i.v. infusion over 30 min. Quinidine (50 mg orally), given the previous evening, did not change the volume of distribution of flecainide (7.9 vs 7.4 l.kg-1), but significantly increased its half-life (8.8 vs 10.7 h). This was attributable to a reduction in total clearance (10.6 vs 8.1 ml.min-1 x kg-1), most of it being accounted for by a reduction in non-renal clearance (7.2 vs 5.2 ml.min-1 x kg-1). The excretion of the metabolites of flecainide over 48 h was significantly reduced. These findings suggest that quinidine inhibits the first step of flecainide metabolism, although it may also reduce its renal clearance, but to a lesser extent (3.5 vs 2.9 ml.min-1 x kg-1). The effects of flecainide on ECG intervals were not altered by quinidine. Thus, quinidine tends to shift extensive metabolizer status for flecainide towards poor metabolizer status and may also alter its renal excretion.

Adult↗
PubMed1992

Influence of quinidine on the pharmacokinetics of trimipramine and on its effect on the waking EEG of healthy volunteers. A pilot study on two subjects.

The pharmacokinetics and pharmacodynamics (waking EEG) of 75 mg trimipramine taken orally were determined in two healthy volunteers on two separate occasions, once without and once after comedication with 2 x 50 mg quinidine. Quinidine, a potent cytochrome P-450IID6 inhibitor, is used as a pharmacological tool to mimic a lack of this enzyme in man. In this study, it markedly altered the pharmacokinetics of trimipramine, almost doubling its plasma half-life and decreasing its apparent clearance and volume of distribution. These results strongly suggest that trimipramine is a substrate of cytochrome P-450IID6. These modifications of trimipramine metabolism were accompanied by measurable changes in some EEG variables, most notably with regard to the relative power in the alpha and theta bands, which showed higher and longer-lasting effects of trimipramine. Since cytochrome P-450IID6 is deficient in 5-10% of Caucasian subjects, this may have consequences in trimipramine-treated subjects, especially with regard to the effects of the drug on the EEG.

Administration, Oral↗
PubMed1992

[Prognosis in brain stem infarction].

UNLABELLED: A retrospective study of patients who suffered cerebrovascular accidents (CVA particularly brainstem damage) was conducted to look for risk factors which, present on admission, indicated the chance of survival. The evolution of 100 patients, hospitalized in the Neurology Department, University Hospital Lausanne, after having had their first CVA was studied. The risk factors chosen were age, sex, hypertension, smoker, late onset diabetes, hypercholesterolemia as well as the conscious state, the location of the lesion and whether it was bi- or unilateral. Analysis of the data was performed by means of a stepwise multiple logistic regression program. The results demonstrated that diabetes or bilateral lesions, regardless of their position in the brainstem, or the combination of these two factors, indicated an unfavorable outcome, associated with a short term mortality rate greater than 30%. In their absence and despite the presence of the other risk factors, it was less than 2%. At one month the mortality rate was shown to be very high. At two month it was non insignificant and thereafter it became similar to that of the Swiss population. Brainstem lesions extending to the vital centres or respiratory complications related to the state of dependence were the most common causes of short term deaths. At long term the aetiology of death was the same as for the population as a whole. CONCLUSION: The results obtained show the importance of the prevention and treatment of patients at risk of CVA, particularly diabetes. To avoid the fatal complications, that arise from severe handicap in bedridden patients, the management must be rapid and efficient (physiotherapy and drugs).

Adult↗
PubMed1991

Absence of metabolic effects of the topical carbonic anhydrase inhibitors MK-927 and sezolamide during two-week ocular administration to normal subjects.

Potential systemic effects of the racemic carbonic anhydrase inhibitor MK-927 and its S-enantiomer, sezolamide hydrochloride, after topical ocular administration were investigated in a double-masked, randomized, placebo-controlled study in 16 healthy volunteers. A controlled diet was started 4 days before initiation of treatment and continued throughout the study. For 14 days six volunteers received bilaterally one drop of 2% MK-927 (1.2 mg) q.i.d., six received one drop of 1.8% sezolamide (1.1 mg) q.i.d., and four received the common vehicle q.i.d. Blood and urine electrolytes and acid-base profiles were measured before and on days 1, 7, and 14 of treatment, and 24-hour urine samples were collected daily. All values were compared with those on the pretreatment day. Taking the circadian variations of the parameters into account, no significant treatment effect was observed in either the daily profiles or the 14-day cumulative sodium, potassium, and citrate excretions. Because the usual variability of the measured biologic parameters has been reduced markedly by the stringent requirements of this study, it can be concluded that the induction of clinically significant metabolic changes by topically administered MK-927 or sezolamide is unlikely.

Administration, Topical↗
PubMed1990

Right arm involvement and pain extension can help to differentiate coronary diseases from chest pain of other origin: a prospective emergency ward study of 278 consecutive patients admitted for chest pain.

In a prospective study of 278 consecutive patients admitted to an emergency ward for chest pain, the 115 clinical and paraclinical parameters available at the time of admission were evaluated by computer comparison with the final diagnoses. The most valuable items for making the diagnosis were classified according to their sensitivity, specificity and predictive value. Among the 278 patients, 100 individuals had myocardial infarctions (MI), 47 had unstable angina, 25 had stable angina and 106 patients had a non-coronary disease. The twelve most sensitive items for distinguishing MI from other conditions were the following: sudden onset of pain (70%); duration of more than 60 min (88%); constriction and squeezing (79%); oppression (75%); prior anginal attacks (61%); sex male (72%); age over 60 years (74%); abnormal heart auscultation (62%); abnormal electrocardiogram (ECG) (98%); segment (ST) disturbances (86%); increased glucose level (77%); CKMB fraction greater than 6% of total creatine kinase (CK) level (63%). Among the twelve most specific items, also with the best positive predictive value, irradiation in the right arm is of most importance; among the 51 patients with right arm involvement, 48 suffered from a coronary disease and 41 from a myocardial infarction. The largest extension of pain was reported in the latter group. It is concluded that chest pain with a wide irradiation involving the right arm strongly suggests that a myocardial infarction is ongoing.

Arm↗
PubMed1988

[Diagnosis, clinical presentation and triage criteria of emergency patients admitted for chest pain: prospective study of 278 cases].

A prospective study of the clinical findings and transfer decision in 278 patients admitted to the emergency ward for chest pain showed that a combination of 115 clinical and ECG data makes it possible to predict 86% of acute myocardial infarctions and unstable angina (specificity 76%). However, the diagnosis of the emergency medical team was adequate in 91% of cases, yielding a 5% rate of unjustified admissions to the intensive care unit. Therefore, the utility of a decision algorithm based upon clinical and ECG data, as proposed by American authors, is questionable. Finally, the indication for transfer to the intensive care unit was not followed in a quarter of patients due to old age and/or associated diseases.

Acute Disease↗
PubMed1988

[Dose-response curve and preliminary clinical study of a laxative, lactilol].

15 women complaining of chronic constipation were included in a prospective open trial to determine the laxative action and minimal effective dose of lactitol. Through the administration of increasing doses, an ED50 of 0.25 g/kg/day, was established. During a 15-day treatment period at the minimal effective dose, all patients had reduced symptoms of constipation as compared with a previous 15-day control period. Side effects of minor intensity were frequently recorded (flatulence, rumblings, wind, and, less frequently, abdominal cramps or nausea). Thus, the use of lactitol for symptomatic treatment of constipation deserves further clinical studies to determine better its indications and benefit.

Adult↗
PubMed1987

The effect of rectal and nasal administration of salmon calcitonin in normal subjects.

In order to ascertain the blood levels and the biologic responses obtained after administration of two noninjectable forms of salmon calcitonin (SCT) (i.e., a nasal spray and a suppository), two doses of 200 IU each were administered at 3 hour intervals nasally to 8 normal subjects, and rectally to 9 normal subjects. Five untreated subjects served as controls. All were given a standardized diet for 2 days before the test. Plasma salmon-calcitonin, ionized calcium, phosphate, sodium, proteins, creatinine, and alkaline phosphatase were measured repeatedly after the administration of the drug. Modifications in fractionated urinary calcium, phosphate, sodium, and creatinine excretions (and hydroxyproline for the 8 subjects treated by the nasal spray) were compared with the values measured on the previous day. Plasma concentrations of SCT were found to increase sharply with both routes of administration, the peaks being high and short after rectal administration, low but more sustained after nasal application. Despite these differences, almost similar biologic effects could be demonstrated: transient hypocalcemia, increased calciuria, phosphaturia, and natriuria. Urinary hydroxyproline excretion decreased. Plasma sodium did not increase, whereas it did in the controls. In conclusion, nasal sprays and suppositories of SCT appear to exert the known biologic effects of SCT, and might be favored for long-term treatment in diseases representing indications for calcitonin therapy.

Administration, Intranasal↗