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Biomedical subjects

L Perret

Publications and source records attributed to L Perret.

At least 19 recordsLinked to original sources
PubMed1998

Primary heterologous carcinosarcoma (metaplastic carcinoma) of the urinary bladder: a clinicopathologic, immunohistochemical, and ultrastructural analysis of eight cases and a review of the literature.

BACKGROUND: Heterologous carcinosarcomas of the urinary bladder are rare neoplasms, the histogenesis of which is still disputed. METHODS: The clinicopathologic, immunohistochemical, and ultrastructural features of eight cases were analyzed. RESULTS: The patients, 5 males and 3 females, had a median age of 70 years. Gross hematuria, dysuria, and urinary tract infections were the main presenting symptoms. Tumors were solitary in all cases and located in the right wall in six cases. Tumor size ranged from 2 to 12 cm (median, 5 cm). Four patients died of disease 2, 6, 17, and 42 months postoperatively, respectively. Microscopically, the tumors consisted mostly of a varied mixture of high grade transitional cell carcinoma with chondrosarcoma, osteosarcoma, rhabdomyosarcoma, and undifferentiated spindle cell (leiomyosarcoma-like) components with occasional transitional features between one component and another. All tumors but one invaded the muscularis propria or the perivesical fatty tissue. Immunohistochemically, keratin expression was observed focally in the sarcoma component as well as the carcinoma component. Reactivity for vimentin, desmin, muscle specific actin, and S-100 protein was observed in poorly differentiated areas in addition to the expected positivity of each histologic subtype of sarcoma. Ultrastructurally, one tumor showed evidence of both epithelial and chondrosarcomatous differentiation, whereas three contained rhabdomyosarcomatous elements. CONCLUSIONS: On the basis of the current series and a review of 55 reports from the literature, primary heterologous carcinosarcoma of the urinary bladder proved to be a highly malignant type of neoplasm occurring predominantly in elderly males that was most often in an advanced stage at presentation and rapidly became lethal. Histogenetically, some heterologous carcinosarcomas should be regarded as a variant of sarcomatoid carcinoma (metaplastic carcinoma) that shows prominent heterologous differentiation.

Aged↗
PubMed1996

[Anti-synthetase syndrome: a special subgroup of idiopathic inflammatory myopathies. Apropos of 3 case reports].

Anti-synthetase antibodies are found in 20 to 25% of all idiopathic inflammatory myopathies and allow identification of a syndrome associating myositis with interstitial pulmonary disease (50 to 70%), polyarthritis, Raynaud's phenomenon and mechanic's hands. Anti-Jo-1 is the most common anti-synthetase antibody. If anti-Jo-1 is present, interstitial lung disease must be looked for, because this is the most important determinant of the outcome. Treatment with high doses of corticosteroids is required. Immunosuppressive drugs are added in resistant cases or as corticosteroid-sparing agents.

Adult↗
PubMed1990

Pharmacokinetics of perindopril and its metabolites in healthy volunteers.

Perindopril, an angiotensin converting enzyme (ACE) inhibitor, is converted in vivo to its active diacid metabolite, perindoprilat and to a perindoprilat glucuronide. The pharmacokinetic parameters of perindopril, perindoprilat and perindoprilat glucuronide were evaluated after single administration to healthy volunteers (N = 12) of 8 mg of perindopril tert-butylamine salt by oral route (treatment A), by intravenous route (bolus in 5 min, treatment B) and of an equimolar dose of perindoprilat (6.1 mg) by intravenous route (infusion over 2 h, treatment C). The treatments were administered as a randomised 3-way cross-over design. Plasma samples were collected up to 96 h and urines up to 120 h. Perindopril is rapidly absorbed with an oral bioavailability of 95% and is mainly eliminated by metabolic processes. The formation of perindoprilat is slow and about 20% of the available parent drug is transformed into this metabolite. Elimination profile of perindoprilat is biphasic, with a rapid renal excretion of the free fraction and a long terminal half-life of the fraction bound to ACE. Perindoprilat glucuronide is mainly obtained from perindopril by a pre-systemic first pass metabolism.

Administration, Oral↗
PubMed1989

[Not Available].

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History of Medicine↗
PubMed1989

Experience with perindopril in normal volunteers.

The new orally active angiotensin converting enzyme (ACE) inhibitor perindopril was evaluated in normotensive men. Doses of 2 to 16 mg were given once a day for up to one week. Single oral doses of perindopril were found to blunt the pressor response to exogenous angiotensin I in a dose-dependent manner. The drug-induced ACE inhibition, as estimated by the measurement of plasma ACE activity, was maximal 4 to 8 hours post drug intake. ACE activity was still importantly reduced 24 hours after dosing. Plasma levels of angiotensin II and aldosterone decreased significantly whereas plasma renin activity and blood angiotensin I levels rose during peak ACE inhibition induced by the 4 and 8 mg doses. However, circulating levels of angiotensin II returned to baseline 24 hours after dosing, both on the first day of treatment and after one week of administration. ACE inhibition with perindopril did not affect blood pressure and heart rate in any consistent manner. There was no evidence for drug accumulation during repeated administration. The novel ACE inhibitor was well tolerated and produced no change in routine laboratory tests. The long-acting ACE inhibitor perindopril appears therefore to be effective when given orally in a dose range of 4 to 16 mg.

Angiotensin I↗
PubMed1989

Experience with perindopril in normal volunteers.

The new orally active angiotensin converting enzyme (ACE) inhibitor perindopril was evaluated in normotensive men. Doses of 2 to 16 mg were given once a day for up to one week. Single oral doses of perindopril were found to blunt the pressor response to exogenous angiotensin I in a dose-dependent manner. The drug-induced ACE inhibition, as estimated by the measurement of plasma ACE activity, was maximal 4 to 8 hours post drug intake. ACE activity was still markedly reduced 24 hours after dosing. Plasma levels of angiotensin II and aldosterone decreased significantly, whereas plasma renin activity and blood angiotensin I levels rose during peak ACE inhibition induced by the 4 and 8 mg doses. However, circulating levels of angiotensin II returned to baseline values 24 hours after dosing, both on the first day of treatment and after one week of administration. ACE inhibition with perindopril did not consistently affect blood pressure and heart rate. There was no evidence for drug accumulation during repeated administration. The novel ACE inhibitor was well tolerated and produced no change in routine laboratory tests. The long-acting ACE inhibitor perindopril therefore appears to be effective when given orally in a dose range of 4 to 16 mg.

Acetylcholinesterase↗
PubMed1988

Evaluation of the dose-effect relationship of a new ace inhibitor (perindopril) by an automatic blood pressure recorder.

Repeated blood pressure recordings by non-invasive devices are of better predictive value than single measurements in the evaluation of antihypertensive treatment. Such a method has been used to establish the dose-effect relationship of perindopril. After a two-week placebo run-in period, 40 patients with essential hypertension (age 56.6 +/- 1.5 years, 31 males, nine females) were treated with placebo or 2, 4 or 8 mg of perindopril once daily for one month following a randomized double-blind design. They were included if at least 75% of diastolic blood pressure recordings, made over an 8 h diurnal period using an automatic blood pressure recorder, were greater than 95 mmHg on placebo. Values (mean +/- SEM) before and after treatment were assessed using analysis of variance. These data showed a significantly greater reduction of blood pressure with 4 mg and 8 mg daily doses compared to placebo and the 2 mg daily dose. Such results were not obtained with blood pressure levels recorded by a mercury sphygmomanometer, confirming the value of an automatic blood pressure recorder as a tool in therapeutic trials.

Adult↗
PubMed1988

Peripheral haemodynamic effects of perindopril compared in patients with congestive heart failure and in normal volunteers.

The effects of perindopril, 4 mg orally, on brachial artery blood flow and diameter (pulsed Doppler) and on forearm vascular resistance were investigated and compared in six normal subjects and 10 congestive heart failure patients (New York Heart Association class III or IV). Pre-drug values of brachial artery blood flow and diameter were significantly lower in patients with congestive heart failure than in normal subjects, the reverse being true for forearm vascular resistance. In normal subjects perindopril increased brachial artery blood flow and decreased forearm vascular resistance, while in patients with congestive heart failure the same effects were observed but they were more pronounced and brachial artery diameter was increased. In patients with congestive heart failure, when perindopril effects were maximal, brachial artery blood flow remained below the baseline values of normal subjects but brachial artery diameter was normalized. Finally, there was a correlation between the drug-induced decrease in forearm vascular resistance and basal plasma noradrenaline values in all subjects taken together. These results indicate that: (1) the renin-angiotensin system plays a major role in vasoconstriction in patients with congestive heart failure; (2) this vasoconstriction affects both large arteries and arterioles; (3) perindopril is able to considerably improve peripheral haemodynamics in congestive heart failure; and (4) this improvement is linked to the initial sympathetic tone.

Adult↗
PubMed1988

Effects of perindopril on renal haemodynamics and natriuresis in essential hypertension.

Renal haemodynamics and natriuresis were studied before and 6 h after oral intake of perindopril (8 mg) in eight hypertensive patients without renal failure. The patients were then treated with perindopril (8 mg per day) and renal haemodynamics were measured on the fifth day, 6 h after the morning intake. Sodium intake was controlled during the study (100 mmol sodium per day). Renal blood flow and the glomerular filtration rate were measured by the clearance method using 131I-hippuran and 125I-iothalamate, respectively. Mean blood pressure decreased from 135 to 110 after 6 h, and was 118 mmHg on the fifth day (P less than 0.001, respectively). Renal vascular resistance decreased significantly after acute drug intake from 0.19 to 0.15 arbitrary units (P less than 0.001) and on the fifth day to 0.16 arbitrary units (P less than 0.001). Renal blood flow rose from 708 to 723 after 6 h, and to 750 ml/min per 1.73 m2 on the fifth day but the change was no significant. There was no alteration in the glomerular filtration rate so that the filtration fraction decreased from 0.27 to 0.26 (after 6 h), and to 0.25 on the fifth day (P less than 0.02). Natriuresis increased after the first intake between the first and tenth hours. On the fifth day, maximum natriuresis was observed between the fourth and sixth hours. Perindopril caused strong renal vasodilation after the first intake and during the following days, with no change in the glomerular filtration rate. There was a significant decrease in the filtration fraction, indicating efferent, as well as afferent, arteriolar vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Perindopril, a new angiotensin converting enzyme inhibitor--clinical pharmacological studies in healthy subjects.

Perindopril is a new angiotensin converting enzyme (ACE) inhibitor which is activated after hydrolysis in vivo to a diacid (S9780). Oral administration of perindopril (1-16 mg) to groups of 6 healthy males led to a long lasting and dose-elated inhibition of plasma ACE and rises in plasma renin activity with no evidence of accumulation of drug or effect. At higher doses there was a modest fall in blood pressure. S9780 given intravenously in doses of 1,2 or 4 mg caused an immediate inhibition of plasma ACE. The concentration of S9780 in plasma which led to 50% inhibition of plasma ACE was 1.55 +/- 1.14 ng/ml (mean +/- S.D.). Clinical trials with 2-8 mg once daily in essential hypertension are currently in progress.

Administration, Oral↗
PubMed1986

Single and repeated dosing of the converting enzyme inhibitor perindopril to normal subjects.

The new orally active angiotensin converting enzyme (ACE) inhibitor perindopril (S9490-3) was evaluated in 18 normotensive men. In three subjects the pressor response to exogenous angiotensin I was tested. A 8 mg oral dose reduced the pressor response by greater than 80%. Single oral perindopril doses of 2, 4, 8, and 16 mg were given to groups of five subjects each. Eight and 16 mg decreased plasma ACE activity within 4 hours to less than 10% of control; 72 hours later, plasma ACE activity was still reduced by at least 40%. Doses of 4 and 8 mg po once a day were then given for 8 days to two groups of six subjects. Four hours after the first and the last morning doses, plasma angiotensin II, aldosterone, and plasma ACE activity fell significantly, whereas blood angiotensin I and plasma renin activity rose. There was no evidence of drug accumulation. No significant change in blood pressure or heart rate was observed. Thus in normotensive subjects, perindopril seems an effective, orally active, long-lasting ACE inhibitor.

Acetylcholinesterase↗
PubMed1985

[Not Available].

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Education, Medical↗
PubMed1982

Control of breathing in children with interstitial lung disease.

Control of breathing at rest was studied in 14 children (4-16 years old) with interstitial lung disease (ILD). Four of them were tested several times. Breathing pattern and the mouth occlusion pressure (P0.1) were measured. Results in ILD children were compared to values in healthy children previously reported. Respiratory frequency and minute ventilation were increased (P less than 0.02). Inspiratory time (TI) was shortened (P less than 0.001), the shortening in TI being significantly related to the increase in lung elastance (EL). The ratio of TI to the total duration of the respiratory cycle (TI/TTOT) was lowered (P less than 0.01). Tidal volume (VT) both in ml and normalized for body weight (BW) was normal. P0.1 was higher than predicted. The increase in P0.1 was significantly related to change in arterial O2 pressure (PaO2) which was reduced in 10 cases. There was a significant relationship between the increase in P0.1 and in EL. The increase in mean inspiratory flow (VTBW/TI) was related to the increase in EL. But VTBW/TI was not increased as much as P0.1. Consequently the effective inspiratory impedance was enhanced. This high effective inspiratory impedance was related to the increased lung elastance.

Adolescent↗