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Biomedical subjects

M Bertrand

Publications and source records attributed to M Bertrand.

At least 127 records · Page 7Linked to original sources
PubMed1990

Prospective randomized comparison of fluorouracil versus fluorouracil and high-dose continuous infusion leucovorin calcium for the treatment of advanced measurable colorectal cancer in patients previously unexposed to chemotherapy.

Seventy-nine patients with advanced, measurable, metastatic colorectal cancer previously unexposed to chemotherapy were randomly assigned to treatment with either fluorouracil (FUra) administered intravenously at a dose of 370 mg/m2/d for 5 days or the combination of FUra in the same dose and schedule with high-dose continuous infusion leucovorin calcium (500 mg/m2/d) beginning 24 hours before the first dose of FUra and continuing for 12 hours after the completion of FUra therapy. Patients whose disease progressed on treatment with FUra alone were, if eligible, crossed over to receive leucovorin and FUra. Three patients on the FUra plus leucovorin arm of the study were excluded from the analysis because they did not meet eligibility requirements. The treatment arms were well balanced for prognostic criteria including performance status, age, prior radiotherapy, distribution of metastatic sites, and on-study carcinoembryonic antigen (CEA), lactic dehydrogenase, and serum albumin. FUra plus leucovorin was superior to FUra alone for response (P = .0019) and for time to progression or death (log-rank, P = .045). Response rates were 16 of 36 (44%) versus five of 40 (13%), and median time to progression or death was 164 versus 120 days in the two arms of the trial, respectively. Overall survival, however, while longer in the FUra and leucovorin arm was not significantly so. An analysis of the toxicities experienced by the patients in the two treatment groups showed that, except for significantly more stomatitis in the leucovorin arm of the study, the side effects experienced by patients treated with either regimen were comparable. These results suggest that the efficacy of FUra in patients with advanced, measurable, metastatic colorectal cancer can be enhanced significantly by administration of a continuous high-dose infusion of leucovorin calcium.

Adenocarcinoma↗
PubMed1990

Interspecies comparison of the metabolic pathways of perindopril, a new angiotensin-converting enzyme (ACE) inhibitor.

1. The metabolism of perindopril (non-thiol angiotensin-converting enzyme inhibitor) was studied in rat, dog and monkey after single oral and i.v. administration of 14C-perindopril, and in man after a single oral dose. 2. Six biotransformation products of perindopril from urine, faecal and plasma samples (bile only for rats) were identified. 3. The main route of biotransformation in all species is the hydrolysis of the carboxylic ethyl ester side-chain, with the formation of perindoprilate, the active metabolite. 4. A minor route of biotransformation led to the acyl glucuronides of perindopril and perindoprilate. 5. Internal dehydration of perindopril and perindoprilate into cyclic lactam structures occurs. This route of metabolism is of minor importance except in humans.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

[Baroreflex activity in carotid endarterectomy during general anesthesia].

The baroreceptor reflex was studied in eleven patients, aged 69 +/- 6 years, scheduled for carotid endarterectomy under general anaesthesia. Nine were hypertensive. The anaesthetic protocol was the same for all the patients: premedication with morphine and scopolamine, induction with 5 mg.kg-1 thiopentone, 6 micrograms.kg-1 fentanyl and 0.01 mg.kg-1 pancuronium bromide. All the patients were intubated and ventilated with a mixture of nitrous oxide and oxygen. Fentanyl, 100 micrograms, was routinely given at the time of incision. Baroreflex sensitivity was tested using Smyth's method, with a bolus of 75 micrograms trinitrin and plotting changes in heart rate against those in systolic blood pressure. Electrocardiogram, invasive arterial blood pressure and airway pressure were simultaneously recorded. PaCO2 and PaO2 were measured during arterial clamping. The tests were carried out before clamping, 2 min later and 10 to 20 min after the last injection of fentanyl. In the seven patients for whom clamping lasted more than 15 min, a further test was carried out after administration of 0.4 +/- 0.05 vol% halothane (Datex analyser) for 5 min. During anaesthesia, baroreflex sensitivity was low (1.8 +/- 0.3 ms.mmHg-1). After clamping, there was only a significant change in Pasys, with no changes in heart rate or blood gas values (129 +/- 8 mmHg before clamping; 167 +/- 12 mmHg after clamping; n = 8; p less than 0.01). After halothane administration, the sensitivity slope decreased, but not significantly. Moreover, halothane decreased the R-R intervals (1140 +/- 84 after clamping; 963 +/- 76 under halothane; n = 6; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

Perioperative cardiac complications of surgical repair of infrarenal aortic aneurysms.

From 1985 to 1987, 261 patients (241 male, 20 female; mean age 66.5 years, range 38-90 years) were hospitalized for elective repair of infrarenal aortic aneurysms. One-hundred forty seven patients (56%) had coronary artery disease, attested to by past history of myocardial infarction or angina pectoris, electrocardiographic signs at rest, or abnormalities of dipyridamole thallium scintigraphy (performed in 72 patients). Ten patients had coronary arteriography and one patient then underwent aortocoronary bypass. Only two patients were not offered operation. All patients operated on had perioperative monitoring using Swan-Ganz catheters. Forty-five patients (17.5%) had a total of 62 postoperative events related to coronary artery disease. These included 40 cases of myocardial ischemia (15%), 16 cases of left heart failure (6%), and six myocardial infarctions (2%). There were nine (3.4%) postoperative deaths, four of which were due to cardiac causes (1.5%). In spite of the frequency of preexisting coronary artery disease and of intra- or postoperative myocardial ischemia, surgical repair of abdominal aortic aneurysm was not responsible for increased perioperative cardiac morbidity or mortality. In this population of aged patients, abdominal aortic aneurysm repair does not necessitate extending the indications for preoperative coronary arteriography or aortocoronary bypass.

Adult↗
PubMed1989

Apolipoprotein B immunochemical heterogeneity in dialysed patients with chronic renal failure and patients with coronary artery stenosis.

Serum cholesterol, triglyceride, apolipoprotein B (apo B) and the cholesterol and phospholipid content of apo-B-containing particles was determined in 41 male patients on dialysis for chronic renal failure, in 41 male patients with coronary artery disease selected on the basis of a total cholesterol level below 6.72 mmol/l and in 41 male control subjects of similar age. Apo B was assessed as total B protein determined using polyclonal antibodies and also by measuring the expression of epitopes recognized by three different monoclonal antibodies (BL3, BL5 and BL7). Triglyceride was increased (p less than 0.01) and cholesterol was decreased (p less than 0.01) in the dialysed patients with chronic renal failure. Total apo B was similar in the three tested groups while the expression of the BL7 epitope was increased in the group of dialysed patients with chronic renal failure (p less than 0.001). The expression of BL3 and BL5 epitopes was increased in patients with coronary artery disease (BL3: p less than 0.05; BL5: p less than 0.02) but not in dialysed patients with chronic renal failure. These results suggest an abnormal composition and an immunological heterogeneity of apo-B-containing lipoprotein particles in patients with coronary artery stenosis and in dialysed patients with chronic renal failure.

Antibodies, Monoclonal↗
PubMed1989

Refractory metastatic breast cancer: salvage therapy with fluorouracil and high-dose continuous infusion leucovorin calcium.

Sixty women with metastatic breast cancer refractory to at least one chemotherapeutic regimen were treated with fluorouracil (FUra) and high-dose continuous infusion folinic acid (leucovorin calcium). One complete remission lasting 8.7 months and nine partial remissions ranging in duration from 1.3 to 12.8 months were observed, for an objective response rate of 17% (95% confidence interval for response, 8% to 27%). Nine of the ten responding patients had metastatic disease that had objectively progressed on previous chemotherapy with a FUra-containing regimen. This program was well tolerated, with toxicities consisting mainly of stomatitis and granulocytopenia. These results suggest that augmentation of the reduced folate levels of metastatic breast carcinomas may enhance the effectiveness of the fluoropyrimidines in this disease.

Adenocarcinoma↗
PubMed1989

Protective effect of a purified flavonoid fraction against reactive oxygen radicals. In vivo and in vitro study.

S 5682 is a purified flavonoid fraction containing 90% diosmin (flavone derivative) and 10% hesperidin (flavanone derivative). In this study the scavenging properties of S 5682 on active oxygen radicals were demonstrated in vivo and in vitro. The activity of intravenous S 5682 was evaluated in the rat by measuring the degree of hyperglycemia provoked by an intravenous injection of alloxan, the metabolism of which produces active oxygen radicals which are toxic to B cells of the pancreas. S 5682 produced a decrease in the hyperglycemia in a dose-dependent manner (25 mg/kg and 50 mg/kg). The production in vitro of active oxygen radicals during phagocytosis by polymorphonuclear cells and macrophages is accompanied by emission of photons which can be amplified in the presence of luminol. Measurement of this chemiluminescence is a way of determining the quantity of active oxygen radicals generated in the medium, this may be reduced either by a decrease in production or by an increase in neutralisation through a reducing effect. Results demonstrated that S 5682 had a scavenging effect on active oxygen radicals for concentrations between 2 x 10(-8) mol/l and 2 x 10(-4) mol/l. The concentration of S 5682 reducing the chemiluminescence by 50% was 1.6 x 10(-5) mol/l. These scavenging properties imply that S 5682 has a pharmacological action on capillary hyperpermeability as well as an anti-inflammatory and anti-oedematous action.

Animals↗
PubMed1988

Improvement of diaphragmatic function by a thoracic extradural block after upper abdominal surgery.

The effects on diaphragmatic function of a thoracic epidural block were assessed in 13 patients after upper abdominal surgery (UAS). Lung volumes and tidal changes in chest wall circumferences and gastric (delta Pgas) and esophageal (delta Pes) pressures were measured pre- and postoperatively. Volume displacement of the abdomen divided by tidal volume (delta VAB/VT) and delta Pgas/delta Pes were taken as indices of the diaphragmatic contribution to tidal breathing. These respiratory variables were obtained in the postoperative period, before and after epidural injection of 0.5% plain bupivacaine to achieve a block up to the T4 segment. UAS was constantly associated with a decrease in VT, delta VAB/VT, delta Pgas/delta Pes, and forced vital capacity (FVC). Epidural block was associated with an increase in VT, delta VAB/VT, and FVC. delta Pgas and delta Pgas/delta Pes returned to their preoperative values. It is concluded that: 1) diaphragmatic dysfunction observed after UAS is partially reversed by thoracic epidural block; and 2) that inhibitory reflexes of phrenic activity arising from the abdominal compartment (abdominal wall and/or viscera) could be involved in this diaphragmatic dysfunction.

Abdomen↗