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Biomedical subjects

B Leclercq

Publications and source records attributed to B Leclercq.

At least 55 records · Page 3Linked to original sources

Influence of adiposity (genetic or hormonal) on the metabolism of amino acids and nutritional responses.

The data published on the modifications of amino-acid metabolism associated with variations of obesity from genetic or hormonal origin have been reviewed. In the first part monogenic models of mice and rats are described. Obesity in humans is analysed in the second part. Lastly, non-ruminant genotypes or hormone-treated ones (chickens and pigs) are reviewed in the third part. Although different mechanisms are probably at the origin of these differences, many similarities can be drawn. Obesity is always associated with: 1) less efficient utilization of dietary amino acid; 2) a high concentration of branched-chain amino acids in plasma; 3) a deviation of carbon from amino acid towards gluconeogenis and lipogenesis; and 4) a less pronounced sensitivity to amino-acid imbalance in the diet.

Adipose Tissue↗

Pulsatility of plasma growth hormone and hepatic growth hormone receptor characteristics of broiler chickens divergently selected for abdominal fat content.

1. Plasma growth hormone (GH) pulsatility and hepatic GH receptor characteristics were compared in experimental lines of meat-type chickens selected for high (HF) or low (LF) abdominal fat content. 2. Mean GH concentration, baseline and amplitude of pulses were slightly, but not significantly, greater in LF chickens. Length and frequency of pulses were similar. 3. LF chickens exhibited higher plasma triiodothyronine (T3) concentrations. This difference between genotypes disappeared when the diet was supplemented with 1 mg/kg T3. 4. Specific binding of GH to liver membranes was higher for the fat line but was depressed by T3 supplementation to the same level in both lines. No difference was observed between lines for affinity constants. 5. It is concluded that direct selection for leanness has a less pronounced, if any, effect on GH pulsatility as compared with selection for food conversion efficiency; therefore, different physiological mechanisms are triggered to achieve leanness.

Abdomen↗

Comparative responses of genetically lean and fat chickens to lysine, arginine and non-essential amino acid supply. I. Growth and body composition.

1. Three experiments were performed to study the effects of amino acid imbalance on the growth of genetically lean (LL) or fat (FL) male chickens from 28 to 42 d of age. In experiment 1, five concentrations of digestible lysine were compared (4.75, 6.75, 7.75, 8.75 and 9.75 g/kg). In experiment 2, four concentrations of digestible arginine were compared (6.53, 7.69, 8.84 and 10.0 g/kg). In experiment 3, three diets were compared: a high-protein diet (189 g CP/kg), a low-protein diet containing added essential amino acids (EAA) (144 g CP/kg) and this low-protein diet supplemented with 40 g/kg of non-essential amino acids (NEAA) (glutamic acid+aspartic acid). 2. LL birds exhibited a lower growth rate than the FL when the diet was deficient in either lysine or arginine. Plotting weight gain against lysine or arginine intake suggested that most of this effect was caused by variations in food intake. 3. When protein gains (body or total proteins) were plotted against lysine or arginine intake, LL chickens appeared more efficient than FL chickens. 4. Similar growth rates, although slightly lower in FL, were obtained with low- and high-protein diets. However, NEAA supplementation of the low-protein diet reduced adiposity of LL and did not modify that of FL. Increasing crude protein content (all amino acids) was more effective than NEAA supplementation in decreasing the adiposity of both lines.

Amino Acids↗

Comparative responses of genetically lean and fat chickens to lysine, arginine and non-essential amino acid supply. II. Plasma amino acid responses.

1. Three experiments performed to study the effects of amino acid imbalances on the growth of genetically lean (LL) and fat (FL) male chickens from 28 to 42 d of age were described by Leclercq et al. (1994). The plasma amino acid concentrations of birds on selected treatments from that paper are reported here. In experiment 1, three dietary concentrations of digestible lysine were compared (4.75, 6.75 and 7.75 g/kg). In experiment 2, two dietary concentrations of digestible arginine were compared (6.53 and 10.00 g/kg). In experiment 3, three diets were compared: a high-protein diet (189 g CP/kg), a low-protein diet containing added essential amino acids (144 g CP/kg), and this low-protein diet supplemented with 40 g/kg of non-essential amino acids (NEAA; glutamic and aspartic acids). 2. The present results are compared with two earlier reports on the same genotypes. The LL consistently had lower plasma concentrations of methionine, cystine, phenylalanine, isoleucine and valine, and higher concentrations of histidine, than the FL chickens. In 4 of 5 experiments, LL leucine concentrations were lower, and glutamic acid, tyrosine, glutamine and alanine were higher, than in the FL. The other amino acids measured; arginine, lysine, aspartic acid, glycine and serine, exhibited variable responses among the experiments. 3. When the limiting essential amino acids, lysine and arginine, were added to a deficient diet, the plasma concentration of the supplemented amino acid increased while the others remained constant or decreased. 4. When glutamic and aspartic acids were added to the low protein diet, plasma amino acid responses were similar to those of adding a limiting amino acid to a deficient diet, except that alanine exhibited a dramatic increase. 5. Although there were genotype by diet interactions for several amino acids, the interactions were caused by differences in the degree of the responses, not in their direction. 6. These results suggest that the FL and LL genotypes do not utilise various amino acids with the same efficiency and, as a consequence, the ideal profile of dietary amino acids should not be the same for both lines. The results support the hypothesis that selection for fatness and leanness changed the amino acid requirements independently of the effects of food intake.

Amino Acids↗

Myocardial imaging with technetium-99m-tetrofosmin: comparison of one-day and two-day protocols.

UNLABELLED: There is no evidence of myocardial redistribution after tetrofosmin injection, therefore, two separate injections are needed to differentiate scar from ischemia with this tracer. The injections can be given on the same day (one-day protocol) or on separate days (two-day protocol). As part of a Phase II clinical study, a one-day protocol was compared with a two-day protocol. METHODS: Fifty-five patients with suspected coronary artery disease were studied according to the following protocol: on the first day at rest, anterior, left lateral, left anterior oblique 40 degrees and 70 degrees images were acquired 30 min after injection of 8 mCi of tetrofosmin for 5 min each. Two days later, exercise and rest images were acquired on the same day. At peak exercise, 8 mCi of tetrofosmin were injected and 30 min later the same four standard planar images were recorded as on Day one. Four hours after the exercise injection, 24 mCi of tetrofosmin were injected at rest and imaging was repeated 30 min later. Qualitative comparisons between the one- and two-day protocols were performed in 50 patients in whom all data were available following blinded evaluation of images by three readers. RESULTS: All three readers reported identical results for the 26 patients. A difference in extent or location between the observers was found in seven patients, differences between normal and abnormal in eight patients, while discrepancies between ischemia and necrosis were noted in four patients. In five patients, an ischemic area was found according to the one-day protocol, but according to the data of the two-day protocol, this area was judged to be necrotic. One observer reported the opposite in one patient. These discrepancies between the reversibility of defects were restricted to the inferior wall. Comparison with 201Tl data showed no systematic pattern of variation. CONCLUSION: Tetrofosmin can be used in a one-day protocol. However, in planar imaging, the inferior wall should be reported with caution.

Coronary Disease↗

Treatment of peritoneal carcinomatosis by intraperitoneal chemo-hyperthermia: reliable and unreliable concepts.

Intraoperative peritoneal chemo-hyperthermia (IPCH) is a promising treatment of peritoneal carcinomatosis arising from digestive tumors. After presenting the rationale for the use of IPCH, this review reports the results published to date by different groups. Unfortunately, data with respect to technical aspects, indications and results are unclear, inhomogeneous and questionable. The discussion presents reliable and unreliable points, mainly concerning the technical aspects of IPCH: what is the maximal desirable tumor thickness before initiating treatment? What is the ideal temperature? Is central hyperthermia beneficial? What is the ideal duration? What is the most effective antimitotic drug? A new classification of peritoneal seeding before cytoreductive surgery and before the initiation of IPCH, is proposed, and a suggestion concerning the reporting of drug concentrations made. Numerous prospective studies need to be conducted to test different technical modalities and to evaluate the results of IPCH.

Animals↗

Technetium-99m-tetrofosmin myocardial imaging: a comparison with thallium-201 and angiography.

UNLABELLED: Images recorded after intravenous administration of 99mTc-tetrofosmin were compared to those obtained with 201Tl in a series of 40 patients with angiographically documented coronary artery disease. These patients were part of a Phase II tetrofosmin study and presented anamnestic or laboratory evidence suggestive of ischemic heart disease. METHODS: Thirty-seven patients had one or more coronary obstructions greater or equal to 70% of luminal diameter. Three patients studied after bypass surgery or angioplasty had patent grafts, absence of disease progression or no significant restenosis. Twenty-six patients had evidence of previous myocardial infarction. All images were processed into a common display format by a core laboratory. They were identified by code and read by concensus of four investigators. Each segment was classified as normal or abnormal and these readings were combined and categorized into normal, reversible, fixed or mixed regional defects. RESULTS: There was good segmental correspondence between thallium and tetrofosmin (kappa values ranged from 0.43 to 1.00). The ability of thallium and tetrofosmin to recognize and localize myocardial infarction was excellent, since corresponding abnormalities were present in respectively 24 and 25 of the 26 patients with previous myocardial infarction. Abnormalities in noninfarcted territories were recognized with both tracers in 16 of 28 patients presenting with coronary lesions involving vessels unrelated to the infarct. CONCLUSION: In comparison to rest tetrofosmin, thallium redistribution shows more reversibility in areas with myocardial infarction but less reversibility in areas of myocardial ischemia. Current Phase II results suggest that tetrofosmin is a sensitive and reliable tracer for detecting myocardial infarction and ischemia. Results should be confirmed in a larger group of patients.

Aged↗

Combination of interleukin-2 and gamma interferon in metastatic renal cell carcinoma.

The use of high-dose interleukin-2 (IL2), alone or in association with lymphokine activated killer cells in patients with metastatic renal cell carcinoma (MRCC) results in a 20-25% response rate. However, the toxicity of IL2 is substantial and despite many clinical trials, response rates initially reported have not been improved. The aim of this study was to evaluate a combination of IL2 and gamma interferon (IFN) in MRCC with respect to both efficacy and tolerance. IL2 was given by continuous intravenous infusion at a daily dose of 24 x 10(6) U/m2 for 2 consecutive days during 5 consecutive weeks. Gamma IFN was given subcutaneously at a daily dose of 5 x 10(6) U/m2 on the same days as IL2. 33 patients with MRCC entered the study. Clinical responses were comparable with other published series: 7 patients (21%) achieved partial response, 13 (39%) were stable and 13 had progression, despite therapy. Immunological profile observed with this regimen showed a major increase in natural killer cells which became the predominant lymphocyte population at the end of the therapy. Tolerance was good with 92.5% of the planned doses actually received by the patients. This was reflected by an early discharge from the hospital in 95% of the cycles, increasing acceptability of the regimen by the patients.

Adult↗

Comparative utilisation of sulphur-containing amino acids by genetically lean or fat chickens.

1. Genetically lean (LL) or fat (FL) male chickens were fed from 28 to 47 days of age on 5 experimental diets differing by their methionine+cystine content (5.4, 5.8, 6.2, 6.6 and 7.0 g/kg, respectively). 2. Growth rate of LL chickens was reduced by the lower sulphur-containing amino acid (SAA) concentrations whereas that of FL was not modified. 3. LL chickens exhibited a larger feather protein gain than FL, which was stimulated by SAA intake. 4. SAA retention, when plotted against SAA consumption, was always greater in LL than in FL. 5. Large differences were observed between genotypes for plasma-free amino acids. Lysine, glutamic acid, histidine and serine were found at significantly higher concentrations in LL birds. Branched amino acids, aromatic amino acids, SAA and arginine were found at higher concentrations in FL. No differences were observed for aspartic acid, glycine, alanine and total amino acids. Methionine supplementation decreased free amino acid concentrations, with the exceptions of arginine and leucine. 6. It is concluded that lean chickens require a higher dietary concentration of SAA than FL. This is mainly caused by their lower food consumption and their greater feather synthesis. However, LL use SAA more efficiently than FL.

Amino Acids↗

Are genetically lean broilers more resistant to hot climate?

1. Genetically lean (LL) or fat (FL) male chickens were exposed to either high (32 degrees C) or control (22 degrees C) ambient temperature up to 9 weeks of age. They were fed on one of two isoenergetic diets differing in protein content: 190 or 230 g/kg. 2. At 22 degrees C, weight gain of LL broilers was the same as in FL chickens, but at the high temperature LL birds grew to a greater weight than FL ones. 3. Food conversion efficiency was not affected by ambient temperature in LL chickens but was depressed in FL ones at 32 degrees C. 4. Increasing dietary protein content did not alleviate heat-induced growth depression irrespective of the genotype. 5. Gross protein efficiency was higher in LL chickens and was less depressed at 32 degrees C than in FL birds. 6. Fat deposition decreased with increasing protein concentration at normal temperature in both genotypes; at high temperature, high protein content enhanced fatness, particularly in LL chickens. 7. Thus, genetically lean broilers demonstrated a greater resistance to hot conditions: this was indicated by enhanced weight gain and improved food and protein conversion efficiencies.

Animal Feed↗

Test dose-guided administration of cisplatin in an anephric patient: a case report.

BACKGROUND: Although cisplatin pharmacokinetics is well documented in patients with various degrees of renal dysfunction, no information is available concerning cisplatin administration to anephric patients. Since anephric patients may sometimes need cisplatin therapy, it is therefore of importance to define therapeutic guidelines for cisplatin administration in this patient population. PATIENT AND METHODS: Cisplatin was administered to an anephric patient (bilateral nephrectomy) requiring cisplatin therapy for a metastatic carcinoma of the urothelium. A test dose of 12 mg (7.5 mg/m2) of cisplatin was first administered as a 1 hour infusion in order to determine the patient's pharmacokinetic parameters. Filterable and total platinum levels were determined by flameless atomic absorption spectrophotometry. Haemodialysis was started 30 min before the beginning of the cisplatin infusion and was maintained for 4 h thereafter. RESULTS: Under haemodialysis, filterable and total platinum pharmacokinetics after the test dose were comparable with a patient with normal renal function, i.e. with peak plasma concentrations of 126 ng/ml and 166 ng/ml for the filterable and the total platinum, respectively. The area under the curves (AUC) were 154 ng.h/ml for the filterable and 11486 ng.h/ml for the total platinum. The terminal half-lives of filterable and total platinum were 0.42 h and 101 h, respectively. Based on the test dose platinum pharmacokinetics, a therapeutic dose of 100 mg (63 mg/m2) of cisplatin was administered. Following the therapeutic dose, peak plasma concentrations reached 1,120 ng/ml for the filterable and 1,280 ng/ml for the total platinum. The AUCs were 1,609 and 65,556 ng.h/ml for the filterable and the total platinum, respectively, as expected from the predicted AUCs obtained from the test dose pharmacokinetics. The terminal half-lives of filterable and total platinum were similar to the ones observed after the test dose, i.e. 0.36 h and 86 h, respectively. Although the patient died of rapidly progressive hepatic failure, the feasibility of the test dose-guided cisplatin administration in an anephric patient is demonstrated. CONCLUSION: This approach may be helpful in monitoring cisplatin therapy in similar cases requiring cisplatin administration.

Antineoplastic Combined Chemotherapy Protocols↗

[Gene therapy and hospital strategy].

Gene therapy raises strong interrogations among hospital managers. Actually, hospital environment is disturbed and moving as well in a legislative political and statutory level as in an economical (competition, consumerism, proximity of the establishments) and demographic one (ageing, new pathologies). The fast development of medical technologies amplifies this disturbance. In front of that environment, the hospital has to anticipate the arriving of gene therapy without underestimating the deontological, medical, economical and judicial risks. The decisions of implantation have to be taken in a collective way, and seriously planned and estimated on a medical and economical level. The way to train people and to forecast their careers don't have to be underestimated in consideration of the challenge which is represented by the gene therapy.

Ethics, Medical↗

Lipogenesis in turkeys and chickens: a study of body composition and liver lipogenic enzyme activities.

1. Carcase composition, fat deposition and the activities of three liver lipogenic enzymes were compared in turkeys and chickens fed ad libitum on two different isocaloric diets, respectively adapted to chickens (C) and to turkeys (T). Diets differed in their protein content, being higher by 60 g/kg in diet T. 2. Chickens were much fatter than turkeys and exhibited higher activities of acetyl-coenzyme A carboxylase (EC 6.4.1.2) and malic enzyme (EC 1.1.1.40). 3. The carcase composition of turkeys was not influenced by the type of diet administered, while chickens fed on diet C were fatter than chickens fed on diet T. Compared to diet T, diet C enhanced malic enzyme activity, whatever the species and age. 4. A good correlation between abdominal fat and total fatness was observed in both species but especially in turkeys. 5. In conclusion, hepatic lipogenesis is much lower in turkeys than in chickens.

Acetyl-CoA Carboxylase↗

Wegener's granulomatosis presenting as diffuse pulmonary hemorrhage.

A 35-year-old woman experienced diffuse intraalveolar haemorrhage with respiratory distress and acute renal failure. Renal histology and evolution confirmed Wegener's granulomatosis. Early use of immunosuppressive drugs allowed weaning from mechanical ventilation and temporary improvement of the renal failure. A review of the literature emphasizes the rarity of alveolar hemorrhage as an initial symptom of Wegener's granulomatosis and the necessity of aggressive management.

Adult↗

Further investigations on protein requirement of genetically lean and fat chickens.

1. Genetically lean (LL) or fat (FL) chickens were fed from 28 to 42 d of age on one of 6 diets with different protein contents (from 73 to 208 g/kg). In order to keep a constant amino acid balance the experimental diets were made by diluting a well-balanced protein-rich diet with a protein-free diet. 2. Dietary protein influenced the growth rate of both genotypes similarly. However, maximum weight gain was reached in LL at a lower protein intake than in FL. 3. Regression between total protein gain (body protein + feather protein) or body protein gain and protein intake exhibited significantly different slopes, that of LL being superior to that of FL. 4. At a given protein intake, feather protein gain was also superior in LL to FL. Moreover feather protein, as a percentage of total protein gain, was superior in LL to FL. When the dietary protein fell below 126 g/kg, feather protein represented a higher proportion of total protein gain. 5. Multiple linear regressions of protein intake (as the dependent variable), and body weight and protein gain or weight gain (as the independent variables) suggest that the maintenance requirement for protein is similar in both lines but that the protein efficiency for growth is significantly superior in LL. 6. In a second experiment both genotypes were offered either a single high protein diet (232 g/kg) or a single medium protein diet (186 g/kg) or had free-choice between a high (269 g/kg) and a low protein (145 g/kg) diet. In free-choice feeding, FL chickens selected an overall dietary protein content which was significantly lower (179 v. 200 g/kg) to that of LL. In both genotypes, free-choice feeding led to fatter and less efficient chickens than predicted by the linear regression between adiposity or food conversion and protein content.

Amino Acids↗