[Arterial heterogeneity]. / Artériopathie et hétérogénéité artérielle.

More and more clinical observations and trials support the concept of heterogeneity of atheroma according to the arterial bed. In a pilot study named "Étude Comparative des Lésions Athéromateuses" (ECLA), we have shown that carotid and femoral plaques possess different characteristics. Carotid arteries display increased lipid content compared to femoral arteries whereas femoral arteries are more prone to calcify and to develop osteoid metaplasia. These observations should lead the researcher and the clinician to look at the cellular and molecular mechanisms governing the heterogeneity of atheromas. At last, a better understanding of the characteristics of plaques should help us to determine plaque stability, to prevent cardiovascular events and to choose the best medical, endovascular or surgical option.

Energy and protein metabolism during recovery from malnutrition due to nonneoplastic gastrointestinal disease.

The magnitude of metabolic adaptation to malnutrition is still debated and few studies have investigated the phase of recovery from malnutrition. The aim of the present work was to determine whether refeeding was associated with adaptive changes in 1) energy expenditure, 2) maximal capacity for oxidizing lipids, and 3) whole-body protein turnover. Eleven malnourished patients with nonneoplastic gastrointestinal diseases were studied by using indirect calorimetry and L-[1-13C]leucine infusion while being infused with lipid-rich total parenteral nutrition (TPN). The same study was performed before initiation of TPN and after a mean gain of 6.5 kg body wt. In absolute values, resting energy expenditure (REE) increased after refeeding (4.05 +/- 0.85 compared with 4.60 +/- 1.05 MJ/d). Change in REE adjusted for fat-free mass (FFM) correlated significantly with change in body weight (r = 0.850, P = 0.01) and change in body fat (r = 0.798, P = 0.01) but not with change in FFM (r = -0.06, NS). Lipid oxidation decreased significantly after body weight gain (0.93 +/- 0.28 compared with 0.50 +/- 0.37 mg.kg-1.min-1). When expressed per kg FFM, protein turnover and breakdown increased significantly during body weight gain. Moreover, the change in protein turnover correlated with the rate of change in FFM, suggesting that FFM accretion requires increased interorgan exchange of amino acids. Our data suggest that in patients similar to those studied here and during recovery from malnutrition, the degree of change in adjusted REE during refeeding is correlated with change in fat mass and not with change in FFM, and that there is a decrease in oxidation of infused lipids. These mechanisms may contribute to body fat repletion and regulation during weight gain.

Energy and protein metabolism in malnutrition due to nonneoplastic gastrointestinal diseases.

Although a reduction in both energy expenditure and protein turnover has been demonstrated in starved volunteers, few metabolic data are available for patients in whom malnutrition is due to nonneoplastic gastrointestinal diseases. Chronically malnourished, unstressed adult patients with nonneoplastic gastrointestinal diseases (body mass index, 15.8 +/- 2.5 kg/m2, n = 13) and healthy control subjects (n = 10) were studied in the postabsorptive state using indirect calorimetry, as well as substrate fluxes of L[1-13C]leucine, L-[2-15N]glutamine (seven patients and six controls), and D[6,6-2H2]glucose (seven patients and eight controls). Resting energy expenditure (REE) expressed in kilocalories per 24 hours was significantly lower in patients than in controls; REE expressed per unit of fat-free mass (FFM) was not significantly different in both groups. Whole-body leucine turnover, oxidation, and nonoxidative disposal rates, based on either 13C-leucine or 13C-alpha-ketoisocaproic acid (KIC) enrichments, and glucose turnover rate were not significantly different between malnourished patients and controls. Moreover, glutamine turnover was increased by 28% in malnourished patients as compared with normal volunteers (429.8 +/- 86.8 v 334.9 +/- 15.9 mumol/kg/h, P = .02). These results suggest that hypometabolic adaptation, although previously documented in starved volunteers, is not operative during states of chronic malnutrition due to gastrointestinal disease. The increase in glutamine turnover rate might represent an adaptative mechanism to malnutrition for preservation of visceral mass or function.

Effect of chemotherapy on resting energy expenditure in patients with non-Hodgkin's lymphoma. Results of a sequential study.

This study compared the resting energy expenditure (REE) modifications observed during successive intensive identical chemotherapy courses in non-Hodgkin's lymphoma patients to assess indirectly the metabolic changes induced by the cytotoxic effect of drugs on the tumor. With this therapeutic regimen, reduction of tumor mass is mostly achieved during the first course of chemotherapy. The study included 10 non-Hodgkin's lymphoma adult patients receiving three intensive 5-day courses of Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), cyclophosphamide, vindesine, and bleomycin. Resting energy expenditure was evaluated by indirect calorimetry during each course, first within the first 2 days before chemotherapy and then on days 2, 3 and 5. Initial REE (day 0) on entry into the study (21.8 +/- 1.2 kcal/kg.d-1) represented 99 +/- 6.7% of theoretical REE. Resting energy expenditure on day 0 was lower during course 2 and 3 (19.1 +/- 0.7 and 18.4 +/- 1.8 kcal/kg/d) than during course 1 (21.8 +/- 1.2 kcal/kg/d). The REE profile was different among the 3 courses: course 1 induced a significant REE decrease on days 3 and 5 (P less than 0.01); during course 2, REE remained stable and was lower than during course 1; during course 3, REE increased on days 2, 3, and 5 (P less than 0.05). Energy balance was positive during the three courses and nutritional status remained stable. The REE decrease observed during course 1 may be regarded as the metabolic effect of chemotherapy on the tumor metabolism.

Comparison of the effects of continuous and cyclic nocturnal parenteral nutrition on energy expenditure and protein metabolism.

Although cyclic nocturnal total parenteral nutrition is a widely used technique, its metabolic consequences have not been fully investigated. During two successive 7-day periods, 12 patients received randomly either standard continuous (infusion 24 hr/day) or cyclic (infusion between 5 pm and 9 am) total parenteral nutrition (TPN). Calorie and nitrogen intakes were identical during both periods. Energy expenditure was investigated by indirect calorimetry and showed practically no difference between continuous standard (1383 +/- 41 kcal/day-1) and cyclic total parenteral nutrition (1428 +/- 46 kcal/day-1). However, in the cyclic regimen, when compared with continuous infusion, energy expenditure was higher between 5 pm and 9 am and lower between 9 am and 5 pm. At the end of the noninfusion period, the 24-hr profile of the nonprotein respiratory quotient showed a slight decrease in patients receiving the cyclic infusion, in contrast with the stability of the quotient in the standard regimen. However, the nitrogen balance and variations in nutritional status did not differ significantly. In conclusion cyclic TPN is efficient for achieving a positive energy and nitrogen balance and in addition it induces a metabolic profile closer to physiological conditions.

Change in energy and protein status during chemotherapy in patients with acute leukemia.

The energy and protein status of 12 adult patients with acute leukemia (AL) was investigated during induction chemotherapy. Parenteral nutrition (PN) (nonprotein [NP], 31.4 kcal/kg/d; nitrogen [N], 0.177 g/kg/d) was started on day 6 after the beginning of chemotherapy and continued through all of the cytopenic phase. A clinical and metabolic evaluation, including measurement of resting energy expenditure (REE) by indirect calorimetry, was performed on each patient within the 2 days before beginning chemotherapy (D0), on the third day of chemotherapy (D3), and then weekly from day 7 until the end of the cytopenic phase. Measured REE at day 0 (29.5 +/- 1.4 kcal/kg/d) was significantly higher (+34 +/- 6%) than theoretical REE. Chemotherapy induced a significant decrease in REE at day 3 (26.2 +/- 1.7 kcal/kg/d; P less than 0.05), but during the cytopenic phase REE was not different significantly from its initial values (D0). A positive energy balance was observed during the whole study after the beginning of PN. In contrast, mean nitrogen balance remained negative always, due to a sharp increase in urinary nitrogen loss during the cytopenic phase. The fact that nutritional support falls short of its goal may explain why no improvement in tumor response to therapy has been described in most studies.