A Simple Questionnaire as a First-Step Tool to Detect Specific Frailty Profiles: The Lorraine Frailty-Profiling Screening Scale.

OBJECTIVES: To propose a simple frailty screening tool able to identify frailty profiles. DESIGN: Cross-sectional observational study. SETTING: Participants were recruited in 3 different clinical settings: a primary care outpatient clinic (RURAL population, N=591), a geriatric day clinic (DAY-CLINIC population, N=76) and healthy volunteers (URBAN population, N=147). PARTICIPANTS: A total of 817 older adults (>70 years old) living at home were included. INTERVENTION: A 9-item questionnaire (Lorraine Frailty Profiling Screening Scale, LoFProSS), constructed by an experts' working group, was administered to participants by health professionals. MEASUREMENTS: A Multiple Correspondence Analysis (MCA) followed by a hierarchical clustering of the results of the MCA performed in each population was conducted to identify participant profiles based on their answers to LoFProSS. A response pattern algorithm was resultantly identified in the RURAL (main) population and subsequently applied to the URBAN and DAY-CLINIC populations and, in these populations, the two classification methods were compared. Finally, clinically-relevant profiles were generated and compared for their ability to similarly classify subjects. RESULTS: The response pattern differed between the 3 sub-populations for all 9 items, revealing significant intergroup differences (1.2±1.4 positive responses for URBAN vs. 2.1±1.3 for RURAL vs. 3.1±2.1 for DAY-CLINIC, all p<0.05). Five clusters were highlighted in the main RURAL population: "non-frail", "hospitalizations", "physical problems", "social isolation" and "behavioral", with similar clusters highlighted in the remaining two populations. Identification of the response pattern algorithm in the RURAL population yielded a second classification approach, with 83% of tested participants classified in the same cluster using the 2 different approaches. Three clinically-relevant profiles ("non-frail" profile, "physical frailty and diseases" profile and "cognitive-psychological frailty" profile) were subsequently generated from the 5 clusters. A similar double classification approach as above was applied to these 3 profiles revealing a very high percentage (95.6%) of similar profile classifications using both methods. CONCLUSION: The present results demonstrate the ability of LoFProSS to highlight 3 frailty-related profiles, in a consistent manner, among different older populations living at home. Such scale could represent an added value as a simple frailty screening tool for accelerated and better-targeted investigations and interventions.

A case of life-threatening lactic acidosis after smoke inhalation - interference between beta-adrenergic agents and ethanol?

A 49-year-old male developed bronchospasm and severe lactic acidosis after exposition to fire smoke. The correction of lactic acidosis following beta-adrenergic agents withdrawal, and the transitory increase in lactate after salbutamol reintroduction are consistent with hypersensitivity to salbutamol. However, the plasma lactate concentration (32.6 mmol/l) that we observed 9.5 h after admission is far above those currently seen after administration of beta-adrenergic agents. We searched for causes able to potentiate the adverse effects of these drugs and we noticed that our patient had a high plasma ethanol level (2.4 g/l). Alcohol metabolism in the liver results in generation of high NADH/NAD+ ratios, thus reducing lactate liver clearance. This observation suggests that plasma lactate levels should be monitored closely in alcoholic patients treated with beta-mimetic agents.

Lactate metabolism and glucose turnover in the subterranean crustacean niphargus virei during post-hypoxic recovery

Glucose and lactate metabolism were studied in a hypoxia-resistant subterranean crustacean, Niphargus virei, using an injection of l-[U-14C]lactate and tracer d-[6-3H]glucose either in normoxic conditions or after a 24 h exposure to severe hypoxic. Post-hypoxic animals (H animals) were compared with two treatment groups of normoxic animals. In the first normoxic group (NLL animals), animals were simultaneously injected with labelled and unlabelled lactate to obtain a lactate load similar to that of H animals. In the second normoxic group (N, control animals), animals were only injected with labelled lactate. During a 24 h recovery period, the incorporation of 14C and 3H into glycogen, lactate, glucose, amino acids, lipids and CO2 was measured. During recovery, glucose turnover rate was enhanced in H and depressed in NLL compared with N animals. However, when energy expenditure was taken into account, the changes were due only to a reduction of glucose turnover rate by lactate load. It was concluded that gluconeogenesis was not the main source of glyconeogenesis. Equivalent lactate loading in NLL and H animals resulted in an equivalent enhancement (fivefold) of lactate utilization in both groups when energy expenditure was taken into account. Lactate label incorporation appeared later in glycogen than in glucose, but remained high 24 h after the injection. Since glucose is mainly an extracellular metabolite, this observation may be consistent with the hypothesis of two distinct sites for glycogen restoration in hypogean crustaceans: a gluconeogenic organ (a liver equivalent) and a glyconeogenic organ (a muscle equivalent). The oxidative pathways of glucose and lactate were depressed in post-hypoxic N. virei and to a lesser extent in the NLL group. Since there is no evidence of marked protein utilization, it is postulated that, during recovery, repayment of the O2 debt relies on an increase in lipid utilization. During recovery from severe hypoxia or after a lactate load, the subterranean N. virei appeared to implement a strategy of lactate removal quite different from that observed in epigean crustaceans, favouring lactate-supported gluco- and glyconeogenesis and rapid glycogen replenishment instead of rapid lactate removal via oxidative pathways.

[Metabolic myocardial modifications following surgical revascularization]. / Modifications métaboliques myocardiques après revascularisation chirurgicale.

The effects of aorto-coronary bypass surgery on myocardial lactate, free fatty acid and certain amino acid metabolism were studied in 30 coronary patients presenting with unstable, invalidating angina resistant to medical therapy. These patients had electrical signs of anterior wall ischemia without necrosis, significant proximal stenosis of the left anterior descending artery with good distal run-off, and underwent bypass surgery on this artery without signs of postoperative myocardial infarction. This study involved pre- and postoperative hemodynamic investigation with a Swan-Ganz catheter and a metabolic study of the coronary arteriovenous lactate (n = 30), free fatty acid, alanine and glutamate (n = 12) levels under basal conditions and after atrial pacing. These results were compared with those in 10 non-coronary control patients, operated for monovascular replacements. The increase of the pulmonary capillary pressure associated with a fall in systolic index at the 6th postoperative hour showed a reduction in left ventricular performance which tended to correct itself at the 24th hour. In the coronary patients, myocardial lactate production increased, alanine production increased and the uptake of free fatty acids fell during atrial pacing after surgery. These metabolic changes reflect the stimulation of anaerobic glycolysis secondary to myocardial ischemia which disappeared after surgery to compare with the control subjects. Therefore, effective myocardial revascularisation in patients with coronary artery disease is accompanied by the regression of the metabolic stigmata of myocardial ischemia.

[Transfer of reduced equivalents in the cell: lactate excess]. / Transfert des équivalents réduits dans la cellule: l'excès de lactate

The classical biochemical diagram that explains the part played by lactate in hypoxia is shortly recalled. The systems that insure the transfer of reducing equivalents of the cytoplasma towards the mitochondria (and conversely) are then described with full details. The excess lactate concept (XL) advanced by Huckabee (1958) in order to differentiate an hyperlactatemia with hypoxic genesis from an another one is object of discussion. This concept is false from the theoretical point of view and has no longer to be used nowadays.

Comparison of glycogen stores in 3- and 7-month-old lean and obese Zucker rats under fed and fasted conditions.

Glycogen content (mg/g) and stores (mg) were determined in 3- and 7-month-old obese and lean Zucker rats, under fed and fasted (48 hr) conditions. Hepatic content was higher in fed obese than in lean rats (3 months: 90 vs 70; 7 months: 107 vs 74); it was exhausted after fasting in lean but decreased by 56% in obese rats. Muscle content in fed obese and lean animals did not differ; it decreased comparably after fasting. Myocardial content was higher in fed obese than lean rats (3 months: 7.2 vs 3.6; 7 months: 7.5 vs 6.3); it was enhanced with fasting (10.0 vs 7.5). Total glycogen stores were higher in obese than in lean animals (3 months: 2500 vs 1400; 7 months: 4000 vs 2000) because of the hepatic store. The discussion includes a comparison with available data, taking into account methodological aspects, lipid stores and the FFA/carbohydrate interrelationship.

Lactate-glucose interrelations, glucose recycling and the Cori cycle in normal fed rats.

1. Turnover and oxidation rates of glucose and lactate were determined using a priming dose-continuous infusion of 14C-(u)-glucose and 14C-(U)-lactate in anesthetized and mechanically ventilated non-fasted rats. The rates of glucose-lactate interconversions were computed from the two-compartment model of Depocas and De Freitas (1970). The rate of total glucose recycling is known as the difference between the rate of true glucose turnover measured with 3H-(2)-glucose (RGT) and the rate of apparent glucose turnover measured with 14C-glucose (RG). This value was compared with the Cori cycle. 2. In normal conditions 17% of RG come from lactate, 43% are directed to lactate and 49% are oxidized. 3. 71% of the rate of lactate turnover come from glucose, 28% are directed to glucose and 51% are oxidized. 4. The rate of total glucose recycling (RGT-RG) is 3.7 mg - mn(-1) per kg0.75 and represents 60% of RG or 38% of RGT. 5. The Cori cycle is 0.8 - 1.2 mg - mn(-1) per kg0.75 and represents 8 - 20% of the rate of glucose turnover and 20 - 32% of total glucose recycling.

Effect of fasting on liver and muscle glycogen in rats and guinea pigs.

The effect of a 48 hr fasting period on liver and muscle glycogen was studied in rats and guinea pigs. Total content of glycogen in the liver was similar in both species of fed animals and was totally exhausted after the fasting period. Muscle glycogen was twice as high in fed guinea pigs as in fed rats. The loss during fasting in guinea pigs was also twice that in rats. The differences in glycogen stores may explain the different metabolic response to fasting previously observed in the two species : hypoglycemia and decreased glucose production in fasted rats and constancy of these parameters in fasted guinea pigs.

[Simultaneous use of carbohydrates and amino acids during total ischemia in the isolated rat heart (author's transl)]. / Utilisation simultanée des glucides et des acides aminés au cours de l'ischémie totale du coeur de rat.

The simultaneous utilization of carbohydrates and amino acids in the metabolic response to oxygen deprivation was studied i the isolated rat heart initially perfused according to Langendorff and submitted to periods of 2, 5, 10 and 15 min of complete ischemia. The results of the measurement of metabolite contents showed : (1) an immediate decrease of glycogen, pyruvate, alpha-ketoglutarate and aspartate; (2) a delayed decrease of citrate and glutamate; (3) an immediate and continuous increase of lactate and succinate; (4) a delayed increase of alanine; (5) a transient increase of malate + fumarate. The end products of anaerobic metabolism are lactate, which is an index of glycolytic activity, and alanine and succinate, which are indexes of amino acid fermentation. Succinate originates from aspartate, and alanine originates from glutamate. The amino acid pathway does not seem of importance in the production of ATP compared to glycolysis. However, its eventual role and the physiological implication of these reactions in the resistance of strict aerobic organisms to oxygen deprivation are discussed.

[Effect of physical training on the metabolic response of the isolated working heart during hypoxia (author's transl)]. / Effet de l'entraînement physique sur la réponse métabolique à l'hypoxie du coeur isolé de rat.

The increased tolerance to O2 deprivation of the myocardium after physical training was studied using the isolated working heart preparation and rats moderately trained by swimming. Glycolytic utilization of exogenous glucose and lactate production were determined under oxygenated conditions (Po2 # 500 Torr, 10 min), during severe hypoxia (P02 less than 50 Torr, 10 min) and during post-hypoxic perfusion (Po2 # 500 Torr, 15 min). The energetic state (CP, ATP, ADP, AMP) and glycogen store were determined at the end of the experimental procedure. The beneficial effect of training was evidenced by the restoration of aortic flow in the post-hypoxic period in hearts from trained animals (CE), whereas it did not return to the prehypoxic level in hearts from sedentary animals (CS). The increase in glycolytic utilization of exogenous glucose during hypoxia (x 2.5) was not very different in CE and CS, whereas lactate production was higher (+ 50%) and of longer duration in CE than in CS, This higher lactate production was the consequence of the larger glycogen store in CE than in CS. Moreover, glycogen resynthesis during the post-hypoxic period was higher in CE than in CS. Thus, a changed glycogen metabolism, and also higher CP and ATP contents in CE compared to CS, are examples of metabolic events implicated in the increased tolerance to O2 deprivation of the myocardium induced by physical training.

Lactate kinetics estimated by single injection and continuous infusion of [14C-(U)]-lactate in rats.

1 Identical values of the rate of lactate turnover determined with [14C-(U)]-lactate were found with single injection or continuous infusion techniques in anaesthetized and mechanically ventilated rats. 2 The mean transit time and total minimal body mass of lactate determined graphically (Katz et al., 1974 a, b) were higher with single injection than with continuous infusion of the tracer.

Determination of glucose turnover in sea bass Dicentrarchus labrax. Comparative aspects of glucose utilization.

1. Parameters of in vivo glucose utilization by sea bass (132 +/- 6 g, mean +/- SEM) acclimated at 15 degrees C in sea-water were measured after single injection of labelled glucose. 2. Glucose turnover rate (RG; mumol . min-1 . kg-1) was found to be 0.55-065 (2-3H glucose) and 0.34 +/- 0.42 (U14C glucose). 3. Glucose transit time was 443-449 min, glucose mass 233-261 mumol . kg-1, and glucose recycling 37%. 4. Oxygen consumption (MO2) amounted to 94 +/- 6.2 mumol . min-1 . kg-1. 5. The comparison with other fish species, mammals and birds, taking into account body size, temperature, diet, exercise, in poikilotherms and homeotherms leads to the calculation of a glucose turnover index (RGI = RG x 6 x 100 x MO2(-1)). 6. Value of this, generally lower in ectotherm teleosts (2-9), than in endotherms: mammals, birds and thunidae (22-60), confirms the minor quantitative importance of glucose in the metabolism of most fish.

Depressed gluconeogenesis and ureogenesis in isolated hepatocytes after intermittent hypoxia in rats.

1. Rats were exposed to hypobaric hypoxia (equivalent altitude 4500 m), 2 x 2 hr per day, for 5 days. Isolated hepatocytes were prepared on day 6 after 18 hr of fast and also from control normoxic animals. The hepatocytes were incubated (120 min) with various substrates. 2. ATP contents were lower in hepatocytes from exposed as compared to control animals whether at the beginning (14%) or at the end (-6 to -33%) of incubation depending on the substrate. 3. Gluconeogenesis from all precursors (lactate, alanine, pyruvate, glutamine) was significantly reduced (40-50%) in exposed as compared to control animals. 4. Ureogenesis from alanine and from pyruvate + NH4Cl was also markedly depressed in exposed animals but no differences were noticed with glutamine or lactate + NH4Cl and alanine + NH4Cl. 5. Results are discussed in relation to known effects of acute and chronic hypoxia, interrelationship between gluconeogenesis and ureogenesis, taking into account the inhomogeneity of liver and the metabolic properties of periportal and perivenous hepatocytes.