[Omental infarct after a gastric by-pass]. / Infarctus épiploïque après by-pass gastrique.

The authors describe the case of a 56 year old woman 25 days status post laparoscopic gastric bypass who presented with an acute onset of severe epigastric pain with signs of inflammation and localized peritoneal irritation. Although her findings suggested a late anastomotic leak, an abdominal CT scan revealed only necrosis of the greater omentum beneath the left hepatic lobe. This finding permitted a non-surgical approach; after observation over several days, the patient's symptoms resolved completely.

[Prevalence of undernutrition in 143 patients before liver transplantation. The Lausanne experience between 1997 and 2005]. / Prévalence de la dénutrition chez 143 adultes en bilan prétransplantation hépatique. Experience lausannoise de 1997 a 2005.

The prevalence of undernutrition was prospectively studied in 143 patients before liver transplantation between 1997 and 2005. Nutritional assessment is a particularly tricky problem in cirrhosis and mid-arm muscle circumference is considered as the best reliable anthropometric tool. In this prospective study, prevalence rate is very high (61%) and undernutrition is more frequent in alcoholic cirrhotic patients. In conclusion, these patients should benefit from an early dietician intervention before liver transplantation.

[Nutritional approach for patients with amyotrophic lateral sclerosis]. / Approche nutritionnelle des patients atteints de Sclérose Latérale Amyotrophique.

Prevalence of malnutrition in ALS ranges between 16 and 53 p. 100. The percentage of loss of weight greater than 10 p. 100 or, in a more inconstant way, body mass index lower than 18.5, are relevant criteria of malnutrition because predictive of survival. Arm muscle circumference and bioelectrical impedance analysis can assess body composition, but their impact on disease progression has not been evaluated. Measurement of serum albumin levels is of no interest. NUTRITIONAL REQUIREMENTS: Considering that energy expenditure is increased 10 to 20 p. cent in the majority of patients, energy needs can be estimated to be approximately 35 kcal/kg/d. In order to limit the accumulation of fat mass in the sub-group of patients with decreased energy expenditure, monitoring of triceps skin fold or impedance could be proposed, but their interest remains to be evaluated. In the absence of available data on protein requirements in ALS, an intake ranging between 1 and 1,5 g/kg/d seems reasonable, knowing that there is a risk of deficiency when intake is less than 1 g/kg/d and that an increase to 1,5 g/kg/d, considered as harmless, could be useful in the event of hypercatabolism. Supplementation with creatine, antioxidants or amino acids has not proven to be effective. These nutrients being provided by a balanced diet, specific supplementations have no proven utility provided that the patient receives sufficient proteins and energy. Systematic supplementation with vitamin D is however warranted to prevent osteoporosis due to the known risk related to a common state of deficiency. RELEVANCE OF GASTROSTOMY: Studies with good methodological quality evaluating percutaneous endoscopic gastrostomy (PEG) in ALS are not available. Because of the impact of malnutrition on survival, PEG must be considered when oral intake becomes insufficient. Retrospective studies suggest that the PEG tube is usually inserted too late during the disease course, minimizing expected benefits. Criteria useful for making the decision to installation a PEG tube should be the subject of randomized controlled studies. Mortality in the month which follows PEG, approximately 10 p. cent, is primarily due to respiratory failure. It occurs more frequently among patients having a forced vital capacity<50 p. cent. To avoid a degradation of pulmonary function in this sub-group of patients, several approaches are suggested in the literature: earlier PEG, peri-operative noninvasive ventilation, and radiological gastrostomy which does not require a general anesthesia. Whatever the technique used for gastrostomy, it should be carried out in an expert centre, because patients with ALS are more exposed to complications than others.

Flux-force relationships in intact cells: a helpful tool for understanding the mechanism of oxidative phosphorylation alterations?

On isolated mitochondria, numerous studies of the relationships between fluxes and their associated forces have led to the description of some properties of the oxidative phosphorylation pathway. However whether such an approach can be applied to understanding the actual situation in intact living cells needs further consideration. In this study on isolated hepatocytes, we describe the dependence of the respiratory rate on the three thermodynamic forces linked to oxidative phosphorylation (i.e. the redox span over the respiratory chain, the electrical potential difference across the inner mitochondrial membrane and the free energy of ATP synthesis reaction). Even if this description is phenomenological and some objections may be raised regarding the relevance of such a bulk-phase force estimation, we present some results showing that the study of flux-force relationships in intact cells may be a helpful approach for understanding the mechanisms by which oxidative phosphorylation activity is changed.

Chronic ethanol ingestion increases efficiency of oxidative phosphorylation in rat liver mitochondria.

The efficiency of oxidative phosphorylation was compared between rats chronically fed with ethanol and controls. (i) Results showed that the liver mitochondria state 4 respiratory rate was strongly inhibited, while the corresponding proton-motive force was not affected; (ii) the cytochrome oxidase content and activity were decreased and (iii) the oxidative-phosphorylation yield was increased in the ethanol exposed group. Furthermore, oxidative phosphorylation at coupling site II was not affected by ethanol. Cytochrome oxidase inhibition by sodium-azide mimicked the effects of ethanol intoxication in control mitochondria. This indicates that the decrease in cytochrome oxidase activity induced by ethanol intoxication directly increases the efficiency of oxidative phosphorylation.

[Epidemiology of hepatocellular carcinoma in the department of Calvados]. / Epidémiologie du carcinome hépatocellulaire dans le département du Calvados.

OBJECTIVES: The aim of this study was to determine the epidemiological characteristics of hepatocellular carcinoma in a non-selected population. METHODS: Between 1984 and 1990, all cases of hepatocellular carcinoma were registered at the Registry of Digestive Tumors of Calvados. Standardized incidence rates were calculated for males and females. Prognostic factors were determined by the Cox multivariate method. RESULTS: 213 patients with hepatocellular carcinoma were registered. Standardized incidence rates were 7.5/100,000 in men and 0.4/100,000 in women. Sex-ratio was 18.3. Mean age was 66.4 years; hepatocellular carcinoma was uncommon (3%) before the age of 50. Cirrhosis was associated in 85.9% of patients. The cause of cirrhosis was known in 150 cases: alcoholic: 73.3%, cryptogenetic: 8.7%, viral B or C: 7.3%, alcoholic and viral B or C: 5.3%, and genetic hemochromatosis: 4.7%. The overall survival rate in 203 patients was 21%, 8% and 3% at 1 year, 3 years and 5 years, respectively. The multivariate study identified 4 prognostic factors: number of tumors < or = 2, lack of ascites, serum alpha-fetoprotein < or = 10 mg/mL, and hepatocellular carcinoma revealing a well-compensated liver disease until the time of diagnosis. CONCLUSION: The occurrence of hepatocellular carcinoma seems to be linked to cirrhosis, male sex, and age > 50, which could be used as the main selection criterias for the screening of hepatocellular carcinoma.

[Anaphylactoid reactions to an injectable solution of a cremophor-containing solution of multivitamins]. / Réactions anaphylactoïdes à une solution polyvitaminée injectable contenant un crémophore.

We report four anaphylactoid reactions after intravenous administration of a cremophor-containing multivitamin hydrosol (Hydrosol Polyvitaminé Roche), observed over an 8-month period in a small region of France. The reactions occurred immediately following intravenous infusion of either ionic solutions or parenteral nutrition mixture containing the multivitamin solution. In three cases, erythema and dyspnoea appeared within minutes. The infusion was rapidly stopped and corticosteroids were given to two patients. The fourth patient had erythema and swelling of the face within 30 min of infusion, and severe bronchoconstriction and hypotension within 60 min, before infusion was stopped. In-vivo histamine release from mast cell was proved. These reactions are highly suggestive of an anaphylactoid mechanism, due to the multivitamin solution, as all the other drugs were continued without subsequent reactions. The responsible agent is thought to be polyethoxylated castor oil (Cremophor EL), as it is known to produce such effects. Medical practitioners should evaluate the risk/benefit ratio each time they give this drug.

Randomised clinical trial: enteral nutrition does not improve the long-term outcome of alcoholic cirrhotic patients with jaundice.

BACKGROUND: Malnutrition and jaundice are independent prognostic factors in cirrhosis. AIM: To assess the impact of enteral nutrition on the survival of alcoholic cirrhotic patients with jaundice but without acute alcoholic hepatitis. METHODS: The study was a multicentre prospective randomised controlled trial comparing effects of enteral nutrition vs. a symptomatic support in patients with alcoholic cirrhosis and jaundice (bilirubin ≥51 µmol/L) but without severe acute alcoholic hepatitis. A total of 99 patients were randomised to receive either the conventional symptomatic treatment (55 patients) or the symptomatic support associated with 35 kcal/Kg/day of enteral nutrition during 4 weeks followed by an oral nutritional support during 2 months (44 patients). Randomisation was stratified on nutritional status. One-year survival curves were compared using the Kaplan-Meier method and Logrank test. RESULTS: Populations in both arms were similar. One-year survival was similar in the overall population (27/44 patients (61.4%) in the enteral nutrition arm vs. 36/55 (65.5%) in the control arm; Logrank P = 0.60) and in the subgroup suffering from malnutrition [18/29 patients (62.1%) in the enteral nutrition arm vs. 20/32 (62.5%) in the control arm; Logrank P = 0.99]. There was no statistical difference for bilirubin, prothrombin rate, Child-Pugh score, albumin or nutritional assessment. Complications during treatment (bleeding, encephalopathy, infection) occurred in 23% of patients in the enteral nutrition group (10/44) vs. 16% (9/55) of the control patients (P = 0.59). CONCLUSION: Enteral nutrition does not improve the survival and hepatic or nutritional parameters of cirrhotic patients with jaundice.

Uncoupling effect of polyunsaturated fatty acid deficiency in isolated rat hepatocytes:effect on glycerol metabolism.

The effects of a 4-week deficiency in polyunsaturated fatty acids (PUFA) in isolated rat hepatocytes have been investigated for oxidative phosphorylation and fatty acid, dihydroxyacetone (DHA) or glycerol metabolism. Oxygen uptake was significantly increased (by 20%) with or without fatty acid addition (octanoate or oleate) in the PUFA-deficient group compared with controls. The effect persisted after oligomycin addition but not after that of potassium cyanide, leading to the conclusion that, in these intact cells, the mitochondria were uncoupled. The PUFA-deficient group exhibited a significant decrease in the cytosolic ATP/ADP ratio, whereas the mitochondrial ratio was not affected. PUFA deficiency led to a 16% decrease in DHA metabolism owing to a 34% decrease in glycerol kinase activity; the significant decrease in the ATP/ADP ratio was accompanied by an increase in the fractional glycolytic flux. In contrast, glycerol metabolism was significantly enhanced in the PUFA-deficient group. The role of the glycerol 3-phosphate dehydrogenase step in this stimulation was evidenced in hepatocytes perifused with glycerol and octanoate in the presence of increased concentrations of 2,4-dinitrophenol (Dnp): uncoupling with Dnp led to an enhancement of glycerol metabolism, as found in PUFA deficiency, although it was more pronounced than in controls. The matrix/cytosol gradients for redox potential and ATP/ADP ratio were lower in cells from PUFA-deficient rats, suggesting a decreased mitochondrial membrane potential in accordance with the uncoupling effect. Moreover, a doubling of the mitochondrial glycerol 3-phosphate dehydrogenase activity in the PUFA-deficient group compared with controls led us to conclude that the activation of glycerol metabolism is the consequence of two mitochondrial effects: uncoupling and an increase in glycerol 3-phosphate dehydrogenase activity.

Mitochondrial respiratory chain adjustment to cellular energy demand.

Because adaptation to physiological changes in cellular energy demand is a crucial imperative for life, mitochondrial oxidative phosphorylation is tightly controlled by ATP consumption. Nevertheless, the mechanisms permitting such large variations in ATP synthesis capacity, as well as the consequence on the overall efficiency of oxidative phosphorylation, are not known. By investigating several physiological models in vivo in rats (hyper- and hypothyroidism, polyunsaturated fatty acid deficiency, and chronic ethanol intoxication) we found that the increase in hepatocyte respiration (from 9.8 to 22.7 nmol of O(2)/min/mg dry cells) was tightly correlated with total mitochondrial cytochrome content, expressed both per mg dry cells or per mg mitochondrial protein. Moreover, this increase in total cytochrome content was accompanied by an increase in the respective proportion of cytochrome oxidase; while total cytochrome content increased 2-fold (from 0.341 +/- 0.021 to 0.821 +/- 0.024 nmol/mg protein), cytochrome oxidase increased 10-fold (from 0.020 +/- 0.002 to 0.224 +/- 0.006 nmol/mg protein). This modification was associated with a decrease in the overall efficiency of the respiratory chain. Since cytochrome oxidase is well recognized for slippage between redox reactions and proton pumping, we suggest that this dramatic increase in cytochrome oxidase is responsible for the decrease in the overall efficiency of respiratory chain and, in turn, of ATP synthesis yield, linked to the adaptive increase in oxidative phosphorylation capacity.

Oxidative phosphorylation in intact hepatocytes: quantitative characterization of the mechanisms of change in efficiency and cellular consequences.

Two mechanisms may affect the yield of the oxidative phosphorylation pathway in isolated mitochondria: (i) a decrease in the intrinsic coupling of the proton pumps (H+/2e- or H+/ATP), and (ii) an increase in the inner membrane conductance (proton or cation leak). Hence three kinds of modifications can occur and each of them have been characterized in isolated rat liver mitochondria (see preceding chapter by Rigoulet et al.). In intact isolated hepatocytes, these modifications are linked to specific patterns of bioenergetic parameters, i.e. respiratory flux, mitochondrial redox potential, DY, and phosphate potential. (1) The increase in H+/ATP stoichiometry of the mitochondrial ATP synthase, as induced by almitrine [20], leads to a decrease in mitochondrial and cytosolic ATP/ADP ratios without any change in the protonmotive force nor in the respiratory rate or redox potential. (2) In comparison to carbohydrate, octanoate metabolism by beta-oxidation increases the proportion of electrons supplied at the second coupling site of the respiratory chain. This mimics a redox slipping. Octanoate addition results in an increased respiratory rate and mitochondrial NADH/NAD ratio while protonmotive force and phosphate potential are almost unaffected. The respiratory rate increase is associated with a decrease in the overall apparent thermodynamic driving force (2deltaE'o - ndeltap) which confirms the 'redox-slipping-like' effect. (3) An increase in proton conductance as induced by the protonophoric uncoupler 2,4-dinitrophenol (DNP) leads to a decrease, as expected, in the mitochondrial NADH/NAD and ATP/ ADP ratios and in deltapsi while respiratory rate is increased. Thus, each kind of modification (proton leak, respiratory chain redox slipping or increase in H+/ATP stoichiometry of ATPase) is related to a specific set of bioenergetic parameters in intact cells. Moreover, these patterns are in good agreement with the data found in isolated mitochondria. From this work, we conclude that quantitative analysis of four bioenergetic parameters (respiration rate, mitochondrial NADH/ NAD ratio, protonmotive force and mitochondrial phosphate potential) gives adequate tools to investigate the mechanism by which some alterations may affect the yield of the oxidative phosphorylation pathway in intact cells.

The mitochondrial consequences of uncoupling intact cells depend on the nature of the exogenous substrate.

In isolated mitochondria the consequences of oxidative phosphorylation uncoupling are well defined, whereas in intact cells various effects have been described. Uncoupling liver cells with 2,4-dinitrophenol (DNP) in the presence of dihydroxyacetone (DHA) and ethanol results in a marked decrease in mitochondrial transmembrane electrical potential (DeltaPsi), ATP/ADP ratios and gluconeogenesis (as an ATP-utilizing process), whereas the increased oxidation rate is limited and transient. Conversely, when DHA is associated with octanoate or proline, DNP addition results in a very large and sustained increase in oxidation rate, whereas the decreases in DeltaPsi, ATP/ADP ratios and gluconeogenesis are significantly less when compared with DHA and ethanol. Hence significant energy wastage (high oxidation rate) by uncoupling is achieved only with substrates that are directly oxidized in the mitochondrial matrix. Conversely in the presence of substrates that are first oxidized in the cytosol, uncoupling results in a profound decrease in mitochondrial DeltaPsi and ATP synthesis, whereas energy wastage is very limited.

Exogenous Mg-ATP induces a large inhibition of pyruvate kinase in intact rat hepatocytes.

Mg-ATP infusion in vivo has been reported to be beneficial both to organ function and survival rate in various models of shock. Moreover, a large variety of metabolic effects has been shown to occur in several tissues due to purinergic receptor activation. In the present work we studied the effects of exogenous Mg-ATP in rat liver cells perifused with dihydroxyacetone to investigate simultaneously gluconeogenetic and glycolytic pathways. We found a significant effect on oxidative phosphorylation as characterized by a decrease in oxygen consumption rate and in the cellular ATP-to-ADP ratio associated with an increase in lactate-to-pyruvate ratio. In addition, exogenous Mg-ATP induced rapid and reversible inhibition of both gluconeogenesis and glycolysis. The main effect on gluconeogenesis was located at the level of the fructose cycle, whereas the decrease in glycolysis was due to a strong inhibition of pyruvate kinase. Although pyruvate kinase inhibition induced by exogenous Mg-ATP was allosteric when assessed in vitro after enzyme extraction, we found a large decrease in the apparent maximal velocity when kinetics were assessed in vivo in intact perifused hepatocytes. This newly described short-term regulation of pyruvate kinase occurs only in the intact cell and may open new potentials for the pharmacological regulation of pyruvate kinase in vivo.

Mitochondrial adaptation to in vivo polyunsaturated fatty acid deficiency: increase in phosphorylation efficiency.

Polyunsaturated fatty acid (PUFA) deficiency affects respiratory rate both in isolated mitochondria and in hepatocytes, an effect that is normally ascribed to major changes in membrane composition causing, in turn, protonophoriclike effects. In this study, we have compared the properties of hepatocytes isolated from PUFA-deficient rats with those from control animals treated with concentrations of the protonophoric uncoupler 2,4-dinitrophenol (DNP). Despite identical respiratory rate and in situ mitochondrial membrane potential (delta psi), mitochondrial and cytosolic ATP/ADP-Pi ratios were significantly higher in PUFA-deficient cells than in control cells treated with DNP. We show that PUFA-deficient cells display an increase of phosphorylation efficiency, a higher mitochondrial ATP/ADP-Pi ratio being maintained despite the lower delta psi. This is achieved by (1) decreasing mitochondrial Pi accumulation, (2) increasing ATP synthase activity, and (3) by increasing the flux control coefficient of adenine nucleotide translocation. As a consequence, oxidative phosphorylation efficiency was only slightly affected in PUFA-deficient animals as compared to protonophoric uncoupling (DNP). Thus, the energy waste induced by PUFA deficiency on the processes that generate the proton motive force (pmf) is compensated in vivo by powerful adaptive mechanisms that act on the processes that use the pmf to synthesize ATP.

Prevalence of electrocardiographic and echocardiographic abnormalities in ambulatory ischemic colitis.

The aim of this study was to evaluate the prevalence of cardiac arrhythmia and intracardiac embolic process in ambulatory ischemic colitis. From November 1994 to November 1997, 33 consecutive cases of ambulatory ischemic colitis were detected. This study included 21 women and 12 men with a mean age of 71 years. All patients underwent a cardiovascular investigation including questioning, electrocardiogram, 24-hr ambulatory electrocardiography and transthoracic echocardiography. A prior history of ischemic colitis was found in four cases (12%). Cardiac arrhythmia was detected in eight cases. Transthoracic echocardiography showed an intracardiac process, potentially responsible for a peripheral embolism, in four cases. In conclusion, the aggregate, in 33% of the patients, there was potential cardiac etiology. This suggests that when ambulatory ischemic colitis occurs, it is necessary to perform an exhaustive cardiovascular evaluation similar to those performed in other ischemic diseases.

[Castleman's disease of the abdomen]. / Maladie de Castleman à localisation abdominale.

Plasmocytic variants of Castleman's disease are uncommon. We report a new case of abdominal location with a rapidly fatal outcome. Another particularity of that case was the negativity of Kaposi's sarcoma associated herpesvirus, a virus recently implicated in human immunodeficiency virus associated Castleman's disease.