[Sertraline-induced chronic eosinophilic pneumonia]. / Pneumopathie chronique à éosinophiles induite par la sertraline.

INTRODUCTION: Sertraline is a selective serotonin reuptake inhibitor which is often used as first-line treatment for depression. Several patterns of interstitial lung disease attributable to sertraline have been reported in the literature. CASE REPORT: A 69-year-old patient, who had been taking sertraline to treat severe depression for 10 months, presented with a deterioration in his general condition and respiratory symptoms found to be associated with bilateral pneumonitis. An exhaustive assessment did not reveal any infectious or autoimmune aetiology. Transthoracic lung biopsy revealed a pattern of eosinophilic lung disease. Sertraline-induced lung toxicity was then suspected and this treatment was therefore stopped. The patient's symptoms resolved and the chest imaging normalized. CONCLUSIONS: Our observation suggests that sertraline was the cause of chronic eosinophilic pneumonia characterized by an insidious clinical presentation several months after starting the medication. Given its widespread prescription, we encourage any clinician facing this disease to pay attention to possible drug-induced origins of lung disease.

[Women and acute coronary syndrome with ST elevation: Excess mortality related to longer delays and spontaneous coronary dissection]. / Syndromes coronariens aigus avec sus-ST chez la femme: une surmortalité liée aux délais de prise en charge et dissection coronaire spontanée.

The outcome of patients with ST elevation acute coronary syndrome (ACS) has been increasingly improving in the general population over the past few decades. However, detailed analysis of the results show that the reduction in mortality rates is higher in males compared to their female counterparts. The excess mortality rate observed in women, though sometimes questioned, has been widely reported in the literature. The higher mortality rate observed in women with ST elevation ACS can be explained by the presence of aggravating clinical factors such as older age, a higher percentage of diabetics, and a higher frequency of cardiogenic shock. Other factors pertaining to patient management seem to negatively impact the outcome. These factors include a lower use of reperfusion strategies, longer time to treatment mainly as a result of diagnostic uncertainty with respect to a disease, which is believed to affect principally the male gender. The doubts that female patients themselves and their families have about the nature of their symptoms are also present in the medical environment but cease to exist in the catheterization laboratory. This is illustrated in the first clinical case that we present here. Coronary reperfusion is the cornerstone of the therapeutic management of MI. In this context, bleeding complications associated with the implemented treatments can also result in an increased mortality rate in this more vulnerable population. When all the factors likely to influence the prognosis are taken into account, excess mortality seems to persist in women, especially in younger patients. As described in the second clinical case, a distinct physio-pathological factor, more frequent in women, could account for this higher mortality rate. Indeed, spontaneous coronary dissection and intramural hematoma are not always easy to diagnose and may not be adequately managed by reperfusion treatments. In addition, these coronary reperfusion strategies are probably not adapted to this type of ACS. It is, therefore, very important to identify them by angiography coupled with intra-coronary imaging examination when necessary and to carry out further research to adjust our PCI techniques to this pathology.

Rangeland Rummy - a board game to support adaptive management of rangeland-based livestock systems.

Rangeland-based livestock systems have to deal with the significant instability and uncertainty of the agricultural context (policy changes, volatility of input prices, etc.), and especially of the climatic context. Thus, they are particularly concerned by adaptive management strategies. To support the development of such strategies, we developed a board game including a computer model called "Rangeland Rummy". It is to be used by groups of farmers and agricultural consultants in the context of short workshops (about 3 h). Rangeland Rummy builds upon five types of material object: (i) a game board; (ii) a calendar stick indicating the starting date of the game board; (iii) sticks marked with the feed resources available for combinations of vegetation types and their management practices; (iv) cards to define animal groups and their feeding requirements throughout the year; (v) cards related to types of feed that can be attributed to animal groups throughout the year. Using these material objects, farmers collectively design a rangeland-based livestock system. This system is immediately evaluated using a computer model, i.e. a spreadsheet providing graphs and indicators providing information on, among other things, the extent to which quantitative and qualitative animal feeding requirements are covered across the year. Playing the game thus consists in collectively and iteratively designing and evaluating rangeland-based livestock systems, while confronting the players with new contextual challenges (e.g. interannual variability of weather, volatility of input prices) or new farmers' objectives (e.g. being self-sufficient for animal feeding). An example of application of Rangeland Rummy with 3 farmers in southern France is reported. Applications show that it tends to develop farmers' adaptive capacity by stimulating their discussions and the exchange of locally-relevant knowledge on management strategies and practices in rangeland-based livestock systems.

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.

[Influence of palmar digital artery patency on neurological recovery of palmar digital nerve lesions]. / Influence de la perméabilité de l'artère digitale palmaire sur la récupération nerveuse dans les lésions des nerfs digitaux palmaires.

Should the palmar digital artery be repaired in the pedicular section of the finger? This repair is discussed in the case of a unilateral pedicular lesion on a vascularised finger, and often neglected in current surgical practice. The problem is knowing the role of a permeable artery in sensory recovery and cold intolerance. The author presents a retrospective study on palmar digital nerve reinnervation after section with or without palmar digital artery section. Artery permeability was studied by doppler ultrasonography. Forty nerves in 35 patients were studied after at least 3 years had passed. Twenty-five nerves were associated with a permeable artery, 15 with a non permeable artery. The functional result was evaluated with the Weber test (S2PD) and by the presence or absence of cold intolerance. This work demonstrates the statistically significant role of the palmar digital artery in sensitive recovery quality and cold intolerance appearance. Its permeability ensures a better sensitive result with an 8.84 mm S2PD versus 13.47 mm with a non permeable artery. The benefit of the systematic repair of palmar digital artery is thus demonstrated for the first time. This repair is all the more justified if local conditions are unfavorable, in particular in contuse wounds with associated lesions (tendinous or bone).

[Retrospective study of complications and imperfections in superior pedicle breast reduction: 100 cases]. / Etude rétrospective des complications et imperfections : à propos de 100 cas de mammoplastie de réduction à pédicule supérieur.

A retrospective study was made to assess complications of superior pedicle breast reduction, in the Besançon hospital plastic surgery ward. One hundred patients operated between 2003 and 2007 were reexamined. In every case, the intervention was performed by the same operator (Pr Tropet) using the same technique. The average postoperation time range was 2 years (from 8 months to 5 years). The interview's minutes were formalized via a revisions sheet, including medical files, photos, and pre- and postoperative measures. Complications (hematoma, infection, necrosis, suture disunion, thromboembolic disease) were reported in 16 % of the cases. These lead to three emergency reoperations for drainage, and six delayed reoperations. Result imperfections were related to areola and nipple, and to scars. Two patients requested a scar revision. The results match reported data. Technical modifications are suggested to reduce complications or imperfections.

[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.

[Polylactic acid injections: usefullness for the treatment of facial lipoatrophy in HIV+ patients under tritherapy]. / Injections d'acide polylactique: intérêt dans la correction des lipoatrophies faciales chez les patients VIH+ sous trithérapie.

BACKGROUND: The aim of the study was to evaluate the mean-term efficacy and tolerance of the polylactic acid injections (New-Fill) for the correction of facial lipoatrophy occurring in HIV-positive patients under tri-therapy. MATERIAL AND METHOD: The patients were managed at the University Hospitals of Besançon and Strasbourg (France) from January 2002 to December 2005 for a prospective study. The patients were consecutively included in this study once their consent was obtained. Patients not stabilized by their antiretroviral treatment were excluded. Facial lipoatrophy was classified in four clinical stages (stage I: mild, stage II: moderate, stage III: important, stage IV: severe) after a clinical examination. The polylactic acid solution was prepared according to the manufacturer's recommendations, and injected in a retrotracing manner in the hypoderm at the rate of one 5 ml flask per side, with an interval of one month. The number of sessions varied according to the severity of the stage. Treatment efficacy, assessed after a minimal follow-up of one year, was established clinically by comparing the initial and final photographs (changes in the clinical stage) and by the patient's and surgeon's satisfaction rate (from zero to ten). Treatment tolerance was established on the painfulness of injections and on socioprofessional constraints reported by the patients and made on a visual analogical scale. The occurrence of adverse-effects was checked. Finally, we compared the cost of the treatment with that of lipostructure. RESULTS: Twenty-five patients were included (mean age: 44, sex-ratio: 23 male/2 female patients). The mean body mass index was 21. The mean CD4 cell count was 600/mm(3). The mean HIV-1 RNA was 276 copies/ml. The severity of the lipoatrophy was stage one in two patients (8%), stage two in 12 patients (48%), stage three in nine patients (36%), and stage four in two patients (8%). The mean number of sessions was 5.2. The mean follow-up time was 26 months. In 76% of the cases we observed a complete correction of lipoatrophy (100% of stages I, 92% of stages II, 66% of stages III, 0% of stages IV). However, among stages II, III, and IV that were incompletely corrected, an improvement was noticed in all patients (grading to an inferior stage, at least). The mean satisfaction rate was 8/10 by patients and 7.2/10 by surgeons. In six patients (24%) a renewal of the treatment was proposed because of inadequate results. The painfulness of injections was rated at 3.3/10 and constraints at 3/10 by patients. One single case of visible and palpable sub-cutaneous granuloma was noticed in a patient at the end of the follow-up period (18 months). DISCUSSION: The use of polylactic acid is a safe and efficient procedure for the treatment of facial lipo-atrophy in HIV-infected patients, however severe the clinical stage may be, after a two-year follow-up period. We recommend hypodermic (and not dermic) injections to prevent adverse effects. This treatment is not more expensive then lipo-structure and the progressive correction is considered as an important advantage by patients. Considering our results, the simplicity of the procedure, and the low rate of complications observed, the injection of poly-lactic acid has become our first intention treatment for this condition.

Nutritional risk score is not sensitive enough to predict weight loss in diseased elderly subjects.

OBJECTIVES: malnutrition is highly prevalent in diseased elderly people, especially in hospital departments, and weight loss also occurs during hospital stays. Among the tools proposed to define malnutrition and to screen persons at risk of malnutrition, the nutritional risk score (NRS) has been suggested as a simple tool. DESIGN AND PARTICIPANTS: the aim of the present study was to test the validity of the NRS to predict weight changes 3 months after discharge. NRS and visual analogue scales for hunger, early satiety, thirst, fatigue and pain were performed in 106 patients aged 65 yrs and over, 67 treated for cancer, without overt malnutrition. RESULTS: forty six patients lost more than 1 kg. None of the parameters tested was correlated with weight changes, except NRS which was weakly correlated (r=-0.22, P=0.037). However a 0 score at NRS was associated with weight changes ranging -9 to +5 kg. Furthermore, the 11 patients with a high NRS score and weight loss were in a clinical situation that made it very likely that they would lose weight. In conclusion, NRS is not a valid score to predict weight change.

[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.

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.

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.

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.

[Withdrawal syndromes of newborns of pregnant drug abusers maintained under methadone or high-dose buprenorphine: 246 cases]. / Syndromes de sevrage des nouveau-nés de mères toxicomanes substituées par la méthadone ou la buprénorphine haut dosage.

UNLABELLED: Perinatal prognosis of pregnant drug abusers is better with intensive prenatal care and substitution maintenance programs. There is a large body of data in the literature on methadone (MTD), but very little on high-dose buprenorphine (HDB). The objective of this study was to compare 2 groups of pregnant women maintained on MTD or HDB for perinatal events. STUDY DESIGN: Prospective multicentric study; all neonates (NN) whose mothers has been maintained during pregnancy on MTD or HDB were included by 34 French perinatal centers with specialized staff for care of these pregnant drug abusers. RESULTS: Two hundred and forty-six pregnant women were included: 93 (38%) MTD and 153 (62%) HDB. Social and perinatal data, prenatal care and factors correlated with poor prenatal care are reported. Forty-six percent of the pregnant women had good prenatal care; 88% had peridural analgesia; mean birthweight=2838g; mean gestational age=38.7 weeks; prematurity<37 weeks=13; intra-uterine growth retardation=32%. Sixty-five percent neonates had withdrawal neonatal syndrome (WNNS) at a mean age of beginning at H40, mean highest Lipsitz score was 8.2 at H78. Half of the neonates with WNNS received treatment, mainly with morphine chlorhydrate. Neonatal mortality was 0/246. Discharge of the neonates was 60% with their father and their mother, and 32% with their mother alone; 4% were placed in foster homes by judicial decision. The only statistically significant differences between the MTD and HDB groups were: maintenance program was more frequently initiated before this pregnancy for the HDB vs MTD group (p<0.03); MTD maintenance was more often supervised by maintenance specialized centers and HDB by general practitioners (p<0.001); prematurity was 18% for MTD group vs 9% for HDB group (p<0.04); mean age of maximum Lipsitz score was H92 for MTD group vs H70 for HDB group (p<0.001). CONCLUSIONS: The perinatal medical and social prognosis of these 246 pregnant drug abusers and of their neonates appeared to be improved by the specialized prenatal care, comparatively with literature data. Perinatal impact of substitution program during pregnancy would be similar with MTD or HDB.

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.

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.

[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.

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.