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Biomedical subjects

B Bernard

Publications and source records attributed to B Bernard.

At least 19 recordsLinked to original sources

In vivo radionuclide uptake quantification using a multi-pinhole SPECT system to predict renal function in small animals.

PURPOSE: In vivo quantification of radiopharmaceuticals has great potential as a tool in developing new drugs. We investigated the accuracy of in vivo quantification with multi-pinhole single-photon emission computed tomography (SPECT) in rats. METHODS: Fifteen male Lewis rats with different stages of renal dysfunction were injected with 50 MBq 99mTc-dimercaptosuccinic acid. Four to six hours after injection, SPECT of the kidneys was acquired with a new four-headed multi-pinhole collimator camera. Immediately after imaging the rats were sacrificed and the kidneys were counted in a gamma-counter to determine the absorbed activity. SPECT data were reconstructed iteratively and regions of interest (ROIs) were drawn manually. The absolute activity in the ROIs was determined. RESULTS: Uptake values ranging from 0.71% to 21.87% of the injected activity were measured. A very strong linear correlation was found between the determined activity in vivo and ex vivo (r2=0.946; slope m=1.059). CONCLUSION: Quantification in vivo using this multi-pinhole SPECT system is highly accurate.

Animals↗

[Jejunal perforation by a fish bone diagnosed by CT-Scan: report of two cases].

The authors relate two cases of peritonitis secondary to jejunal perforation by a fish bone. Clinically, the first patient presented signs and symptoms of acute diverticulitis and the second had signs of duodenal perforation. In both cases, the diagnosis was made by the CT-scan revealing a linear radio-opaque object suggestive of a fish bone perforating the jejunum. At laparotomy of the first case, we found a perforation located above several loops of small bowel densely adhered to the nonabsorbable intra-abdominal mesh. Removal of the fish bone, suture of the jejunal perforation, washing and drainage of the abdominal cavity were performed. The mesh was removed and replaced by a polyglycolic acid mesh. In the second case, jejunal perforation occurred in an unaltered small bowel loop and a short intestinal resection was performed. The postoperative course was uneventful for both patients. These clinical cases allow us to discuss the several fish bone perforation site and our patients precipitating factors.

Aged↗

Asphalt volcanism and chemosynthetic life in the Campeche Knolls, Gulf of Mexico.

In the Campeche Knolls, in the southern Gulf of Mexico, lava-like flows of solidified asphalt cover more than 1 square kilometer of the rim of a dissected salt dome at a depth of 3000 meters below sea level. Chemosynthetic tubeworms and bivalves colonize the sea floor near the asphalt, which chilled and contracted after discharge. The site also includes oil seeps, gas hydrate deposits, locally anoxic sediments, and slabs of authigenic carbonate. Asphalt volcanism creates a habitat for chemosynthetic life that may be widespread at great depth in the Gulf of Mexico.

Animals↗

Apoptosis participates to liver damage in HSV-induced fulminant hepatitis.

BACKGROUND: HSV fulminant hepatitis is a rare pathology. Rapid hepatic failure, as a consequence of extended liver damage, has generally been attributed to necrosis. As apoptosis can constitute another way for hepatocytes to die, we decided to investigate whether programmed cell death took place during HSV fulminant hepatitis. METHODS: Liver sections were obtained from two cases of fulminant herpetic hepatitis as well as from hepatitis B virus and Rickettsia-infected livers. Herpes simplex virus infection was confirmed using in situ hybridization. Apoptosis was assessed by histopathological examination, p53, activated-caspase 3 and Fas immunohistochemistry and TUNEL labeling. RESULTS: We report that the number of cells expressing activated-caspase 3 was largely increased in fulminant herpes simplex virus hepatitis, when compared to livers chronically infected by hepatitis B virus or from a Rickettsial acute hepatitis. Apoptosis of hepatocytes was confirmed by a positive double-staining for activated-caspase 3 and hepatocytes. Finally, the apoptotic process has progressed beyond the step of nuclear DNA cleavage as demonstrated by TUNEL labeling. CONCLUSION: These data as a whole show that apoptosis is responsible, at least partially, for liver damage during HSV fulminant hepatitis.

Apoptosis↗

Flumazenil vs. placebo in hepatic encephalopathy in patients with cirrhosis: a meta-analysis.

BACKGROUND: Randomized controlled trials testing flumazenil in hepatic encephalopathy have shown conflicting results. AIM: To compare flumazenil and placebo in hepatic encephalopathy in patients with cirrhosis. METHODS: An overview of randomized controlled trials comparing flumazenil and placebo in hepatic encephalopathy in patients with cirrhosis was performed. For each end-point, heterogeneity and treatment efficacy were assessed by Peto and Der Simonian methods. As most trials were crossover in nature, a sensitivity analysis was performed including the two treatment periods. RESULTS: Six double-blind randomized controlled trials, including 641 patients (326 treated with flumazenil and 315 with placebo), were identified. The treatment duration ranged from 5 min to 3 days. Heterogeneity tests between control groups were not significant. The mean percentages of patients with clinical improvement (five trials) were 27% in treated groups and 3% in placebo groups. This difference was significant by both methods (Peto: odds ratio=6.15; 95% confidence interval, 4.0-9.5; P < 0.001; Der Simonian: mean rate difference, 29%; 95% confidence interval, 17-41; P < 0.001). The mean percentages of patients with electroencephalographic improvement were 19% in treated groups and 2% in placebo groups. This difference was significant only with the Peto method (odds ratio=5.8; 95% confidence interval, 3.4-9.7; P < 0.001). The sensitivity analysis showed similar results. CONCLUSIONS: This meta-analysis shows that flumazenil induces clinical and electroencephalographic improvement of hepatic encephalopathy in patients with cirrhosis.

Coma↗

Comparison of the effect of terlipressin and albumin on arterial blood volume in patients with cirrhosis and tense ascites treated by paracentesis: a randomised pilot study.

BACKGROUND: Patients with cirrhosis and tense ascites treated by paracentesis alone have a decrease in effective arterial blood volume after ascites removal. Although intravenous albumin is effective in preventing paracentesis induced decreased arterial blood volume, its clinical use is controversial. As paracentesis induces arteriolar vasodilation which plays a role in the development of decreased effective arterial blood volume, administration of a vasoconstrictor (terlipressin) could prevent circulatory alterations due to paracentesis. AIMS: To perform a pilot study comparing the effects of terlipressin and albumin on effective arterial blood volume in patients with cirrhosis treated by paracentesis for tense ascites. METHODS: Twenty patients with cirrhosis and tense ascites were randomly assigned to be treated by either paracentesis and terlipressin or paracentesis and albumin. Terlipressin (3 mg) or albumin (8 g/l of removed ascites) were administered on the day of paracentesis. Effective arterial blood volume was assessed by measuring plasma renin concentrations at baseline and on the day of hospital discharge (4-6 days after treatment). Decreased effective arterial blood volume was defined as an increase in plasma renin concentrations on the day of hospital discharge of more than 50% of baseline values. RESULTS: Irrespective of the treatment group, mean values for plasma renin concentrations at hospital discharge did not differ from their respective baseline values (p=0.10). Baseline plasma levels of renin concentrations did not differ between the terlipressin and albumin groups (p=0.61). Changes from baseline in plasma renin concentrations did not differ between groups (p=0.39). Three patients in the terlipressin group and three in the albumin group developed decreased arterial blood volume. CONCLUSIONS: This randomised pilot study suggests that terlipressin may be as effective as intravenous albumin in preventing a decrease in effective arterial blood volume in patients with cirrhosis treated by paracentesis for tense ascites.

Albumins↗

[Effect of climatic changes on the phenology of plants and the presence of pollen in the air in Switzerland].

The phenologic observations carried out in Switzerland since 1951 show a clear tendency to the earlier appearance of the spring phases of development of the vegetation during last decades. As these phases are strongly influenced by the temperature, these results reinforce the hypothesis according to which the climatic reheating in progress strongly influences the development of the vegetation. The flowering and the release of the pollen of the plants allergens are significant phenologic phases for human health. Modifications in their dates of manifestation lead to a displacement of the periods of allergic risk. The analysis of the aerobiologic data of the Swiss stations over one duration of more than 20 years showed that the species which flower in winter and in spring were subject to the influence of the soft winters of the years 1990 to 2000. In certain areas the pollen of birch, for example, is nowadays waited on average 3 weeks earlier than 20 years ago, whereas the pollen of ash appears with one month in advance. The phenologic and aeropalynologic studies thus prove sensitive witnesses of the climatic change in progress. This last intervenes like an indirect but significant component of human health, in particular when the field of the allergies is considered.

Air↗

[Dependence for daily life activities in the prison population in Western France].

OBJECTIVE: As the mean age of the penitential population rises and the duration of imprisonment grows longer, health services are confronted with the problem of prisoners dependent for daily life activities. The purpose of this study was to determine the number of prisoners dependent for daily life activities and quantify their dependency on human and material support. METHODS: A survey was conducted in the summer of 2,000 in the western region of France (19 prisons in the following regions: Pays-de-Loire, Brittany, Lower Normandy). RESULTS: Among the 4,168 persons incarcerated in these regions, 32 dependent prisoners were identified: 21 men (mean age 57 years) and 11 women (mean age 48 years). Among these persons, 19 suffered from major or moderate dependence (GIR 1-4). The main problems involved toilet facilities, dressing, transfers, and moving about. When human support was available, it was generally provided by other prisoners. Material help was scarce. DISCUSSION: The questions of prisoner's rights, human assistance, the status of caregivers, and the need for adapted architectural, material, and medical facilities are discussed. The information collected here provides a better knowledge of prisoners' needs for support and for changes which would be necessary in the prison environment.

Activities of Daily Living↗

Early administration of vapreotide for variceal bleeding in patients with cirrhosis.

BACKGROUND: In patients with cirrhosis, pharmacologic or endoscopic treatment may control variceal bleeding. However, the effects of early administration of a somatostatin analogue followed by endoscopic treatment are unknown. METHODS: We studied the effects of treatment with vapreotide, a somatostatin analogue, begun before endoscopic treatment in 227 patients with cirrhosis who were hospitalized for acute upper gastrointestinal bleeding. The patients were randomly assigned to receive vapreotide (a 50-microg intravenous bolus followed by an infusion at a rate of 50 microg per hour for five days) or placebo within a mean (+/-SD) of 2.3+/-1.5 hours after admission. All the patients received endoscopic treatment a mean of 2.6+/-3.3 hours after the infusion was begun. After the exclusion of 31 patients whose bleeding was not caused by portal hypertension, there were 98 patients in each group. RESULTS: At the time of endoscopy, active bleeding was evident in 28 of 91 patients in the vapreotide group (31 percent), as compared with 43 of 93 patients in the placebo group (46 percent) (P=0.03). During the five-day infusion, the primary objective--survival and control of bleeding--was achieved in 65 of 98 patients in the vapreotide group (66 percent) as compared with 49 of 98 patients in the placebo group (50 percent) (P=0.02). The patients in the vapreotide group received significantly fewer blood transfusions (2.0+/-2.2 vs. 2.8+/-2.8 units, P=0.04). Overall mortality rates at 42 days were not significantly different in the two groups. CONCLUSIONS: In patients with cirrhosis and variceal bleeding, the combination of vapreotide and endoscopic treatment is more effective than endoscopic treatment alone as a method of controlling acute bleeding. However, the use of combination therapy does not affect mortality rates at 42 days.

Blood Transfusion↗

Staurosporine-induced apoptosis of HPV positive and negative human cervical cancer cells from different points in the cell cycle.

In the present study, we compare the sensitivity of CaSki and HeLa cells (HPV positive, wild-type p53) and C33A cells (HPV negative, mutated p53) to a protein kinase inhibitor, the staurosporine (ST). We show that ST can reversibly arrest the three cervical-derived cell lines, either in G1 or in G2/M. Beyond certain ST concentrations or/and over 24 h exposure, the cells underwent apoptosis. This process took place in G1 and G2/M for C33A and CaSki plus HeLa cell lines, respectively. By using an in vitro cell-free system, we demonstrated that cytoplasmic extracts from apoptotic cells were sufficient to induce hallmarks of programmed cell death on isolated nuclei. Moreover, we found that only G2/M cytoplasmic extracts from viable CaSki and HeLa cells supplemented with ST, triggered apoptosis while exclusively G1 cytoplasmic fractions from C33A cells were efficient. Our study describes a possible involvement of the HPV infection or/and p53 status in this different ST-induced apoptosis susceptibility.

Apoptosis↗

Focal neurological signs in hepatic encephalopathy in cirrhotic patients: an underestimated entity?

OBJECTIVES: Focal neurological signs have been poorly documented in the course of hepatic encephalopathy in cirrhotic patients because they are not mentioned in any textbooks of liver diseases. Having the opportunity to observe such cases, we underwent a prospective study to determine incidence, characteristics, associated factors, prognostic significance, and outcome of this rare form of hepatic encephalopathy. METHODS: Over a 12-month period, all cirrhotic patients hospitalized in the intensive care unit of our department for hepatic encephalopathy were prospectively studied. Patients with clinical and electroencephalogram evidences of hepatic encephalopathy were examined by a senior physician and, in cases of focal neurological signs, underwent examination by a neurologist, CT scan, lumbar punction, and cerebral magnetic resonance imaging and echo Doppler examination of neck and head vessels. Clinical and biological parameters were compared in patients during episodes with and without focal neurological signs, and outcome was noted. RESULTS: Thirty-four cirrhotic patients were hospitalized for 48 episodes of hepatic encephalopathy; two of these patients with cerebral hematoma were excluded. Twenty-four patients exhibited 38 hepatic encephalopathy episodes without focal neurological signs (82.6%), and eight patients exhibited eight hepatic encephalopathy episodes with focal neurological signs (17.4%) that were hemiplegia and hemiparesia in six patients (75%). In all patients, cerebral CT scan and cerebrospinal fluid examination disclosed no abnormalities, as neither did cerebral magnetic resonance imaging (n = 5) and echo Doppler examination of neck and head vessels (n = 5). Except for female sex, which was more often encountered in patients with focal neurological signs (p < 0.05), there were no differences between episodes with and without focal neurological signs for any of the parameters studied. In surviving patients who recovered from hepatic encephalopathy (7/8), focal neurological signs disappeared without recurrences after follow up of 6 months (3-12). CONCLUSIONS: Hepatic encephalopathy with focal neurological signs when carefully searched is not uncommon. It could be more frequent in cirrhotic females, is reversible, and has no prognostic significance.

Case-Control Studies↗

Staging of the commitment of murine cardiac cell progenitors.

The staging of murine cardiomyocyte specification and determination was investigated in cultures of tissue explants from pre- and postgastrulated embryos and after transplantation of cardiac or cardiogenic tissues from mouse embryos into 2-day-old chick embryos in different locations. The development of transplanted and cultured cells in cardiomyocytes was evaluated by testing the expression of several cardiac transcription factor genes (Nkx 2.5, eHAND, dHAND, GATA-4), alpha-cardiac actin mRNA, and beta-myosin heavy chain protein. In vitro analyses showed that cells with the potential to form cardiac muscle were present prior to gastrulation in 6.5-day postconception (dpc) epiblasts, as indicated by the expression of Nkx 2.5, eHAND, dHAND, and GATA-4 cardiac transcription factors; desmin transgene; alpha-cardiac actin; and beta-myosin heavy chain. Conversely, epiblasts transplanted into the chicken somitic environment did not exhibit full cardiogenic cell differentiation. It was determined that chick host axial structures did not influence cardiogenesis in transplants. Mesoderm from late streak explants was capable of differentiating into the cardiac phenotype in the avian heterotopic environment, indicating that the specification of cardiac precursors (under way by 6.5 dpc) became irreversible at around the late streak stage in mouse embryo. Although in vitro analyses showed that interaction with endoderm is not required for the specification of murine cardiac cells, the presence of endoderm in explant cultures between mid- and late streak stages stimulated emerging mesodermal cells to adopt a myocardial pathway, whereas ectoderm had no influence on cardiomyogenesis.

Animals↗

First human studies with a high-molecular-weight iron chelator.

The release of free, reactive iron from cellular iron stores has been implicated as an important contributor to tissue damage in a variety of clinical situations, including ischemia and reperfusion injury, hemorrhagic shock, and burn injury. Deferoxamine mesylate (DFO), the only iron chelator currently approved for clinical use, is used for the treatment of iron overload, including acute iron poisoning and treatment of chronic iron overload in transfusion-dependent anemias such as beta-thalassemia. However, it is not suitable for acute care situations because of its toxicity, primarily hypotension when given at high intravenous doses, and its short plasma half-life. We have produced a high-molecular-weight iron chelator by chemically coupling DFO to hydroxyethyl starch. This novel chelator (HES-DFO) was administered to healthy male subjects by intravenous infusion over a 4-hour period. The drug was well tolerated, and signs of DFO acute toxicity were not observed. Maximum plasma chelator levels of approximately 3 mmol/L were achieved with HES-DFO, which is more than an order of magnitude higher than has been reported with injections of DFO. Drug residence time in plasma was markedly prolonged, with an initial half-life of 22 to 33 hours. Urinary iron excretion was 7.1 +/- 2.2 mg in 48 hours in the highest dose group, as compared with 0.06 +/- 0.15 mg in control subjects who received normal saline infusions. Intravenous infusion of HES-DFO is well tolerated, produces substantial and prolonged plasma chelator levels, and markedly stimulates urinary iron excretion.

Adult↗

Blood neutrophil functions and cytokine release in severe alcoholic hepatitis: effect of corticosteroids.

BACKGROUND/AIMS: Several observations point to an important role of interactions between polymorphonuclear neutrophils and cytokines in severe alcoholic hepatitis. The polymorphonuclear neutrophil activation status and the local and systemic pro- and anti-inflammatory cytokine responses were quantified. The effect of corticosteroids, widely used in this setting, was evaluated using these parameters. METHODS: We studied blood polymorphonuclear neutrophil functions in terms of L-selectin and beta2-integrin expression, H2O2 production and IL-8 and tumor necrosis factor alpha synthesis capacity. We also measured IL-8, tumor necrosis factor alpha and IL-10 plasma and liver tissue levels. Fifteen patients with alcoholic hepatitis were compared to 15 patients with alcoholic cirrhosis without alcoholic hepatitis, and to 10 healthy volunteers. The impact of a 28-day course of corticosteroids on blood neutrophils activation status and cytokine levels was evaluated in patients with alcoholic hepatitis. RESULTS: Blood polymorphonuclear neutrophils were activated, as shown by increased H2O2 production (48+/-6 vs 29+/-6 MFI in healthy controls), and decreased L-selectin expression (300+/-61 vs 449+/-59 in healthy controls). Upon stimulation, polymorphonuclear neutrophils synthesized large amounts of IL-8 (21.7+/-9.2 ng/ml vs 8.8+/-10 ng/ml in healthy controls) and tumor necrosis factor alpha (524+/-132 pg/ml vs 79+/-144 pg/ml in healthy controls). Tumor necrosis factor alpha and IL-8 plasma and tissue levels were markedly increased as IL-10 was barely detectable in alcoholic hepatitis patients, compared to cirrhotic patients and healthy controls. During steroid therapy, plasma levels of the pro-inflammatory cytokine IL-8 fell as early as day 14, while levels of the anti-inflammatory cytokine IL-10 increased on day 21. Finally, polymorphonuclear neutrophil functions returned to normal after treatment. CONCLUSION: Severe alcoholic hepatitis appears to be associated with polymorphonuclear neutrophil activation and an imbalance between pro- and anti-inflammatory cytokines; during steroid therapy a normalization of these parameters was observed.

Adrenal Cortex Hormones↗