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R Dumas

Publications and source records attributed to R Dumas.

At least 37 records · Page 2Linked to original sources

[Comparison of primary trapezometacarpal cup fixation using mechanical tests].

INTRODUCTION: In order to optimise the primary fixation of the cup of the Arpe (Biomet Merck) trapeziometacarpal prosthesis, several geometries have been studied. The mechanical strengths of the primary fixations ensured by cup "with slots", "bladed" and "with crown", have been assessed and compared to the one obtained for the primary anchorage of the Arpe cup. METHOD: For each cup, the strength of the primary fixation has been assessed in torsion (torque along the cup axis) and bending (torque perpendicular to the cup axis). Tests have been performed on prototype cups set up in a vertebral body of lamb cancellous bone. Torque recording allowed the assessment of the maximum strength for each cup type. RESULTS: Arpe and cup "with slots" showed an effective bending strength, respectively due to the three anchorage picks and to the equatorial over-thickness. However, the cup "with crown" demonstrated a better bending strength with a mean torque of pulling out Cbending = 0.89 Nm. In torsion, the three anchorage picks of the Arpe cup did not allow a solid anchorage. For such a loading, the cup "with crown" also showed the best torsion strength with a mean unsealing torque Ctorsion = 0.83 Nm. DISCUSSION: The equatorial over-thickness seems to give good bending and torsion strengths to the "bladed" and "with crown" cups, with a press-fit effect. Replacing the fixation points of the Arpe cup by a crown also allowed the improvement of its torsion strength.

Arthroplasty, Replacement↗

Enzymology, structure, and dynamics of acetohydroxy acid isomeroreductase.

Acetohydroxy acid isomeroreductase is a key enzyme involved in the biosynthetic pathway of the amino acids isoleucine, valine, and leucine. This enzyme is of great interest in agrochemical research because it is present only in plants and microorganisms, making it a potential target for specific herbicides and fungicides. Moreover, it catalyzes an unusual two-step reaction that is of great fundamental interest. With a view to characterizing both the mechanism of inhibition by potential herbicides and the complex reaction mechanism, various techniques of enzymology, molecular biology, mass spectrometry, X-ray crystallography, and theoretical simulation have been used. The results and conclusions of these studies are described briefly in this paper.

Alcohol Oxidoreductases↗

Effect of a single embryonic exposure to alcohol on glucose transporter (GLUT-1) distribution in brain vessels of aged mouse.

Distribution of glucose transporter (GLUT-1) in brain microvascular endothelium, representing the anatomic site of the blood-brain barrier (BBB), was studied with electron microscopy in 24-month-old mice, which had been exposed prenatally (on 9th day of gestation) to a single teratogenic dose of ethanol. Offspring of mice that had received an equivalent volume of isocaloric dextrose served as controls. Sections of brain samples embedded at low temperature in hydrophilic resin Lowicryl K4M were exposed to anti-GLUT-1 antiserum followed by gold-labelled secondary antibodies. By using morphometry, the labelling density was recorded over luminal and abluminal plasma membranes of the endothelial cells of blood microvessels supplying four brain regions: cortex, hippocampus, cerebellum and olfactory bulb. We found that the density of immunosignals for GLUT-1, represented by colloidal gold particles, was unchanged in the olfactory bulb and slightly lowered in the abluminal plasmalemma of the vascular endothelium in the cerebral cortex of the ethanol-treated mice. In contrast, statistical analysis using Mann-Whitney U-test revealed that in the hippocampus and cerebellum, the density of immunolabelling of both plasma membranes of microvascular endothelial cells was significantly lowered in the ethanol-treated mice. These findings suggest that prenatally applied ethanol had a different influence on the vasculature supplying different brain regions. In effect, the inefficient supply of glucose to selected brain regions can be one of the factors leading to the previously observed deficit in long-term memory in a similar alcohol-treated group of mice.

Aging↗

Argon plasma endoscopic section of biliary metallic prostheses.

We report our recent experience of using argon plasma to endoscopically cut biliary Wallstent prostheses in these patients. The first patient had a bleeding duodenal ulceration caused by the impaction of the prosthesis meshes whereas the second patient had an ill-positioned biliary stent with impaction into the opposite duodenal wall. Both prostheses were shortened using argon plasma. In the third patient, the lower extremity of a obstructed biliary Wallstent was positioned in the third duodenum preventing its endoscopic catheterization. After shortening using argon plasma, a new plastic stent could be inserted to allow drainage. The outcomes in these cases demonstrate the feasibility of endoscopically shortening metallic Wallstents after release using argon plasma.

Aged↗

Safety and immunogenicity of a pediatric formulation of inactivated hepatitis A vaccine in Argentinean children.

BACKGROUND: Children are a reservoir of hepatitis A virus and must be considered as primary targets of any immunization strategy. The safety and immunogenicity were evaluated for a new formulation of an inactivated hepatitis A vaccine, Avaxim 80 units, containing one-half the antigen dose of the adult formulation. METHODS: The safety of two doses of this vaccine given 6 months apart was evaluated in an open study in 537 Argentinean children 12 months to 15 years old. Immunogenicity was evaluated at Weeks 0, 2, 24 and 27 in a subgroup of 120 subjects. RESULTS: Two weeks after the first vaccine dose, >99% of initially seronegative children had seroconverted (titers > or =20 mIU/ml), with a geometric mean titer of 98.5 mIU/ml. Before booster at 24 weeks all subjects had seroconverted. A strong anamnestic response was observed after the second dose at which time the geometric mean titer had increased >35-fold, and antibody titers were consistent with long term protection. Immediate adverse reactions were observed in 3 of 537 (0.6%) subjects after the first dose. Local reactions were mild and transient and did not increase with subsequent doses. Among the systemic events reported during the 7-day follow-up period, 37 cases of fever after the first dose and 22 cases after the second dose were reported. Only 3 cases of fever were clearly related to vaccination (< or =38.2 degrees C) after the first injection, all of which subsided in less than 1 day. CONCLUSIONS: This study demonstrated the safety and immunogenicity of a pediatric formulation of hepatitis A vaccine in children ages 12 months to 15 years in healthy children ages 12 to 47 months.

Adolescent↗

Crystal structure of threonine synthase from Arabidopsis thaliana.

Threonine synthase (TS) is a PLP-dependent enzyme that catalyzes the last reaction in the synthesis of threonine from aspartate. In plants, the methionine pathway shares the same substrate, O-phospho-L-homoserine (OPH), and TS is activated by S-adenosyl-methionine (SAM), a downstream product of methionine synthesis. This positive allosteric effect triggered by the product of another pathway is specific to plants. The crystal structure of Arabidopsis thaliana apo threonine synthase was solved at 2.25 A resolution from triclinic crystals using MAD data from the selenomethionated protein. The structure reveals a four-domain dimer with a two-stranded beta-sheet arm protruding from one monomer onto the other. This domain swap could form a lever through which the allosteric effect is transmitted. The N-terminal domain (domain 1) has a unique fold and is partially disordered, whereas the structural core (domains 2 and 3) shares the functional domain of PLP enzymes of the same family. It also has similarities with SAM-dependent methyltransferases. Structure comparisons allowed us to propose potential sites for pyridoxal-phosphate and SAM binding on TS; they are close to regions that are disordered in the absence of these molecules.

Amino Acid Sequence↗

Evidence for two distinct effector-binding sites in threonine deaminase by site-directed mutagenesis, kinetic, and binding experiments.

A three-dimensional structure comparison between the dimeric regulatory serine-binding domain of Escherichia coli D-3-phosphoglycerate dehydrogenase [Schuller, D. J., Grant, G. A., and Banaszak, L. J. (1995) Nat. Struct. Biol. 2, 69-76] and the regulatory domain of E. coli threonine deaminase [Gallagher, D. T., Gilliland, G. L., Xiao, G., Zondlo, J., Fisher, K. E., Chinchilla, D. , and Eisenstein, E. (1998) Structure 6, 465-475] led us to make the hypothesis that threonine deaminase could have two binding sites per monomer. To test this hypothesis about the corresponding plant enzyme, site-directed mutagenesis was carried out on the recombinant Arabidopsis thaliana threonine deaminase. Kinetic and binding experiments demonstrated for the first time that each regulatory domain of the monomers of A. thaliana threonine deaminase possesses two different effector-binding sites constituted in part by Y449 and Y543. Our results demonstrate that Y449 belongs to a high-affinity binding site whose interaction with a first isoleucine induces conformational modifications yielding a conformer displaying a higher activity and with enhanced ability to bind a second isoleucine on a lower-affinity binding site containing Y543. Isoleucine interaction with this latter binding site is responsible for conformational modifications leading to final inhibition of the enzyme. Y449 interacts with both regulators, isoleucine and valine. However, interaction of valine with the high-affinity binding site induces different conformational modifications leading to reversal of isoleucine binding and reversal of inhibition.

Arabidopsis↗

Endoscopic bilateral metal stent placement for malignant hilar stenoses: identification of optimal technique.

BACKGROUND: The aim of this study was to identify factors that facilitate bilateral insertion of metal stents in malignant hilar stenoses, for which plastic stents often result in incomplete drainage and subsequent cholangitis. METHODS: Between January 1994 and April 1998, we collected 45 cases of advanced (Bismuth stage II or higher) hilar malignant stenoses. The insertion technique was progressively modified and the success rate in the early period (1994 to 1995) was compared with that of a later period (1996) and the most recent period (1997 to 1998). RESULTS: Overall success rate was 73.3% (33 of 45). The success rates for the three periods were 50%, 67%, and 88% (p = 0.008), respectively. Cholangitis occurred in 3 of the patients with unilateral stents compared with 1 with bilateral stents. CONCLUSION: We have described a technique for endoscopic insertion of bilateral metallic stents for malignant hilar stenoses that results in high (>88%) and reproducible success rates.

Aged↗

Endoscopic management of sump syndrome after choledochoduodenostomy: retrospective analysis of 30 cases.

BACKGROUND: Side-to-side choledochoduodenostomy is a frequently performed operation. Postoperative biliary "sump syndrome" is infrequent, a complication for which endoscopic sphincterotomy is regarded as the treatment of choice. METHODS: We retrospectively analyzed 30 cases of sump syndrome and describe the symptoms, the delay before the appearance of symptoms, laboratory abnormalities, the nature of the biliary obstruction, and the outcome of endoscopic sphincterotomy including its efficiency and complications. RESULTS: The median clinical latency was 5 years (range 1 month to 28 years), the median delay between surgery and diagnosis was 6 years (range 1 month to 28 years). Fourteen patients had abdominal pain with fever, 5 had isolated abdominal pain, 4 had post-prandial pain, 4 had hepatic abscesses, and 3 had acute pancreatitis. Liver function tests were abnormal in 79%. During endoscopic retrograde cholangiopancreatography, food debris was identified in 18 patients in the biliary sump, biliary calculi in 10 patients, and a mixture of food and calculi in 2 patients. All patients underwent endoscopic sphincterotomy without complication. Recurrence during a median follow-up of 36 months (range 3 months to 11 years) was not observed. CONCLUSIONS: Sump syndrome most often becomes symptomatic only after a long delay. Abdominal pain with fever was the most frequent symptom. Liver function tests were abnormal in the majority of patients. Food debris was the most frequent cause. Endoscopic sphincterotomy appeared to be a safe, reliable treatment.

Adult↗

Fmr1 knockout mouse has a distinctive strain-specific learning impairment.

The Fmr1 gene knockout mouse is a model for the human Fragile X mental retardation syndrome. Fmr1 knockout mice with a C57BL/6-129/OlaHsd hybrid background have been reported to have only a very mild deficiency in learning the Morris water maze task. We compared the effect of this knockout mutation on learning in mice with either an FVB/N-129/OlaHsd hybrid background or a C57BL/6 background. When FVB-129 mice were tested in a cross-shaped water maze task, the knockout mice showed a pronounced deficiency in their ability to learn the position of a hidden escape platform in comparison to normal littermates. In contrast, knockout mice with a C57BL/6 background learned the maze just as well as their normal littermates. Fear conditioning did not reveal differences between knockout and normal mice in either background. These results show that silencing the Fmr1 gene clearly interfered with learning a specific visuospatial task in FVB/N-129 hybrid mice but not in C57BL/6 mice. The strain dependence may model the influence of genetic background in the human Fragile X syndrome.

Animals↗

Structure of spinach acetohydroxyacid isomeroreductase complexed with its reaction product dihydroxymethylvalerate, manganese and (phospho)-ADP-ribose.

Acetohydroxyacid isomeroreductase catalyses a two-step reaction composed of an alkyl migration followed by an NADPH-dependent reduction. Both steps require a divalent cation and the first step has a strong preference for magnesium. Manganese ions are highly unfavourable to the reaction: only 3% residual activity is observed in the presence of this cation. Acetohydroxyacid isomeroreductase has been crystallized with its substrate, 2-aceto-2-hydroxybutyrate (AHB), Mn(2+) and NADPH. The 1.6 A resolution electron-density map showed the reaction product (2,3-dihydroxy-3-methylvalerate, DHMV) and a density corresponding to (phospho)-ADP-ribose instead of the whole NADP(+). This is one of the few structures of an enzyme complexed with its reaction product. The structure of this complex was refined to an R factor of 19.3% and an R(free) of 22.5%. The overall structure of the enzyme is very similar to that of the complex with the reaction-intermediate analogue IpOHA [N-hydroxy-N-isopropyloxamate; Biou et al. (1997), EMBO J. 16, 3405-3415]. However, the active site shows some differences: the nicotinamide is cleaved and the surrounding amino acids have rearranged accordingly. Comparison between the structures corresponding to the reaction intermediate and to the end of the reaction allowed the proposal of a reaction scheme. Taking this result into account, the enzyme was crystallized with Ni(2+) and Zn(2+), for which only 0.02% residual activity were measured; however, the crystals of AHB/Zn/NADPH and of AHB/Ni/NADPH also contain the reaction product. Moreover, mass-spectrometry measurements confirmed the -cleavage of nicotinamide.

Adenosine Diphosphate Ribose↗

A new source of drug-induced acute pancreatitis: codeine.

A variety of drugs have been reported to cause acute pancreatitis during the past 40 years. We report the first series of four cases of acute pancreatitis related to codeine ingestion. Four patients (three female, mean age 50.2 yr) presented with clinical, biochemical, and radiological evidence of acute pancreatitis. All four had ingested a therapeutic dose of codeine 1-3 h before the onset of abdominal symptoms. Unintentional rechallenge occurred in three cases and was followed by recurrence of acute pancreatitis in all three. All patients made a full recovery. All four patients had had a previous cholecystectomy. The likely underlying pathophysiological mechanism is codeine-induced spasm of the sphincter of Oddi combined with sphincter of Oddi dysfunction related to a previous cholecystectomy. Codeine ingestion leads to acute pancreatitis in some individuals. Previous cholecystectomy seems to predispose to codeine-induced pancreatitis.

Acute Disease↗

A randomized placebo-controlled double-blind trial of lipid-lowering strategies in patients with renal insufficiency: diet modification with or without fenofibrate.

BACKGROUND: Renal insufficiency is characterized by lipoprotein abnormalities including elevated triglyceride levels. PATIENTS AND METHODS: The safety and efficacy of micronized fenofibrate as a treatment for dyslipidemia in patients with progressive renal insufficiency was evaluated in a randomized, placebo-controlled double-blind study comparing fenofibrate and dietary modification to dietary modification alone. Patients were evaluated following a 3-month pre-randomization period of dietary counseling. Twenty-eight patients with moderate renal insufficiency and triglyceride levels 2.3 mmol/l or LDL/HDL ratio 5 were randomized to placebo (n = 12) or fenofibrate (n = 16) therapy. Treatment and dietary counseling continued for 6 months. RESULTS: Ten of 16 patients (63%) treated with fenofibrate achieved a 30% reduction in triglyceride levels or LDL/HDL ratio reduction < 5 compared to 2 of 17% in the placebo group (p = 0.015). Triglyceride levels were significantly reduced in the fenofibrate group (-31%) versus placebo (+1.3%, p = 0.003). In compliant patients (n = 25) there was also a significantly greater increase in HDL cholesterol levels in the fenofibrate group (+19.9%) compared to placebo (-4.7%, p = 0.001). Changes in measured creatinine clearance were not significantly different between the groups and there were no serious adverse effects of treatment. CONCLUSION: Fenofibrate therapy combined with dietary modification effectively reduced triglyceride levels in renal insufficiency patients without serious adverse effects.

Adult↗

Immunogenicity and safety of an inactivated hepatitis A vaccine in Taiwanese adults and children.

The safety and immunogenicity of an inactivated hepatitis A vaccine (AVAXIM, 160 antigen units) was evaluated in 190 subjects: 50 children aged from 2 to 5 years, 70 children aged from 6 to 17 years and 70 adults aged from 18 to 30 years in a monocentric, open, non-controlled, phase III trial conducted in Taipei, Taiwan from December 1996 to October 1997. The vaccine was administered intramuscularly, with a two-dose schedule 6 months apart. Clinical adverse events were monitored during the seven days following each injection. Hepatitis A virus (HAV) antibody titers were measured by modified radioimmunoassay on the day of inclusion and four weeks after both the first dose and booster injection. Among the 190 subjects who received the first dose, 174 (91.6%) were initially HAV seronegative and 16 (8.4%) were HAV seropositive at inclusion. One hundred and seventy-four subjects (91.6%) received the booster dose and completed the study. One month after the first dose, all the subjects, whatever the age, presented HAV antibody titers over 20 mIU/ml. In children (2 to 17 years), the GMT was 136 mIU/ml at week 4 and 7,906 mIU/ml four weeks after the booster dose. In adults (> or = 18 years), GMT values were 93 mIU/ml at week 4 and 3,655 mIU/ml four weeks after the booster. These results show a strong anamnestic response to the second dose of vaccine and are compatible with long-term antibody persistence in each age group. The vaccine was safe and well tolerated. No vaccine-related serious adverse event occurred. No immediate reaction occurred. The majority of the reactions were reported by adults after the primary injection. Local reactions (pain and redness) were reported by 9.0% and 4.0% of the subjects after the primary and the booster doses, respectively. Systemic reactions (mainly myalgia/arthralgia or asthenia) affected less than 10% of the subjects after the first dose and less than 3% after the booster. Results from this study in a Taiwanese population are consistent with those obtained with the same vaccine in previous European studies in children and adults, and suggest that AVAXIM (160 AU) is suitable for use in all subjects aged over 2 years.

Adolescent↗