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Biomedical subjects

R Dumas

Publications and source records attributed to R Dumas.

At least 73 records · Page 4Linked to original sources

Long term treatment of biliary stricture due to chronic pancreatitis with a metallic stent.

The exact role of endoprostheses in the management of chronic pancreatitis-associated biliary strictures has not yet been clearly established. We report an unusual case of a patient with this condition who was treated for an unexpectedly long term with a self-expanding metallic endoprosthesis. There has only been one previous report of the use of metallic stents in this situation. It appears that metallic endoprostheses may have a role to play in the management of selected patients who have chronic pancreatitis-associated bile duct stricture.

Cholestasis, Extrahepatic↗

Migraine history and migraine-induced stroke in the Dijon stroke registry.

Two thousand three hundred and eighty-nine patients with first-ever stroke were registered in the population-based Dijon Stroke Registry over an 11-year period. There was a history of migraine in 49 cases (2%), with a majority of women (2.8% versus 1.1% men) with the following distribution: 27 cases among 1,380 large-artery cerebral infarctions (1.9%), 6 cases among 358 small-artery cerebral infarctions (1.6%), 6 cases among 412 cerebral infarctions due to cardiac embolism (1.4%), 7 cases among 191 cerebral hemorrhages (3. 6%) and 3 cases among 47 subarachnoid hemorrhages (6.3%). The male/female ratio was 0.58 for the 49 strokes with a history of migraine versus 1.27 for the 2,340 strokes with no history of migraine. Twelve migraine-induced ischemic strokes occurred with an infarction of the posterior area of the brain in young patients. The annual incidence was 0.80/100,000/year (confidence interval, CI = 0. 37-1.57) with a predominance of women (1.02/100,000/year, CI = 0. 52-1.25; men: 0.57/100,000/year; CI = 0.28-1.04). We conclude that a history of migraine is more frequent in women, in particular in those with hemorrhagic strokes, and that the incidence of migraine-induced stroke in our population-based study is higher in women, although it remains low.

Adolescent↗

Incidence trends of ischemic stroke and transient ischemic attacks in a well-defined French population from 1985 through 1994.

BACKGROUND AND PURPOSE: The changing incidence of ischemic stroke is of major concern in view of its public health impact, to define the population concerned, to identify risk factors, and to set up health-care systems. The aim of this study was to evaluate the time trends associated with the incidence of all the subtypes of ischemic stroke and transient ischemic attacks in a well-defined population for 10 years. METHODS: Since 1985, a population registry has recorded each patient living in Dijon (France) who suffered from a cerebrovascular disease (CVD) regardless of the type of management. This study involved all patients suffering from their first ischemic stroke and their first transient ischemic attacks (TIAs) during 1 calendar year between January 1, 1985 and December 31, 1994. The incidence changes according to age, sex, and type of cerebral ischemic event (cortico-subcortical infarct, lacunar infarct, and TIA) were studied on the basis of their annual variations. RESULTS: During the 10-year study period, 834 cortico-subcortical infarcts (52.1%), 296 lacunar infarcts (18.5%), 369 TIAs (23.1%), and 101 undetermined ischemic strokes (6.3%) were collected. The incidence of all ischemic events was relatively stable in both sexes over the 10-year period. However, the incidence rates differed according to age and type of ischemia. An increased incidence of cerebral cortico-subcortical infarct was observed in patients older than 75 years of age (+5.45% annual change [AC] in men, P<0.05; +5. 09% AC in women, NS). In parallel, a higher proportion of emboligenic cardiac arrhythmias was observed in these patients (P<0. 001). The incidence of lacunar infarcts tended to decrease, regardless of age but mainly in men under younger than 75 years of age (-12.74% AC in men, NS; +0.31% AC in women, NS). The incidence of TIAs was relatively stable in both sexes. Because our population consisted of a large number of elderly subjects, the increase in cardioembolic causes could partially explain the increased incidence of cerebral cortico-subcortical infarcts in patients older than 75 years of age. CONCLUSIONS: These preliminary data emphasize the importance of stroke surveillance in considering the variations of the different mechanisms of ischemic cerebrovascular disease. Although the incidence of TIA is stable and the incidence of lacunes tends to decrease in men, mainly before 75 years of age, we emphasize the rise of the crude incidence of cortico-subcortical infarcts in men older than 75 years of age, induced by an increase in cardioembolic causes.

Age Factors↗

Extensive aetiological investigations in acute pancreatitis: results of a 1-year prospective study.

BACKGROUND: Epidemiological data on acute pancreatitis are poorly defined. AIMS: To prospectively evaluate the aetiology of acute pancreatitis and to assess the benefits of intensive investigations. METHODS: In a prospective, 1-year study all cases of acute pancreatitis in the Nice catchment area were enrolled. Subjects underwent routine (serum calcium, phosphate and triglycerides; abdominal ultrasonography and CT scan) and additional, delayed intensive investigations (ERCP with bile sampling and/or endoscopy ultrasonography). RESULTS: One hundred and twenty-one cases were included. After routine investigations, a biliary, alcoholic, miscellaneous or unknown origin was diagnosed in 43%, 31.4%, 9.9% and 15.7%, respectively. In subjects with biliary pancreatitis, 43% had no previous history of biliary disease. In the alcohol-related subgroup, pancreatitis recurred in 18.5% during 114.5 days mean follow-up. In subjects with a first episode of alcoholic pancreatitis, delayed supplemental investigations revealed underlying chronic pancreatitis in 92.8%. After routine investigations, a diagnosis of pancreatitis of unknown origin was made in 15.7% (n = 19) of subjects. Additional investigations revealed an underlying cause in 57.8% of these patients (n = 11), including malignancy (n = 3) and biliary disease (n = 4), reducing the overall rate of pancreatitis with no apparent cause to 6.6%. CONCLUSIONS: Investigative techniques, particularly ERCP, will reveal the underlying aetiology of pancreatitis in the majority of patients presenting with 'idiopathic' pancreatitis and should be considered when routine tests are negative.

Acute Disease↗

[Writing disorder using a word processor: role of the left hand].

A young female secretary developed a writing disorder, exclusively expressed when using a word processor, following an ischemic vascular event involving the insula and the right posterior parietal region. There was no disturbance of laterality. The neurological examination, completed by neuropsychological tests eliminated any persistent phasic or gnostic disorders. The analysis of the text produced revealed abnormalities leading to the conclusion that the left hand was responsible for all the errors observed. A sensorimotor integration disorder produced a melokinetic apraxia which appeared to be the cause of the writing disorder which would have most likely remained unknown had the subject not been a secretary.

Adult↗

Allosteric activation of Arabidopsis threonine synthase by S-adenosylmethionine.

Plant threonine synthase, in contrast to its bacterial counterpart, is strongly stimulated by S-adenosylmethionine via a noncovalent interaction [Giovanelli et al. (1984) Plant. Physiol. 76, 285-292]. The mechanism of activation remained, however, largely unknown. To further characterize this unusual role for S-adenosylmethionine, the Arabidopsis thaliana threonine synthase was overexpressed in Escherichia coli, purified to homogeneity, and then used for kinetic and enzyme-bound pyridoxal 5'-phosphate fluorescence equilibrium-binding experiments. We observed that the activating effect of S-adenosylmethionine results from an 8-fold increase in the rate of catalysis and from a 25-fold decrease in the Km value for the O-phosphohomoserine substrate. The data can be well fitted by a kinetic model assuming binding of two S-adenosylmethionine molecules on the native enzyme. We suggest that the dramatic modifications of the enzyme kinetic properties originate most presumably from an allosteric and cooperative transition induced by S-adenosylmethionine. This transition occurs at a much faster rate in the presence of the substrate than in its absence.

Allosteric Site↗

A loop deletion in the plant acetohydroxy acid isomeroreductase homodimer generates an active monomer with reduced stability and altered magnesium affinity.

Plant acetohydroxy acid isomeroreductase is a stable homodimer which catalyzes in the presence of magnesium an alkyl migration followed by a NADPH-dependent reduction. Since the enzyme exhibits no kinetic cooperativity either for its cofactor (NADPH and magnesium) or for its substrates, the reason for dimerization of this enzyme was not obvious. Recently, crystallographic studies [Biou, V., et al. (1997) EMBO J. 16, 3405-3415] revealed that the loop of residues 422-431 plays a major part in the dimer interface. To understand the role of the quaternary structure of the enzyme, we have deleted residues 423-430 and substituted Phe 431 for serine. This mutant was further overproduced in Escherichia coli, purified to homogeneity, and characterized. Gel filtration and thermodynamic experiments disclosed that this mutant behaves as an active monomer with reduced thermal stability. Furthermore, kinetic and fluorescence experiments showed that the behavior of the monomer with respect to magnesium was greatly altered. These results demonstrate the function of the quaternary structure of plant acetohydroxy acid isomeroreductase in the stabilization of the tertiary structure but also in the stabilization of a high-affinity magnesium binding site.

Alcohol Oxidoreductases↗

Kinetic and mass spectrometric analyses of the interactions between plant acetohydroxy acid isomeroreductase and thiadiazole derivatives.

Plant acetohydroxy acid isomeroreductase (EC 1.1.1.86), the second enzyme of the branched chain amino acid biosynthetic pathway, has been submitted to high-throughput screening for herbicide discovery. We report here the discovery of a new class of compounds belonging to the thiadiazole family, which exhibit a strong inhibitory effect on this plant enzyme. Kinetic analyses revealed that these compounds act as either reversible or irreversible noncompetitive inhibitors of the plant enzyme. Reversibility or irreversibility of these compounds can be attributed to the nature of the additional groups of the thiadiazole ring favoring or not favoring the formation of a covalent adduct. Mass spectrometric experiments on the complex between an irreversible compound belonging to the thiadiazole family and the plant enzyme identified Cys498 as the binding site of the inhibitor.

Alcohol Oxidoreductases↗

Cloning and mapping of a cDNA for methionine synthase reductase, a flavoprotein defective in patients with homocystinuria.

Methionine synthase catalyzes the remethylation of homocysteine to methionine via a reaction in which methylcobalamin serves as an intermediate methyl carrier. Over time, the cob(I)alamin cofactor of methionine synthase becomes oxidized to cob(II)alamin rendering the enzyme inactive. Regeneration of functional enzyme requires reductive methylation via a reaction in which S-adenosylmethionine is utilized as a methyl donor. Patients of the cblE complementation group of disorders of folate/cobalamin metabolism who are defective in reductive activation of methionine synthase exhibit megaloblastic anemia, developmental delay, hyperhomocysteinemia, and hypomethioninemia. Using consensus sequences to predicted binding sites for FMN, FAD, and NADPH, we have cloned a cDNA corresponding to the "methionine synthase reductase" reducing system required for maintenance of the methionine synthase in a functional state. The gene MTRR has been localized to chromosome 5p15.2-15.3. A predominant mRNA of 3.6 kb is detected by Northern blot analysis. The deduced protein is a novel member of the FNR family of electron transferases, containing 698 amino acids with a predicted molecular mass of 77,700. It shares 38% identity with human cytochrome P450 reductase and 43% with the C. elegans putative methionine synthase reductase. The authenticity of the cDNA sequence was confirmed by identification of mutations in cblE patients, including a 4-bp frameshift in two affected siblings and a 3-bp deletion in a third patient. The cloning of the cDNA will permit the diagnostic characterization of cblE patients and investigation of the potential role of polymorphisms of this enzyme as a risk factor in hyperhomocysteinemia-linked vascular disease.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

A study of the effect of age on pancreatic duct morphology.

BACKGROUND: Interpretation of endoscopic pancreatograms is difficult in elderly patients. Age-related parenchymal changes and associated ductographic changes are ill-defined, and it is sometimes difficult to distinguish these from pathologic processes. METHODS: To define age-related pancreatogram changes, all endoscopic retrograde pancreatograms performed in patients older than 70 years of age over a 6-year period were analyzed and compared with those of a control group (younger than 50 years of age). RESULTS: Of the 136 elderly subjects included in the study, 31 (22.8%) were found to have definite pathology. Comparing the remaining 105 subjects with the control group, the mean main pancreatic duct diameter (in millimeters) was larger in the head (5.3 vs. 3.3), body (3.7 vs. 2.3), and tail (2.6 vs. 1.6) (p < 0.05). The duct diameter also increased significantly in each of the age cohorts (70 to 79, 80 to 89, and 90 to 99 years). Only 33 of 105 (31.4%) of the elderly patients had duct diameters within defined normal limits. In the majority (63.3%), dilatation was global but in a minority it was confined to the head and/or body. In 21 subjects the ductal diameter was greater than 2 standard deviations above normal, and in 5 subjects it was greater than 3 standard deviations above normal. Dilatation of secondary ducts was also observed. CONCLUSION: The majority of elderly patients who do not have pancreatic pathology have a dilated pancreatic duct by comparison with younger patients. Patient age must be considered when interpreting endoscopic pancreatograms.

Adolescent↗

First report of association of chronic pancreatitis, primary biliary cirrhosis, and systemic sclerosis.

We report an original observation of chronic pancreatitis associated with primary biliary cirrhosis and systemic sclerosis. The diagnosis of each of these conditions was unequivocally confirmed. Pancreatic involvement in this case was asymptomatic. The association of chronic pancreatitis with primary biliary cirrhosis has been previously reported and pancreatitis has been associated with other autoimmune disorders. We hypothesize about the underlying pathogenic mechanisms of chronic pancreatitis in our case.

Aged↗

Clinical patterns of acute stroke among the three health-care systems in France.

Data from 959 consecutive patients registered with the Dijon Stroke Registry were used to compare the characteristics of the patients who were admitted to the public hospital within the first days after their first stroke with those admitted to the private hospitals or who remained at home. Seven hundred and one patients (73%) were admitted to the public hospital, 185 (19%) were admitted to private hospitals and 73 (8%) remained in the community. The results show that the clinical patterns of the stroke are quite different among the three health-care systems. The clinical patterns of stroke managed in the public hospital are characterized by: a younger age (63-years-old vs, 77 and 76-years-old), earlier coma (29% vs 2.8 and 1.5%), more severe deficit (71% vs 15 and 5%), more hemorrhagic mechanism (23 vs 4.5% and 1.7%), more associated ischemic heart disease (31% vs 18 and 15%), more cardiac arrhythmia (38% vs 11 and 8%), higher case fatality rate (39% vs 8 and 2%). Therefore, we have identified three clinical patterns among the three health-care facilities. These three clinical patterns are quite different on the point of view of the clinical severity, and the associated co-morbidities. The socio-economic status is not a criteria in the choice of the health-care facility. This observed distribution is not the consequence of a voluntary policy. Copyright 1998 Lippincott Williams & Wilkins

Journal Article↗

Headache in hypothyroidism. Prevalence and outcome under thyroid hormone therapy.

OBJECTIVE: To evaluate the frequency of headache in patients with hypothyroidism. DESIGN: A prospective study of a cohort of patients with hypothyroidism. SETTING: Outpatients or inpatients in a headache clinic and endocrinological clinic. PATIENTS: 102 adults, ages 35 to 78 (83F, 19M) experiencing clinical and biological hypothyroidism. RESULTS: Thirty-one patients with hypothyroidism of 102 (30%) presented with headache 1 to 2 months after the first symptoms of hypothyroidism. The headache was slight, nonpulsatile, continuous, bilateral, and salicylate responsive and disappeared with thyroid hormone therapy. CONCLUSION: The authors believe there is a prevalence of nonspecific headache in hypothyroidism and that it has a particular response to thyroid hormone therapy. Hypothyroidism is another cephalalgia with an endocrinological cause after menstrual cephalalgia. We suspect a metabolic or vascular pathophysiological process.

Adult↗

The role of therapeutic endoscopy associated with extracorporeal shock-wave lithotripsy and bile acid treatment in the management of Caroli's disease.

BACKGROUND AND STUDY AIMS: Caroli's disease causes relapsing episodes of cholangitis due to the presence of intrahepatic lithiasis. Strategies for cholangitis prevention are still widely debated. Ursodeoxycholic acid, hepaticojejunostomy, partial hepatectomy, or transplantation, have all been proposed as therapeutic options. The aim of this study was to evaluate the role of therapeutic endoscopy, and especially endoscopic sphincterotomy (ES), in the management of Caroli's disease. PATIENTS AND METHODS: Between 1983 and 1995, six patients with Caroli's disease (mean age 52, range 17-75) underwent endoscopic retrograde cholangiopancreatography (ERCP) for acute cholangitis. Sphincterotomy was performed if common bile duct stones were present. Extracorporeal shock-wave lithotripsy, (ESWL) or intraductal electrohydraulic lithotripsy (IEL) were performed if necessary. RESULTS: The mean number of endoscopic sessions per patient was four (range three to seven). Sphincterotomy was performed in five patients and cholangioscopy in three. ESWL was performed twice in each of four patients. A Strecker expandable metal stent was placed in one patient to maintain sphincterotomy patency. In one patient, two sessions of IEL and pulsed laser were carried out. Complete clearance of intrahepatic stones was achieved in four of the six subjects (66.6%) and partial clearance in two patients. No morbidity or mortality was observed. During the follow-up (mean 6.2 years; range: 2.1-16.3), only two patients had acute cholangitis at nine months and three years, respectively, after the endoscopic treatment. Both had residual intrahepatic stones left after the initial endoscopic attempt at clearance. CONCLUSION: ERCP is a necessary diagnostic procedure which should always be carried out in patients with Caroli's disease. Our experience shows that ES does not result in an increased incidence of cholangitis and that therapeutic endoscopy allows complete clearance of intrahepatic stones in the majority of patients with unresectable symptomatic Caroli's disease. Nevertheless, the oncological risk in these patients remains unchanged, and they still have an increased risk of cholangiocarcinoma.

Caroli Disease↗