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Biomedical subjects

R Dumas

Publications and source records attributed to R Dumas.

At least 91 records · Page 5Linked to original sources

Coagulation abnormalities in lacunar and cortical ischemic stroke are quite different.

In order to clarify the coagulation profile accompanying ischemic stroke, which may have implications on therapeutic strategies, we performed a prospective study to evaluate the hemostatic parameters in the first 24 h after the onset of cortical atherothrombotic infarct and lacunar infarction. Twenty-seven patients with cortical atherothrombotic infarction and 27 patients with lacunar infarction, diagnosed on clinical and CT-scan criteria, had blood samples taken within the first 24 h after onset of the stroke, and before anticoagulant treatment had been started. Levels of fibrinogen, von Willebrand factor, D-dimers, prothrombin factors 1 + 2, anti-thrombin III, and C-protein and S-proteins, were measured. Laboratory tests detected the following abnormalities: a protein C deficiency was observed in 1 case of cortical infarction and in 1 case of lacunar infarction; a decrease in S-protein was observed in 1 case of cortical infarction, and the presence of lupus anticoagulant in 4 cases (2 in cortical and 2 in lacunar infarction). Various degrees of coagulation activation were observed. Statistically significant activation of the coagulation was observed in the patients with cortical infarction, compared to normal patients adjusted for age: the levels of DDI were significantly raised (2298 +/- 2221 ng ml-1 vs. 750 +/- 400 ng ml-1) (p < 0.03) as were F1 + 2 levels (3.9 +/- 2.8 nmol l-1 vs. 1.5 +/- 0.9 nmol l-1). (p < 0.01). In the lacunar infarction group, there was a significant rise in F1 + 2 compared with normal patients adjusted for age (2.2 +/- 1.7 nmol l-1 vs. 1.5 +/- 0.9 nmol l-1) (p < 0.01), while the DDI level was in the normal range, when age was taken into account. In the cortical infarction group, we observed a significantly raised fibrinogen level (4.8 +/- 1.7 g l-1 vs. 3.7 +/- 1.0 g l-1) (p < 0.05) and von Willebrand factor level (271 +/- 104% vs. 178 +/- 103%) (p < 0.01) compared to the lacunar infarction group. In addition, we observed a significantly low level of S-protein in the cortical infarction group (105 +/- 29%) compared to the lacunar infarction group (127 +/- 28%) (p < 0.01). Confirmation of the role of enhanced thrombin activity in the pathogenesis of acute stroke may be an important determinant in its therapeutic management.

Aged↗

The natural history of hereditary chronic pancreatitis: a study of 12 cases compared to chronic alcoholic pancreatitis.

The aim of this study was to document the natural history of chronic hereditary pancreatitis and to compare its evolution to that of chronic alcoholic pancreatitis. Twelve subjects with chronic hereditary pancreatitis were followed up for a mean duration of 15.8 years (range, 1-23) and compared to subjects with chronic alcoholic pancreatitis who were followed up from 1972 to 1980. The subjects with chronic hereditary pancreatitis, when compared to those with chronic alcoholic pancreatitis, were found to have an earlier onset of symptoms (10.5 vs. 46.0 years, p < 0.05); a significant delay in diagnosis (14.3 vs. 3 years); a similar prevalence of pancreatic calcification (58 vs. 57%); a similar amount of pancreatic insufficiency; both endocrine (50 vs. 70%) and exocrine 42 vs. 38%); and a higher prevalence of pseudocysts (33 vs. 10%, p < 0.05). Only one pancreatic adenocarcinoma was diagnosed in a patient with chronic alcoholic pancreatitis. Apart from the earlier onset and the delay in diagnosis, chronic hereditary pancreatitis has a natural history similar to that of chronic alcoholic pancreatitis. The disease is progressive with a high incidence of complications, but all subjects were alive after follow-up.

Adolescent↗

Endoscopic treatment of wirsungo-cysto-pleural fistula.

A case is reported of a female with chronic alcoholic calcifying pancreatitis who presented with a wirsungo-cysto-pleural fistula. Endoscopic retrograde pancreatography demonstrated the fistulous tract and a naso-pancreatic drain was inserted. Subsequently, this drain was replaced by a pancreatic endoprosthesis. This endoscopic therapy led to full resolution of the fistula. We suggest that endoscopic intervention is the first-line treatment for this condition and that surgical intervention should be reserved as a second-line treatment.

Adult↗

Epilepsy in patients with multiple sclerosis: radiological-clinical correlations.

PURPOSE: To determine potential mechanisms of epilepsy in patients with multiple sclerosis (MS). METHODS: Among 402 patients with clinically and radiologically defined MS, including de novo cases, presenting to the Neurology Service, University Hospital of Dijon, we identified 17 with epileptic seizures (4.25%). Among them, the percentage with partial seizures (50%) was greater than that in the reference population. RESULTS: In most of the patients with MS, plaques were localized in the frontal region, associated with frontal and callosal atrophy, a frontal syndrome, and severe disability status (as assessed by a standard scale). Magnetic resonance imaging (MRI) showed numerous subcortical plaques. Seizures generally were well controlled with antiepileptic drugs (AEDs). CONCLUSIONS: Our data suggest that the subcortical plaques of MS underlie seizure activity in patients with MS and epilepsy.

Adult↗

Evaluation of the safety and pharmacokinetic profile of a new, pasteurized, human tetanus immunoglobulin administered as sham, postexposure prophylaxis of tetanus.

In a monocentric, double-blind, randomized trial, we examined the safety and pharmacokinetic profile of a new, pasteurized, human tetanus immunoglobulin (P-HTIG). As part of the purification process, P-HTIG has undergone a heat treatment step (10 h at 60 degrees C) and the removal of Merthiolate. Forty-eight adults with a history of tetanus vaccination were randomized into four groups (n = 12 per group) to receive one of two different batches of this P-HTIG simultaneously with either tetanus-diphtheria (Td) vaccine (sham, postexposure prophylaxis of tetanus) or placebo. Local reactions at the injection site were followed for the first 3 days after injection, and systemic reactions were followed during the entire study period, i.e., up to 42 days posttreatment. Blood samples for tetanus antibody titer determination (enzyme-linked immunosorbent assay method) were drawn prior to treatment on day 0 and on days 1, 2, 3, 7, 14, 21, 28, 35, and 42. A normalization of tetanus antibody titers (subtraction of the day 0 value for each subject at each time period) was performed to assess the additive effect of P-HTIG on tetanus antibody titers. The pharmacokinetic parameters were determined by both a compartmental analysis (modelization) and a noncompartmental analysis. No severe adverse reactions were reported. The rate of local reactions at the P-HTIG injection site was 27%. All local reactions were mild and resolved within 2 days. In contrast, local reactions at the vaccine injection site were seen in 79% of the subjects. The rate of systemic reactions was similar in the P-HTIG plus Td vaccine group (33%) and in the P-HTIG plus placebo group (21%), and all these reactions were mild. In the P-HTIG plus placebo group, tetanus antibody titers rose to a maximum of 0.313+/-2.49 IU/ml after 4.4 days; in the P-HTIG plus Td vaccine group, a maximum concentration of 15.2+/-2.42 IU/ml was reached 19 days postinjection. In both groups, 100% of the patients had seroprotective levels of tetanus antibodies (> or = 0.01 IU/ml) 2 days following treatment. An anamnestic response to Td vaccine appeared 7 days postimmunization. In conclusion, P-HTIG has a good safety and pharmacokinetic profile. Our results confirm that immunoglobulin should be associated with vaccine in the treatment of tetanus-prone wounds.

Adolescent↗

Immunogenicity and safety of a new inactivated hepatitis A vaccine in Thai young adults.

In view of the increasing median age of hepatitis A virus (HAV) infection observed recently in Asia, and the resulting increased number of symptomatic cases occurring in adults, with the concomitant risk of outbreaks, immunization against this agent on a national scale might be considered. An open clinical trial was conducted in Thai adolescents and young adults in order to establish the immunogenicity and safety of a new inactivated hepatitis A vaccine. At 24-week intervals, two doses (primary dose and booster) of the hepatitis A vaccine (160 antigenic units per dose) were administered to 80 HAV-seronegative healthy volunteers, their ages ranging from 16 to 25 years. Local and systemic reactions were recorded within the first 7 days after each injection. Anti-hepatitis A virus antibody concentrations were measured by a modified radioimmunoassay before and one month after each injection. No serious adverse reactions were reported. Local reactions were confined to transient pain at the injection site, occurring within 24 hours after injection in 42.5% of the subjects after the first dose and 24.1% of the patients after the booster dose. Systemic reactions (particularly asthenia or myalgia) were observed in 35.0% and 8.9% of subjects after the first and the booster injection, respectively. Most of these reactions were transient. One month after the first dose, all 78 formerly seronegative subjects had attained satisfactory seroconversion levels of anti-HAV antibody concentrations (> or = 20 mIU/ml) which they maintained until the booster. The booster dose elicited a 21-fold increase of HAV antibody levels, with a geometric mean titer of 2,964 mIU/ml (95% CI, 2,467-3,560), indicative of long-term protection. This new inactivated hepatitis A vaccine appears to be safe and highly immunogenic upon administration of a primary dose followed by a booster dose after 24 weeks. In countries where socio-economic improvement has postponed hepatitis A infection from early childhood (mostly asymptomatic) towards adolescence and adulthood, with the symptoms increasing in severity, inclusion of inactivated hepatitis A vaccine in a preventive vaccination program might be of benefit.

Adolescent↗

Endoscopic retrograde cholangiopancreatography in patients with Billroth II gastrectomy.

AIM: Endoscopic retrograde cholangiopacreatography and associated therapeutic procedures are widely used in routine clinical practice. The changes in the upper gastrointestinal anatomy after a Billroth II anastomosis may present technical difficulties at endoscopic retrograde cholangiopacreatography. METHODS AND PATIENTS: The case records of all patients who underwent endoscopic retrograde cholangiopacreatography at our Unit from January 1985 to December 1995 were reviewed. All patients who had had a previous Billroth II anastomosis or gastroenteroanastomosis were included in this analysis. Of the 5994 procedures performed, 124 patients with Billroth II surgery and 10 with a gastroenteroanastomosis were identified. RESULTS: In these patients, the papilla was located in 89% of cases from 1985 to 1990 and in 100% of cases from 1991 to 1995. Overall, the success rates for pancreatography, cholangiography, and endoscopic sphincterotomy were 94%, 97.7%, and 100%, respectively. The morbidity and mortality rates were 7.4% and 0%, respectively. CONCLUSIONS: The success rate for endoscopic retrograde cholangiopacreatography in patients with Billroth II gastrectomy is similar to that of a normal population.

Adult↗

The crystal structure of plant acetohydroxy acid isomeroreductase complexed with NADPH, two magnesium ions and a herbicidal transition state analog determined at 1.65 A resolution.

Acetohydroxy acid isomeroreductase catalyzes the conversion of acetohydroxy acids into dihydroxy valerates. This reaction is the second in the synthetic pathway of the essential branched side chain amino acids valine and isoleucine. Because this pathway is absent from animals, the enzymes involved in it are good targets for a systematic search for herbicides. The crystal structure of acetohydroxy acid isomeroreductase complexed with cofactor NADPH, Mg2+ ions and a competitive inhibitor with herbicidal activity, N-hydroxy-N-isopropyloxamate, was solved to 1.65 A resolution and refined to an R factor of 18.7% and an R free of 22.9%. The asymmetric unit shows two functional dimers related by non-crystallographic symmetry. The active site, nested at the interface between the NADPH-binding domain and the all-helical C-terminus domain, shows a situation analogous to the transition state. It contains two Mg2+ ions interacting with the inhibitor molecule and bridged by the carboxylate moiety of an aspartate residue. The inhibitor-binding site is well adjusted to it, with a hydrophobic pocket and a polar region. Only 24 amino acids are conserved among known acetohydroxy acid isomeroreductase sequences and all of these are located around the active site. Finally, a 140 amino acid region, present in plants but absent from other species, was found to make up most of the dimerization domain.

Alcohol Oxidoreductases↗

Purification and characterization of a fusion protein of plant acetohydroxy acid synthase and acetohydroxy acid isomeroreductase.

The nucleotide sequence coding for the Arabidopsis thaliana acetohydroxy acid synthase was genetically fused in frame with the nucleotide sequence coding for the Spinacia oleracea acetohydroxy acid isomeroreductase and expressed in Escherichia coli. This construction allowed the production of large amounts of soluble fusion protein. The pure chimeric enzyme exhibits high acetohydroxy acid synthase and acetohydroxy acid isomeroreductase specific activities. Fusion and native enzymes exhibit similar Km values for their substrates and for most cofactors. Furthermore, whereas native plant acetohydroxy acid synthase is highly unstable, the stability of this enzyme in the fusion has been increased. Thus, the chimeric enzyme appears to be a useful tool for the determination of kinetic and structural properties of plant acetohydroxy acid synthase.

2-Acetolactate Mutase↗

Buspirone, a 5-hydroxytryptamine1A agonist, is active in cerebellar ataxia. Results of a double-blind drug placebo study in patients with cerebellar cortical atrophy.

OBJECTIVE: To establish the antiataxic effect of buspirone hydrochloride, a serotonergic 5-hydroxytryptamine1A (5-HT1A) agonist, in a homogenous group of patients characterized by the same well-defined single condition, cerebellar cortical atrophy. SETTING: University ataxia research center. METHODS: Double-blind randomized study of buspirone vs placebo during a 4-month period. PATIENTS: Nineteen patients met the inclusion criteria; all completed the study. Of these 19 patients, 9 were treated with placebo and 10 were treated with the drug. MAIN OUTCOME MEASURES: A semiquantitative scale for kinetic and static ("postural") cerebellar functions; quantitative clinical measurements measuring time in standard tests that evaluated stance, speech, writing, and drawing; and posturographic analysis of the sway path and sway area of the center-of-foot pressure. The primary end point was improvement of the posttherapeutic change of one of the semiquantitative ataxic scores. The secondary end points were modification of the changes of quantitative measures--clinical or posturographic. RESULTS: In intention-to-treat analysis, a significant improvement of the primary end point, ie, the posttherapeutic change of the ataxic kinetic score, was shown. Among secondary end points, the maximum time of standing with feet together also was significantly improved. CONCLUSIONS: Buspirone is active in cerebellar ataxia of patients with cerebellar atrophy. These results confirm the data suggested by open-label studies with buspirone. However, the effect is partial and not clinically major. These pharmacological results might be due to serotonergic mechanisms and confirm a possible link between cerebellar ataxia and the metabolism of serotonin.

Adult↗

Mutations in the X-linked form of Charcot-Marie-Tooth disease in the French population.

The present study reports eight additional mutations in the connexin32 gene associated with the X-linked form of Charcot-Marie-Tooth disease. One of these mutations was found twice in two apparently unrelated families. This form of the disease is demyelinating and dominant. However, patient selection for mutational screening should not be limited to these criteria since presentation can either be familial or sporadic, and some patients may be incorrectly classified as suffering from an 'axonal' form. These new mutations complete our previously published work on 12 other mutations and enable meaningful observation in a representative sample of the French population. Mutations are found in all regions of the gene. The most frequently observed mutations were those affecting arginines and mainly involved CpG sequences. Compared with other sources, some of the mutations were present at a higher frequency in the French population.

Adolescent↗

[Hypercalciuria: etiologies and treatment].

Hypercalciuria is a rare biological symptom with multiple possible etiologies in children. Normal calcium excretion rate in children is defined as lower than 4 mg/kg per day, significantly higher values being observed in infants. When using urinary calcium: creatinine ratio, normal values are below 0.22 mg/mg in children, and below 0.6 to 0.8 mg/mg in infants. In our experience half patients with hypercalciuria have idiopathic hypercalciuria. Idiopathic hypercalciuria can be hereditary with a dominant autosomal mode of inheritance. Its pathophysiology is unclear, increased calcium intestinal absorption and impaired renal tubular calcium reabsorption being the two main underlying anomalies. Patients with hypercalciuria should be informed about the risk of urolithiasis and its possible prevention by a high water intake. In those patients with nephrocalcinosis or recurrent episodes of lithiasis, hydrochlorothiazide can be effective in reducing hypercalciuria. However, adverse effects of hydrochlorothiazide on serum lipids have been recently reported and make this treatment questionable in the long term.

Calcium↗

Is biliary lithogenesis affected by length and implantation of cystic duct? Study of 270 patients with endoscopic retrograde cholangiopancreatography.

The gallbladder seems to play an important role in lithogenesis. Moreover, the morphology and the implantation of the cystic duct may also influence this process. Our purpose was to evaluate if the length and the implantation of the cystic duct may affect the formation of gallstones. Between April 1992 and March 1994, 270 patients who underwent endoscopic retrograde cholangiopancreatography were included in the study, and the radiological length of the cystic duct was carefully recorded. Patients were divided into two groups: I, absence of lithiasis: 113 patients (65 men, 48 women); and II, gallbladder lithiasis or lithiasis in the common bile duct with or without gallbladder lithiasis: 157 patients (73 men, 84 women). A statistically significant difference was observed among the two groups regarding the insertion of the cystic duct: implantation on the left side of the common bile duct represented a risk factor of lithiasis. The length of the cystic duct was not directly implicated. Hypokinesis of the gallbladder is currently recognized as being a major factor in the initial steps of lithogenesis, but the implantation of the cystic duct can play an important role by increasing cystic duct resistance and causing a reduced washout effect of the gallbladder contents, including cholesterol crystals.

Adult↗

Stroke in children under 16 years of age. Clinical and etiological difference with adults.

OBJECTIVES: The aim of this study was to re-evaluate the clinical features of stroke in children, their outcome and the place of the different mechanisms, in the light of CT-scan and magnetic resonance imaging. METHODS: A 10-year review of the Dijon Childhood Neurology Clinic experience (1985-1995) identified 54 patients with arterial stroke. Diagnosis was established by CT-scan and angiography and by magnetic resonance imaging from 1987. When an hemorrhagic stroke was identified, a cerebral arteriogram and an investigation of the coagulation factors were performed. When an ischemic stroke was identified, the following tests were performed: an ultrasound examination of the cervical arteries, a cerebral arteriogram, a lumbar puncture, an investigation of the coagulation factors and lipid status, a measurement of homocystine in the plasma and the urine, an electrocardiogram, a Holter procedure and a cardiac echography. RESULTS: During the 11 full calendar years of this study, we observed 54 stroke patients. There were 31 cases of ischemic stroke, representing some 57% of the total, as well as 23 cases of hemorrhagic stroke, representing 43% of the total. Of the 31 cases with ischemic stroke, 4 had no known predisposing condition, 6 occurred in children with pre-existing heart disease, 2 had moya-moya disease, 2 had leukemia, 2 had a carotid dissection, 1 had an hemolytic-uremic syndrome, and 14 were observed in patients with other associated conditions, such as infections (7 cases) or slight cranial trauma (7 cases). On CT-scan, a basal ganglia infarction was identified in 14 cases. Among the 23 hemorrhagic strokes, 9 were due to arteriovenous malformations, 2 to arterial aneurysm and 5 to cavernomas. Two cases occurred in hemophilia, 2 in idiopathic thrombocytopenic purpura, and 2 after throat infections. One case had no etiologic factor. Clinical course was marked by a low mortality rate even in hemorrhagic stroke, long-lasting seizures, and hemidystonia. CONCLUSION: This neuro-imaging survey focused on the real place of hemorrhage and basal ganglia infarctions in children under 16 years of age, compared to adulthood. Follow-up demonstrated good or complete resolution of neurological deficits despite the frequent late hemidystonia and late epilepsy.

Adolescent↗

Unilateral lenticular infarcts: radiological and clinical syndromes, aetiology, and prognosis.

OBJECTIVES: To analyse the clinical features induced by lenticular infarction found in 20 patients, and to analyse the radiological and clinical correlations. METHODS: Eight women and 12 men, mean age 73 years, were included in this study, which was carried out from 1 January 1994 to 30 November 1996. They were characterised by the onset of a lenticular infarction, shown by CT and MRI. A complete neurological and neurocognitive examination, and photon emission computed tomography (SPECT), were performed in all the patients and there was a long clinical follow up. RESULTS: Two distinct clinical syndromes were identified corresponding to the two anatomical areas of the lenticular nucleus: behavioural and cognitive disorders were associated with infarcts within the globus pallidus, whereas both motor disorders (dystonia) and cognitive disorders were associated with infarcts within the putamen. Outcome was excellent in all the patients for motor function, but slight cognitive disorders, problems with short term memory, and dysphasia persisted for several months. The size of the lesion did not explain these symptoms. By contrast, the slight reduction in cerebral blood flow found in the adjacent frontotemporal area may explain them by a deafferentation or a diaschisis phenomenon. CONCLUSION: It is possible to identify the clinical symptoms of a single lesion in the pallidus nucleus and in the putaminal nucleus, in which behavioural, cognitive, and movements disorders are important. After an acute and spectacular onset, outcome is in general excellent. A disease of the small arteries must be involved.

Aged↗

A hospital-based and a population-based stroke registry yield different results: the experience in Dijon, France.

BACKGROUND AND PURPOSE: The aim of this study was to demonstrate the different results obtained from a population-based and a hospital-based stroke study in the same city. METHODS: Between January 1 and December 31, 1993, we collected information on all of the first strokes in the population of the city of Dijon, in conjunction with the Dijon Stroke Registry, collecting the first-ever strokes from patients living in Dijon as well as on all the first strokes in residents and nonresidents of Dijon who were treated at Dijon University Hospital. Demographic details, medical history, vascular risk factors, stroke subtype, as diagnosed by CT scan, and mortality rates were compared between the strokes observed in the population of the city of Dijon among residents as well as nonresidents in Dijon who were treated at Dijon University Hospital. RESULTS: We collected information on 210 strokes observed in the population of Dijon city, 171 Dijon residents and 395 non-Dijon city residents hospitalized at the University Hospital of Dijon. These three groups were quite different. The residents of Dijon treated for stroke at the University Hospital were younger and their incidence of cerebral hemorrhage, cardiac arrhythmia, ischemic heart disease and case fatality rate were higher than those from the Dijon Stroke Registry. CONCLUSIONS: Type of stroke data bank is very important in order to describe cerebrovascular disease. Hospital-based studies tend to include more severe strokes, those occurring in a younger population, and those having a higher mortality. Population-based studies, on the other hand, give a somewhat different picture of stroke.

Age Distribution↗