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Biomedical subjects

O Meyer

Publications and source records attributed to O Meyer.

At least 109 records · Page 6Linked to original sources

Spontaneous spinal epidural hematoma with spinal cord compression complicating plasma cell myeloma. A case report.

STUDY DESIGN: A case is reported in which a patient had acute paraplegia with sensory loss caused by a spontaneous epidural hematoma that was ascribed to bleeding of pre-existing myeloma lesions of the thoracic vertebrae. OBJECTIVES: To highlight the causes of secondary epidural hematomas with special attention to pre-existing vertebral or epidural lesions. SUMMARY OF BACKGROUND DATA: There are no apparent previous reports of epidural spinal hematomas ascribed to underlying malignant diseases. Benign dysplasia, such as hemangioma or Paget's disease, has been implicated in a few cases. METHODS: A case of spontaneous dorsal epidural hematoma is reported in a patient followed up for plasma cell myeloma with osteolytic lesions in the lower thoracic spine. There was no history of major trauma or coagulation disorders. Complete loss of motor and sensory function in both lower limbs was noted, with sphincter dysfunction. Magnetic resonance imaging of the thoracic spine showed a large posterolateral epidural hematoma responsible for spinal cord compression. RESULTS: The patient failed to improve despite surgical decompression within 6 hours of symptom onset. He died 13 days later of refractory bacterial pneumonia. A large epidural hematoma adjacent to myelomatous lesions of the thoracic vertebrae was found at autopsy. CONCLUSIONS: This is the first reported case of spontaneous epidural hematoma ascribed to underlying malignant disease, with confirmation of the diagnosis by postmortem examination. Possible mechanisms include tumor-related epidural inflammation and fragility of epidural venous plexuses.

Aged↗

Effect of molybdate and tungstate on the biosynthesis of CO dehydrogenase and the molybdopterin cytosine-dinucleotide-type of molybdenum cofactor in Hydrogenophaga pseudoflava.

The molybdenum-containing iron-sulfur flavoprotein CO dehydrogenase is expressed in a catalytically fully competent form during heterotrophic growth of the aerobic bacterium Hydrogenophaga pseudoflava with pyruvate plus CO. We have adopted these conditions for studying the effect of molybdate (Mo) and tungstate (W) on the biosynthesis of CO dehydrogenase and its molybdopterin (MPT) cytosine-dinucleotide-(MCD)-type molybdenum cofactor. W was taken up by the Mo transport system and, therefore, interfered with Mo transport in an antagonistic way. Depletion of Mo from the growth medium as well as inclusion of excess W both resulted in the absence of intracellular Mo and led to the biosynthesis of CO dehydrogenase species of proper L2M2S2 subunit structure that carried the two 2Fe:2S type-I and type-II centers and two FAD molecules. EPR, ultraviolet/visible and CD spectroscopies established the full functionality of the cofactors. Due to the absence of the Mo-MCD cofactor, the enzyme species were catalytically inactive. Unexpectedly, the following cytidine nucleotides were present in inactive CO dehydrogenase: CDP, dCDP, CMP, dCMP, CTP or dCTP. The sum of cytidine nucleotides was two/mol enzyme. The binding specificities of inactive CO dehydrogenase for cytidine nucleotides (oxy > deoxy; diphosphate > monophosphate > triphosphate), and the absence of MPT suggest that, in active CO dehydrogenase, the cytidine diphosphate moiety of Mo-MCD provides the strongest interactions with the protein and determines the specificity for the type of nucleotide. In H. pseudoflava, the biosynthesis of MPT (identified as form A) was independent of Mo. Mo was, however, strictly required for the conversion of MPT to MCD (identified as form-A-CMP) as well as the insertion of Mo-MCD into CO dehydrogenase. These data support a model for the involvement of Mo in the biosynthesis of the Mo-MCD cofactor and of fully functional CO dehydrogenase in which the synthesis and insertion of Mo-MCD require Mo, and protein synthesis including integration of the FeS-centers and FAD are independent of Mo.

Aldehyde Oxidoreductases↗

Cationic liposomes coated with polyethylene glycol as carriers for oligonucleotides.

Modification of liposome surface with polyethylene glycol was used to improve oligodeoxyribonucleotide (ODN) loading, stability of the resulting complexes, and specificity of cellular delivery of ODN by cationic liposomes. Liposomes composed of a cationic lipid (DOTAP, DOGS, DDAB), a neutral lipid (DOPE), and a phospholipid derivative of polyethylene glycol (PEG-PE) formed a complex with 18-mer phosphorothioate up to ODN/lipid molar ratio of 0.25. The complexes showed intact vesicular structures similar to original liposomes and their size (100-130 nm) was unchanged after several weeks of storage, whereas complexes lacking PEG-PE showed progressive aggregation and/or precipitation. After exposure to human plasma, PEG-modified cationic liposomes retained over 60% of the originally bound ODN. PEG-coated complexes resulted in 4-13-fold enhancement of the ODN uptake by human breast cancer cells in serum-supplemented growth medium, relative to free ODN. Complexes containing conjugated anti-HER2 F(ab') fragments at the distal termini of PEG chains efficiently delivered ODN primarily into the cytoplasm and nuclei of HER2 overexpressing cancer cells and greatly enhanced the biological activity of antisense ODN. The development of PEG-modified cationic liposomes may lead to improved ODN potency in vivo.

Animals↗

[Definition, diagnosis, and classification of lupus].

Polysystemic lupus erythematosus is a disease of unclear origin. Spontaneous course is characterized by flares followed by remissions. The classification criteria are often used as diagnostic criteria, but they are insensitive for early diagnosis purpose. Decisional trees and ponderation of the various criteria have been reported to help clinicians for early diagnosis. Clinical variants of lupus erythematosus are numerous such as initial clinical manifestations; epidemiological considerations have shown different subsets with different manifestations depending on ethnicity, age at first symptoms, environmental factors (drug-induced lupus). Genetic background influences the autoantibody profile. Correlations have been reported between serological and clinical presentation.

Decision Trees↗

Copolymers of N-isopropylacrylamide can trigger pH sensitivity to stable liposomes.

Stable liposomes were rendered pH-sensitive by complexation to a polymer that undergoes marked temperature- and pH-dependent water solubility changes. The N-isopropylacrylamide-methacrylic acid copolymer was prepared with or without octadecyl acrylate. At pH below the phase transition of the polymer, egg phosphatidylcholine liposomes quickly released a part of their contents only when associated with the octadecyl aliphatic chain grafted polymer at 37 degrees C. Similarly, sterically stabilized liposomes also quickly released a significant part of the entrapped fluorescent markers at pH 5.5-4.9, values corresponding to those of endosomes/lysosomes. This new pH-sensitive liposome-polymer system may further improve the efficiency of liposomal drug delivery.

Acrylamides↗

[Immunogenetic bases of systemic lupus erythematosus in humans].

INTRODUCTION: Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown pathogenesis. Familial studies and concordance rates among affected twins suggest that human SLE has a strong genetic basis. CURRENT KNOWLEDGE AND KEY POINTS: Recent studies have emphasized that SLE, like other autoimmune diseases, is a complex genetic trait with contributions of both major histocompatibility complex (MHC) associated genes and multiple non-MHC genes. Recent significant advances have been made in the genetic analysis of complex traits, which allow the identification of new candidate genes in SLE. Among the genes reviewed in this article, some polymorphisms of Fc gamma receptor genes and other genes or loci localized on the long arm of the human chromosome 1 appear to be very promising. FUTURE PROSPECTS AND PROJECTS: The identification of new susceptibility genes in SLE will certainly provide important insights into the breakdown of self-tolerance mechanisms leading to autoimmune diseases. To achieve this objective, the recruitment of a large number of genetic traits of multiplex families presenting with SLE is therefore essential. More than 125 multiplex families have been collected to date in France.

Animals↗

[A case of post-partum remission of acquired dyserythropoiesis, a rare cause of anemia in disseminated lupus erythematosus].

INTRODUCTION: Amongst the various causes of anemia in systemic lupus erythematosus, isolated and acquired erythrocyte dysplasia is rare and most often part of global dysmyelopoiesis. EXEGESIS: The authors report a case of acquired erythrocyte dysplastic syndrome that occurred in a 34-year-old woman in whom previous diagnosis had evidenced systemic lupus erythematosus of rather benign course. Other causes of dysmyelopoiesis were ruled out. Myeloid stem cell cultures showed selective inhibition of erythroid cells growing, with no particular effect of the patient's serum. While a corticosteroid treatment with prednisone (1 mg/kg/d) did not show any efficacy upon anemia, the patient's pregnancy was followed by prolonged correction of hemoglobin, making possible the tapering of prednisone down to 10 mg/d. CONCLUSION: Acquired erythrocyte dysplastic syndrome remains a rare cause of anemia in systemic lupus erythematosus. This case report suggests an immunological phenomenon, but the mechanisms underlying both the appearance and long-lasting remission after pregnancy remain unexplained.

Adult↗

Mobilization of peripheral blood progenitor cells by disease-specific chemotherapy in patients with soft tissue sarcoma.

We investigated peripheral blood progenitor cell (PBPC) mobilization by disease-specific chemotherapy in patients with metastatic soft tissue sarcoma (STS). Nine patients, five females and four males, aged 12-51 years, pretreated by one to nine courses of cytotoxic chemotherapy, underwent STS-specific mobilization followed by G-CSF at 5 microg/kg/day. PBPC were collected by 19 conventional-volume aphereses (8-12 l) with one to four procedures in individual patients. Leukaphereses started on median day 15 (range 13-18) from the first day of mobilization chemotherapy at medians of 25.8 x 10(3) WBC/microl (6.8-46.9), 3.5 x 10(3) MNC/microl (1.1-8.8), 122 x 10(3) platelets/microl (72-293) and 30.7 CD34+ cells/microl (6.7-207.8). Cumulative harvests resulted in medians of 4.6 x 10(8) MNC/kg (3.0-6.4), 2.9 x 10(6) CD34+ cells/kg (1.1-11.1) and 12.0 x 10(4) CFU-GM/kg (2.0-37.8). Eight patients underwent high-dose chemotherapy (HDCT) followed by PBPC rescue. Seven patients recovered hematopoiesis at medians of 12 days (8-15) for ANC >0.5 x 10(3)/microl and 14 days (8-27) for platelets >20 x 10(3)/microl. One patient, who received 1.6 x 10(6) CD34+ cells/kg, exhibited delayed ANC recovery on day +37 and failed to recover platelets until hospital discharge on day +55. We conclude that in patients with metastatic STS, who are pretreated by standard chemotherapy, PBPC can be mobilized by a further course of STS-specific chemotherapy plus G-CSF. One to four conventional-volume aphereses result in PBPC autografts that can serve as hematopoietic rescue for patients scheduled for HDCT.

Adolescent↗

Reliability of epidural pressure measurement in clinical practice: behavior of three modern sensors during simultaneous ipsilateral intraventricular or intraparenchymal pressure measurement.

OBJECTIVE: In recent years, new devices for epidural pressure (EDP) measurement have been developed, with claims of improved accuracy. However, there have been no new data from simultaneous pressure measurements to reverse the skepticism regarding this technique. METHODS: The reliability of EDP recording was investigated in 26 patients with severe head injuries, during simultaneous measurement of ipsilateral intraventricular pressure (IVP) or intraparenchymal pressure (IPP). RESULTS: Periods of simultaneous measurement ranged from 3.3 to 168 hours. Technical failure occurred in five cases. Clinically significant erroneous pressure values (defined as differences of >10 mm Hg between EDP and IVP or IPP, lasting for >10 min) occurred in 7 of 21 measurements (33%). In three of these seven cases (43%) the difference between the EDP and the IVP or IPP remained nearly stable throughout the period of observation, whereas in four cases (57%) significant drifting over time was observed. Analysis of the transfer function calculated for the first to sixth harmonics between the EDP and the IVP or IPP showed no significant differences between the pulse pressure waveforms, even when significant drifting of more than 20 mm Hg occurred. CONCLUSION: The reliability of EDP measurement has not improved, compared with 10 years ago. Using this technique, one must be aware of the possibility of overestimating intracranial pressure by more than 10 mm Hg and the possibility of significant drifting of EDP over time, which argues against the use of this method even for trend analysis.

Brain Edema↗

Analysis of CD34-expressing cells in clinical practice.

The flow cytometric determination of haemopoietic cells defined as CD34-expressing cells has greatly added to the improvement of the management of harvesting circulating haemopoietic cells for subsequent autologous reinfusion in the setting of high-dose chemo/(radio)-therapy. Additionally, this flow cytometric determination has replaced, in some institutions, the in-vitro culture test for CFU-GM as the measure to estimate the haemopoietic potential of the cells to be reinfused/transplanted.

Antigens, CD34↗

Effect of heart rate reduction by 4-(N-ethyl-N-phenyl-amino)-1,2-dimethyl-6-(methylamino)pyrimidinium chloride on infarct size in dog.

Heart rate (HR) reduction may reduce the severity of myocardial ischemia. ZD7288 (4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino)pyrimidinium++ + chloride) is a novel bradycardic agent with a specific effect on the sinoatrial node without having any other direct effects on the heart. In the present study, the effect of ZD7288 on infarct size and regional myocardial function during regional myocardial ischemia and reperfusion was investigated. Seventeen anesthetized open chest dogs (control, n = 8, and ZD7288, n = 9) underwent 1 h of left anterior descendent artery (LAD) occlusion followed by 6 h of reperfusion. In one group, ZD7288 was given intravenously (0.7 mg/kg body weight) 45 min before LAD occlusion. Regional myocardial function was assessed by sonomicrometry as systolic wall thickening fraction (sWTF) in the anteroapical (interest region, IR) and the posterobasal wall (control region, CR). Ischemic regional myocardial blood flow (RMBF) was determined by colored microspheres and infarct size (IS) by triphenyltetrazolium staining. ZD7288 injection decreased HR from 104 +/- 5 to 74 +/- 3 bpm (mean +/- SEM, p < 0.001 vs control, vs baseline), but did not change sWTF. During reperfusion, sWTF of the IR was significantly greater in the ZD7288 group (26 +/- 12 vs -14 +/- 13%, 1 h reperfusion, p < 0.05), while sWTF of CR stayed equal (120 +/- 13 vs 111 +/- 16%, p = ns). IS was markedly reduced in the ZD7288 group (4.7 +/- 1.8 vs 18.0 +/- 5.2% of IR, p < 0.05). There was no difference in ischemic endocardial RMBF (ZD7288 11.0 +/- 4.3 vs control 12.3 +/- 6.5 ml/min/100 g, p = ns). ZD7288 reduces HR without having direct effects on regional myocardial function. This HR reduction leads to a smaller IS and to a better regional functional recovery.

Animals↗

Anti-Ro(SS-A)

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Antibodies, Antinuclear↗

Clinical usefulness of antibodies to U1snRNP proteins in mixed connective tissue disease and systemic lupus erythematosus.

OBJECTIVES: To determine whether the anti-68 kDaU1snRNP antibody is associated with mixed connective tissue disease and not with SLE; to evaluate correlations between anti-U1snRNP titers and disease activity; and to look for associations between anti-U1snRNP specificities and specific clinical features. PATIENTS AND METHODS: 40 patients with a positive double diffusion test for anti-68 kDa U1snRNP were studied, including 21 with mixed connective tissue disease, 14 with systemic lupus erythematosus and five with other connective tissue diseases. IgGs to 68 kDa U1snRNP were assayed using an ELISA. Clinical features, disease activity and antibody test findings were evaluated longitudinally in nine patients. RESULTS: Both proportions of patients with anti-68 kDa U1snRNP and titers of IgG to 68 kDa U1snRNP were similar in the mixed connective tissue disease and systemic lupus erythematosus groups. Patients with mixed connective tissue disease were significantly more likely to have anti-A U1snRNP or anti-C U1snRNP than those with systemic lupus erythematosus (P < 0.03 and P < 0.04, respectively). No significant correlations were found between any of the features of mixed connective tissue disease (e.g., Raynaud's phenomenon, myositis, or sausage digits) and a specific anti-U1snRNP antibody. During follow-up (mean, seven years; range, 1-25 years), changes occurred in the anti-U1snRNP profile and in the anti-68 kDa U1snRNP titer. These changes were not correlated with disease activity. CONCLUSIONS: IgGs to 68 kDa U1snRNP are not associated with a specific pattern of anti-RNP-positive connective tissue disease. No useful information can be gained by monitoring anti-68 kDa U1snRNP IgG titers over time. A Western blot profile including anti-A U1snRNP or anti-C U1snRNP indicates a high likelihood of U1snRNP-associated mixed connective tissue syndrome (MCTD).

Adolescent↗

[Extra-articular manifestations of rheumatoid polyarthritis].

Rheumatoid arthritis is mainly a chronic and disabling articular disease. If most patients do well (because of limited form or efficient treatment), in some cases they present with extra-articular rheumatoid arthritis. The clinical manifestations of extra-articular rheumatoid arthritis are wide, ranging from common and benign manifestations such as rheumatoid nodules to severe events such as Felty's syndrome or systemic vasculitis. The incidence of systemic rheumatoid arthritis seems cumulative over the course of the chronic disease, and the severity of individuals lesions when fully developed can be of major importance and even life threatening. A classification of the main features of extra-articular rheumatoid arthritis is given (even if not perfect), and the clinical manifestations are described.

Adult↗

N2 fixation by Streptomyces thermoautotrophicus involves a molybdenum-dinitrogenase and a manganese-superoxide oxidoreductase that couple N2 reduction to the oxidation of superoxide produced from O2 by a molybdenum-CO dehydrogenase.

N2 fixation by Streptomyces thermoautotrophicus follows the equation N2 + 4-12MgATP + 8H+ + 8e- --> 2NH3 + H2 + 4-12MgADP + 4-12Pi and exhibits features which are not obvious in the diazotrophic bacteria studied so far. The reaction is coupled to the oxidation of carbon monoxide (CO) by a molybdenum-containing CO dehydrogenase that transfers the electrons derived from CO oxidation to O2, thereby producing superoxide anion radicals (O-2). A manganese-containing superoxide oxidoreductase reoxidizes the O-2 anions to O2 and transfers the electrons to a MoFeS-dinitrogenase for the reduction of N2 to ammonium. Among the most striking properties of the S. thermoautotrophicus nitrogenase system are the dependence on O2 and O-2, the complete insensitivity of all components involved toward O2 and H2O2, the inability to reduce ethine or ethene, and a low MgATP requirement. In addition, the subunit structure of the S. thermoautotrophicus nitrogenase components and the polypeptides involved seem to be dissimilar from the known nitrogenases.

Aldehyde Oxidoreductases↗