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Biomedical subjects

M Goudemand

Publications and source records attributed to M Goudemand.

At least 37 records · Page 2Linked to original sources
PubMed1993

General cortical involvement in a late-onset case of Alzheimer disease. A biochemical approach by quantitation of abnormal tau proteins.

We have performed a biochemical mapping of the neurofibrillary degeneration in all cortical areas of Alzheimer patients, using the immunological quantification of pathological tau 55, 64, and 69. These abnormally phosphorylated proteins, which are the basic components of PHF, are reliable markers of the degenerating process in Alzheimer disease. Here, we report our biochemical findings on a brain from a 90-yr-old woman with an 8-yr history of Alzheimer disease who exhibited dramatic and general cortical involvement. The detection of these markers was very high in all Brodmann areas, even in primary motor, somatosensory, or visual cortex. This case report contrasts with other studies, which suggested that a more virulent disease process is generally associated with an early onset and argues for the heterogeneity of the disease. Moreover, we show here that the immunodetection of abnormal tau proteins using the western blot method is a precise, reliable, and reproducible way to quantify the degenerating process in AD.

Adult↗
PubMed1993

Cerebral blood flow in major depression and dysthymia.

Using single photon emission computerized tomography (SPECT) with a 99mTc-HMPAO perfusion technique, we studied the regional cerebral blood flow (rCBF) of 42 drug-free inpatients suffering from Major Depression' (n = 21) or dysthymia with the super-imposed diagnosis of a major depressive episode (n = 21). The patients with Major Depression had a significantly lower frontal and posterior rCBF ratio than those with Double Depression. Left frontal region indices showed a slight overlap between the two groups. There was no correlation between the severity of the illness and the rCBF indices. Different qualitative cerebral dysfunctions may be implicated in these two affective disorder sub-types.

Adult↗
PubMed1993

Biological effects of a S/D-treated, very high purity, von Willebrand factor concentrate in five patients with severe von Willebrand disease.

A highly purified von Willebrand factor (vWf) concentrate with low factor VIII (FVIII) content was tested to evaluate its biological effects in five patients with severe von Willebrand disease (vWd). The patients were infused with a single dose of this product corresponding to approximately 65 IU vWf:RCo and approximately 11 IU FVIII:C/kg and were followed up for 48 h. The plasma levels of FVIII and vWf and the multimeric pattern of vWf were determined before and 1, 3, 6, 12, 24 and 48 h after infusion. In all patients the recovery (93 +/- 14%) and half-life (13 +/- 1 h) of vWf were consistent and normal and sustained FVIII levels were attained. In four patients both the duration and the volume of shed blood were measured after one incision with a standardized template method of bleeding time (BT). The duration of bleeding was completely corrected in two out of the four patients and partially corrected in the other two while the volume of shed blood was completely corrected in three patients and partially corrected in the fourth. However, the time for correction of both BT parameters was variable between patients. These data indicate that the vWf concentrate can correct the quantitative defects related to plasma vWf deficiency in vWd patients whereas the effect on template BT is less reproducible.

Adolescent↗
PubMed1992

Clinical and biological evaluation in von Willebrand's disease of a von Willebrand factor concentrate with low factor VIII activity.

This study was carried out to assess the clinical efficacy in von Willebrand's disease (vWD) of a new, very high purity (VHP), solvent/detergent (SD)-treated, vWF concentrate (VHP Human von Willebrand Factor Concentrate, Biotransfusion) characterized by a high specific ristocetin cofactor (vWF:RCo) activity and a low factor VIII (FVIII) coagulant activity (FVIII:C). Nine patients (four type I, one type IIA, one type IIB, one type IIC, one type III and one acquired type II) were infused on 13 occasions including a pharmacokinetic study. Satisfactory haemostasis was achieved in all cases, including the treatment of spontaneous haemorrhages and the prevention of bleeding following surgery. The bleeding time was corrected for 6-12 h in 6/9 patients and shortened in the others. Furthermore, it was shown that the plasma vWF multimeric pattern of types II and III patients was greatly improved. When measured in eight patients 1 h after infusion, the vWF:RCo recovery was 77.3 (+/- 10.7)% while the F VIII:C recovery was strikingly higher (876 +/- 906%). This high recovery is likely related to the predominant 'pseudo-synthesis' of FVIII following the restoration of normal vWF levels. Maximum levels of FVIII:C occurred 6-12 h after the first infusion and normal levels of FVIII:C were maintained throughout the treatments with a dosage of 26-39 IU/kg vWF:RCo and only 0.2-5 IU/kg FVIII:C. The half-lives of the vWF-related parameters determined in a type III vWD patient were 20.6 h for vWF antigen, 17.8 h for vWF:RCo, 14 h for the high molecular weight multimers of vWF, 55.3 h for FVIII:Ag and 74 h for FVIII:C. In conclusion, it does not appear necessary that vWF concentrates intended for the treatment of vWD should contain FVIII in addition to vWF to be clinically effective in most patients.

Adult↗
PubMed1991

A highly purified factor VIII:c concentrate prepared from cryoprecipitate by ion-exchange chromatography.

A new ion-exchange chromatographic procedure has been developed to produce a highly purified factor VIII (FVIII) concentrate from plasma cryoprecipitate. Solubilized cryoprecipitate, after adsorption on aluminium hydroxide and cold precipitation, was treated with 0.3% tri(n-butyl)phosphate and 1% Tween 80 at 25 degrees C for at least 8 h to inactivate lipid-enveloped viruses. The fraction was then loaded onto a column packed with DEAE-Fractogel TSK 650 M and chromatographed. Most proteins and TnBP-Tween 80 flowed through the gel unretarded. FVIII:c, which bound to the gel, was eluted by increasing the ionic strength, then was directly filter-sterilized without ultrafiltration or addition of a protein stabilizer. Chromatographic recovery of FVIII:c was 80-90%. After freeze-drying, FVIII:c was at a concentration of 42.5 +/- 9.5 IU/ml and had a specific activity of 175.4 +/- 37.8 IU/mg (n = 40), corresponding to a purification factor of over 12,000 from plasma. The typical yield of the freeze-dried FVIII:c from cryoprecipitate was 55-65%. FVIII:c was stable for over 24 h at room temperature in the liquid state. The mean content of fibrinogen and immunoglobulin G was only 65 and 100 mg/l, respectively, corresponding to 1.4 and 2.3 mg/1,000 IU FVIII:c. This concentrate, which is much purer than traditional FVIII concentrates, has been found to be well tolerated and effective in clinical treatment of hemophilia A patients.

Adsorption↗
PubMed1991

In vitro evaluation of a very-high-purity, solvent/detergent-treated, von Willebrand factor concentrate.

A very highly purified von Willebrand factor (vWF) concentrate was analyzed in order to evaluate its suitability for the treatment of von Willebrand's disease (vWD). The functional activity of vWF assessed by its ristocetin cofactor activity (vWF:RCo) correlated with the level of vWF antigen (vWF:Ag), with the vWF:RCo/vWF:Ag ratios ranging from 0.56 to 1.02, and the specific activity being always greater than 50 IU vWF:RCo/mg protein. Electrophoretic analysis showed a normal pattern of high, intermediate and low-molecular-weight multimers of vWF. The biological activity of vWF was also evaluated by studying its ability to bind to collagen and to platelet receptors in the presence of either ristocetin or thrombin. Furthermore, these functional activities of vWF were confirmed by the capacity of this concentrate to induce platelet adhesion to collagen in a perfusion system. Moreover, the vWF present in this preparation was able to bind factor VIII. All these in vitro data suggest that this preparation is likely to be effective in the treatment of vWD patients.

Detergents↗
PubMed1991

[Delusional melancholia and multiple lacunar infarcts of the basal ganglia].

A 72 years-old man presented with melancholia with delusions, possibly resulting from multiple lacunar infarcts in the basal ganglia. This case is akin to the syndrome of psychic akinesia and compulsive activity, resulting from lenticular nucleus lesions or frontal lobe lesions. We suggest that melancholia could be a consequence of a certain type of stereotyped mental activity and we would compare this stereotyped mental activity to stereotyped verbal activity in aphasia. Cognitive impairment might then be a cause of depression.

Aged↗
PubMed1990

Hemoglobin Calais [beta 76 (E20) Ala----Pro]: a hemoglobin variant with decreased intrinsic oxygen affinity.

Hb Calais [beta 76 (E20) Ala----Pro] is a new human hemoglobin variant displaying a decreased oxygen affinity. The only electrophoretical difference with Hb A was a slightly more acidic isoelectric point. A 2-fold decrease in the oxygen affinity was found by equilibrium measurements performed in a suspension of intact red blood cells and in the lysate. It was confirmed by kinetic studies of the purified abnormal hemoglobin. The rate of methemoglobin formation at 37 degrees C of Hb Calais was also increased relative to Hb A. The mechanism by which the Pro for Ala substitution of an external residue in the beta-chains results in these profound functional abnormalities is unclear. Subtle changes at the heme pocket, at a distance from the mutation, may be a plausible explanation for the effects observed.

Adult↗
PubMed1990

Validation of a procedure for potency assessing of a high purity factor VIII concentrate--comparison of different factor VIII coagulant assays and effect of prediluent.

The assessment of factor VIII coagulant activity (FVIII:C) in recently available highly purified and concentrated FVIII therapeutic products calls for careful evaluation of assay methodologies. We assayed more than 130 batches of a concentrate with a specific activity of about 150 FVIII:C units/mg protein, using one-stage and two-stage clotting and chromogenic methods. There was good agreement between the potency estimates obtained with the different methods. We also compared the FVIII:C potencies obtained after predilution in buffer or FVIII-deficient plasma using either calibrated plasma or FVIII concentrate as references. With the one-stage assay we found a marked discrepancy between the potency values obtained with buffer and with FVII-deficient plasma used as prediluents. In order to validate our "in vitro" data we performed 6 "in vivo" analyses in severe haemophilia A patients. On the basis of the overall data obtained we chose to label FVIII potency by using FVIII-deficient plasma as prediluent, reference plasma as standard and the chromogenic assay method.

Blood Coagulation Tests↗
PubMed1990

[Evaluation after 2 years of substitutive treatment of PiZZ emphysema with alpha-1 antitrypsin. 9 cases].

Homozygous PiZZ individuals with a serum deficiency due to a defect in the secretion of the alpha 1-antitrypsin protein are at risk of developing severe panlobular emphysema. Tobacco smokers are particularly exposed to the disease which begins at an earlier age. Treatment by substitutive therapy with alpha 1-antitrypsin concentrates seems to be the only possibility. A two years' clinical trial was performed in 9 PiZZ patients, with more than 1,500 infusions being administered weekly. Serum AAT levels were used as guidelines to follow biochemical changes in the protease-antiprotease balance. From 0.16 g/l initially, the AAT level rose to 0.57 g/l after 7 months. No adverse reaction was observed during the trial; the concentrated protein was well accepted, ant the antielastase activity of the protein recovered after injection was equivalent to the activity injected. An attempt to administer the infusions monthly was stopped when we observed a dramatic decrease of the serum AAT level. Clinically, stabilization of the symptoms was noted. No degradation was observed in the patients who took part in the trial, even if no real improvement was detected.

Adult↗
PubMed1990

A new von Willebrand factor (vWF) defect in a patient with factor VIII (FVIII) deficiency but with normal levels and multimeric patterns of both plasma and platelet vWF. Characterization of abnormal vWF/FVIII interaction.

The patients with inherited bleeding diathesis related to quantitative, structural, and/or functional abnormalities of von Willebrand factor (vWF) are said to have von Willebrand's disease (vWD). We report here the clinical and laboratory features of a 50-year-old woman with a life-long history of excessive bleeding. Her particular laboratory data are factor VIII (FVIII) deficiency, subnormal bleeding time, and the presence of all plasma and platelet vWF multimers in normal amounts. Infused with FVIII/vWF concentrate, she showed a persistent increase in FVIII that led us to discard hemophilia A carrier or "acquired hemophilia" diagnoses. vWF devoid of FVIII purified from normal and patient's plasma by immunoaffinity on anti-vWF monoclonal antibody (MoAb) was immobilized onto polystyrene tubes that were further incubated with purified normal FVIII. The bound FVIII was evidenced using radiolabeled anti-FVIII MoAb. The data showed that the patient's vWF, in contrast to vWF purified from normal plasma, was unable to bind FVIII. Furthermore, no inhibitor of FVIII/vWF interaction was evidenced in incubating purified normal vWF with the patient's plasma before the addition of FVIII and anti-FVIII MoAb. These results support the concept that the bleeding diathesis of this patient appears to be due mainly to her abnormal vWF preventing FVIII/vWF interaction. This abnormality, which is not yet described in present classification of vWD, could be considered as a new variant of vWD.

Factor VIII↗
PubMed1990

Evidence for a von Willebrand factor defect in factor VIII binding in three members of a family previously misdiagnosed mild haemophilia A and haemophilia A carriers: consequences for therapy and genetic counselling.

A plasma von Willebrand factor (vWf) defect limited to its failure to bind factor VIII (FVIII) was previously characterized in a woman with FVIII deficiency and normal primary haemostasis. By using in vitro tests we found a similar pattern in three siblings of another family previously thought to be affected with mild haemophilia A. Furthermore, a decrease in vWf ability to bind FVIII was found in the parents and the brother of the three patients. This decrease was consistent with heterozygous expression of a recessive vWf gene abnormality. FVIII deficiency was corrected by infusion with a vWf concentrate almost devoid of FVIII coagulant activity. FVIII recovery and half-life thus obtained showed that this treatment was more effective than a FVIII infusion performed by way of comparison. These results indicate that this vWf defect may account for FVIII deficiency in patients without the usual laboratory and clinical features of von Willebrand's disease. Changes in therapy and genetic counselling following the new diagnosis in this family emphasize the need to search for such a vWf defect in patients in whom FVIII deficiency is not obviously X-linked.

Child↗
PubMed1990

A double-blind multicentre comparison of remoxipride, at two dose levels, and haloperidol.

A total of 186 patients who met the DSM-III criteria for schizophrenia were admitted to a double-blind randomized multicentre trial in which the efficacy and safety of remoxipride at two dose levels was compared with those of haloperidol. Over a period of six weeks the patients received remoxipride 100-300 mg/day (n = 60), remoxipride 200-600 mg/day (n = 61), or haloperidol 10-30 mg/day (n = 64). There was no significant difference between the three treated groups with regard to the Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression (CGI) scores obtained. Remoxipride, at both dosage ranges used, thus had comparable therapeutic efficacy to that of haloperidol. In contrast, extrapyramidal symptoms occurred significantly more frequently in the group treated with haloperidol. Laboratory tests and cardiovascular investigations showed no specific drug effect in any of the treated patients. Remoxipride is thus effective in acute treatment of schizophrenia at both dosage levels and has an advantage over haloperidol in neurological acceptability.

Adolescent↗
PubMed1989

Primary structure of the major O-glycosidically linked carbohydrate unit of human von Willebrand factor.

A reduced tetrasaccharide chain was obtained from human von Willebrand factor (vWF) by mild alkaline borohydride treatment. The purification of this O-glycosidically-linked oligosaccharide was achieved by serial affinity chromatography on immobilized concanavalin A and Lens culinaris agglutinin and finally gel filtration. Its structure was determined by a combination of methylation studies and 500 MHz 1H-NMR spectroscopy to be: NeuAc(alpha 2-3)Gal(beta 1-3)[NeuAc(alpha 2-6)]GalNAc-ol.

Carbohydrate Conformation↗