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Biomedical subjects

J Batlle

Publications and source records attributed to J Batlle.

At least 37 records · Page 2Linked to original sources

Prevalence, follow-up and clinical significance of the anticardiolipin antibodies in normal subjects.

To date very few studies that analyze the prevalence of anticardiolipin antibodies (ACA) in healthy subjects have been reported. No data based on a systematic analysis of normal subjects with positive ACA is available. The aim of the present study was to evaluate the prevalence of ACA; its clinical significance and relationship to the lupus anticoagulant (LA) and other autoimmune parameters in an apparently healthy population. 552 normal blood donors from a blood bank were randomly selected. ACA positive donors who consented were monitored over a period of twelve months and tested every three months. ACA (IgG and IgM isotypes) were quantitated by enzyme linked immunoassay (ELISA). The prevalence for IgG ACA in our donor population was estimated to be 6.5%, and 9.4% for IgM ACA, which is similar to the one previously reported for IgG and slightly higher for IgM. It is worth noting that in our study ACA positive donors exhibited a progressive negativization. Eight donors with IgG ACA and seven with IgM ACA remained positive for nine months. Five donors with IgG ACA and four with IgM ACA had family history of thromboembolic disease. One donor with IgG ACA and two with IgM ACA had had unexplained miscarriages in the past. We did not find any relationship between ACA and LA, nor between ACA positivity and the clinical and laboratory data studied. Pseudopositivity for lues was not found. No thrombotic event occurred in donors that were positive for ACA during the 12-month follow-up.

Adult↗

[Comparative multicenter study of a rabbit high-sensitivity thromboplastin and a recombinant thromboplastin with synthetic phospholipids].

PURPOSE: The purpose of the present study was to compare the results obtained with a human recombinant thromboplastin (Innovin, Baxter) (IN) and a high-sensitivity rabbit brain reagent (Thromboplastin IS, Baxter) (IS), on the performance of prothrombin time (PT) test and the functional assay of factors included in the extrinsic coagulation system, in order to establish possible differences on imprecision, diagnostic accuracy and sensitivity to the oral anticoagulant defect, between the two products. MATERIAL AND METHODS: Six Spanish hospital took part in the study. Plasma samples from 221 healthy subjects, 100 patients with severe liver disease, 27 with dysfibrinogenaemia, 10 with lupus anticoagulant and from 13 individuals propositus and their relatives with congenital deficiencies of the extrinsic coagulation pathway, and their relatives were studied; 188 patients stabilized on oral anticoagulant therapy and 82 on heparin therapy were also included. The in vitro effect of heparin was tested by addition of increasing amounts of heparin (0.3 to 10.0 IU/mL) to aliquots of normal plasma. RESULTS: Both in the intra-assay and in the inter-assay imprecision study, a better coefficient of variation was obtained with IN when the PT was performed on abnormal samples. Prothrombin time ratio from patients with liver disease had significantly higher values with IS. On the contrary, IN had a higher sensitivity in samples from patients with dysfibrinogenaemia or from those stabilized on oral anticoagulant therapy. In showed a very low sensitivity to heparin at concentrations corresponding to the therapeutic range. CONCLUSIONS: The results of this field study indicate that IN, compared with a high-sensitivity rabbit brain thromboplastin, is a suitable reagent for PT determination in normal subjects, patients with liver disease or with congenital deficiencies of clotting factors. It shows a higher sensitivity in cases of dysfibrinogenaemia and in patients on oral anticoagulant therapy. In addition, the recombinant reagent had better reproducibility when the PT was performed on abnormal samples, and it was hardly affected by heparin within the therapeutic range.

Afibrinogenemia↗

Activity-dependent plastic changes in the motor nerve terminals of the adult rat.

Small and short-lasting physiologic variations in the locomotor activity of normal adult rats can induce remodelling in the motor nerve endings of the fast extensor digitorum longus muscle. The specificity and relative importance of the different plastic adaptations occurring in the presynaptic axonal tree have been studied, in silver impregnated nerve endings, by using an automatic image analysis treatment of the nerve terminals' geometric properties and a discriminant analysis of the morphometric parameters. Changes observed, like selective length variations in certain terminal segments and positional rearrangements, agree with a mechanism of neural connectivity regulation in the adult that arises as a consequence of normal neuromuscular activity.

Adaptation, Physiological↗

[Therapy of disseminated intravascular coagulation in acute promyelocytic leukemias. Apropos of 19 cases].

PURPOSE: To evaluate our experience in the treatment of disseminated intravascular coagulation (DIC) associated to AML-M3 with substitution therapy with or without heparin. PATIENTS AND METHODS: The clinical records of 19 patients diagnosed of AML-M3 in the Hospital Juan Canalejo, in La Coruña, between 1986 and 1991 were revised. DIC was defined by abnormalities in one or more of the following: prothrombin time, activated partial thromboplastic time, thrombin time, fibrinogenaemia, fibrin/fibrinogen degradation products, D-dimers. The treatment given to 13 patients was only substitutive including platelets, fresh-frozen plasma, cryoprecipitates and antithrombin III. Low-dose sodium heparin (Kabi) in continuous intravenous infusion was associated to the treatment of the remaining 6 patients. With regard to the leukaemic therapy, most of the patients received daunorubicin, 2 mg/kg/day x 5 days, and AraC, 100 mg/Kg/day x 7 days. RESULTS: All patients showed haemorrhagic symptoms at diagnosis, and laboratory data of DIC were present in 11 cases (57%). The mean duration of DIC was 6.5 days for the patients receiving substitutive treatment and 9.5 days for those given heparin. Complete remission (CR) of the leukaemia was attained in 12 cases (63%); of the patients treated with heparin, 50% achieved CR whereas 75% of those receiving substitute therapy attained CR. The 24-months survival rate was 30% for the patients treated with substitutive therapy and 16% for those treated with heparin. The incidence of death associated to haemorrhage during induction therapy was 30% for the substitutive treatment group and 50% for the heparin group. CONCLUSION: Shorter duration of DIC, lesser rate of early death, higher CR rate and longer 2-year survival were found in those AML-M3 patients not receiving heparin.

Adolescent↗

Further evidence for recessive inheritance of von Willebrand disease with abnormal binding of von Willebrand factor to factor VIII.

A new family with a bleeding diathesis and FVIII deficiency secondary to abnormal binding of von Willebrand factor (vWF) to factor VIII (FVIII) is described. Two propositi of this family, an 18-year-old male and a 33-year-old female, both with a history of epistaxis, bruising, bleeding from the gums, epistaxis, hemarthrosis, and hematoma, were analyzed. Also additional members of the same family with no bleeding history were also studied. The propositi showed normal vWF activities, low FVIII activity; one of them had been diagnosed as having hemophilia A and the other was a hemophilia A carrier. Both showed a very poor response to treatment with FVIII concentrates and desmopressin (DDAVP) but a good clinical response to cryoprecipitate. APTT was prolonged and no inhibitory activity was noticeable in their plasmas. Thirty-five units per kilogram body weight of Hemofil M was infused to both propositi and FVIII reached basal level within 60 minutes of the infusion. No FVIII response at all was observed in the female after intravenous DDAVP administration. However, the male who received the infusion of 35 U/kg body weight of Humate-P achieved a normal FVIII level that was maintained for 12 hours. Multimeric analysis of vWF was normal in all the members studied. Von Willebrand factor domain for FVIII binding was assayed in the two propositi and in six other members of the same family by using a non-isotopic and sensitive method, a modification of the one previously described, using the Hemofil M concentrate as exogenous FVIII. The data obtained showed that both propositi had similar binding to that observed by using plasma of a patient with severe von Willebrand disease. Furthermore, five siblings had a decreased binding of vWF to FVIII, when compared with plasma from normal individuals or patients with hemophilia A. We also observed that, for screening purpose, the ratio of bound FVIII/immobilized vWF (at saturation of the anti-vWF and offering of 1 U/ml of exogenous FVIII) distinguished two levels of abnormality (normal range 0.70-1.15, propositi 0.004-0.007, and remaining members affected 0.25-0.42). The most probable explanation is that the propositi are homozygous or double heterozygous, the other five siblings affected being heterozygous for a recessive vWF defect. This more accessible assay presented here may be of help in routine analysis for diagnosing this type of von Willebrand disease, which has important implications for therapy and genetic counseling.

Deamino Arginine Vasopressin↗

Pattern of arborization of the motor nerve terminals in the fast and slow mammalian muscles.

A silver impregnation method and a morphometric approach were used to define differences existing in the motor nerve terminal branching pattern between a fast-twitch muscle (extensor digitorum longus) and a slow-twitch one (soleus) of the normal adult rat. Because no single measure can describe precisely all geometrical properties (ie both topology and metrics) of the nerve terminals, we evaluated morphologic parameters defining length and angular characteristics in the different terminal segments classified according to their centrifugal order. The main results indicate that the distal free-end segments in the extensor digitorum longus muscle are shorter and less divergent than in the soleus nerve terminals. The endings in the two muscles have different fractal dimensions. Findings are discussed in the context of the hypothetical mechanisms governing motor nerve terminal size and complexity.

Animals↗

Pregnancy outcome in hematologic malignancies.

By means of a mail questionnaire, information on a series of 56 pregnancies i in 48 women diagnosed with leukemia or lymphoma was collected from ten hospitals. Seven patients conceived while receiving treatment for their neoplasms; in 22 patients, the hematologic disease was diagnosed during pregnancy, and the remaining 27 patients became pregnant after completion of the antineoplastic treatment. When a comparison was made of the evolution of these pregnancies to that of pregnancies in a healthy population, no increase in the incidence of complications was observed: 64% of the pregnancies went to term, 9% resulted in spontaneous abortion, and 5% resulted in premature births. The observed incidence of one major malformation in 56 pregnancies did not differ from the frequency of malformations in the offspring of healthy individuals. There were no fetal losses in six pregnancies in which conception occurred during the first year after chemotherapy. In spite of the inherent limitations derived from the design of this type of study and the type of subject analyzed, the data here support the hypothesis that the cytostatic treatment of hematologic malignancies, if deemed necessary, should not be postponed because of pregnancy. Moreover, the authors agree with advice recommending that no antifolic or alkylating agents be used for prolonged periods and that radiotherapy be avoided, especially to those fields involving the pelvic area.

Abortion, Induced↗

Abnormal proteolytic degradation of von Willebrand factor after desmopressin infusion in a new subtype of von Willebrand disease (ID).

We describe two members of a single family, father and son, with mild factor XII deficiency associated to von Willebrand disease (vWD) with aberrant structure in whom distinct multimeric abnormalities and an abnormal proteolytic processing of von Willebrand factor (vWF) after desmopressin (DDAVP) administration were present. They had a mild bleeding history, low levels of vWF-related activities, and a prolonged bleeding time. Low-resolution agarose gel electrophoresis showed a vWF with all size multimers in plasma and platelets. Higher-resolution agarose gels demonstrated that the main band was present, but the relative proportion of the satellite bands was markedly reduced. The smallest oligomer was not increased. After the infusion of DDAVP to the father, a transient increase in the relative proportion of the satellite bands was seen, as described in normal individuals. No difference in the structure of vWF was observed when blood was collected with proteinase inhibitors. The analysis of native subunits of vWF and their proteolytic derived fragments, after DDAVP administration, showed a temporary augmentation of the 176 kDa fragment, as seen in normal subjects, as well as an increase of the 189 kDa fragment. This finding had not been reported previously either in normal individuals or in patients with vWD.

Adult↗

Acquired von Willebrand disease in multiple myeloma secondary to absorption of von Willebrand factor by plasma cells.

A case of acquired von Willebrand disease (AvWD) associated with an IgA lambda multiple myeloma is reported. No form of inhibitor could be detected. SDS-agarose gel electrophoresis patterns of von Willebrand factor (vWF) both in plasma and platelet lysates were normal but a decrease in all-sized multimers with a type IA pattern was seen. After 1-deamino-8-D arginine vasopressin (DDAVP) infusion, vWF multimers larger than those seen in the resting state appeared in patient plasma, which were progressively cleared. Indirect immunofluorescence studies with a monoclonal antibody to vWF showed that vWF was selectively absorbed into myelomatous cells. This is the first case of AvWD associated with multiple myeloma resulting from the selective absorption of vWF into abnormal plasma cells. This feature established a new pathophysiological mechanism of AvWD in multiple myeloma and probably in other lymphoproliferative diseases.

Absorption↗

Motor nerve terminal morphologic plasticity induced by small changes in the locomotor activity of the adult rat.

The possible existence of plastic changes in the branching pattern and the complexity of silver-impregnated motor nerve terminals was studied in the extensor digitorum longus muscle of adult rats housed in metabolic cages or trained to walk. Results indicate a precise inverse relation between the amount of locomotor activity and the complexity finally attained by the motor nerve terminals.

Animals↗

High levels of plasma FVIII and vWF in the toxic epidemic syndrome patients.

Factor VIII and von Willebrand factor proteins were evaluated in 115 patients having the chronic phase of the Toxic Epidemic Syndrome (TES), a new multisystemic disease probably caused by the ingestion of denatured rapeseed oil, and in 50 control volunteers. Higher circulating levels of factor VIII procoagulant activity (VIII:C) (158 +/- 58.4 U/dl), von Willebrand factor antigen (vWF:Ag) (166.1 +/- 55.5 U/dl) and von Willebrand factor ristocetin cofactor activity (vWF:RCo) (178.7 +/- 55.2 U/dl) were seen in TES patients (p less than 0.001, TES patients versus control subjects, for each parameter). The increased levels of vWF:Ag and vWF:RCo observed in TES patients correlated with the scleroderma like lesion of the skin, with the sicca syndrome and with Raynaud's phenomenon (p less than 0.01), but not with other clinical manifestations. The multimeric analysis of vWF in 92% of the TES patients was similar to that found in normal plasma, but in the remaining 8% a very slight increase of larger vWF multimers in plasma were observed. The raised levels of vWF found in TES patients in the chronic phase may reflect an "in vivo" vascular injury.

Adolescent↗

Type IIB von Willebrand's disease associated with a complex thrombocytopenic thrombocytopathy.

A familial bleeding disorder characterized by an association of Type IIB von Willebrand's disease (vWD) with a complex thrombocytopenic thrombocytopathy is described in two patients from the same generation. Findings typical of type IIB vWD included enhanced ristocetin-induced binding of patient von Willebrand factor (vWF) to platelets of patients and normal individuals in association with the absence of larger multimers from plasma. Abnormalities in platelet function included deficient platelet aggregation to ADP, collagen, epinephrine, and arachidonic acid; and defective release of 14C-serotonin, vWF, and platelet factor 4 (PF4) in response to thrombin, collagen, or ADP. Platelet factor 4 and platelet vWF were decreased when measured per mg of total platelet protein. In addition, the binding of normal vWF to patient platelets stimulated with thrombin was decreased. Platelet size was increased with a very heterogeneous distribution width. Electron microscopic evaluation showed giant platelets with dense and alpha bodies present. The platelet count was borderline or slightly decreased in the resting state and declined to frankly thrombocytopenic levels at the time of acute bleeding episodes; this state was associated with the presence of platelet aggregates in blood smears.

Antibodies, Monoclonal↗