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Biomedical subjects

D Varon

Publications and source records attributed to D Varon.

At least 91 records · Page 5Linked to original sources

Ventricular defibrillating properties of catecholamine uptake inhibitors.

Ventricular fibrillation (VF) is a fatal event in humans unless electrical defibrillation is applied within minutes. Recent publications describe spontaneous termination of VF in various animals and even in humans. Certain drugs can transfer a fatal, sustained VF (SVF) into a self-terminating, transient VF (TVF). Based on results obtained in animals of various species and ages, we have suggested that the occurrence of TVF requires a high cardiac catecholamine level at the time of VF. According to our hypothesis, drugs which decrease catecholamine reuptake by the sympathetic nerve terminals will increase the ability of the heart ventricles to defibrillate spontaneously. In the present study, we examined the effects of desipramine, maprotiline, mianserin, iprindole, cocaine and amphetamine on the type of VF in cats exhibiting SVF prior to the treatment. The results show that the ability of these compounds to transfer SVF to TVF is closely related to their potency to inhibit catecholamine reuptake. The establishment of the catecholamine related mechanisms of TVF may lead to the development of a new class of antiarrhythmic-defibrillatory drugs.

Amphetamine↗

Circumcision in hemophilia: the use of fibrin glue for local hemostasis.

Circumcision can be fatal in hemophilia patients unless they are treated with the missing coagulation factor. We describe 10 severe hemophilia patients in whom circumcision was performed with local fibrin glue instead of infusion of factor concentrate. Of the 10 patients 3 had postoperative bleeding and only 2 of them required infusion of factor VIII concentrate. Fibrin glue is a useful treatment modality for circumcision in patients with bleeding diathesis, and it is safer and cheaper than the infusion of factor concentrate.

Adolescent↗

Adjusted dose continuous infusion of factor VIII in patients with haemophilia A.

Surgical interventions in patients suffering from haemophilia A require infusions of large doses of factor VIII (F VIII) concentrates. These are expensive and may pose a burden on the immune system, which is already compromised in many haemophiliacs. F VIII is usually given as bolus injections, although there are reports on fixed dose continuous infusion. We have developed a continuous infusion programme with dosage adjusted according to daily calculation of the clearance of F VIII. Twenty-four haemophiliacs received a total of 205 d of continuous infusion with F VIII (168 d in hospital, 37 d home therapy). Eighteen patients underwent surgeries (11 elective, seven emergency) and six were treated for serious haemorrhages. We observed a significant, progressive decrease of the clearance of F VIII over the first 5 d from 3.2 (2.8-3.5) to 1.7 (1.3-1.9) ml/kg/h (median and interquartile range). The decrease of the clearance together with the fact that a continuous infusion requires less drug than bolus injections to keep the same minimal concentration, contributed to much lower doses of F VIII than reported in the literature or than required by historical controls, matched for the type of operation. Other advantages of our method are improved safety with stable activities of F VIII, lack of hazardous troughs below the haemostatic range, and the convenience, which permits ambulant therapy even when high doses of F VIII are required.

Adolescent↗

[Congenital afibrinogenemia with bleeding, bone cysts and antibodies to fibrinogen].

Congenital afibrinogenemia is a rare hereditary disorder which has been described in only 150 families. The main clinical manifestations include spontaneous bleeding into the skin and into the gastrointestinal and genitourinary tracts. Skeletal manifestations are seldom reported. Laboratory findings include coagulation disorders corrected by administration of plasma, cryoprecipitate or fibrinogen. Development of antibodies to treatment with fibrinogen is rare. We report congenital afibrinogenemia in a 25-year-old man with rare complications which included skeletal manifestations such as bone cysts, and the development of antibodies to fibrinogen. Fibrinogen levels could only be maintained in the normal range by continuous infusion of cryoprecipitate, but not by bolus injections.

Adult↗

Evaluation of ketanserin as a tocolytic agent in third trimester pregnant rats.

Ketanserin, as a 5HT2 selective antagonist, was evaluated for its tocolytic effects in pregnant Charles River (CR) rats, at total doses of 1.5 and 3.5 mg/kg IU from day 22 to day 25 of pregnancy. After 18 hours of ethenyl estradiol induction, tocolytic evaluation was carried out by recording uterine activity. When compared to the control group, the administration of Ketanserin resulted in an apparent, nondose dependent suppression of uterine contractility.

Animals↗

A correlation between the structure of myocardial cells and prolonged Q-T interval in young rats.

In the present study, we examined the electrocardiogram and the structure of myocardial cells in young rats at different postnatal ages. The offspring of rats were sacrificed on different postnatal days following electrocardiographical recordings, and sections of their hearts were examined microscopically. In a number of newborns, we observed definite prolongation of the Q-T interval in the electrocardiogram on the first day of life. Normal shortening of the Q-T interval with age was demonstrated in the majority of the offspring while, in some of them, the Q-T interval remained prolonged. In the "affected" offspring, which exhibit a typical pattern of Q-T prolongation with clear ST segment, definite retardation of histological differentiation of the myocardium was found at various ages. In these cases, there were large numbers of "myoblasts" scattered between normal myocytes in different parts of the ventricular walls and septum. These myoblasts were rarely identified in newborns and offspring with a normal Q-T interval. Our results clearly show a correlation between the ratio of persistence of undifferentiated myoblasts at any age and the typical prolonged Q-T pattern in the electrocardiogram (r = 0.9). Due to the possible clinical significance, the hearts of patients with prolonged Q-T syndrome should be examined so as to reach for abnormal differentiation of the myocytes.

Animals↗

The prevalence and interaction of human immunodeficiency virus and hepatitis B virus infections in Israeli hemophiliacs.

The prevalence, clinical manifestations and serological markers of hepatitis B virus (HBV) and human immunodeficiency (HIV) infections were studied in 117 Israeli hemophiliacs. Positive serological markers for HBV infection (HB surface antigen, antibody to HB surface antigen or antibody to HB core antigen) were more common in patients treated with non heat-treated F-VIII concentrates (NHTC) than with cryoprecipitate (48/49 vs. 23/29, P less than 0.05), and in patients treated with greater than 10,000 factor units/year (90% vs. 62%, P less than 0.05). Of the 117 patients, 55% were HIV negative, 29% had asymptomatic HIV seropositivity and 16% had symptomatic HIV infection (lymphadenopathy syndrome, AIDS-related complex or AIDS). HIVB seropositivity was more common in patients treated with NHTC than in those treated with cryoprecipitate (83% vs. 11%, P less than 0.001), and in patients treated with greater than 100,000 compared to less than 10,000 F-VIII units/year (70% vs. 15%, P less than 0.001). Hypergammaglobulinemia correlated with HIV seropositivity, alanine aminotransferase levels and type and amount of concentrate therapy. Of 50 HIV-seropositive patients, 40 (98%) had serological markers of HBV infection compared with only 40 of 52 HIV-negative patients (77%) (P less than 0.01). Symptomatic HIV infection was more common in patients with a positive history of jaundice, 7 of 18 (38%) compared with 12 of 99 (12%) (P less than 0.005). These findings suggest that HBV and HIV infections are less prevalent in cryoprecipitate-treated patients, and that HBV seropositivity is a predictor of HIV seropositivity in hemophiliacs.

Factor VIII↗

Chronic active hepatitis following splenectomy for autoimmune thrombocytopenia.

Two patients with immune thrombocytopenic purpura underwent splenectomy following the failure of steroid therapy. In neither patient was there evidence of liver disease prior to the splenectomy. Both had autoimmune parameters before the operation. They both received blood compounds; one patient remained negative for hepatitis B surface antigen (HBsAg) and antibodies, and the other had anti-HBs and anti-HBc. Antibodies for hepatitis C virus were found in both patients. In the two patients hepatitis developed 4 and 6 weeks, respectively, following splenectomy, and liver biopsies performed 6 months and 2 years post splenectomy revealed chronic active hepatitis. The relationship between the two disorders is discussed and a possible role of the splenectomy in the development of chronic active hepatitis in these two cases is suggested.

Autoimmune Diseases↗

Dental extraction for patients on oral anticoagulant therapy.

Dental extraction in patients receiving long-term oral anticoagulant therapy is a controversial issue. Continuation of anticoagulation exposes the patient to serious hemorrhage, whereas cessation of therapy increases the risk of thromboembolism. Forty patients treated by coumarin underwent 63 tooth extractions, without a change in the therapeutic protocol of anticoagulation. The biologic adhesive Beriplast was used successfully to achieve local hemostasis at the site of the surgical wound. Apart from one patient who had mild oozing, there were no incidences of postsurgical hemorrhage.

Administration, Oral↗

Human monoclonal antibody derived from an autoimmune thrombocytopenic purpura patient, recognizing an intermediate filament's determinant common to vimentin and desmin.

Human monoclonal antibody (mAb) technology has been helpful in identifying autoantibodies that are involved in various autoimmune disorders. We report here the results of such an attempt to immortalize antibody-forming cells from spleen of an autoimmune thrombocytopenic purpura (ATP) patient and characterize the resulting mAb. The human mAb we derived, denoted (4G9), binds to the cytoskeletal network. Using immunofluorescence analyses of permeabilized and fixed cell lines and tissues, the 4G9 mAb was shown to be anti-vimentin specific by virtue of its intracellular staining pattern, decoration of cell lines of mesenchymal (but not epithelial) origin, and by the fact that polyclonal anti-vimentin (and not anti-actin, prekeratin, tubulin or vinculin) antibodies inhibited its binding to intermediate filaments of a fibroblastoid cell line. The presence of vimentin in platelets was also confirmed in the present study by immunoblotting of platelet extract using murine anti-vimentin mAb. Interestingly, in addition to vimentin the 4G9 mAb decorated intermediate filaments in desmin-expressing muscular cells, suggesting that the 4G9 epitope is most likely located within the homologous sequences that are known to be shared between vimentin and desmin.

Animals↗

Clinical and pathological features of non-Hodgkin's lymphoma of the tonsil. Review of the literature and report of 10 cases.

Ten patients with tonsillar lymphomas diagnosed and treated in our hematology unit from 1979 to 1986 are reported. The heterogeneous histology at presentation, the aggressiveness of the histologic types during relapse, and the relatively low incidence of gastrointestinal tract involvement are discussed. A review of the literature is presented. In view of the better survival rate obtained with chemotherapy or combined chemo- and radiotherapy, we confirm that lymphomas of the tonsil should be aggressively treated, regardless of the staging. Among our 10 cases, 2 are of special interest since they progressed into highly malignant disorders: B-acute lymphoblastic leukemia and Burkitt's lymphoma.

Adult↗

An attempt to prevent or delay denervation changes in rat muscles.

A number of drugs which are known to affect lysosomes and their enzyme activities were used in an attempt to inhibit or delay the onset of denervation changes in rat muscles. The following parameters were used: the occurrence of fibrillations in electromyographs; diameters of muscle fibers; acid phosphatase activity; acetylcholinesterase activity and distribution in end plates. Differences between denervated and non-denervated limbs were evaluated and compared in the different treatment groups. The various parameters were differently affected by the different drugs. Chloroquin, thiouracil and streptomycin appeared to be more effective than other treatments in the inhibition of denervation changes.

Animals↗

Gray platelet syndrome in the elderly.

A 68-year-old male who suffered from thrombocytopenia and mild splenomegaly for 18 years was found to present agranular gray platelets on peripheral blood smear. Bone biopsy revealed a mild, diffuse, reticular fibrosis with no collagen, and electron microscopy of the platelets showed an absence of almost all the alpha-granules. Platelet thrombospondin and fibronectin analysed by SDS-polyacrylamide gel electrophoresis and Rocket immunoelectrophoresis were absent. Follow-up of 4 years showed the same parameters with no evidence of active myeloproliferative or dysmyelopoietic disorders. Hemorrhagic diathesis was limited to ecchymoses and postprostatectomy bleeding, necessitating platelet transfusion. This led us to conclude that our patient probably had a constitutional primary alpha-granule deficiency or gray platelet syndrome. This extremely rare defect has been described in less than 10 patients, all of them very young. Our observation shows that these patients may have a long, uneventful survival.

Aged↗

A new group of defibrillatory drugs in the classification of antiarrhythmic agents.

Ventricular antiarrhythmic therapy is aimed traditionally at preventing arrhythmias and ventricular fibrillation. Recently, a new approach has been introduced, where drug therapy facilitates the ability of the heart for spontaneous defibrillation. The chemical features and the electrophysiologic properties are discussed below. The introduction of this new group of defibrillating antiarrhythmic drugs implies the extension of the common classification of antiarrhythmic drugs.

Animals↗