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Biomedical subjects

H R Gralnick

Publications and source records attributed to H R Gralnick.

At least 145 records · Page 8Linked to original sources
PubMed1977

Intravascular coagulation. 2. Underlying conditions and therapy.

Therapy for intravascular coagulation is directed primarily against the underlying disorder. If the latter is not readily correctable or if the patient is bleeding actively, anticoagulation with intermittent administration of heparin by the intravenous route is indicated. If thrombocytopenia is present, heparinization must be accompanied by platelet transfusion. The efficacy of therapy is judged by the cessation of bleeding or thrombosis, improvement of organic dysfunction, and correction of the levels of the coagulation factors, particularly factor V and fibrinogen.

Antithrombins↗
PubMed1977

Studies on the mechanism of ristocetin-induced platelet agglutination. Effects of structural modification of ristocetin and vancomycin.

The mechanism by which ristocetin induces platelet agglutination in the presence of the von Willebrand factor was studied by chemically altering ristocetin and a similar antibiotic, vancomycin, by reaction with a water-soluble carbodiimide in the presence of glycine methyl ester at pH 4.75. Altering ristocetin's phenolic groups (which are thought to be important in its peptide-binding properties) resulted in a loss of both platelet-agglutinating and antibiotic activities. Restoring the phenolic groups with hydroxylamine restored both activities. Vancomycin has antibiotic and peptide-binding properties similar to ristocetin's, but differs structurally in having a free carboxyl group and thus a less positive charge at neutral pH. It does not induce platelet agglutination and actually inhibits ristocetin-induced agglutination. Reacting vancomycin with the water-soluble carbodiimide resulted in alteration of phenolic groups and permanent conversion of the carboxyl to a neutral derivative. Restoring the phenolic groups with hydroxylamine (but leaving the carboxyl neutralized) produced a compound with charge properties similar to ristocetin's which induced platelet agglutination as ristocetin does. These data suggest both a binding requirement (mediated through phenolic groups) and a strong positive charge requirement for ristocetin-induced agglutination. The data are consistent with a model wherein positively charged ristocetin binds, via its phenolic groups, to sites on the platelet surface and reduces the platelet's negative charge. This could reduce the electrostatic repulsion between platelets and/or between platelets and the negatively charged von Willebrand factor, and permit the macromolecular von Willebrand factor to cause agglutination by bridging between platelets.

Carbodiimides↗
PubMed1977

Comparison of polymerization of ancrod and thrombin fibrin monomers.

The polymerization of thrombin and ancrod fibrin monomers was studied with a standardized technique that evaluated turbidity changes and protein incorporation into the clot. Ancrod fibrin monomers were found to polymerize more slowly and form less turbid clots (at identical protein concentrations). Changes in ionic strength and pH influences ancrod fibrin monomer polymerization to a greater extent than thrombin fibrin monomer polymerization. Benzyltriethylammonium chloride was shown to be a potent inhibitor of fibrin monomer polymerization, with a greater inhibitory effect on ancrod fibrin monomers than on thrombin fibrin monomers. The differences between ancrod and thrombin fibrin may play a role in the infrequent thrombotic complications reported with ancrod therapy.

Ancrod↗
PubMed1977

Characteristics of blast crisis in chronic granulocytic leukemia.

The terminal phase of most patients with Ph1-positive chronic granulocytic leukemia (i.e., blast crisis) resembles acute leukemia. The clinical and hematologic features of blast crisis in 73 patients with chronic granulocytic leukemia have been reviewed. Two major morphological subgroups, lymphoblastic and myeloblastic, were identified. The lymphoblastic group in general had more profound thrombocytopenia and a greater number of blasts, while the myeloblastic group had more severa anemia. Extramedullary leukemia was documented in 27 patients. In 12 patients extramedullary leukemia preceded or occurred simultaneously with blast crisis in the bone marrow and peripheral blood. On the basis of this study we present hematologic criteria for the diagnosis of blast crisis and emphasize the importance of extramedullary leukemia in heralding the onset of blast crisis.

Blood Cell Count↗
PubMed1977

Heterogeneity of human whole blood platelet subpopulations. I. Relationship between buoyant density, cell volume, and ultrastructure.

A quantitative high yield method utilizing isosmotic arabino-galactan (Stractan) solutions and isopycnic centrifugation was developed to isolate and to fractionate total human platelet populations into density-dependent subpopulations. Isolated platelets were free of factor VIII/von Willebrand factor and other plasma proteins. They responded to ADP, epinephrine, and collagen with a sensitivity equal to platelet-rich plasma platelets. The correlation of platelet density with volume and ultrastructure was examined for normal subjects. Recovery of total platelet populations averaged 92.76%+/-3.64% (SD). Normal individuals exhibited a narrow range of platelet buoyant density distribution. Computerized probability plot analysis of platelet volume distribution for 15 normal subjects' total platelet populations showed a mean volume of 5.17+/-0.46 cu mum (SD). Platelets with buoyant density less than or equal to 1.062 g/ml had a mean volume of 4.50+/-0.48 cu mum, while platelets with buoyant density greater than 1.071 g/ml, but less than or equal to 1.084 g/ml, had a mean volume of 5.32+/-0.63 cu mum (SD). The volume difference by paired t test was significant, p less than 0.001. Thin-section electron microscopy demonstrated a significant reduction of granule content in light platelets, as compared to heavy platelets, but an equal number of mitochondria for both groups. These differences of platelet volume and structure between light and heavy platelets suggested that aging may be a determinant of platelet heterogeneity.

Adult↗
PubMed1976

Molecular defects in haemophilia A and von Willebrand's disease.

A model is proposed for the synthesis of the factor VII/von Willebrand factor protein. The defect(s) in von Willebrand's disease are related to abnormalities of the protein subunit and/or its carbohydrate content, while in haemophilia the abnormality is related to a deficiency or abnormality of the X-dependent enzyme or protein which is involved in the generation of procoagulant activity of the factor VII/von Willebrand factor multimer.

Blood Coagulation Factors↗
PubMed1976

Carbohydrate deficiency of the factor VIII/von Willebrand factor Protein in von Willebrand's disease variants.

Study of the normal human factor VIII/von Willebrand factor reveals a macromolecular glycoprotein composed of apparently identical subunits. This purified glycoprotein has procoagulant, antigen, and von Willebrand factor activities. In three patients with a variant of the von Willebrand's disease syndrome, their factor VIII/von Willebrand factor protein was present in normal amounts and had normal procoagulant and antigen activities; however, this protein was deficient in both carbohydrate and von Willebrand factor activity. The carbohydrate portion of the factor VIII/von Willebrand factor glycoprotein is of major importance in its interactions with platelets or the blood vessel wall, or both.

Antigens↗
PubMed1976

Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group.

A uniform system of classification and nomenclature of the acute leukaemias, at present lacking, should permit more accurate recording of the distribution of cases entered into clinical trials, and could provide a reference standard when newly developed cell-surface markers believed to characterize specific cell types are applied to cases of acute leukaemia. Proposals based on conventional morphological and cytochemical methods are offered following the study of peripheral blood and bone-marrow films from some 200 cases of acute leukaemia by a group of seven French, American and British haematologists. The slides were examined first independently, and then by the group working together. Two groups of acute leukaemia, 'lymphoblastic' and myeloid are further subdivided into three and six groups. Dysmyelopoietic syndromes that may be confused with acute myeloid leukaemia are also considered. Photomicrographs of each of the named conditions are presented.

Acute Disease↗
PubMed1976

Platelet to leukocyte adherence phenomena associated with thrombocytopenia.

Two patients developed thrombocytopenia associated with an in vitro platelet to leukocyte adherence phenomenon (PLAP). In one patient, whole serum, intact plasma, and the IgG fraction of the serum could induce the PLAP of normal platelets in normal whole blood or buffy coat preparations. Passage of serum over a Sepharose column coupled with antihuman IgG resulted in the loss of all the PLAP activity. Activity could not be recovered from the whole serum or the IgG fraction of serum of the second patient; however, the PLAP was transferred to her newborn infant. In both patients, an unusual pulmonary illness accompanied the PLAP and thrombocytopenia.

Adult↗
PubMed1976

The pH dependence of quantitative ristocetin-induced platelet aggregation: theoretical and practical implications-a new device for maintenance of platelet-rich plasma pH.

Quantitative ristocetin-induced platelet aggregation of normal platelet-rich plasma (PRP) decreased with time after PRP preparation. An increase in p H of the PRP with time proved to be responsible for this finding. Diffusion of CO2from the plasma is the prime determinant of the change in pH. Since a complex combination of factors influences CO2 diffusion (surface area-to-volume relationship, capping, mixing, etc.) The change in pH is variable with time. Thus, quantitative ristocetin aggregation should be pH controlled. A simple device for maintaining PRP pH constant by control of the ambient pCO2 was designed and found effective in keeping both pH and quantitative ristocetin aggregation constant over a prolonged period of time. It can be adapted for use in platelet aggregation studies employing other reagents. The pH dependence of ristocetin-induced platelet aggregation is consistent with other data supporting an elctrostatic interaction between the platelet, von Willebrand factor, and ristocetin. We favor a model wherein ristocetin neutralizes some of the platelet's negative change and permits the von Willebrand factor to bridge sites on separate platelets to induce agglutination.

Blood Coagulation Tests↗
PubMed1975

Effects of vancomycin on platelets, plasma proteins and hepatitis B surface antigen.

The antibiotic vancomycin shares many similarities with ristocetin, an agent noted for its effects on platelets and plasma fibrinogen. Vancomycin did not aggregate platelets as ristocetin, but platelets were incorporated into precipitates induced by vancomycin. Fibrinogen and factor VIII were precipitated from plasma at low concentrations of vancomycin. The precipitated fibrinogen remained clottable. Hepatitis B surface antigen was selectively precipitated from serum and could be recovered from the precipitate. Rabbits receiving bolus intravenous injections of high doses of vancomycin developed hypofibrinogenemia and thrombocytopenia within minutes and often went on to die. Studies with 125I-vancomycin revealed little stable binding of the antibiotic to platelets or fibrinogen. A relationship is suggested between the potent protein precipitating effects and phlebitis at the infusion site commonly associated with vancomycin therapy.

Animals↗
PubMed1975

American Burkitt's lymphoma: a clinicopathologic study of 30 cases. I. Clinical factors relating to prolonged survival.

The presenting clinical characteristics and the results of therapy in 30 cases of American Burkitt's lymphoma are described. Five patients presented with localized disease. The abdomen was the most frequent site of involvement (19 cases). Serum lactic dehydrogenase (LDH) levels closely correlated with extent of tumor mass. Of the 22 patients treated with large doses of parenteral cyclophosphamide, complete remission was achieved in 13 (59 per cent). Of these only four have had a relapse, all within 12 months of treatment. The remainder are alive, free of disease and have not received any treatment for up to 80 months or more. The site and volume of tumor mass predicted for prolonged survival. None of the six patients with bone marrow or central nervous system involvement remained tumor-free. A complete remission was achieved in 8 of 9 patients with presenting LDH levels of less than 700 IU/ml and they have remained free of disease, whereas only 4 of 13 patients with LDH levels greater than 700 IU/ml had a complete response and 3 of these had a relapse within 12 months. In six cases, the massive tumor regression following chemotherapy was associated with serious metabolid consequences including hyperkalemia (six cases), hypocalcemia, hyperphosphatemia (one case) and lactic acidosis (one case). There were four sudden deaths in less than 48 hours after chemotherapy; two of these were attributable to hyperkalemia. In all cases therw were large tumor masses and/or elevated serum LDH levels.

Abdomen↗
PubMed1975

American Burkitt's lymphoma: a clinicopathologic study of 30 cases. II. Pathologic correlations.

Thirty cases of malignant lymphoma, undifferentiated, Burkitt's type are reviewed. An older median age and a predominance of presentation in abdominal and pelvic sites rather than in the jaw distinguishes this series of American patients from those reported from endemic regions in Africa. Bone marrow involvement invariably consisted of massive infiltration recognizable in smear, clot and biopsy preparations. Involvement of the central nervous system or bone marrow was always associated with short survival. In all eight long-term survivors lymphoma was apparently confined to a single site at presentation. At autopsy, the most consistent finding was widespread multiorgan involvement without predilection for lymphoreticular structures. The histologic appearance of the tumor changed after chemotherapy, varying from diffuse necrosis within 48 hours of initial therapy to extreme pleomorphism of tumor cells after 9 months of therapy. In one patient, there was almost complete absence of lymphoma at autopsy in an organ site shown clinically to have been extensively involved by tumor prior to treatment. The diagnostic and therapeutic implications of these findings are discussed.

Abdomen↗