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Biomedical subjects

W Krivit

Publications and source records attributed to W Krivit.

At least 163 records · Page 9Linked to original sources
PubMed1979

Phase II study of VM-26 in acute leukemia, neuroblastoma, and other refractory childhood malignancies: a report from the Children's Cancer Study Group.

VM-26, a semisynthetic podophyllotoxin, was tested for antitumor activity and clinical toxicity in 181 children. The drug was administered iv at weekly intervals, beginning at a dose of 130 mg/2/week. The dose was increased, as tolerated, after 3 and 6 weeks to 150 and 180 mg/m2/week, respectively. The only major toxicity was hematologic, with neutropenia predominating. Anaphylaxis occurred in one patient. The drug demonstrated significant activity in acute lymphocytic leukemia (four responses among 15 patients) and neuroblastoma (ten responses among 31 patients). Objective responses were also noted in one patient each with acute myelogenous leukemia, Hodgkin's disease, histiocytic lymphoma, Wilms' tumor, Ewing's sarcoma, undifferentiated carcinoma, and sacrococcygeal sarcoma. Further trials of VM-26 in these childhood malignancies are warranted.

Acute Disease↗
PubMed1979

Micellar properties of 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestan-26-oyl taurine and relationship to in vitro red cell disruption.

Patients with a metabolic block in the conversion of THCA to cholic acid develop cirrhosis and hemolysis. Tauro-THCA has been shown to distort hepatic architecture and cause hemolysis in bile-fistula rats. In this study, the critical micellular concentration of tauro-THCA was found to be one fourth of that measured for the primary human bile salt, taurocholate. In short-term incubations with intact red cells, tauro-THCA was more effective than taurocholate in removing red cell membrane lipid, inducing morphological red cell sphering, and decreasing functional cellular membrane surface area. These detergent biological membrane effects were most apparent at a concentration above the critical micellar concentration, with the membrane toxicity of the two bile salts roughly paralleling their differences in critical micellar concentration. The lower critical micellar concentration, greater hydrophobicity, and enhanced surface-active properties of tauro-THCA are speculated on as possible factors contributing to the bile salt's toxicity in vivo.

Animals↗
PubMed1979

Adriamycin cardiotoxicity amelioration by alpha-tocopherol.

Adriamycin has become a potent member of the cancer chemotherapeutic program. However, the full utilization of adriamycin is limited by its cardiotoxicity. In experimental animals, alpha-tocopherol has been shown by some to ameliorate or prevent cardiac dysfunction without impairing antitumor effectiveness. During adriamycin therapy, future clinical research should consist of biochemical measurements of vitamin E in plasma, lipoperoxidation in red cells and platelets, while cars to indicate deficiency, should be considered as one method of ameliorating toxicity.

Animals↗
PubMed1979

Evaluation of cyclocytidine in children with advanced acute leukemia and solid tumors.

Cyclocytidine, a slow-release form of cytosine arabinoside, was evaluated in 69 children with advanced acute leukemia and solid tumors. One child with acute lymphocytic leukemia attained a complete remission. This child had received intrathecal cytosine arabinoside prior to the cyclocytidine. Eighteen of the 31 patients with acute lymphocytic leukemia/acute undifferentiated leukemia who did not respond received two or more courses of the drug. There were no responses in 15 children with acute myelogenous leukemia, in 11 children with neuroblastoma, or in 11 children with various solid tumors of childhood. A dose of 600 ng/m2/day for 10 consecutive days is tolerated in children.

Adolescent↗
PubMed1979

Transient myeloid metaplasia associated with an unusual hemoglobin in a newborn infant.

A newborn infant presented with hepatosplenomegaly, rash, anemia, and leukocytosis at one day of age and manifested characteristic myeloid metaplasia by one mouth of life. Vitamin B12 and leukocyte alkaline phosphatase were elevated and platelet aggregation was impaired. Myelofibrosis was not present and neutrophil function was preserved. An unidentified high isoelectric point hemoglobin with unusual chromatographic and electrophoretic behaviors was found to comprise 12% of the total hemoglobin. The myeloid metaplasia and mutant hemoglobin disappeared over the subsequent months without biochemical or clinical residual. The available evidence was consistent with the mutant hemoglobin representing either a gamma chain or clonal embryonic chain variant. The inability to clarify prognostic factors in these unusual myeloproliferative syndromes suggests caution in the initiation of cytotoxic therapy.

Electrophoresis, Cellulose Acetate↗
PubMed1978

Sclerodermatous graft-versus-host disease limited to an area of measles exanthem.

A female patient with severe idiopathic aplastic anaemia received a successful bone-marrow transplant from her HLA-identical, mixed-lymphocyte-culture-compatible, brother. 8 months after transplantation she had localised cutaneous measles. Chronic sclerodermatous changes developed which were indistinguishable from chronic graft-versus-host disease and were limited to the areas of the original exanthem. Interaction between viral infection and minor histocompatibility differences probably resulted in graft-versus-host disease in this patient.

Adolescent↗
PubMed1978

Wiskott-Aldrich syndrome: detection of carrier state by metabolic stress of platelets.

A stress test has been designed which shows a consistent abnormality in platelets from carriers of the Wiskott-Aldrich-syndrome (W.A.S.) gene. 2-deoxy-D-glucose (D.D.G.), an inhibitor of glycolysis, completely inhibited second-wave adrenaline (epinephrine)-induced aggregation of platelets from 10 W.A.S. carriers, whereas it had no effect on the response of control platelets. Antimycin A (Ant A), an inhibitor of oxidative phosphorylation, had no effect on adrenaline-induced platelet aggregation of either carriers or controls. Incubation of control platelets with a combination of Ant A and D.D.G. inhibited aggregation in a way comparable to the effect of D.D.G. alone on carrier cells. Thus, W.A.S. carriers have a defect in platelet metabolism similar to that produced in normal platelets with Ant A. The D.D.G. stress test is a simple reproducible assay for detection of W.A.S. carriers.

Blood Coagulation Tests↗
PubMed1978

Oral contraceptive use alters the balance of platelet prostaglandin and thromboxane synthesis.

The ability of platelet microsomes to generate platelet aggregating activity on addition of arachidonic acid was evaluated in women taking oral contraceptives and in controls taking no medication but matched for age, sex, and family history. Oral contraceptive users generated significantly more platelet aggregating activity per 100 ug of platelet microsomal protein than controls. Variation in generation of platelet aggregating activity during the menstrual cycle was also observed with highest activity during the third week. These studies show an altered balance of platelet prostaglandin and thromboxane synthesis in oral contraceptive users which may contribute to their increased incidence of thromboembolic phenomena.

Adult↗
PubMed1978

Spontaneously acquired factor IX inhibitor in a nonhemophiliac child.

A 2 1/2-year-old, previously healthy child developed progressive swelling of the left leg and a hematoma of the anterior chest wall associated with a falling hemoglobin concentration, as a result of a spontaneously acquired Factor IX inhibitor. Successful management of her condition required a four-volume exchange transfusion and immunosuppressive therapy consisting of cyclophosphamide for four days and prednisone for one month. A brief review of the literature regarding the occurrence and nature of acquired coagulation factor inhibitors and the role of immunosuppressive therapy is also presented.

Blood Coagulation↗
PubMed1978

Platelet storage pool deficiency and prostaglandin synthesis in chronic granulocytic leukaemia.

Platelet function was evaluated in eight patients with chronic granulocytic leukaemia (CGL), seven Ph1 positive and one Ph1 negative. Seven of the eight patients' platelets had an absence of the second wave of adrenaline induced aggregation on at least one occasion, while five had impaired collagen aggregation. The platelets of all seven patients with abnormal responses to adrenaline, aggregated with arachidonic acid, thus ruling out a cyclo-oxygenase deficiency. A marked decrease in the ADP, serotonin, and dense body content of platelets was found in all five patients evaluated. Mixtures of CGL patient platelets with platelets from normal donors who had ingested aspirin gave a normal biphasic response to adrenaline. Normal release of the storage pool contents from aspirin treated platelets was shown by stirring a mixture of CGL platelets and 14C-serotonin labelled aspirin treated platelets with adrenaline. The CGL platelets alone or in the mixture produced malondialdehyde in response to adrenaline. These experimental results suggest that CGL platelets have a storage pool deficiency but can synthesize prostaglandins and thromboxanes in response to arachidonic acid and adrenaline.

Adenosine Diphosphate↗
PubMed1978

Automated metabolic profiling of organic acids in human urine. II. Analysis of urine samples from "healthy" adults, sick children, and children with neuroblastoma.

Normalized median, minimum, and maximum values (analytical concentration factors) are given for 134 organic acids in urine of nine adult control subjects, five juvenile control subjects, and five children with neuroblastoma. The organic acids, separated by anion-exchange chromatography, were analyzed by a gas chromatograph-mass spectrometer-computer system. Sixty substances in this fraction are positively identified, and, of these, mean absolute concentrations are listed for 20. An additional 81 substances, sought but not found by this method, and 16 other substances found in a subset of these urines by another analytical method, are also listed. Measured retention indices on 5% OV-17 and a selected discriminating ion are given for each of the total of 231 compounds. Results are compared for the three groups of subjects, and the value of normalizing the data is discussed.

Adolescent↗
PubMed1977

Familial leukemia and inherited chromosomal aberration.

This communication contributes a family with 12 cases of cancer and two cases of leukemia. Chromosomal analysis was performed on three occasions, 9 months apart. In unaffected first-degree relatives, we have demonstrated high frequency of tetraradial figures: in parents, 1:243 mitoses, and in all first degree relatives, 1:328 mitoses. The rate of chromosomal breakage was moderately elevated in comparison with carefully matched controls, mainly in father (6.17), mother (4.01) and one sister (4.07). G-banded and C-banded karyotypes revealed no structural chromosomal abnormality in relatives of leukemic children. This family is one of five leukemic families investigated. Analogous methods of chromosomal analysis have been employed in all, but chromatid exchange figures and elevated chromosomal breakage were detected only in the presently reported pedigree. It has been postulated that in this family there exists a possible relation between increased incidence of chromatid exchange figures and increased tendency to leukemia.

Adolescent↗
PubMed1977

The effect of L-asparaginase of plasma coagulation factors in acute lymphoblastic leukemia.

Serial coagulation studies were performed in 26 pediatric patients with acute lymphoblastic leukemia during initial induction therapy with vincristine, prednisone, and L-asparaginase. Prolongation of screening coagulation tests was frequent: prothrombin time (in 16 of 26 patients), partial thromboplastin time (23/26) and thrombin time (21/26). In all 26 patients fibrinogen levels fell below .20 g/100 ml and 16 had levels below .10 g/100 ml. Sixteen patients had plasma coagulation factor assays performed. In these 16 patients, Factor XI was less than 40% in 14 and Factor XI was less than 70% in 9, with only a few scattered low levels of other factors. There were no clinical bleeding episodes. Coagulation abnormalities returned to normal at the completion of L-asparaginase therapy while the patients remained on vincristine and prednisone.

Afibrinogenemia↗
PubMed1977

Overwhelming postsplenectomy infection.

One of the more intriguing aspects of the spleen is the protection against certain bacterial infections afforded by its unique vascular and immune function. There have been extensive clinical surveys which indicate an incidence of overwhelming postsplenectomy infection (OPSI) above that of the disease for which the splenectomy was done. In the absence of the spleen, either congenital or subsequent to surgical removal, this overwhelming sepsis has a 50% case fatality rate. The most common infective organism has been Diplococcus (tstreptococcus) pneumoniae (D. pneumoniae). Intensive investigations indicated loss of phagocytic function of the spleen, depression of serum IgM levels, a possible suppression of the lymphocyte responsiveness, and changes in opsonin-alternative complement system as potential causes of OPSI. Preventive measures against OPSI include trials of prophylactic Phenoxymethyl Penicillin (penicillin) and pneumococcal vaccine.

Adolescent↗
PubMed1977

An immunoenzyme histochemical technique for the detection of platelet antibodies from the serum of patients with idiopathic (autoimmune) thrombocytopenic purpura (ITP).

The resent report describes a simple, reproducible, semi-quantitative immunohistochemical assay for the detection of antiplatelet antibody. Evaluation of the technique in 10 children with active idiopathic (autoimmune) thrombocytopenic purpura (ITP), seven children with thrombocytopenia due to other causes, and 12 normal individuals revealed that the assay consistently and reliably distinguished children with ITP from the other groups. Individuals who had had multiple platelet transfusions and individuals with systemic lupus erythematosus (SLE) also had antiplatelet antibodies detectable using this technique although the levels were less than those of individuals with ITP. The method can be used effectively to monitor the course of ITP and the effects of therapy.

Adolescent↗
PubMed1977

Total-body irradiation with a high-dose-rate linear accelerator for bone-marrow transplantation in aplastic anemia and neoplastic disease.

Nine children with various hematologic disorders underwent bone-marrow transplantation following total-body irradiation with 750 rads at a rate of 26 rads/min. from a 13-MeV linear accelerator in conjunction with cytotoxic drugs. This treatment was tolerated reasonably well, with acceptable side effects. Three patients were alive and well at 18, 11, and 7 months post-transplantation at the time this paper was written.

Anemia, Aplastic↗