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Biomedical subjects

J Lazerson

Publications and source records attributed to J Lazerson.

At least 37 records · Page 2Linked to original sources

Assessment of thrombogenicity of prothrombin complex concentrates in a porcine model.

Infusion of prothrombin complex concentrates into pigs resulted in evidence of disseminated intravascular coagulation manifested by positive fibrin monomer tests, depletion of coagulation factors and platelets, and the presence of fibrin in small blood vessels at autopsy. All of the nine prothrombin complex concentrates were found to be thrombogenic. The response appeared to be dose-related, and the two activated materials were more thrombogenic than the non-activated products. In contrast, a purified factor IX concentrate resulted in minimal transient changes in only 2 of 5 animals tested, and autopsy findings were negative for fibrin deposition in all. Four of these animals received 200 factor IX units/kg, which was twice the dose used for any of the other products. Control animals received human plasma or albumin with no evidence of coagulation changes or fibrin deposition at autopsy. The porcine model is more sensitive than other animal models for detection of the thrombogenic effects of prothrombin complex concentrates and may be useful for testing new products found to be non-thrombogenic in other test procedures.

Animals↗

A new variant of dominant type II von Willebrand's disease with aberrant multimeric pattern of factor VIII-related antigen (type IID).

A new type II variant form of von Willebrand's disease has been recognized in a mother and daughter who have bleeding manifestations typical of von Willebrand's disease. Laboratory findings include consistently prolonged bleeding times, with normal levels of factor VIII procoagulant and antigen, but decreased ristocetin cofactor activity. Electrophoresis in SDS 1.5% agarose gel and reaction with 125I-labeled anti-factor VIII-related antigen rabbit IgG, followed by autoradiography, revealed that both plasma and platelets lack the large multimers of factor VIII-related antigen. In 2.5% gel, the propositus plasma lacked the normal "triplet" pattern. In 3.0% gel, a 5-band pattern was observed in normal, type IIA, and type IIB plasma, whereas type IIC plasma revealed a 2-band pattern. The patient's plasma revealed a 4-band pattern distinctly different from normal or other type II variants. We suggest that this new variant be labeled type IID, until a more appropriate nomenclature is developed.

Adult↗

Arc-aggregation: a new method of range of motion analysis in hemophilia.

Arc-aggregation is a new graphic method of analysis of progressive loss of range of motion that can be applied to any diarthrodial joint undergoing a specific degenerative process. It is based on the premise that loss of motion (LOM) for a specific condition occurs in a predictable way or pattern. Using this method to analyze a population of 48 hemophilic patients with various stages of joint involvement, we studied 95 knees, 93 ankles, and 83 elbows for a total of 271 joints. We found a predictable pattern of progressive loss of range of motion for each joint. To detect the early onset of joint involvement, the first LOM is important. The early loss with the knee was in flexion, which gravitated toward fusion at 40 degrees. For the elbow, the early LOM was extension with fixation, occurring at 90 degrees of flexion, the preferred position for fusion. For the ankle, the early LOM was dorsiflexion with final ankylosis in slight equinus.

Adolescent↗

Philadelphia chromosome-negative chronic myelogenous leukemia in a child with t(8;9)(p11 or 12;q34).

Approximately 78% of chronic myelogenous leukemia patients have the standard Ph' chromosome-negative defect as their only chromosomal abnormality. CML has been extensively studied due to the availability of tumor tissue and the frequency and consistency with which such abnormalities are noted. There have been few cases reported, however, of Ph' chromosome-negative CML with an abnormality involving rearrangement and breaks at the 9q34 band. We report here a unique case of the fourth Ph'-negative patient who demonstrates this break.

Child, Preschool↗

Hepatocellular enzyme patterns and hepatitis B virus exposure in multitransfused young and very young hemophilia patients.

Thirty-eight children with severe hemophilia A, 11 years of age and under, were evaluated by initial and follow-up liver function tests (LFTs) in relation to age of onset of transfusion therapy. Each child had at least two complete evaluations within one year for a follow-up period of at least one year. The mean number of exposure days was 36 with a mean of 275 units of factor VIII per exposure day prior to initial LFTs. At initial testing, 30% of patients demonstrated antibody to HBsAg and 39--51% at least one abnormal serum enzyme level (AST, ALT, LDH). During an average follow-up period of 34.8 months, two children developed HBsAg-positive icteric hepatitis. Of those initially serologically negative for HBsAg or antibody, 44% became antibody-positive. Intermittent abnormalities of at least one serum enzyme were observed in 79% of the patient group, with 13% and 8% being persistently normal and abnormal. Eleven children born after January 1976, receiving only third-generation RIA-tested products for HBsAg, constituted a subgroup. Although only one child at first assessment had evidence of hepatitis B virus exposure, 55% had elevated ALTs, indicating considerable frequency of non-A, non-B hepatitis in this very young group.

Child↗

Processing of human beta-globin mRNA precursor to mRNA is defective in three patients with beta+-thalassemia.

Nucleated bone marrow cells from normal individuals and from three patients with homozygous beta+-thalassemia were pulse-labeled with tritiated nucleosides. The processing of the newly synthesized globin mRNA precursors was monitored by inhibiting additional transcription with actinomycin D for 30 min. Human beta-globin mRNA is derived from its precursor via a series of reactions that generate processing intermediates. In nonthalassemic cells the precursor is processed efficiently to mature mRNA during the chase. In contrast, in beta+-thalassemic cells the processing of beta-globin RNA is defective. In one patient the beta-globin mRNA precursor turns over during the chase, but some of the intermediate RNAs accumulate and are not processed to mRNA. In two other patients a large fraction of the precursor and intermediate RNAs is not processed to mRNA. The alpha-globin mRNA precursor and intermediates are processed efficiently to mRNA-sized molecules in thalassemic and normal cells. The reduction in the rate of beta-globin but not alpha-globin RNA processing accounts for the alpha/beta globin mRNA imbalance in thalassemic erythroid cells. We discuss the possibility that the genetic lesions in beta+-thalassemia are at splicing signal sites within intervening sequences of the beta-globin gene.

Bone Marrow↗

Hemophilia.

The development of federally funded centers throughout the United States for the diagnosis and treatment of hemophilia, incorporating the concept of comprehensive care by the multidisciplinary team, has brought to the forefront the importance of understanding the role of the "specialist" in the team. The laboratory technologist, as part of this team, must understand the nature of this disorder to be an active participant in the decision-making process for patients with hemophilia. With this information the technologist, in conjunction with the comprehensive care team, can help streamline laboratory care of the patient as well as provide expertise for testing and interpretation of laboratory results.

Decision Making↗