Modulation of erythrocyte membrane mechanical stability by 2,3-diphosphoglycerate in the neonatal poikilocytosis/elliptocytosis syndrome.

To explain the transient anemia and poikilocytosis seen during infancy in hereditary elliptocytosis (HE), we resealed erythrocyte (RBC) ghosts from affected children or their elliptocytic parents with 2,3-diphosphoglycerate (DPG) (0-8 mM), a compound that dissociates membrane skeletons, then measured ghost mechanical stability in the ektacytometer. Without added 2,3-DPG, ghost mechanical stability was subnormal in infantile poikilocytosis (IP) and HE but was even more abnormal in hereditary pyropoikilocytosis (HPP). Addition of 2,3-DPG (2.55 mM) to IP or HE ghosts, decreased their stability to that of HPP ghosts (without 2,3-DPG). Nonphysiological 2,3-DPG levels (6-8 mM) were required to elicit a similar effect in normal ghosts. The data suggest that free 2,3-DPG, present in neonatal RBC as a consequence of diminished binding to HbF, may render HE susceptible to in vivo fragmentation. The developmental switch from fetal to adult hemoglobin, by diminishing available free 2,3-DPG, may explain the abatement of poikilocytosis and hemolytic anemia that accompanies maturation.

The prevalence of cholelithiasis in sickle cell disease as diagnosed by ultrasound and cholecystography.

Gallbladder disease is known to be increased in sickle cell disease (SS). The prevalence of cholelithiasis in children with SS has been reported as 10% to 37%. Gallbladder ultrasound, cholecystography, and/or abdominal radiography were used to evaluate 31 patients aged 2 to 18 years with no systematic evidence of gallbladder disease for cholelithiasis, Overall prevalence of gallstones was found to be 29%. Cholelithiasis was detected in children as young as 4 years of age. Prevalence below the age of 10 years and above the age of 10 years was found to be 11% and 55% respectively. The increased prevalence of cholelithiasis in children with sickle cell disease suggests the use of diagnostic ultrasonography as a routine screening procedure.

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.

Feminism and group psychotherapy: an ethical responsibility.

In response to Martin Lakin's (1991) IJGP article, "Some Ethical Issues in Feminist-Oriented Therapy Groups for Women," this article examines recent developments in feminist theory and proposes that a feminist perspective is both ethical and can make significant contributions to the practice of group psychotherapy. The overview of feminist theory focuses on (1) the importance of the social context, (2) contributions and challenges to psychoanalytic and developmental theory, (3) attention to power relations, (4) the connection between the personal and political, and (5) recognition and integration of diversity and difference. Clinical examples illustrate ways in which male and female group therapists can take a feminist perspective and become "ethical advocates."

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.

A simple method for platelet sizing.

A simple, inexpensive, and rapid method for sizing platelets, using EDTA-anticoagulated peripheral blood smears, is described. Platelet diameter is compared to standard-sized polystyrene spheres.

Hemophilia: cost consideration for prescribing therapeutic materials.

Costs for therapeutic products utilized in treating hemophilia can be prohibitive to patients. The costs can be effectively reduced by understanding the elements comprising the total cost of these products. By calculating appropriate dosage schedules, avoiding indiscriminate purchasing practices, and monitoring costs to patients, physicians can help reduce the total financial burden to patients and third party payers.

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.

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.

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.

Olfactory neuroblastoma (esthesioneuroblastoma) in a 2-year-old boy.

A 2-year-old boy presented with sudden blindness and epistaxis resulting from olfactory neuroblastoma with intracranial extension. This disease is uncommon in children, with only 27 cases reported in patients less than 17 years of age. This article reviews the clinical and histological features of this tumor and discusses treatment. Therapy has generally consisted of surgery and radiation. Our child and 2 others treated with radiation and combination chemotherapy (including cyclophosphamide and anthracyclines) have done well with follow-ups of up to 9 1/2 years. Chemotherapy is an important form of adjuvant therapy in this disease.

The prevalence of bulimia among college students.

A survey was conducted to determine the prevalence of bulimia and bulimic symptoms in a nonclinical sample of 907 college freshmen and seniors. Using criteria based on the Diagnostic and Statistical Manual of Mental Disorders, 4 per cent of the women and 0.4 per cent of the men were classified as bulimic. Symptoms of bulimia, such as binge eating, purging behaviors, and extreme fear of gaining weight, were much more prevalent.

Chronic myelogenous leukemia and genetic events at 9q34.

Assessment of cytogenetic patterns associated with chronic myelogenous leukemia (CML) suggests that genetic events at band q34 of chromosome nine are critical in the conversion of benign to malignant hematopoiesis. A break at this band is identified in almost all cases of Philadelphia chromosome (Ph1) positive CML, is also noted in some cases of Ph1 negative CML and cannot be excluded in the remaining cases. The human cellular homolog of the Abelson retrovirus oncogene (c-abl) is situated at band 9q34 and is translocated with the genetic sequences distal to the break point at this site in Ph1 positive disease. This oncogene has been shown experimentally to transform pre-B cells and it is expressed in primitive cells of the granulocytic series which are involved in CML. Although the break in CML chromosomes at 9q34 and the location of c-abl at 9q34 could be unrelated, it seems more likely that the two genetic events are associated with evolution of malignant hematopoiesis of man.

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.

Functional and metabolic studies of platelets from patients with Lesch-Nyhan syndrome.

Platelet function was investigated in three patients with the Lesch-Nyhan syndrome. Platelet count, morphology and size distribution was normal in all patients. Platelet turnover was normal. Electron microscopy did not reveal any ultrastructural abnormality. Template bleeding times were normal and prolonged after aspirin ingestion in two out of the three patients: the patient that failed to respond to the aspirin challenge also had decreased retention of platelets on a glass bead column. Biochemical studies revealed that total platelet ATP was reduced by 34% in the presence of a normal level of ADP in the storage pool. These platelets failed to incorporate radioactive hypoxanthine but did incorporate radioactive adenine to produce adenine nucleotides and a trace amount of guanine nucleotides. The results indicate that normal platelets have a functionally intact pathway for utilizing hypoxanthine as a source of preformed purine, and that the failure to salvage this purine, as in the Lesch-Nyhan syndrome, results in a decreased level of total platelet ATP. These findings suggest that platelets can function normally despite a one third reduction in total ATP content.

Nutrition education curriculum at the University of Nevada School of Medicine.

This article describes a developing nutrition education curriculum for the University of Nevada School of Medicine, a small and progressive, community-based medical school. The curriculum has been planned to reflect the longitudinal, interdisciplinary, and comprehensive integration of nutrition into new required and existing courses so that timely delivery of knowledge and development of skills will occur in the basic science years followed by direct application in the clinical clerkships. The availability of the "Nutrition and Cancer Education Objectives" is timely and provides overall direction and curricular goals for the simultaneous development of nutrition-cancer education. The coordination of the four-year curriculum of the entire medical school can be specifically targeted for the incorporation of this needed information synergistically at a most opportune time.