Patient interleukin-18 GCG haplotype associates with improved survival and decreased transplant-related mortality after unrelated-donor bone marrow transplantation.

Interleukin-18 (IL-18), a proinflammatory cytokine, is elevated in patients with acute graft-versus-host disease (aGVHD). IL-18 induces Th1 differentiation and cytotoxic T-lymphocyte function, both of which have been implicated in the pathogenesis of aGVHD. However, recent studies have shown that neutralization of IL-18 by antibodies leads to an increased risk of aGVHD-related mortality while administration of IL-18 significantly improved survival.

Effect of up-front daclizumab when combined with steroids for the treatment of acute graft-versus-host disease: results of a randomized trial.

The standard initial therapy for acute graft-versus-host disease (GVHD) is corticosteroids. Daclizumab is a humanized monoclonal antibody against the interleukin 2 (IL-2) receptor expressed on activated T lymphocytes. Because of daclizumab's favorable toxicity profile and response rate in steroid-resistant GVHD, a multicenter, double-blinded, randomized study of corticosteroids with or without daclizumab for initial treatment of acute GVHD was conducted.

Germline mutations in BRCA2: shared genetic susceptibility to breast cancer, early onset leukemia, and Fanconi anemia.

The breast cancer susceptibility gene BRCA2 has recently been identified as identical to the Fanconi anemia (FA) gene FANCD1. Here we expand the clinical implications of this discovery. Notably, we identified 6 children in 5 kindreds exhibiting the co-occurrence of BRCA2 mutations, FA, and early onset acute leukemia.

Fatal hemorrhage from androgen-related hepatic adenoma after hematopoietic cell transplantation.

Fanconi anemia is a rare genetic disorder that leads to bone marrow failure. Hematopoietic cell transplantation (HCT) is currently the only treatment option with curative potential. When a suitable HLA-matched sibling donor is not available, patients are often treated with androgenic steroids before considering HCT.

High-producer interleukin-2 genotype increases risk for acute graft-versus-host disease after unrelated donor bone marrow transplantation.

Background: Cytokine polymorphisms may modulate immunologic reactivity, including graft-versus-host disease (GVHD). A single nucleotide polymorphism resulting in a thymine-to-guanine transition in the interleukin (IL)-2 gene promoter region occurs at position -330. In vitro studies have shown that the G allele is associated with early and sustained enhancement of IL-2 production, a so-called high-producer genotype.

Integrating medical management with diabetes self-management training: a randomized control trial of the Diabetes Outpatient Intensive Treatment program.

Objective: This study evaluated the Diabetes Outpatient Intensive Treatment (DOIT) program, a multiday group education and skills training experience combined with daily medical management, followed by case management over 6 months. Using a randomized control design, the study explored how DOIT affected glycemic control and self-care behaviors over a short term. The impact of two additional factors on clinical outcomes were also examined (frequency of case management contacts and whether or not insulin was started during the program).

Involvement of human thalamic neurons in internally and externally generated movements.

Several anatomical studies support the existence of recurrent neural pathways from cortical motor areas to the thalamus via basal ganglia and back to the cortex. Neuronal responses to internally and externally generated sequential movements have been studied in the motor and premotor cortex of monkeys, but the involvement of subcortical motor structures such as the thalamus have not been studied in monkeys or humans. We examined the activity of neurons during a sequential button press task in motor thalamus of parkinsonian as well as chronic pain patients undergoing implantation of deep brain stimulating electrodes.

Successful hematopoietic stem cell transplantation for Fanconi anemia from an unaffected HLA-genotype-identical sibling selected using preimplantation genetic diagnosis.

The only proven cure for Fanconi anemia (FA)-associated bone marrow failure is successful allogeneic hematopoietic stem cell transplantation (HSCT). However, HSCT with donors other than HLA-identical siblings is associated with high morbidity and poor survival. Therefore, we used preimplantation genetic diagnosis (PGD) to select an embryo produced by in vitro fertilization (IVF) that was unaffected by FA and was HLA-identical to the proband.

Analysis of a repressor region in the human neuropeptide Y gene that binds Oct-1 and Pbx-1 in GT1-7 neurons.

The mechanisms dictating the developmental expression of individual neuropeptides within the hypothalamus have not yet been elucidated. In this paper we have studied the cis-acting elements involved in the repression of neuropeptide Y (NPY) gene expression in a gonadotropin-releasing hormone (GnRH) neuronal cell model, GT1-7 cells. Using transient transfection of the human NPY 5(') regulatory region into the GT1-7 neurons, we have found a repressor region located between -867 and -1078.

Interleukin-1 genotype and outcome of unrelated donor bone marrow transplantation.

The interleukin 1 (IL-1) gene family includes three members (IL-1-alpha, IL-1-beta and IL-1Ra) that mediate immune and inflammatory responses through two specific cell surface receptors. Cytosine to thymine transitions at codons -889 and -511 in the IL-1-alpha and IL-1-beta genes, respectively, and an 86-base pair repeat in the IL-1Ra are believed to influence gene transcription. We have genotyped these three polymorphisms in 90 donor/recipient pairs undergoing unrelated donor bone marrow transplantation (BMT) at the University of Minnesota.

Chronic graft-versus-host disease: a prospective cohort study.

Chronic graft-versus-host disease (CGVHD) is a major cause of morbidity and mortality following allogeneic bone marrow transplantation (BMT). We studied 159 patients with CGVHD longitudinally to characterize the natural history of CGVHD and identify reliable predictors of response and long-term mortality. Rates of response to treatment were 61%, 53%, and 50% at 6 months, 1 year, and 2 years, respectively.

Randomized clinical trial of ganciclovir vs acyclovir for prevention of cytomegalovirus antigenemia after allogeneic transplantation.

Cytomegalovirus (CMV) disease remains a major cause of morbidity following allogeneic stem cell transplantation (SCT). In a prospective randomized trial, we tested prophylactic therapy with ganciclovir or acyclovir for patients at high risk of disease. Ninety-one CMV seropositive recipients of related (n = 53) and unrelated (n = 38) donor transplants were enrolled.

Transplantation of unrelated donor umbilical cord blood in 102 patients with malignant and nonmalignant diseases: influence of CD34 cell dose and HLA disparity on treatment-related mortality and survival.

The potential benefits of unrelated donor marrow transplantation are offset by the immunologic complications of graft-versus-host disease (GVHD) and infection. Therefore, we used cryopreserved umbilical cord blood (UCB) as a strategy to reduce the risks of GVHD and treatment-related mortality (TRM) and improve survival. Data on 102 patients (median age 7.

Response of 443 patients to steroids as primary therapy for acute graft-versus-host disease: comparison of grading systems.

Acute GVHD remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). In a retrospective analysis, the response of 443 HSCT patients who received prednisone, 60 mg/m2, for 14 days followed by an 8-week taper, as initial therapy for acute GVHD from 1990 through 1999 at a single institution was examined. Median patient age was 29.

Fluconazole to prevent yeast infections in bone marrow transplantation patients: a randomized trial of high versus reduced dose, and determination of the value of maintenance therapy.

Purpose: To determine the optimal dose and duration of fluconazole antifungal prophylaxis therapy in bone marrow transplantation patients.

Subjects And Methods: Two hundred and fifty-three pediatric and adult bone marrow transplantation patients were randomly assigned to receive fluconazole 400 mg daily (high dose) or 200 mg daily (low dose) while they were neutropenic. After neutrophil recovery, patients were randomly assigned to receive maintenance therapy with either fluconazole (100 mg daily) or clotrimazole troches (10 mg 4 times daily) until 100 days after transplantation.

Early antithymocyte globulin therapy improves survival in patients with steroid-resistant acute graft-versus-host disease.

Second-line therapies for steroid-resistant acute GVHD have been used with limited success. We have reviewed the responses of 79 hematopoetic stem cell transplant (HSCT) patients uniformly treated from 1990-1998 with equine antithymocyte globulin (ATG) for steroid-resistant acute GVHD, defined as progression of acute GVHD after 4 days of treatment with prednisone or no improvement of acute GVHD after 7 days of treatment with prednisone. Patients received HSCT from 34 related (32 matched sibling/2 partially matched) and 45 unrelated (14 HLA-A, -B, -DRB1 matched/31 partially matched) donors.

Nineteenth-century inhibitory theories of thinking: Bain, Ferrier, Freud (and Phineas Gage).

The theories of thinking of Alexander Bain, David Ferrier, and Sigmund Freud are examined and their relation to Phineas Gage explored. During the 19th century Ferrier derived an inhibitory-motor theory of thinking from a similar theory of Bain's, and aspects of Freud's theory of thinking resemble both. All 3 theories were modeled on the sensory-motor reflex, and all proposed that thinking was inhibited action.

John Martyn Harlow: "Obscure country physician"?

If John Martyn Harlow is known at all in the neurosciences, it is because he was the physician who attended Phineas Gage and followed up his case. Although Harlow's brief but insightful accounts of the changes in Gage's personality are fairly well recognized, and his skill in treating Gage often acknowledged, Harlow himself is, for the most part, the shadowy figure caught by the self-depreciatory characterization of the subtitle of this paper. Although his contribution to the neurosciences was singular, literally and figuratively, he deserves a place in the history of the subject.

Predicting mastery level on a large-scale standardized patient test: a comparison of case and instrument score-based models using discriminant function analysis.

Clinical skills assessments have traditionally been scored via experts' ratings of examinee performance. However, this approach to scoring may be impractical in a large-scale context due to logistical and cost considerations as well as the increased probability of rater error. The purpose of this investigation was therefore to identify, using discriminant analysis, weighted score-based models that maximize the accuracy with which mastery level can be estimated for examinees taking a nationally administered standardized patient test.

Restoring Phineas Gage: a 150th retrospective.

September 13 1998 marked the 150th anniversary of the accident to Phineas Gage, one of the most famous cases of survival after massive injury to the brain, and certainly the most famous case of personality change after brain damage. For this article a sample of the current literature about Gage was examined. It was found that although his case is mentioned in about 60% of introductory textbooks in psychology, there is a good deal of inaccuracy in what has been written about him.