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Biomedical subjects

G Hanson

Publications and source records attributed to G Hanson.

At least 19 recordsLinked to original sources
PubMed2000

Effects of growth hormone administration on inflammatory and other cardiovascular risk markers in men with growth hormone deficiency. A randomized, controlled clinical trial.

BACKGROUND: Growth hormone-deficient adults have increased cardiovascular mortality. Growth hormone replacement may affect cardiovascular risk. Inflammation plays an important role in atherosclerosis, and inflammatory markers are predictive of cardiovascular events. OBJECTIVE: To investigate the effect of growth hormone replacement on inflammatory and other cardiovascular risk factors. DESIGN: Randomized, single-blind, placebo-controlled trial. PATIENTS: 40 men with adult-onset growth hormone deficiency. INTERVENTION: Growth hormone or placebo given for 18 months at a dose adjusted for normal serum insulin-like growth factor I level. MEASUREMENTS: Anthropometric, hemoglobin A1c, and central fat values were assessed every 6 months. Levels of glucose, insulin, insulin-like growth factor I, and lipids were measured at 1, 3, 6, 12, and 18 months. C-reactive protein, serum amyloid polypeptide A, inteleukin-6, and lipoprotein(a) levels were determined at baseline and 6 and 18 months. RESULTS: C-reactive protein and inteleukin-6 levels decreased in growth hormone recipients compared with placebo recipients (differences between groups, -1.9 +/- 0.6 mg/L [P = 0.0027] and -1.3 +/- 0.5 ng/L [P = 0.013], respectively). Changes in serum amyloid polypeptide A levels between groups did not reach statistical significance (difference between groups, -2.4 +/- 1.2 mg/L; P = 0.056). Serum cholesterol levels, low-density lipoprotein cholesterol levels, and ratios of total cholesterol to high-density lipoprotein cholesterol decreased in growth hormone recipients in the first 3 months compared with placebo recipients (differences between groups, -0.86 +/- 0.17 mmol/L [-33.2 +/- 6.6 mg/dL] [P < 0.001], -0.63 +/- 0.20 mmol/L [-24.5 +/- 5.9 mg/dL] [P < 0.001], and -0.56 +/- 0.26 [P = 0.040], respectively), but the decrease was not maintained from month 6 to month 18. Lipoprotein(a) levels increased (difference between groups, 22.0 +/- 8.0 mg/L; P = 0.0096). Short-term increases occurred in glucose levels, insulin levels, and insulin-to-glucose ratios (differences between groups, 0.54 +/- 0.16 mmol/L [9.6 +/- 2.8 mg/dL] [P = 0.0018], 37.9 +/- 9.6 pmol/L [P < 0.001], and 6.0 +/- 1.8 [P = 0.0025], respectively), but only the increase in glucose level was maintained over the long term (difference between groups, 0.56 +/- 0.17 mmol/L [10.0 +/- 3.1 mg/dL]; P = 0.0026). Hemoglobin A1c values did not change. Truncal fat-to-total fat ratios decreased (difference between groups, -0.018 +/- 0.007; P = 0.0087). CONCLUSIONS: Long-term growth hormone replacement in men reduces levels of inflammatory cardiovascular risk markers, decreases central fat, and increases lipoprotein(a) and glucose levels without affecting lipid levels.

Adipose Tissue↗
PubMed2000

Cunninghamella infection post bone marrow transplant: case report and review of the literature.

Cunninghamella spp., in the class Zygomycete and order Mucorales, are unusual opportunistic pathogens that have been identified with increased frequency in immunocompromised patients. Infections with this group of organisms have been seen most frequently in patients with hematologic malignancy. We describe an allogeneic bone marrow recipient who developed fungal pneumonitis and disseminated fungal dermatitis caused by Cunninghamella spp. To our knowledge, this is the first reported case of Cunninghamella infection in a BMT recipient. The case highlights the mortality associated with opportunistic infections in immunocompromised patients and confirms the risk factors associated with non-candida fungal infections after bone marrow transplantation.

Bone Marrow Transplantation↗
PubMed1999

Graft-facilitating doses of ex vivo activated gammadelta T cells do not cause lethal murine graft-vs.-host disease.

The purpose of this study was to examine the ability of gamma(delta) T cells to cause graft-vs.-host disease (GVHD) after allogeneic bone marrow transplantation (BMT) and to determine whether these cells offered any therapeutic advantages relative to alphabeta T cells. Due to the paucity of naive gamma(delta) T cells in mice and humans, gamma(delta), T cells (obtained from alpha(beta) T cell-deficient murine donors) were ex vivo activated and expanded in interleukin (IL)-2 so as to achieve sufficient cell numbers and to serve as a more clinically feasible strategy. After transplantation into lethally irradiated hosts, donor gamma(delta) T cells were detected in target organs of GVHD such as the spleen and intestines 2 weeks after BMT and constituted the primary T cell subpopulation. Large doses (150 x 10(6)) of activated gamma(delta) T cells, which we have previously shown capable of facilitating engraftment in MHC-disparate recipients, failed to cause fatal GVHD in lethally irradiated recipients of MHC-incompatible donor marrow grafts (C57BL/6 [H-2b]-->B10.BR [H-2k] and C57BL/6 [H-2b]-B6D2F1[H-2b/d]). The absence of GVHD was confirmed by histologic analysis of target organs, splenic B cell reconstitution, and appropriate negative selection in the thymus, that were all comparable to those observed in mice transplanted with T cell-depleted BM only. While early splenic reconstitution was attributable to donor gamma(delta) T cells, analysis of durably engrafted chimeras 2 months posttransplant revealed that the vast majority of donor splenic T cells expressed the alpha(beta) T cell receptor. The results of secondary adoptive transfer assays showed that these cells were tolerant of recipient alloantigens in vivo, demonstrating that gamma(delta) T cells did not prevent the subsequent development of donor anti-host tolerance in BM-derived alpha(beta) T cells. When comparatively evaluated, the minimal number of naive alpha(beta) T cells necessary for donor engraftment caused significantly more fatal GVHD than the corresponding minimal dose of activated gamma(delta) T cells and thus had a superior therapeutic index. These studies indicate that doses of activated gamma(delta) T cells that are able to promote alloengraftment do not cause lethal GVHD in mice transplanted with MHC-incompatible marrow grafts.

Animals↗
PubMed1999

Herpesvirus 8 inclusions in primary effusion lymphoma: report of a unique case with T-cell phenotype.

We describe a case of primary effusion lymphoma with T-cell phenotype, mixed genotype, and intranuclear herpesvirus inclusions visible with the light microscope. Cells were studied by immunohistochemical analysis, in situ hybridization, immunoglobulin and T-cell receptor gene rearrangement, and polymerase chain reaction. Primary effusion lymphoma cells with T-cell phenotype revealed herpesvirus 8 inclusions predominantly seen in apoptotic cells, suggesting that productive viral infection is associated with cell death. Clinical features were typical of primary effusion lymphoma. Cytologic, molecular genetic, and phenotypic features demonstrated a unique variant of primary effusion lymphoma.

Adult↗
PubMed1998

Ex vivo anti-CD3 antibody-activated donor T cells have a reduced ability to cause lethal murine graft-versus-host disease but retain their ability to facilitate alloengraftment.

The purpose of this study was to determine whether ex vivo anti-CD3 Ab-activated T cells behaved in a biologically similar manner as naive T cells with respect to causing graft-vs-host disease (GVHD) and facilitating engraftment after allogeneic marrow transplantation. This question was addressed using two well-defined MHC-incompatible murine models of GVHD (C57BL/6 (H-2b)-->BIO.BR (H-2k)) and engraftment (C57BL/6 (H-2b)-->AKR/J (H-2k)). Transplantation with anti-CD3-activated T cells significantly reduced GVHD compared with that in animals transplanted with equivalent numbers of naive T cells. Protection from GVHD was not T cell subset dependent, as highly enriched populations of either activated CD4+ or CD8+ T cells caused less lethal GVHD than comparable numbers of purified naive CD4+ or CD8+ T cells. Transplantation with activated T cells also resulted in protection from LPS-mediated GVH lethality in unirradiated F1 recipients. Analysis of immune recovery indicated that animals transplanted with activated T cells had thymic and splenic B cell reconstitution that compared favorably to that in non-GVHD control mice. When engraftment was analyzed, equivalent degrees of donor cell engraftment were observed when animals were transplanted with limiting numbers (5 x 10(5)) of naive vs activated B6 T cells. Further studies indicated that activated CD8+ T cells were exclusively responsible for enhancing engraftment and that facilitation of engraftment was dependent upon the direct recognition of host MHC alloantigens. Collectively, these data demonstrate that transplantation with anti-CD3 Ab-activated T cells results in a reduction in GVHD, but these cells retain their ability to facilitate alloengraftment. The use of this approach in allogeneic marrow transplantation may represent an alternative strategy to mitigate GVHD without compromising engraftment.

Animals↗
PubMed1998

T cell-depleted allogeneic bone marrow transplantation for high-risk non-Hodgkin's lymphoma: clinical and molecular follow-up.

The use of allogeneic BMT in patients with relapsed non-Hodgkin lymphoma (NHL) offers the advantage of tumor-free bone marrow and possibly a 'graft-versus-lymphoma effect' which may decrease the risk of recurrence. However, allogeneic BMT also poses an increased risk of death due to graft-versus-host disease (GVHD) which can be ameliorated by T cell depletion. We performed a retrospective review of 37 patients who underwent T cell-depleted allogeneic BMT for aggressive and indolent NHL between 1988 and 1996. Polymerase chain reaction (PCR) was used to identify indolent NHL patients with the BCL2/IgH translocation which served as a marker of residual disease. Sixteen of 37 patients (44%) are alive and progression-free with a median follow-up of 4.4 years (range 1-10.3). The incidence of grade 2-4 acute GVHD was 36% and extensive chronic GVHD developed in 12%. Patients with aggressive NHL have an overall PFS of 33% (12-54%); those with chemotherapy-resistant and sensitive disease have PFS of 17% (0-47%), and 40% (15-65%) respectively at 5 years. Patients with indolent histologies have overall PFS of 62% (37-86%); those with chemotherapy-resistant and sensitive disease have PFS of 55% (25-85%) and 80% (45-100%) respectively at 5 years. Eight patients with indolent disease had a BCL2/IgH translocation detectable by PCR. Five of these eight patients remain alive and progression free at a median of 6.5 years after BMT (range 2.1-7.4 years), four of whom remain PCR positive from 1.7 to 2.9 years after transplantation. We conclude that T cell-depleted allogeneic BMT poses a low risk for death due to GVHD, and should be considered for patients with relapsed and refractory indolent NHL.

Adolescent↗
PubMed1994

Lipoprotein fractionation in deuterium oxide gradients: a procedure for evaluation of antioxidant binding and susceptibility to oxidation.

Oxidative modifications of lipoproteins appear to contribute to their atherogenicity. Very low and low density lipoproteins (VLDL and LDL) are protected against these modifications by antioxidants that can be incorporated in vivo or in vitro into the particles. We describe here ultracentrifugal procedures for isolation of VLDL and LDL that do not require subsequent dialysis or buffer equilibration. Lipoproteins were isolated in buffers with physiological ionic composition prepared in D2O (deuterium oxide). This allowed measurements of the content of antioxidants and of the susceptibility to oxidation of the isolated LDL without further manipulations. Conventional ultracentrifugal methods use high salt concentrations and require additional steps to eliminate them. This introduces uncertainties in the evaluation of antioxidant binding and on measurements of their effect on VLDL and LDL oxidation. With the method described, the composition of the isolated VLDL and LDL was indistinguishable from that of fractions isolated with KBr gradients. Also, the content of alpha-tocopherol was similar. LDL isolated with KBr solutions appeared to bind 20-45% more of the probucol present in serum than LDL isolated in isotonic solutions prepared with D2O. This was the case with probucol incorporated into plasma or serum in vivo or in vitro. Five out of seven LDL isolated with the D2O procedure from different human sera appeared more resistant to Cu(2+)-catalyzed oxidation than those obtained with KBr gradients from the same serum. In addition to the gradient procedure, we also describe a preparative version of the method that can be used with multiple samples.

Animals↗
PubMed1993

Salvage immunotherapy using donor leukocyte infusions as treatment for relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation: efficacy and toxicity of a defined T-cell dose.

Eight patients who had hematologic relapse of chronic myelogenous leukemia (CML) after undergoing allogeneic bone marrow transplantation (BMT) were treated with leukocyte infusions from the original bone marrow donors. All patients had previously received marrow grafts from HLA-identical siblings. Six patients were in the accelerated phase of their disease and two were in blast crisis. Each patient received a predetermined T-cell dose within a narrow range of 2.5 to 5.0 x 10(8) T cells/kg. Three patients also received short courses of therapy with alpha interferon to control elevated white blood cell counts within the first several weeks after leukocyte transfusions. Seven of eight evaluable patients developed graft-versus-host disease (GVHD) at a median of 32 days after the initial infusion. One patient had fatal GVHD. A second patient had grade 3 acute GVHD, which has responded to immunosuppressive therapy. The remaining patients all had mild grade I GVHD. Six patients continue to require modest doses of prednisone more than 6 months after infusion. Four patients developed marrow aplasia, which in three patients required marrow boosts from the original donors. Two of these three patients have normal hematopoietic function, whereas the third patient remains growth factor and transfusion dependent. Both patients treated in blast crisis have died, one from GVHD and one from disease progression. All six patients in the accelerated phase are alive and in cytogenetic remission at a median of 42 weeks after infusion. Five of these six patients are in molecular remission. This study demonstrates that leukocyte infusions that administered a defined T-cell dose can exert a profound graft-versus-leukemia effect and are an effective form of salvage immunotherapy in allogeneic marrow transplant recipients. This therapeutic approach appears to be a viable alternative to existing chemotherapeutic and immunomodulatory strategies for the treatment of relapsed CML.

Adult↗
PubMed1992

Myocardial catecholamine and neuropeptide Y depletion in failing ventricles of patients with idiopathic dilated cardiomyopathy. Correlation with beta-adrenergic receptor downregulation.

BACKGROUND: Myocardial adrenergic neurotransmitters and beta-adrenergic receptor levels were measured in left and right ventricular myocardial specimens obtained from 30 patients with biventricular failure resulting from idiopathic dilated cardiomyopathy. METHODS AND RESULTS: Nonfailing myocardium obtained from 12 organ donors provided control data. Norepinephrine, dopamine, and neuropeptide Y concentrations were significantly decreased in failing compared with nonfailing control hearts. The mean ratio of dopamine to norepinephrine and of dopamine to neuropeptide Y in failing hearts was also significantly decreased compared with nonfailing control hearts. Compared with nonfailing control hearts, Bmax and beta 1-receptor density were significantly decreased in failing hearts and there were weak but significantly positive correlations of Bmax and beta 1-adrenergic receptors with norepinephrine, dopamine, and neuropeptide Y. CONCLUSIONS: Norepinephrine and its cotransmitter neuropeptide Y are depleted in failing human ventricular myocardium. Decreased norepinephrine stores correlate weakly with beta 1-adrenergic receptor downregulation consistent with the hypothesis that norepinephrine depletion occurs in response to increased adrenergic drive. Decreased dopamine relative to norepinephrine implies that an abnormality of dopamine conversion to norepinephrine is not present in failing human heart.

Adult↗
PubMed1992

Effect of therapeutic dopamine administration on myocardial catecholamine and neuropeptide Y concentrations in the failing ventricles of patients with idiopathic dilated cardiomyopathy.

The purpose of this study was to investigate the relationship between dopamine (DA) exposure and myocardial catecholamine and neuropeptide Y (NPY) concentrations in patients with severe congestive heart failure due to idiopathic dilated cardiomyopathy (IDC). Both nonfailing (NF) and failing (F) hearts were obtained in collaboration with the Utah Cardiac Transplantation Program and the Intermountain Organ Recovery System. The patients were stratified into five groups according to their preoperative exposure to dobutamine (DBT) and/or DA. Compared to 12 untreated, NF control hearts, norepinephrine (NE) concentrations were significantly decreased in 30 untreated F hearts obtained from patients with IDC. Norepinephrine concentrations were also significantly decreased in DA-treated NF hearts and in DA-treated F hearts compared to untreated NF and untreated or DBT-treated failing hearts, respectively. NPY concentrations were significantly decreased in untreated F hearts and were further decreased in dopamine-treated NF and DA-treated F hearts compared to untreated NF and untreated or DBT-treated F hearts. Thus, NE and NPY depletion related to DA administration was evident in both NF and F myocardium and was specific for DA in that it was not evident in patients who received the direct-acting beta-agonist inotrope DBT. These data suggest that the major inotropic mechanism of action of DA is through cardiac adrenergic neurotransmitter release. The data also provide further support for the concept that indirect acting inotropes such as DA may have limited inotropic potential in F hearts where neuronal NE has been depleted.

Adult↗
PubMed1991

Performance of psychomotor skills: a comparison of two teaching strategies.

This study compares two teaching strategies: textbook assignment and videotape with no faculty assistance, and textbook assignment and videotape with faculty assistance (demonstration of skills and supervised practice) to determine their effect on outcome performance (measurement of blood pressure) and on the student's perceived level of confidence. The intent of the study was to ascertain if the use of mediated instruction without faculty input would decrease faculty-student contact time without adversely affecting performance outcomes. Results of the study revealed that faculty contact is an important factor when students are learning to perform a basic psychomotor skill. It was concluded that mediated instruction is not appropriate as a complete substitute for faculty contact.

Clinical Competence↗