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Biomedical subjects

G Hanson

Publications and source records attributed to G Hanson.

At least 19 recordsLinked to original sources

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

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

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

World Health Organization--basic radiographic system (WHO-BRS) unit: experimental clinical evaluation.

The basic radiographic system (BRS) is a simplified version of a standard radiographic unit designed by the World Health Organization and the Pan American Health Organization. The design of the BRS includes the requirement that it should be able to perform routine radiographic examinations with a minimum of operator training. This report describes the performance of a BRS manufactured by Siemens. The physical parameters of this BRS were very good and operation should require a minimum of training. A small number of BRS films were compared with films obtained using the standard equipment in the department. The BRS films were generally regarded as satisfactory. Radiation exposure to patients is equal to, and in some cases less than, exposures with conventional X-ray units.

Developing Countries

Changing risk factor demographics in end-stage renal disease patients entering hemodialysis and the impact on long-term mortality.

Patient survival on hemodialysis has previously been shown to be associated with the presence of comorbid conditions on entrance. Significant comorbid conditions are atherosclerotic heart disease (ASHD), cerebral vascular disease (CVD), nonskin malignancies, chronic obstructive pulmonary disease, diabetes mellitus, and age on entrance to dialysis. Changes in annual mortality have been noted in the United States and at the Regional Kidney Disease Program. The increase in annual mortality was analyzed to determine the impact of risk factors during the time intervals 1976 to 1982 and 1983 to 1987. Patients with no major risk factors have longer survival rates and lower deaths per 1,000 treatment-months from 1983 to 1987 compared with 1976 to 1982. Diabetics have survival rates and deaths per 1,000 treatment-months that are comparable up to age 75. However, over age 75, diabetics have lower survival rates and higher death rates. The presence of comorbid conditions in the diabetic group is high and may account for the increased death rate. The percent of diabetics entering the program has increased from 29% to 48% over the intervals. Nondiabetics with comorbid conditions on entrance had higher deaths per 1,000 treatment-months from 1983 to 1987 compared with 1976 to 1982 across all age categories. Risk factor analysis shows that nondiabetics with major risks are entering with increasing numbers and continuation of comorbid conditions that impact death rates. Peripheral vascular disease, originally not significantly associated with death on dialysis, has dramatically increased from 18% to 60% in nondiabetics with comorbid conditions. In the patients over age 60 with comorbid conditions, 75% of patients now entering dialysis have peripheral vascular disease (PVD). In summary, major shifts in the hemodialysis population have occurred. Diabetics entering dialysis now account for almost 50% of all patients, with the older group having more comorbid conditions. This change alone would increase the annual mortality rate. Patients with comorbid conditions now enter with a higher prevalence of multiple comorbid conditions, which would increase the annual mortality rate. Nondiabetics without comorbid conditions now have better survival across all age categories compared with the previous data. PVD, with its current high prevalence, needs to be reevaluated as a significant risk factor for death on hemodialysis. Therefore, the increase in the annual gross mortality rate is highly predicted based on the change in the diabetic population and the increase in single and multiple comorbid conditions in the nondiabetic population.

Adolescent

Body fluid spaces and blood pressure in hemodialysis patients during amelioration of anemia with erythropoietin.

Blood pressure (BP) may increase in hemodialysis patients during treatment of anemia with recombinant human erythropoietin (r-HuEPO). Since fluid volume is a determinant of BP in dialysis patients, changes in body fluid spaces during r-HuEPO therapy could affect BP. Thus, 51Cr-labeled red blood cell (RBC) volume, inulin extracellular fluid (ECF) volume, and urea total body water (TBW), as well as cardiac output, plasma renin activity (PRA), and plasma aldosterone concentration were determined postdialysis before and after r-HuEPO therapy in patients in whom changes in BP could be managed by ultrafiltration alone. Eleven patients entered the study: one had a renal transplant and two required addition of antihypertensive drug therapy and were excluded; eight, of whom two required antihypertensive drug therapy following the study, were included in the analyses. Results revealed an increase in predialysis hemoglobin from 67 to 113 g/L (6.7 to 11.3 g/dL) (P = 0.001) during 18 +/- 6 weeks of therapy. Predialysis diastolic BP increased from 80 to 85 mm Hg (P = 0.07), while postdialysis diastolic BP was unchanged at 73 mm Hg. 51Cr-RBC volume increased, from 0.7 to 1.3 L (P = 0.004). ECF tended to decrease, from 13.7 to 10.8 L (P = 0.064), while TBW decreased to a similar extent, but not significantly, 34.3 to 31.2 L (P = 0.16). Postdialysis ECF volume was positively correlated with mean arterial BP at baseline (r = 0.89, P = 0.007) and after therapy (r = 0.74, P = 0.035). However, the regression lines for this relationship were different (P = 0.022) before and after therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Molecular basis of complement activation in ischemic myocardium: identification of specific molecules of mitochondrial origin that bind human C1q and fix complement.

Mitochondria may be a source of molecules that activate complement during ischemic injury to myocardium, providing therewith a stimulus for infiltration of polymorphonuclear leukocytes. To identify specific molecules that activate the classical complement pathway, detergent lysates of canine cardiac mitochondria were fractionated by polyacrylamide gel electrophoresis and transferred electrophoretically to nitrocellulose paper (NCP). The NCP replicas of the gels were incubated with isolated C1q and fresh sera as a source of complement, washed briefly, and overlaid with sensitized sheep erythrocytes (RBC) in agarose. A cluster of four to six molecules between 45 and 53 kDa as well as four others, 34, 30, 26, and 23 kDa, consumed complement thereby preventing complement-mediated lysis of sensitized sheep RBC in the agarose overlay. Additional molecules reactive with C1 were identified by their ability to bind isolated human C1q and to serve as assembly sites for later acting complement components. Sites of localization of complement were demonstrated by incubating NCP replicas of fractionated mitochondria with antisera specific for C1q, C3, C5, and C9, followed by peroxidase-conjugated anti-immunoglobulin and substrate. A total of 12 C1q binding molecules ranging in size from 67 kDa to 23 kDa, which can fix later acting complement components, were identified. At least two of these reacted with antisera prepared against canine cardiac lymph collected in the first 3-4 hours after a 45-minute coronary artery occlusion. These studies present direct evidence that specific molecules, released from subcellular fractions of myocardial cells rich in mitochondria, can activate the complement cascade.

Animals

A statewide approach to adolescent tobacco-use prevention: the Minnesota-Wisconsin Adolescent Tobacco-Use Research Project.

Adolescent smoking rates remain high and the use of smokeless tobacco is increasing, especially among males. Despite this continuing public health problem and the recent development of more effective prevention programs, few adolescents now participate in such programs at school. Recent legislation in Minnesota established guidelines for tobacco-use prevention programming and provides financial incentives to school districts to use more effective methods. The Minnesota-Wisconsin Adolescent Tobacco-Use Research Project has implemented an evaluation design that will provide data on the efficacy of this statewide approach to the prevention of tobacco use among adolescents. This article describes the current state of tobacco-use prevention programming in Minnesota schools, current efforts to improve on that record, and the research design set up to evaluate these strategies.

Adolescent

Mechanism of complement activation after coronary artery occlusion: evidence that myocardial ischemia in dogs causes release of constituents of myocardial subcellular origin that complex with human C1q in vivo.

To evaluate whether ischemic myocardium releases molecules that react with the first component of complement, we studied cardiac lymph from eight dogs before and at intervals after coronary artery occlusion and reperfusion. Before occlusion, the dogs were injected intravenously with radiolabeled human C1q. Labeled C1q could be detected in the cardiac lymph within minutes following injection. Rabbit antisera, prepared against substances precipitated from postreprefusion cardiac lymph by anti-human C1q, also reacted with specific constituents of isolated cardiac sarcoplasmic reticulum and mitochondria. To evaluate whether mitochondria are the source of these C1q-binding proteins, we isolated intramyofibrillar and subsarcolemmal mitochondria from canine heart and incubated sonicates of these with purified C1q, immobilized on nitrocellulose. Molecules bound to the immobilized C1q were removed with 0.1% sodium dodecyl sulfate, fractionated under reducing conditions by polyacrylamide gel electrophoresis, and transferred electrophoretically to nitrocellulose paper. Antisera prepared against postreperfusion lymph reacted with a 31,000-32,000-dalton protein in these nitrocellulose paper replicas. Since this protein originates from mitochondria, binds to C1q, and is recognized by antibodies made against postreperfusion lymph, this protein is likely to be one of the subcellular constituents that, upon release from ischemic cells, activates the complement cascade. To evaluate the clinical relevance of these observations, we tested sera from 53 patients obtained 48-72 hours after hospitalization for suspected myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Neurochemical basis for cocaine and methamphetamine interactions.

We have evaluated the responses of rat monoaminergic pathways to combinations of cocaine and methamphetamine (METH) administrations and found that these two commonly abused stimulants significantly interact. A 7-day pretreatment with daily doses of cocaine enhanced the neurochemical changes induced by multiple doses of METH in the dopaminergic and serotonergic systems of the basal ganglia and frontal cortex. When cocaine was administered concurrently, it attenuated or blocked the serotonergic changes caused by multiple doses of METH, but it did not interfere with the METH-mediated changes in the dopaminergic system.

3,4-Dihydroxyphenylacetic Acid

Intraarticular fractures of the distal humerus in the adult.

Intraarticular fractures of the distal humerus are notoriously difficult to treat. Three basic treatment methods are available: closed reduction, traction, and open treatment. In the past, functional results with all these methods generally have been poor because of disabling limitations of elbow motion. Thirteen adult patients were treated by open reduction and application of medial and lateral buttress plates providing rigid internal fixation and early motion. The patients were evaluated for range of motion, infection, nerve injury, avascular necrosis, myositis ossificans, varus/valgus deformity, pain, instability, weakness, and degenerative changes. Ten of the 13 patients were available for follow-up study for an average of two years. Nine of the ten achieved good or excellent results. Based on these observations, the treatment of choice is internal fixation with dual plates combined with early active postoperative motion.

Adolescent

Hydrolysis of peptides by carboxypeptidase A: equilibrium trapping of the ES2 intermediate.

The cobalt absorption and electron paramagnetic resonance (EPR) spectra of cobalt carboxypeptidase undergo unique variations on formation of catalytic peptide and ester intermediates as previously recorded in cryoenzymologic experiments employing rapid-scanning spectroscopy and cryotrapping [Geoghegan, K. F., Galdes, A., Martinelli, R. A., Holmquist, B., Auld, D.S., & Vallee, B. L. (1983) Biochemistry 22, 2255-2262]. We here describe a means of stabilizing these intermediates, which we have termed "equilibrium trapping". It allows peptide intermediates to be observed for longer periods (much greater than 1 min) at ambient as well as subzero temperatures. The reaction intermediate with the rapidly turned over peptide substrate Dns-Ala-Ala-Phe is trapped when the cobalt enzyme (greater than 10 microM) has catalyzed the attainment of chemical equilibrium between high concentrations of the hydrolysis products Dns-Ala-Ala, 10 mM, and L-phenylalanine, 50 mM, and the product of their coupling Dns-Ala-Ala-Phe. Under these conditions, Dns-Ala-Ala-Phe is present in the equilibrated substrate-product reaction mixture at a level that exceeds the one predicted on the basis of K'eq for hydrolysis of this substrate and is close to the enzyme concentration. Other pairs of peptide hydrolysis products yield similar results. Visible absorption and EPR spectra of the cobalt enzyme show that the synthesized peptide binds to the active site in the mode previously recognized as the ES2 catalytic intermediate in peptide hydrolysis. Equilibrium trapping of the ES2 intermediate allows analysis of its physicochemical properties by methods that could not be employed readily under cryoenzymological conditions, e.g., circular dichroic and magnetic circular dichroic spectra.(ABSTRACT TRUNCATED AT 250 WORDS)

Carboxypeptidases