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Biomedical subjects

S Emerson

Publications and source records attributed to S Emerson.

At least 37 records · Page 2Linked to original sources

Recombinant human granulocyte-colony-stimulating factor in the treatment of patients with neutropenia.

The results of an open-label, randomized, Phase III trial of r-methionyl human granulocyte-colony-stimulating factor (r-metHuG-CSF) in 41 patients with severe chronic neutropenia (SCN) are reported. Patients with diagnoses of congenital, cyclic, and idiopathic neutropenia, with histories of recurrent infections, were evaluated. The primary objective of the trial was to evaluate the ability of r-metHuG-CSF to increase the ANC to greater than 1500/mm3. A secondary objective was to evaluate variables associated with infection-related morbidity in SCN. r-metHuG-CSF treatment consisted of 1 month of dose titration followed by 4 months of treatment at an optimal dose. Patients were randomized to either immediate treatment with r-metHuG-CSF (Group A) or four months of observation followed by r-metHuG-CSF treatment (Group B). r-metHuG-CSF was administered by daily, subcutaneous injection with initial doses of 3 to 10 micrograms/kg/day. Forty of 41 patients who received r-metHuG-CSF had a complete response (median ANC greater than 1500/mm3 during 4 months of r-metHuG-CSF treatment). All cases of gingivitis and severe mouth ulcers resolved upon treatment with r-metHuG-CSF. Serious infections were also eliminated. Only one patient failed to show clinical improvement in response to r-metHuG-CSF treatment. Adverse reactions during the first 5 months of treatment were mild. Splenomegaly (mild) was noted in some patients. The administration of r-metHuG-CSF in patients with SCN significantly increased the ANC (P less than 0.001) and was accompanied by a marked reduction in infectious complications.

Agranulocytosis↗

Screening test for detection of metallic foreign objects in the orbit before magnetic resonance imaging.

RATIONALE AND OBJECTIVES: A study was designed to determine whether plain films, used as a screening modality for magnetic resonance imaging (MRI), could reliably detect intraorbital metallic foreign objects. METHODS: In the first experiment, 20 metal particles were placed in five human cadaver orbits. Routine orbital plain film series and computed tomography (CT) were obtained, randomized, and interpreted blinded by three experienced radiologists. RESULTS: The threshold size of particle detection for CT (0.07 mm3) was lower than for plain films (0.12 mm3). Placing metal particles in artificial and true vitreous demonstrated that all particles moved under a magnetic field at 1.5 T. When human globes were exposed to industrial tools (grinder, bandsaw, air hose, etc.), no metal objects penetrated the sclera. CONCLUSIONS: Plain films can be used as a low-cost, low-radiation screening procedure for high-risk patients with occupations involving metal work. CT should be used for patients with a history of eye trauma from other causes.

Costs and Cost Analysis↗

Pharmacodynamic studies of cyclosporine in marrow transplant recipients. A comparison of three assay methods.

We investigated the correlation between trough cyclosporine concentration in plasma measured by polyclonal fluorescence polarization immunoassay (FPIA) and polyclonal radioimmunoassay (RIA) or in whole blood measured by high-performance liquid chromatography (HPLC) and the risk of renal dysfunction or acute graft-versus-host disease in 29 patients undergoing allogeneic bone marrow transplantation for leukemia. The FPIA and RIA values were highly correlated (r = 0.93) and on the average CsA concentrations measured by FPIA were 1.56 times higher than those measured by RIA. Ten patients developed renal dysfunction and 10 developed grades II-IV acute GVHD. Although univariate analysis showed that plasma CsA concentrations measured by either FPIA or RIA were significantly correlated with renal dysfunction, the association was stronger with FPIA. Plasma CsA concentrations measured by FPIA but not RIA remained a significant risk factor for renal dysfunction in a multivariate relative risk model. Amphotericin therapy was significantly associated with renal dysfunction in the univariate analysis but not in the multivariate analysis. No significant associations were found between whole blood CsA or CsA M1 concentration, patients' age, gender, or CsA dose and the risk of renal dysfunction. None of the covariates analyzed significantly correlated with the development of acute GVHD. These data suggest that plasma CsA concentrations measured by nonspecific assays may more accurately correlate with renal dysfunction than whole-blood CsA concentrations measured by HPLC in marrow transplant recipients.

Adult↗

Myeloablative chemoradiotherapy and autologous bone marrow infusions for treatment of neuroblastoma: factors influencing engraftment.

Bone marrow harvested from cancer patients for autologous bone marrow reinfusion (ABMR) after myeloablative treatment may be injured, in both its proliferating and stromal cell pools, by either previous treatment or manipulation at the time of harvest. We have examined the relative effects of seven covariates on hematologic recovery after ABMR in children with neuroblastoma (NBL) using univariate and step-up analysis. We measured recovery by times to achieve (1) white blood cell counts greater than 1,000/microL; (2) absolute neutrophil counts greater than 500/microL; and (3) platelet counts greater than 20,000/microL without transfusion. In univariate analysis, recovery was significantly associated with the amount of prior chemotherapy and the interval between last chemotherapy and marrow harvest. Patient sex, the number of granulocyte-macrophage colonies infused, harvest-to-freeze interval, and use of purging were marginally associated. After adjusting for potential confounders in a multivariate model, the amounts of chemotherapy and granulocyte-macrophage colonies infused were independently significant predictors of time to total white blood cell count recovery; chemotherapy courses and chemo-to-harvest interval were predictors of neutrophil count recovery; and sex, use of purging, and harvest-to-freeze interval were marginal predictors of platelet recovery. The speed of hematologic recovery after ABMR seems to depend mainly on pre-existing factors and marginally on manipulation of the marrow after harvest. These factors may affect both proliferating and stromal cell pools.

Antineoplastic Combined Chemotherapy Protocols↗

Synergistic inhibition by verapamil and quinine of P-glycoprotein-mediated multidrug resistance in a human myeloma cell line model.

In an effort to develop a clinically useful approach to overcoming P-glycoprotein-mediated multidrug resistance (MDR1), we evaluated combined chemosensitization with verapamil and quinine in a multidrug-resistant (MDR) human myeloma cell line model. In clonogenic assay, verapamil was used at concentrations from 0.1 to 1.0 micrograms/mL, bracketing the plasma levels achieved by oral administration and high-dose intravenous (IV) infusion, respectively. The dose of quinine was held constant at 1.0 micrograms/mL, a plasma concentration readily achieved by oral administration. At each dose level of verapamil tested, the combination with quinine proved more effective than either drug individually in reversing resistance to doxorubicin and vinblastine and synergistic chemosensitizing interaction was observed. Verapamil at 0.1 microgram/mL combined with quinine was capable of restoring sensitivity to doxorubicin fully and reduced resistance to vinblastine as effectively as verapamil alone at 1.0 micrograms/mL. Furthermore, the combination of 1.0 mumol verapamil with 10 mumols quinine increased accumulation and retention of anthracycline in the resistant cells to a greater extent than did either drug individually (P less than .001) and inhibited drug efflux as effectively as verapamil alone at 10 mumols. Our findings suggest that combined chemosensitization with verapamil and quinine may prove useful for overcoming MDR1 in patients with drug-refractory B-cell neoplasms such as multiple myeloma or non-Hodgkin's lymphomas.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM): treatment with an anabolic steroid danazol.

Tropical spastic paraparesis or HTLV-I-associated myelopathy is a progressive spastic disorder associated with the human T-lymphotropic virus type I. Some cases have responded to prednisone. Danazol is an attenuated androgen with minimal virilizing effects. It is used in the treatment of endometriosis and various autoimmune hematologic diseases shown to be responsive to prednisone. Because danazol is anabolic, useful in prednisone-responsive diseases, and less toxic than prednisone, we gave danazol to 6 patients with TSP and 1 with HIV, HTLV-I-associated myelopathy. Five patients had a favorable response. Two became ambulatory after having been confined to a wheelchair. Three were able to ambulate greater distances (in walkers) than prior to danazol. Three had noticeable decreases in spasticity. Urinary incontinence resolved in two. Physical therapy was variably employed in all except one patient. Two patients who had not responded to physical therapy responded to physical therapy and danazol. One patient did not tolerate danazol and one patient did not improve. Toxicities noted were mild elevations in liver enzymes in 4 patients; these responded to a decrease in dose of danazol; amenorrhea in one and mild fluid retention in one. We conclude that danazol is a useful agent in the management of TSP.

Adult↗

Disturbed body image in patients with eating disorders.

OBJECTIVE: The authors attempt to answer the question of whether patients with eating disorders experience more distortions in body image than do individuals without eating disorders. METHOD: The study group was composed of 214 women out of 230 patients consecutively admitted to an inpatient eating disorders program. Twelve men and four patients with atypical eating disorders were excluded from study. The 214 patients were divided into three groups: 87 with anorexia nervosa alone, 72 with anorexia and bulimia nervosa, and 55 with bulimia nervosa alone. The comparison group was composed of 61 women drawn from 125 consecutive participants in a survey of university students. Fifty-six men were dropped from the comparison group, along with eight women who fulfilled diagnostic criteria for eating disorders. Each subject used a three-dimensional measure to rate her body size and stated her desired body size at seven points: left biceps, left calf, left thigh, waist, abdomen, hips, and bust. The subjects' measurements at each of these points were taken. Distortion in body image was calculated as the subject's perceived body size divided by her actual body size. All subjects were also given a battery of tests of intelligence, skill, and memory. RESULTS: All three patient groups differed significantly from the comparison group in distortions in body image. Most but not all patients with eating disorders had distortions in their body image. CONCLUSIONS: If replicated, these findings would suggest that the diagnostic criteria regarding disturbance of body image for both anorexia and bulimia need to be revised.

Anorexia Nervosa↗

Maintenance of myelinated fibre g ratio in acute experimental allergic encephalomyelitis.

The spectra of myelin sheath thickness and g ratio (axon diameter/fibre diameter) of guinea pig optic nerves for 8 animals with acute experimental allergic encephalomyelitis (EAE) were compared with those for 6 normal animals. The mean myelin sheath thickness of 0.12 microns for the animals with EAE was significantly lower than the value of 0.16 microns for the normal animals. Since fibre diameter comprises axon diameter plus the thickness of its surrounding myelin sheath, a reduction in mean fibre diameter from 1.52 microns in normals to 1.20 microns in EAE was expected, but it was surprising to find that a mean g ratio of 0.85 obtained for normal nerves was not substantially different from a value of 0.86 for demyelinated optic nerves. A decrease in the mean axon diameter of 1.24 microns for normal animals to 0.94 microns for those with EAE tended to offset the decrease in mean myelin sheath thickness and contributed to the relative stability of the g ratio with acute demyelination. Our results showing reduction in axonal calibre and myelin sheath thickness may offer an explanation for apparent discrepancies between electrophysiological delays in conduction characteristics of experimental and, if not the result of a maturational effect on myelination, human primary demyelinating disorders associated with the scant histopathological demyelination of initial attacks of EAE and the visually asymptomatic patients with multiple sclerosis.

Animals↗

Increased neutrophil elastase release in unstable angina pectoris and acute myocardial infarction.

Neutrophils, a source of proteolytic enzymes and oxygen free radicals, have been shown to participate in animal models of myocardial ischemic injury. To characterize neutrophil activation in human ischemic heart disease, a specific neutrophil elastase-derived fibrinopeptide in plasma was measured in 25 patients with stable angina pectoris, 29 patients with unstable angina pectoris, 17 patients with acute myocardial infarction and 22 control subjects. Mean plasma levels (+/- standard error) of a neutrophil elastase-derived fibrinopeptide (B beta 30-43) measured by a specific radioimmunoassay were fivefold higher in patients with acute myocardial infarction (877 +/- 337 pmol/liter, p less than 0.02) and 13-fold higher in patients with unstable angina (2,277 +/- 613 pmol/liter, p less than 0.006) as compared with control subjects (172 +/- 74 pmol/liter). Mean plasma levels of peptide B beta 30-43 in patients with stable angina (676 +/- 334 pmol/liter), although higher than in control subjects, were not significantly increased (p = 0.64). Total leukocyte counts were 11.0 +/- 0.6 x 10(6)/ml in those with acute myocardial infarction, 9.2 +/- 0.7 x 10(6)/ml in those with unstable angina, 7.1 +/- 0.3 x 10(6)/ml in those with stable angina and 7.7 +/- 0.4 x 10(6)/ml in control subjects. Although total leukocyte counts in patients with unstable angina pectoris and acute myocardial infarction were higher (p less than 0.01) than in patients with stable angina or in control subjects, elevations in peptide B beta 30-43 levels were independent of the differences in both leukocyte count and absolute neutrophil count as well as in history of smoking, hypertension, diabetes mellitus or treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗

Research resources in academic radiology.

Research resources in academic radiology were investigated by analyzing the responses to a survey from 72 North American institutions. The questionnaire addressed five general areas: department size, departmental resources committed to research, availability of research training, research quality control, and research productivity. The highest correlates of grant productivity included measures of departmental resources committed to research, for example, space devoted to research, size of research budget, and full-time employee support for engineers, physicists, and chemists. In a regression model, measures of the number of engineers employed by a department, the number of attending staff, and the number of training lectures given by engineers were found to be most highly associated with dollar value of grant support. The average level of research resources available at responding institutions was generally low, despite a seemingly strong desire to do quality research. This is evidenced by a strong sentiment among respondents in favor of research training and quality control of research.

Humans↗

Functional assessment of T cell depletion from bone marrow prior to therapeutic transplantation using limiting dilution culture methods.

We evaluate the usefulness of limiting dilution culture methods in assessing the extent of T lymphocyte depletion from bone marrow inocula, prior to transplant, using either ex vivo antibody/complement-mediated depletion or immunotoxin treatment. Complement-mediated depletion using anti-Leu-1 antibody was shown to result in a consistent decline of 99%-99.9% in the frequencies of T cells able to proliferate in mitogen-stimulated, interleukin-2 (IL-2)-supplemented cultures. Equivalent declines were demonstrated in frequencies of "helper" T cells able to respond to mitogen by making IL-2, and in "killer" T cells able to give rise to clones of cytotoxic effectors. In most experiments, a second cycle of anti-Leu-1 + complement treatment did not further diminish the fraction of proliferating cells, although T cells able to secrete IL-2 were additionally depleted following a second cycle of antibody and complement. The limiting dilution methods were found to be at least as sensitive as flow cytometric (FACS) methods for detecting residual T cell contamination after protocols involving complement-mediated lysis, and superior to FACS analysis for protocols involving T cell depletion by a ricin A chain-anti-T101 immunotoxin, in which treated T cells suffer functional impairment and eventual death after exposure to immunotoxin, but remain phenotypically detectable during FACS analysis. Although limiting dilution methods do not provide data as rapidly as FACS analyses, they do not require a cytofluorimeter, provide equal or greater sensitivity, and can assess functional impairment, for both helper and killer T cell sets, even in situations in which the depletion procedure does not lead to immediate cytolysis.

Antibodies↗

Effect of Oxygen Tension, Mn(II) Concentration, and Temperature on the Microbially Catalyzed Mn(II) Oxidation Rate in a Marine Fjord.

We present evidence that the oxidation of Mn(II) in a zone above the O(2)/H(2)S interface in the water column of Saanich Inlet, British Columbia, Canada, is microbially catalyzed. We measured the uptake of Mn(II) in water samples under in situ conditions of pH and temperature and in the presence and absence of oxygen. Experiments in the absence of oxygen provided a measure of the exchange of the tracer between the dissolved and solid pools of Mn(II); we interpret the difference between experiments in the presence and absence of oxygen to be a measure of Mn(II) oxidation. Using this method we examined the effect of oxygen tension, Mn(II) concentration, and temperature on the initial in situ Mn(II) oxidation rate (V(0)). Mn(II) oxidation was almost twice as fast under conditions of 67% air saturation (V(0)=5.5 nM h) as with the in situ concentration of 15 muM (5% air saturation; V(0)=3.1 nM h). Additions of ca. 18 muM Mn(II) completely inhibited all Mn(II) oxidation at three different depths in the oxidizing zone, and there was a temperature optimum for Mn(II) oxidation of around 20 degrees C. These results are consistent with biologically mediated Mn(II) oxidation and indicate that the rate is limited by both oxygen and the concentration of microbial binding sites in this environment.

Journal Article↗

COPE: a systematic approach to moving chronic patients into the community.

COPE, a program designed to help chronic psychiatric patients make the transition from institutionalization to independent living in the community, emphasizes both in-hospital training the systematic aftercare as two points on a continuum of treatment. The program includes four training phases, with each phase based upon the skills acquired in the preceding one. The residents are thereby assured of having the necessary skills for progressing to more complex tasks as they proceed through the program. During the last phase, support by the mental health system is gradually replaced by help from community support systems.

Activities of Daily Living↗

Atmospheric carbon dioxide: its role in maintaining phytoplankton standing crops.

The rate of invasion of carbon dioxide into an artificially eutrophic Canadian Shield lake with insufficient internal sources of carbon was determined by two methods: measuring the carbon : nitrogen : phosphorus ratios of seston after weekly additions of nitrogen and phosphorus, and measuring the loss of radon-222 tracer from the epilimnion. Both methods gave an invasion rate of about 0.2 gram of carbon per square meter per day. The results demonstrate that invasion of atmospheric carbon dioxide may be sufficient to permit eutrophication of any body of water receiving an adequate supply of phosphorus and nitrogen.

Carbon Dioxide↗