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Biomedical subjects

R Nelson

Publications and source records attributed to R Nelson.

At least 145 records · Page 8Linked to original sources
PubMed1994

Insulin sensitivity and metabolic clearance rate of insulin in cystic fibrosis.

We have evaluated the metabolic clearance rate (MCR) of insulin and insulin sensitivity in 12 older patients with cystic fibrosis (CF) using the hyperinsulinemic euglycemic clamp method. Compared with a control group matched accurately for age and body mass index (BMI), the MCR of insulin was significantly enhanced in CF CF = 21.85 +/- 1.17 v controls = 16.01 +/- 0.92 mL/kg/min, P < .005), and this difference persisted after correction for lean body mass ([LBM] CF = 26.32 +/- 1.28 v controls = 19.09 +/- 1.09 mL/kg LBM/min, P < .005). Glucose disposal rates (M) were similar in the two groups during the clamp (CF = 7.28 +/- 0.41 v controls = 6.83 +/- 0.60 mg/kg/min, P > .5), but the insulin sensitivity index, M/I x 100 (I = steady-state insulin concentration), was markedly increased in the CF group (CF = 17.62 +/- 1.30 v controls = 11.75 +/- 0.71, P < .005). In conclusion, the MCR of insulin is enhanced in CF, which is in keeping with previous observations on drug metabolism in this disorder. Second, insulin sensitivity is increased in CF, and this points to a compensatory mechanism to counteract the insulinopenia.

Adolescent↗
PubMed1994

Methodological issues in the administration of multiple doses of smoked cocaine-base in humans.

Many methodological issues exist in human laboratory research with smoked cocaine-base that include safety, precision of dose delivery of smoked cocaine, and the lack of an adequate placebo. All of these issues are particularly apparent with studies involving multiple doses of cocaine. Addressing these concerns is important in conducting parametric studies that require examining dose-response effects. The purposes of this study were to determine: 1) the safest interval between doses to deliver smoked cocaine; 2) the accuracy or reproducibility of administering precise and multiple doses of cocaine; 3) the potential for using a control dose of cocaine; and 4) the influence of multiple doses on these parameters. Six black males were given 10 doses of either 5 or 35 mg of cocaine-base at 15-, 30-, and 45-min intervals. The dependent measures included physiological, subjective, and performance responses. These measures were taken prior to dosing and at specific time intervals after each dose of smoked cocaine. The results showed: 1) dosing at 30-min intervals allowed sufficient time for recovery of blood pressure and heart rate to permit up to 10 doses to be safely administered; 2) reproducible blood cocaine levels were obtained with repeated dosing using a heated wire-coil device; 3) significant differences were observed between the 5- and 35-mg dose with 5 mg being a low enough dose to produce minimal effects; 4) acute tolerance was evidenced with multiple doses of cocaine for most of the measures; and 5) considerable between- and within-subject variability was observed in the pattern of responses to cocaine.

Administration, Inhalation↗
PubMed1994

Community screening for diabetes. Low detection rate in a low-risk population.

OBJECTIVE: To evaluate glucose-based community screening for diabetes with regard to detection rate. RESEARCH DESIGN AND METHODS: A retrospective analysis of a community-screening questionnaire data base that included a screening for blood glucose. Referred subjects had fasting glucose levels > 6.4 mM (115 mg/dl) or postprandial levels > or = 8.9 mM (160 mg/dl). An attempt was made to contact referred subjects and to ascertain whether follow-up was undertaken and current status. A random sample of subjects not meeting the glucose criteria (nonreferred) also was contacted in an analogous fashion to referred subjects. RESULTS: In 2,016 questionnaires, glucose-based referral criteria were exhibited by 148 (7.3%) individuals, and subsequent evaluation data were available for 111. Of those 111 individuals, 37 (33%) knew they had diabetes before the screening, and 39 (36%) did not seek further evaluation. Of the remaining 35 subjects, 6 (13%) were told of their new diagnosis of diabetes, and 29 were told they did not have diabetes. Three of 50 nonreferred subjects knew of their diabetes before screening. Thirty percent (14 out of 47) of nonreferred subjects underwent subsequent evaluation, although they were not told to do so. A single new case of diabetes occurred in the nonreferred group. CONCLUSIONS: Community screening for diabetes that is based on measured glucose is of low yield. The known problems of glucose-based screening, coupled with its low yield, make a glucose-based approach difficult to justify. These results indicate that glucose-based community screening should be done only under the careful supervision of a health professional who is trained both in glucose measurement instrumentation and in screening.

Adolescent↗
PubMed1994

An experimental test of retention in residential and outpatient programs.

Previous studies of residential and outpatient drug treatment programs have found that retention is higher in residential than in outpatient programs. This study attempts to verify previous findings by conducting an experiment that controls for ecological, self-selection, and program content biases. The Houston Recovery Campus is a research-focused, multiple-provider drug treatment facility for the indigent of Harris County, Texas. During the study period, 646 applicants were randomly assigned to two comparable 28-day programs. The first program was a residential program; the second was an outpatient day treatment program. Twenty-eight day retention rates were significantly higher for the residential program (76%) compared to the day treatment program (64%).

Adult↗
PubMed1994

It may be time to redefine security as a "profit center" in the healthcare industry.

Security, say the authors, should be viewed as a profit center that protects the patients, staff, visitors, property, and assets of healthcare organizations from violent crime, injury, theft, or vandalism ... and the resulting devastating litigation. Security services, which protect the "bottom line," should be a central part of any healthcare organization.

Hospital Departments↗
PubMed1994

Matrix-assisted laser desorption mass spectrometric analysis of a pegylated recombinant protein.

Matrix-assisted laser desorption ionization mass spectrometry (MALDI) has been investigated as a technique for the characterization of recombinant stem cell factor that had been covalently modified with polyethylene glycol (PEG) chains. The attachment of PEG chains produces a heterogeneous mixture of protein species that differ by 6000 Da. These differences in molecular weight could be readily determined by MALDI. The potential of MALDI as a general strategy for characterizing PEG-modified proteins is discussed.

Biotechnology↗
PubMed1994

Medical education and health system reform.

There is increasing pressure on medical schools to produce more primary care physicians and fewer specialists. Health system reform proposals which rely on a "gatekeeper" approach will keep public attention on this issue. Educators at the University of Iowa say physician training must meet all of society's needs.

Education, Medical↗
PubMed1993

A cohort study of stomach cancer risk in men after gastric surgery for benign disease.

BACKGROUND: For the past 40 years, investigators have suggested that there exists an increased risk of stomach cancer following gastric surgery for benign disease. Recent cohort studies have consistently identified an increased risk of stomach cancer beginning 20 years or more following gastric surgery. Validation of this association and elucidation of risk factors related to gastric cancer have been complicated by variability in study designs. PURPOSE: This cohort study was designed to investigate the risk of stomach cancer following gastric surgery and to identify patient and treatment characteristics that may alter this risk. METHODS: Medical admission records of 17077 male military veterans hospitalized during 1970-1971 in U.S. Department of Veterans Affairs (VA) hospitals were examined. From this initial cohort, 1094 patients who died within the 1st year following gastric surgery were excluded. Data analysis was performed on the final cohort consisting of 15,983 patients divided into the following two groups: 1) an exposed group (gastric surgery group) that included 7609 patients receiving gastric surgery for a documented benign disorder and 2) an unexposed group (comparison group) that included 8374 male patients randomly selected from all other hospitalized male patients in the patient database. The comparison group was matched to the gastric surgery group by age (within 10 years), race, hospital, and year of admission. Mortality follow-up utilized the following three sources to identify vital status: 1) the VA Patient Treatment File (1970-1988), 2) the VA Beneficiary Identification Record Linkage System (1970-1989), and 3) the National Death Index (1979-1988). Death certificates were obtained for 99% of the deceased patients. Analyses included estimations of risk using standardized rate ratios (SRRs) and proportional hazards techniques. RESULTS: A statistically significant increase in risk of stomach cancer was demonstrated among males during the 20 years following gastric surgery (SRR = 1.9; 95% confidence interval [CI] = 1.3-2.4; P = .0001). The risk of developing gastric cancer was greatest during the 2nd to 5th postoperative years (SRR = 2.8; 95% CI = 1.6-4.5; P < .01) and during years 11-15 (SRR = 2.5; 95% CI = 1.2-4.8; P < .01). Also, the risk of developing gastric cancer was greatest among those treated by gastrectomy for any type of ulcer (SRR = 2.6; 95% CI = 1.2-4.9; P < .01) and those having any type of gastric surgery when the primary diagnosis was gastric ulcer (SRR = 2.9, 95% CI = 1.4-5.3; P < .01). CONCLUSIONS: This study confirms that men undergoing gastrectomy for benign disease and men receiving any gastric surgery for gastric ulcer are at increased risk for developing gastric cancer. Unlike earlier studies, we find that the increased risk is not delayed for 20 years.

Adult↗
PubMed1993

Long-term reversal of diabetes by the injection of immunoprotected islets.

The intraperitoneal injection of insulin-producing islets immunoprotected by an alginate-poly(amino acid) membrane is a potential method of reversing diabetes without the need for lifelong immunosuppression. Previous attempts to demonstrate this technology in large animals have failed, preventing application in humans. We have determined that key factors responsible for these past failures include cytokine (interleukins 1 and 6 and tumor necrosis factor) stimulation by mannuronic acid monomers from alginate capsules with weak mechanical integrity, which results in fibroblast proliferation. With this insight, we formulated mechanically stable microcapsules by using alginate high in guluronic acid content and report prolonged reversal of diabetes in the spontaneous diabetic dog model by the intraperitoneal injection of encapsulated canine islet allografts. Euglycemia, independent of any exogenous insulin requirement, was noted for up to 172 days. Graft survival, evidenced by positive C-peptide release, was noted for as long as 726 days in a recipient receiving a single injection of immunoprotected islets. Histological evidence of viable islets retrieved from the peritoneal cavity 6 months posttransplant confirmed the biocompatibility and immunoprotective nature of this capsule formulation. The finding that intraperitoneal injection of alginate-immunoprotected islets, a minimally invasive surgical procedure, is effective in prolonged (> 1 year) maintenance of glycemic control, without the need for lifelong immunosuppression, may have significant implications for the future therapy of type I diabetes in humans.

Alginates↗
PubMed1993

OFF-alpha and OFF-beta ganglion cells in cat retina. I: Intracellular electrophysiology and HRP stains.

Six OFF-alpha ganglion cells and a single OFF-beta ganglion cell were penetrated with intracellular microelectrodes and marked with horseradish peroxidase (HRP) in a perfused cat eyecup. Gaussian center radii (Rc) ranging from 40 to 217 microns were measured for receptive fields mapped with slits, values in agreement with previous extracellular reports. ON and OFF response components revealed nearly identical Rc's and center locations. Although Gaussian diameters (2Rc) were about 80% of dendritic field diameters overall, in this sample dendritic and receptive fields were not well correlated. Spatial tuning of ganglion cells was evidenced in peaked amplitude-vs.-width functions, fit by difference-of-Gaussians models. Such plots yielded Rc values about 40% less than position-vs amplitude plots. Rs values for surrounds ranged from 200 to 1,700 microns. Rod and cone signals were investigated with flicker. Rod flicker signals in OFF-alpha cells were larger and of shorter latency than in either horizontal or AII amacrine cells. Cone flicker signals were also short in latency, with an ON response time constant of 9 msec, and an OFF response time constant of 3 msec. The OFF-alpha rod-cone transition involved a latency increase of 20-30 msec. The spontaneous and light-evoked impulse rates of OFF-alpha responses varied linearly with extrinsic current, but the amplitude of ON hyperpolarization was little affected. After injection of staining current, the OFF-beta cell transiently depolarized at ON, suggestive of ON inhibition with reversed chloride gradient, a result not seen in OFF-alpha responses. Events (peaked, depolarizing voltage fluctuations) of high, low, and intermediate amplitudes were studied in OFF-alpha responses. High amplitude events (impulses), were OFF-correlated with the stimulus, and exhibited mean rise times (transit time from 25 to 75% of peak amplitude) from 255 to 392 microseconds. Intermediate level events (presumed synaptic origin) were also OFF correlated and had longer rise times (325 microseconds to 1.56 microseconds). Low level events (234-685 microseconds) revealed either ON, ON/OFF, or not stimulus correlation.

Action Potentials↗
PubMed1993

OFF-alpha and OFF-beta ganglion cells in cat retina: II. Neural circuitry as revealed by electron microscopy of HRP stains.

An OFF-center alpha and an OFF-center beta ganglion cell in cat retina, which had been recorded from and intracellularly stained with horseradish peroxidase (HRP) were examined by serial section electron microscopy. We counted synapses and identified presynaptic neurons to the HRP-stained cells in 20 microns radial slices through the centers of their dendritic trees. Presynaptic amacrine and bipolar cells were identified on cytological criteria known from previous studies. The OFF-beta cell with a 62 microns dendritic arbor, restricted to S1 and S2 (sublamina a) of the inner plexiform layer (IPL), received 38% bipolar and 62% amacrine cell synapses. The bipolar input was from both cb1 and cb2 cone bipolar types. Input from three distinct amacrine cell types occurred upon the dendrites, namely from: (1) AII amacrine lobular appendages, (2) large pale amacrine profiles (possibly A2 or A3 cells), and (3) small, dark amacrine types (possibly A8 cells). Large pale amacrine profiles (possibly A13) were found on the cell body and apical dendrite in sublamina b of the IPL. In addition, several amacrine profiles synapsed directly on the sides and base of the cell body in the ganglion cell layer. We estimate that the complete dendritic tree of this beta cell received about 1,000 synapses contributed by 12-14 bipolar cells, 7-10 AII amacrines and 28-41 other amacrine cells. The OFF-alpha cell had a dendritic tree size of 680 x 920 microns. A 250 microns length of two major dendrites stratifying narrowly in S2 of the IPL was reconstructed. Amacrine cells provided most of the synaptic input (80%). This input came from: (1) AII amacrine lobular appendages, (2) amacrines exhibiting large, pale synaptic profiles (possibly A2 or A3 cells), (3) pale amacrines with large mitochondria and a few neurotubules (unknown type), and (4) densely neurotubule-filled amacrine profiles (possibly A19 cells). A large pale amacrine cell type (possibly A13) provided synaptic input to the cell body as a serial synaptic intermediary with rod bipolar cells. Cone bipolar synapses were from only one type of cone bipolar, the cb2 type and formed 20% of the total synaptic input. We estimate that a minimum of 142 bipolar cells, 256 AII amacrine cells and 1,011 other amacrine cells, altogether providing 6,000-10,000 synapses, converged on the dendritic tree of this OFF-alpha cell.

Animals↗
PubMed1993

Latex anaphylaxis.

BACKGROUND: Unexplained vascular collapse, airway obstruction, shock, and death after procedures as innocuous as barium enema or anorectal manometry have recently been shown to be due to allergy to latex and anaphylactoid reaction. METHOD: To review existing medical literature on latex anaphylaxis and to determine who is most at risk and what methods might best prevent morbidity from this condition. RESULTS: Those most at risk for this catastrophe are patients whose mucous membranes have been extensively exposed to latex, such as patients with spina bifida who frequently undergo urethral catheterization and individuals who have had many previous operative procedures: CONCLUSIONS: Avoidance of latex exposure is the best prophylaxis in high-risk groups. Prompt resuscitation is critical once the syndrome becomes clinically apparent.

Anaphylaxis↗
PubMed1993

Dose-response and concentration-response relationships: clinical and regulatory perspectives.

There are a number of effective but highly toxic drugs that exhibit a narrow therapeutic index and marked intersubject variability in pharmacokinetics (PK). Examples of these drugs included digoxin, theophylline, aminoglycosides, and anticancer (methotrexate) and immunosuppressive agents (cyclosporin A and FK-506). Optimal therapy with such drugs requires therapeutic drug monitoring (TDM) in order to safely obtain the desired clinical effects. The success of concentration-guided therapy with these drugs underscores the importance of using TDM and pharmacodynamic response (PD) to establish an appropriate balance of efficacy and toxicity through individualization of dosing. Although dose control has been the traditional paradigm for defining efficacy, safety, and dose response, it has recently been proposed that a concentration-oriented strategy of drug evaluation may facilitate the discovery of optimal doses and expedite new drug approval. However, as in medical therapeutics, the implementation of concentration-guided drug development may add to the complexity and cost. Therefore, it is important to assess the relative merits and limitations of dose-response and concentration-response (CR) strategies for establishing rational dosage information (e.g., a useful therapeutic range). Critical factors that have an effect on the ability to characterize dose-response/concentration-response relationships in clinical trials include study design, compliance, method of analysis, and sources of pharmacologic (PK-PD) variability. In this report, we describe the state of the art, based on a selected survey of successful dose-response studies. We give an example of a promising alternative strategy for evaluating CR for an immunosuppressive drug (FK-506) based on target drug concentrations extrapolated from preclinical models.

Animals↗
PubMed1993

Clinical correlates of acoustic neuroma volume.

A computer-assisted, MRI-based technique of tumor volume determination was used to correlate preoperative hearing levels and long-term postoperative facial function with acoustic neuroma volume. Preoperative hearing was studied in a group of 41 patients subjected to direct tumor volume calculations and in another group of 131 patients in whom volume was extrapolated from the acoustic neuroma volume-diameter relation. Similarly postoperative facial function was correlated with acoustic neuroma volume in another 864 patients in whom long-term follow-up was available. Preoperative hearing levels were found not to be significantly related to tumor volume. However, postoperative facial function was significantly associated with tumor volume and was best predicted as a nonlinear function of diameter. Thus, tumor volume changes are important considerations in the clinical management of acoustic neuromas. Patients should be advised that even small changes in tumor diameter (especially in larger tumors) can result in tumor volume changes that may be associated with significant changes in postoperative facial function.

Auditory Threshold↗