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R Nelson

Publications and source records attributed to R Nelson.

At least 127 records · Page 7Linked to original sources
PubMed1995

Formation of ion channels in lipid bilayers by a peptide with the predicted transmembrane sequence of botulinum neurotoxin A.

Synthetic peptides patterned after the predicted transmembrane sequence of botulinum toxin A were used as tools to identify an ion channel-forming motif. A peptide denoted BoTxATM, with the sequence GAVILLEFIPEIAI PVLGTFALV, forms cation-selective channels when reconstituted in planar lipid bilayers. As predicted, the self-assembled conductive oligomers express heterogeneous single-channel conductances. The most frequent openings exhibit single-channel conductance of 12 and 7 pS in 0.5 M NaCl, and 29 and 9 pS in 0.5 M KCl. In contrast, ion channels are not formed by a peptide of the same amino acid composition as BoTxATM with a scrambled sequence. Conformational energy calculations show that a bundle of four amphipathic alpha-helices is a plausible structural motif underlying the measured pore properties. These studies suggest that the identified module may play a functional role in the ion channel-forming activity of intact botulinum toxin A.

Amino Acid Sequence↗
PubMed1995

Dietary sodium intake modulates systemic but not forearm norepinephrine release.

INTRODUCTION: Sodium intake has profound effects on systemic and renal sympathetic activity, but its effects on sympathetic activity in skeletal muscle vascular beds, a site at which local regulatory mechanisms could alter vascular tone directly, are unclear. METHODS: To determine the effect of dietary sodium intake on basal and isoproterenol-stimulated systemic and forearm norepinephrine kinetics, we studied seven healthy male volunteers twice, 4 weeks apart, while they were receiving a low-sodium (10 mmol sodium/24 hours) diet and a high-sodium diet (250 mmol sodium/24 hours). Forearm blood flow, measured by plethysmography, and systemic and forearm norepinephrine spillover, measured by radioisotope dilution, were determined before and after intra-arterial infusion of 60 and 400 ng/min isoproterenol. RESULTS: Baseline (before isoproterenol) systemic norepinephrine spillover was higher when subjects received the low-sodium diet (448.1 +/- 55.7 ng/min) compared with the high-sodium diet (269.7 +/- 42.7 ng/min; p < 0.05). In contrast, sodium intake did not affect local forearm norepinephrine spillover, either at baseline (low-sodium diet, 2.05 +/- 0.48 ng/min versus high-sodium diet, 2.63 +/- 0.79 ng/min; p = 0.50) or after stimulation with isoproterenol in doses of 60 ng/min (low-sodium diet, 8.84 +/- 2.2 ng/min versus high-sodium diet, 6.1 +/- 1.9 ng/min; p = 0.38) or 400 ng/min (low-sodium diet, 16.4 +/- 4.5 ng/min versus high-sodium diet, 16.7 +/- 2.5 ng/min; p = 0.93). CONCLUSIONS: Under conditions of low sodium intake, systemic norepinephrine spillover was increased but forearm norepinephrine spillover was not, suggesting that alteration in sodium intake may produce a differential effect on norepinephrine spillover in different tissues but that decreased local sympathetic activity in skeletal muscle is not the likely mechanism by which a low-sodium diet may lower blood pressure or attenuate stress-induced pressor responses.

Adrenergic beta-Agonists↗
PubMed1995

Comparison of the results of cemented, porous-ingrowth, and threaded acetabular cup fixation. A meta-analysis of the orthopaedic literature.

A meta-analysis of the orthopaedic literature was performed to evaluate the clinical performance of cementless, threaded acetabular cups. The hypothesis for the study was that the clinical performance of the cementless, threaded acetabular cup is equivalent to that of the cemented and porous-ingrowth acetabular cups. Ninety-five articles were included in the study. There were 1,269 cases in the threaded cup group, 1,979 in the porous control group, and 10,230 in the cemented control group. The primary outcome variable tested was the rate of aseptic loosening of the acetabular components as measured by the revision rates following the index total hip arthroplasty procedure. Other measures of acetabular component loosening that were analyzed included clinical rating scores, pain scores, frequency of radiolucencies according to location and size, frequency of radiolucencies as a separately defined outcome variable, progressive radiolucencies, and component migration. The threaded cup group was found to have a significantly higher rate of revision, clinical and pain score failures, progressive radiolucencies and migrations when compared with the cemented and porous control groups (P < .05). Despite the many limitations of meta-analyses and the poor state of the orthopaedic literature database, this study provides a reasonable comparison of the clinical performance of threaded acetabular cups with that of cemented and porous-ingrowth acetabular cups.

Acetabulum↗
PubMed1995

Chest physiotherapy in cystic fibrosis: a comparative study of autogenic drainage and the active cycle of breathing techniques with postural drainage.

BACKGROUND--Autogenic drainage has been suggested as an alternative method of chest physiotherapy in patients with cystic fibrosis. In this study autogenic drainage was compared with the active cycle of breathing techniques (ACBT) together with postural drainage. METHODS--Eighteen patients with cystic fibrosis took part in a randomised two-day crossover trial. There were two sessions of one method of physiotherapy on each day, either autogenic drainage or ACBT. The study days were one week apart. On each day the patients were monitored for six hours. Mucus movement was quantified by a radioaerosol technique. Airway clearance was studied qualitatively using xenon-133 scintigraphic studies at the start and end of each day. Expectorated sputum was collected during and for one hour after each session of physiotherapy. Pulmonary functions tests were performed before and after each session. Oxygen saturation (SaO2) and heart rate were measured before, during, and after each session. RESULTS--Autogenic drainage cleared mucus from the lungs faster than ACBT over the whole day. Both methods improved ventilation, as assessed by the xenon-133 ventilation studies. No overall differences were found in the pulmonary function test results, but more patients had an improved forced expiratory flow from 25% to 75% with autogenic drainage, while more showed an improved forced vital capacity with ACBT. No differences were found in sputum weight and heart rate, nor in mean SaO2 over the series, but four patients desaturated during ACBT. CONCLUSIONS--Autogenic drainage was found to be as good as ACBT at clearing mucus in patients with cystic fibrosis and is therefore an effective method of home physiotherapy. Patients with cystic fibrosis should be assessed as to which method suits them best.

Adolescent↗
PubMed1995

Dietary sodium intake modulates vasodilation mediated by nitroprusside but not by methacholine in the human forearm.

Studies in animals suggest that nitric oxide production is increased under conditions of salt loading and that this increase protects against the development of salt-induced hypertension. To determine the effect of dietary sodium intake on nitric oxide-mediated vascular responses, we studied seven healthy male volunteers twice 4 weeks apart while they were receiving a diet containing 10 or 250 mmol Na+ per 24 hours. Methacholine (0.25 to 8 micrograms/min) and sodium nitroprusside (0.25 to 8 micrograms/min) were infused intra-arterially in incremental doses, and forearm blood flow was measured. The response of forearm blood flow to sodium nitroprusside was greater when subjects received a high sodium diet than when they received a low sodium diet (F = 7.11, P < .05); however, the response to methacholine was not altered by sodium intake (F = 0.57, P = NS). Plasma renin activity was significantly higher (3.99 versus 1.0 ng angiotensin I/mL per hour) when subjects received a low salt diet (P < .05). Systolic pressure, diastolic pressure, heart rate, and baseline forearm blood flow were not affected by sodium status. We conclude that under conditions of salt loading, vasodilation in response to sodium nitroprusside was enhanced, whereas the response to methacholine was not affected, suggesting a differential effect of sodium intake on endothelium-dependent and endothelium-independent responses after the administration of methacholine and sodium nitroprusside, respectively.

Adult↗
PubMed1995

Tachyphylaxis of human forearm vascular responses does not occur rapidly after exposure to isoproterenol.

In vitro and limited in vivo data suggest that rapid desensitization of beta-adrenoceptor responses occurs after exposure to agonist. Tachyphylaxis to a beta-adrenoceptor agonist would represent a potentially important mechanism for the short-term regulation of vascular tone. The effects of a 4-hour infusion of 400 ng/min intra-arterial isoproterenol on forearm blood flow and presynaptic beta-adrenoceptor-mediated norepinephrine release were determined in eight healthy volunteers. Intra-arterial isoproterenol at 400 ng/min resulted in a significant increase in forearm blood flow in all eight subjects at all time points, with no evidence of tachyphylaxis. In fact, forearm blood flow after 4 hours of the isoproterenol infusion (22.8 +/- 3.3 mL/100 mL per minute) was significantly greater than after 7 minutes (14.6 +/- 2.8 mL/100 mL per minute), 15 minutes (15.4 +/- 2.4 mL/100 mL per minute), and 30 minutes (17.4 +/- 3.0 mL/100 mL per minute) of the infusion (P < .05). Similarly, presynaptic beta-adrenoceptor responses showed no evidence of tachyphylaxis, so forearm norepinephrine spillover values after 7 minutes (6.6 +/- 0.94 ng/min), 15 minutes (7.6 +/- 1.5 ng/min), and 4 hours (8.8 +/- 1.1 ng/min) of isoproterenol infusion were increased and similar. Minimal systemic effects were observed, and there was no evidence of tolerance, there being no difference in heart rate after 7 minutes (70.7 +/- 2.7 beats per minute) and 4 hours (72.2 +/- 3.6 beats per minute) of isoproterenol infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Forearm beta adrenergic receptor-mediated vasodilation is impaired, without alteration of forearm norepinephrine spillover, in borderline hypertension.

Impaired beta adrenoceptor-mediated vasodilation associated with enhanced sympathetic activity has been reported in established hypertension. We examined whether altered beta adrenoceptor-mediated vasodilation occurs early in the disease process, when structural vascular changes are likely to be less marked, by measurement of forearm blood flow by strain gauge plethysmography after the intraarterial administration of increasing doses of a beta receptor agonist, isoproterenol, in eight subjects with borderline hypertension (BHT) and 13 normotensive (NT) controls. To determine the role of sympathetic activation in the regulation of responsiveness, we measured local sympathetic activity in the forearm by a radioisotope dilution technique. Vasodilation in response to isoproterenol, measured either as changes in forearm blood flow or forearm vascular resistance, was impaired in the BHT group so that flow at the highest dose of isoproterenol (400 ng/min) increased less (15.2 +/- 1.5 ml/100 ml per min) than in the NT group (24.4 +/- 2.4 ml/100 ml per minute) (P < 0.001). Although, systemic norepinephrine spillover was significantly greater in BHT, the difference in blood flow response to isoproterenol was not accounted for by increased local sympathetic activity since forearm norepinephrine spillover at baseline (BHT 1.0 +/- 0.4 ng/min vs. NT 0.64 +/- 0.13 ng/min) and after the administration of isoproterenol 60 ng/min (BHT 5.2 +/- 1.4 ng/min vs. NT 6.0 +/- 1.5 ng/min) and 400 ng/min (BHT 13.5 +/- 2.9 ng/min vs. NT 16.5 +/- 2.7 ng/min) did not differ between the two groups. We therefore conclude that vasodilation in response to isoproterenol is impaired in subjects with BHT and that this impairment is not explained by locally increased basal, or stimulated, sympathetic activity.

Adult↗
PubMed1995

Directions in HIV/AIDS research. A Minnesota perspective.

Clinical studies involving HIV therapeutics are becoming ever more challenging because of the changing epidemiology of HIV infection, the rapid evolution of standard clinical practice, and a more difficult economic environment for research. Recent studies relating to HIV pathogenesis have provided novel insights into the interactions between HIV, the immune system, and antiretroviral therapies. Current dogma now suggests that the interaction of HIV and the immune system is an incredibly dynamic process. HIV is an intimidating pathogen capable of replicating quickly and mutating very rapidly in response to antiretroviral therapy. An important question being studied by Minnesota-based investigators is how well plasma analysis reflects HIV-immune system interactions in the lymphoid tissue where most virus and CD4+ (T-helper) cells are located. Most of the HIV clinical studies in Minnesota are conducted under the auspices of the AIDS Clinical Trials Group (ACTG) or the AIDS Research Consortium of the Twin Cities (ARCTiC). Much expertise is available in Minnesota addressing a wide range of topics, from epidemiology, to basic virology, to prevention. To optimize patient access to clinical studies, we recommend that physicians discuss available clinical studies with an HIV investigator soon after first seeing a new HIV-infected patient.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Large bowel cancer following gastric surgery for benign disease: a cohort study.

Early studies suggested that gastric surgery for benign ulcer disease was associated with a subsequent increase in the risk of large bowel cancer. Dietary fats, altered bacterial flora, and secondary bile acids are considered to play a major role in the disease etiology. Gastric surgery is known to alter bile salt metabolism as well as bacterial flora in the colon. This cohort study was designed to investigate the risk of large bowel cancer following gastric surgery for benign ulcer disease and to identify potential patient and treatment characteristics that may be associated with this risk. A cohort of 15,983 males was selected from Department of Veterans Affairs hospital admissions in 1970 and 1971. The exposed group (n = 7,609) included all males treated with gastric surgery (resection or vagotomy and drainage) for benign ulcer disease. The unexposed group (n = 8,374) was a random sample of all other male patients from the same time period and database. All subjects were followed through 1989 to identify vital status and cause of death. Deaths were identifiable by computerized linkage of the subjects' social security numbers with the Department of Veterans Affairs Beneficiary Identification Record Locator System and the National Death Index. The cause of death was documented by two certified nosologists from the death certificates of 99% of the deceased patients. Statistical analyses included estimations of risk based on standardized mortality ratios and standardized risk ratios. In this selected cohort, no increase in large bowel cancer risk was detected (risk ratio = 0.81, 95% confidence interval 0.62-1.05). The type of surgical procedure, ulcer diagnosis, age at the time of surgery, and length of follow-up did not alter the risk estimates. Unlike the previously identified increase in gastric cancer risk following ulcer surgery, no elevation in the risk of large bowel cancer following such surgery was detected in this study. Factors that may alter gastric surgery sequelae and resultant site-specific cancer risks deserve further investigations.

Adult↗
PubMed1994

Treatment of fecal impaction with pulsed irrigation enhanced evacuation.

PURPOSE: A new method of treating fecal impaction is described, selecting patients that would otherwise have required operative disimpaction. METHOD: Using the pulsed irrigation enhanced evacuation device, individuals were selected for treatment based on evidence of massive fecal impaction on physical examination or abdominal x-ray. RESULTS: Fourteen individuals were treated for fecal impaction. The patients ranged in age from 13 to 86 years. Only one patient required intravenous sedation, an elderly patient with Alzheimer's disease. The treatment was successful in each case, although repeated treatment was often necessary. No morbidity arose from the treatment. By the midpoint in our study, because of the success of this treatment, no patient required hospitalization for impaction. CONCLUSION: Pulsed irrigation enhanced evacuation has been in our experience a simple, quick, and effective treatment for severe fecal impaction.

Adolescent↗