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Biomedical subjects

J D Elashoff

Publications and source records attributed to J D Elashoff.

At least 37 records · Page 2Linked to original sources
PubMed1992

Noninvasive determinations of the anaerobic threshold. Reliability and validity in patients with COPD.

We compared the intraobserver and interobserver agreement of blood (BGT) and gas exchange (GET) methods for determination of the anaerobic threshold (AT) in patients with COPD. In addition, we determined the sensitivity and specificity of the gas exchange methods for determination of the AT. Two noninvasive methods, the V-slope (VS) and the ventilatory equivalents method (VEM) were compared with two blood sampling methods, the log standard HCO3 (SB) vs log VO2 (SBT) and base excess (BE) vs VO2 (BET). Twenty-nine patients with COPD (FEV1 < 60%) performed incremental exercise tests to exhaustion while breath-by-breath gas exchange measurements were made. Blood samples were drawn at the end of each minute for SB and BE. Two trained observers determined the VO2 at the threshold for each of the four indices on two separate occasions two weeks apart. Our results demonstrated the following: only modest interobserver and intraobserver agreement was noted by Spearman rank correlations; the VEM was as sensitive as the VS in COPD patients; and the presence of a true metabolic acidosis was not reliably predicted by GET methods. Moreover, although the blood methods accurately identified the presence of metabolic acidosis, there was disagreement on the actual point of the BGT. We conclude that gas exchange indices were not helpful for the determination of metabolic acidosis in patients with COPD.

Adult↗
PubMed1991

Effects of anabolic-androgenic steroids on muscular strength.

OBJECTIVE: To assess the effects of anabolic-androgenic steroids on human muscle strength. DATA SOURCES: A MEDLINE search for the period from January 1966 to April 1990, supplemented by manual searches of previous reviews, produced 30 studies in which subjects received more than one dose of the study steroid and in which changes in muscular strength were measured. STUDY SELECTION: Of the 30 studies, 14 were not included in the detailed data summary because they did not use a placebo control, did not randomize subjects to groups, or did not make objective strength measurements, or because percent change in strength data could not be abstracted. DATA EXTRACTION: Details of study design, reporting of results, and the adequacy and correctness of statistical methods were tabulated. Percent improvement in strength for the largest muscle group studied was computed, using the difference between results for the placebo and for the steroid-treated groups. DATA SYNTHESIS: Previously trained athletes show slightly greater improvements in strength in the anabolic-androgenic steroid-treated group than in the placebo group, with a median difference of 5% across the nine studies (range, 1.2% to 18.7%). A meta-analysis of the three studies with enough information to compute effect size showed a mean difference of 1.0 standard deviations (95% CI, 0.49 to 1.5). However, the poor overall quality of the studies in terms of design, sample size, and analysis; the lack of a dose-response effect across the narrow range of dosages tested; and the tendency for differences to be smaller in the larger studies throw these results into question. No evidence was found to support enhanced muscle strength with steroid use in eight studies in untrained normal volunteers. CONCLUSIONS: Anabolic steroids may slightly enhance muscle strength in previously trained athletes. No firm conclusion is possible concerning the efficacy of anabolic steroids in enhancing overall athletic performance. Results for the low steroid dosages studied in the published reports cannot be generalized to steroid-using athletes taking megadose regimens.

Anabolic Agents↗
PubMed1991

Power and validity of methods to identify variability genes.

A variability gene model [Magnus et al., Clin Genet 19:67-70, 1981] hypothesizes that environmental influences on the expression of additive genes for a quantitative trait such as cholesterol are under the control of alleles at a separate nonadditive locus. They suggest identifying such genes using an analysis of variance to compare absolute intrapair monozygotic twin trait differences between the genotypes of the postulated variability locus. However, quantitative traits such as cholesterol often have skewed distributions with a long right tail; what are the effects of such non-normality on the procedure suggested by Magnus et al. [1981]? We show that their method is a special case of the Levene tests, robust tests for variability differences. We introduce a statistical model representing sources of variability in twin pair differences and demonstrate with simulation studies that although the Levene tests have robust Type I error, power is enhanced when nonnormal data are transformed before analysis, and the apparent presence and degree of variability differences are dependent on the scale of analysis. These findings indicate the importance of appropriate transformation of the trait before analysis. Analysis of a well-characterized twin data set illustrates these conclusions.

Aged↗
PubMed1991

Precise gene dosage determination by polymerase chain reaction: theory, methodology, and statistical approach.

We developed a general method of quantifying relative copy numbers of specific DNA sequences based on the theoretical accumulation of polymerase chain reaction (PCR) products when two DNA sequences are amplified together (co-amplified). Our experiments illustrate the development and theory of the technique. The precision of our estimates is demonstrated by statistical confidence intervals. Tests for effects introduced by experimental factors were performed. The precision of the technique was established by examining the relative gene dosage of the X-linked dystrophin gene in human genomic DNAs from a male, a normal female, a 47,XXX female, and a 48,XXXX cell line. The sensitivity was sufficient to distinguish three copies of the gene from four copies; equivalent to detecting loss of heterozygosity in half the cells of a tumour. Confidence intervals allowed us to reject the hypothesis that there was no difference between DNA samples. Four sample pairs would be required to demonstrate relative gene dosage ratios of 2.0 to 1.0; eight sample pairs would be required to demonstrate a relative gene dosage ratio of 1.3 to 1.0. This method should be useful in detecting gene amplification and deletion in a variety of situations.

Base Sequence↗
PubMed1989

A randomized study of maintenance therapy with ranitidine to prevent the recurrence of duodenal ulcer.

After an active duodenal ulcer has healed in response to medical therapy, the rate of recurrence during the subsequent year is relatively high. We therefore enrolled 140 patients with healed duodenal ulcers in a two-year randomized, double-blind trial comparing maintenance therapy (ranitidine, 150 mg nightly) with placebo for the prevention of recurrent duodenal ulceration. We performed endoscopy annually and when symptoms suggested the recurrence of ulcers. Verified recurrent ulcers in either group were treated for four or eight weeks with open-label ranitidine (150 mg twice a day). Patients whose ulcers healed within eight weeks resumed randomized treatment. Prophylactic therapy with ranitidine reduced the rate of ulcer relapses from 63 percent in the placebo group to 37 percent in the ranitidine group (P less than 0.05). Treatment with ranitidine extended the median ulcer-free interval from one to two years (P less than 0.05). The first recurrences of ulcer were asymptomatic in half the ranitidine group and in a quarter of the placebo group. Prophylactic therapy with ranitidine also reduced the frequency of recurrent ulcers that were unhealed by eight weeks, that were bleeding, that were in the stomach, or that were the second recurrent ulcer within six months, from 43 percent in the placebo group to 21 percent. Patients who drank alcohol, smoked, had a history of ulcer disease, or had duodenal scarring or erosion at the time of entry into the study were at the greatest risk for recurrence and benefited the most from prophylactic ranitidine. We conclude that prophylactic treatment with ranitidine is effective in preventing the recurrence of duodenal ulceration.

Clinical Trials as Topic↗
PubMed1988

Designing a clinical trial to demonstrate prevention of ulcer recurrence: modelling simulation approaches.

We describe a Markov chain model for the ulcer recurrence and healing process, review the available literature to obtain appropriate parameter estimates, and use this model to evaluate alternative clinical trial designs. We focus on designs aimed at supporting recurrence prevention claims for a duodenal ulcer maintenance treatment. Our results show that a trial with endoscopies scheduled only at four month intervals is inadequate to support recurrence prevention claims; discrimination between the null and alternative hypotheses is impossible because of the size and direction of expected biases in observed recurrences. Our results suggest that endoscopy intervals should be at most four weeks to establish a claim of ulcer prevention.

Clinical Trials as Topic↗
PubMed1986

Carbamylcholine, but not somatostatin or neurotensin, stimulates prostaglandin E2 release from the isolated perfused rat stomach.

Prostaglandin E2 release by carbamylcholine (10(-6) M), somatostatin (10(-10)-10(-8) M) and neurotensin (10(-10) - 10(-8) M) has been evaluated in the isolated perfused rat stomach. Carbamylcholine significantly stimulated gastric PGE2 release and increased the perfusion pressure, whereas somatostatin and neurotensin had no effect. Combination of carbamylcholine with somatostatin or neurotensin produced no increase over that found with carbamylcholine alone. The relationship between perfusion-pressure and PGE2 release was not causal. The present findings do not support a role for prostaglandins in the mechanism of somatostatin or neurotensin action in the stomach.

Animals↗
PubMed1986

Sex and smoking differences in duodenal ulcer mortality.

Data from the US Census Bureau and the National Center for Health Statistics suggest that differences in male and female smoking habits between 1920 and 1980 may have contributed to changes in duodenal ulcer mortality sex ratios. An attributable risk analysis suggests that between 43 per cent and 63 per cent of duodenal ulcer mortality for males results from smoking; the comparable figures for females being between 25 per cent and 50 per cent.

Aged↗
PubMed1985

Sucralfate therapy in patients with symptoms of alkaline reflux gastritis. A randomized, double-blind study.

The effects of sucralfate (6 g per day) and placebo on symptoms, endoscopic findings, and gastric mucosal histology were compared in 23 patients with symptoms of alkaline reflux gastritis who had undergone Billroth I, Billroth II, or vagotomy and pyloroplasty. Patients were randomly assigned to receive sucralfate (n = 11) or placebo (n = 12) for six weeks. Then all received six weeks of open sucralfate therapy before treatment codes were revealed. Twelve gastric biopsy specimens were obtained before patients began treatment and at six and 12 weeks. The two groups did not differ significantly with respect to symptom scores or endoscopic findings at baseline, after the double-blind phase, or after open sucralfate treatment. There were also no significant differences between the treatment groups with respect to epithelial cell scores and conventional gastritis scores. However, after the six-week, double-blind phase, the inflammatory cell score of the sucralfate-treated group was significantly lower (p less than 0.05) than that of the placebo-treated group (1.3 +/- 0.3 versus 1.9 +/- 0.4). After six weeks of open sucralfate treatment, patients who had initially received placebo had a significant reduction (1.4 +/- 0.3 versus 1.9 +/- 0.4) in their inflammatory cell score. Sucralfate lowered the inflammatory cell scores of patients with symptoms of alkaline reflux gastritis. This reduction, however, was not associated with an improvement in symptoms.

Aluminum↗
PubMed1985

Prostaglandins may not mediate inhibition of gastric acid secretion by somatostatin in the rat.

The role of prostaglandins as mediators of the inhibitory effect of somatostatin on gastric acid secretion has been evaluated in conscious and anesthetized rats. The effect of somatostatin on bethanechol-stimulated gastric acid secretion was determined with or without indomethacin pretreatment. Prostaglandin synthesis inhibition (less than 90%) by indomethacin was verified with PGE2-generation assay on gastric mucosal tissue. In both conscious and anesthetized rats somatostatin significantly inhibited the stimulated acid output in the control and indomethacin pretreated groups. The present findings do not support a role for prostaglandins in the inhibition of gastric acid secretion by somatostatin in the rat.

Anesthesia↗
PubMed1985

Sex differences in peptic ulcer disease.

As recently as 1968, twice as many men as women had peptic ulcer disease in the United States. To determine the current pattern of ulcer disease frequency in men and women, we examined data from the National Center for Health Statistics. These data show that the male predominance in peptic ulcer disease has changed. The male to female ratio is now 1.0 for self-reported period prevalence, and 1.3 for hospitalization and mortality. Ulcer prevalence rates for women have increased whereas rates for men have decreased. For hospitalizations and mortality, the changing sex ratios are primarily due to a more rapid decrease in duodenal ulcer rates for men than for women. Gastric ulcer hospitalizations for women have shown a marked increase for those greater than 65 yr old.

Adult↗
PubMed1985

Somatostatin inhibits gastric acid secretion after gastric mucosal prostaglandin synthesis inhibition by indomethacin in man.

The inhibitory effect of indomethacin, 200 + 200 mg administered per os over 24 hours, on the prostaglandin E2 generative capacity of gastric mucosal tissue was determined in healthy male volunteers. The effect of prostaglandin synthesis inhibition on somatostatin induced suppression of food-stimulated acid secretion was tested. Peptone meal stimulated acid secretion was quantified in five healthy volunteers by intragastric titration with and without indomethacin pretreatment. Somatostatin doses of 200, 400, and 800 pmol/kg/h each significantly inhibited the peptone stimulated acid output. Indomethacin treatment, resulting in 90% inhibition of prostaglandin E2 synthesis, did not affect glucose- or peptone-stimulated acid output or modify the inhibitory action of somatostatin. Clinically, acid inhibition by somatostatin has been used to treat bleeding peptic ulcers. Ulcer haemorrhage may be preceded by an excessive use of drugs that inhibit prostaglandin synthesis such as aspirin or other non-steroidal anti-inflammatory agents. Recent observations in the rat indicate that prostaglandins mediate the inhibitory action of somatostatin on gastric acid secretion. The present results suggest that prostaglandins are not required for inhibition of gastric acid secretion by somatostatin in man.

Adult↗
PubMed1985

Cholecystokinin potently releases somatostatin from canine fundic mucosal cells in short-term culture.

Previous studies indicated that gastrin-17 (G-17) and the octapeptide of colecystokinin (CCK-8) were equally potent in their interaction with receptors for 125I-[Leu15]G-17 on isolated canine parietal cells. These findings were inconsistent with the poor efficacy of CCK-8 compared with G-17 as stimuli of acid secretion in dogs. The present study examines the effects of G-17 and CCK-8 on the release of somatostatinlike immunoreactivity (SLI) from a fraction of small canine fundic mucosal cells separated by elutriation and placed in short-term culture. CCK-8 was considerably more potent and more effective than G-17 as a stimulant of SLI release from these cultured cells. CCK-8 was slightly more potent than G-17 in inhibiting 125I-[Leu15]G-17 binding to receptors in the same elutriator fraction. Our present findings support the hypothesis that the poor efficacy of CCK compared with G-17 as a stimulant of acid secretion may reflect pronounced activation of somatostatin-mediated acid-inhibitory mechanisms by CCK-8. The present data indicate that differences in affinity between CCK-8 and G-17 at the 125I[Leu15]G-17 receptor probably do not account for the greater efficacy of CCK-8; the receptor or cell activation mechanisms underlying this greater efficacy of CCK-8 on SLI release remain to be elucidated.

Animals↗
PubMed1984

Gastrin receptors on nonparietal cells isolated from canine fundic mucosa.

The cellular localization of gastrin receptors was studied using dispersed canine fundic mucosal cells. In previous studies 125I-[Leu15]gastrin-17 (125I-[Leu15]G-17) binding was found to parietal cells, but gastrin binding was also found in the small-cell elutriator fractions (SCEF). In the present study a density gradient was used to further separate the SCEF and the distribution of 125I-[Leu15]G-17 binding correlated with cellular content of somatostatinlike immunoreactivity (SLI). In contrast, 125I-[Leu15]G-17 binding was inversely correlated with the histamine content of the fractions. 125I-[Leu15]G-17 binding to the SCEF was rapid and reversible. Total binding was 0.29 +/- 0.02 fmol/10(6) cells (mean +/- SE, n = 15); excess unlabeled G-17 inhibited 85% of this binding. G-17, [Leu15]G-17, and 127I-[Leu15]G-17 were equipotent in inhibiting 125I-[Leu15]G-17 binding and stimulating SLI secretion from the SCEF placed in short-term culture, whereas 127I-G-17 had a low potency for both effects. Proglumide, known to inhibit cholecystokinin binding to pancreatic acinar cell receptors, also inhibited 125I-[Leu15]G-17 binding to the SCEF and inhibited G-17 stimulated SLI release. We conclude that in the canine fundic mucosa gastrin interacts with receptor sites on parietal cells and somatostatin cells but probably not on fundic mucosal histamine-containing cells. These receptor sites for gastrin may activate counterbalancing mechanisms regulating the secretion of acid.

Animals↗
PubMed1984

Gastrin receptors on isolated canine parietal cells.

The receptors in the fundic mucosa that mediate gastrin stimulation of acid secretion have been studied. Synthetic human gastrin-17-I (G17) with a leucine substitution in the 15th position ( [Leu15]-G17) was iodinated by chloramine T; high saturable binding was found to enzyme-dispersed canine fundic mucosal cells. 127I-[Leu15]-G17, but not 127I-G17, retained binding potency and biological activity comparable with uniodinated G17. Fundic mucosal cells were separated by size by using an elutriator rotor, and specific 125I-[Leu-15]-G17 binding in the larger cell fractions was highly correlated with the distribution of parietal cells. There was, however, specific gastrin binding in the small cell fractions, not accounted for by parietal cells. Using sequential elutriation and stepwise density gradients, highly enriched parietal and chief cell fractions were prepared; 125I-[Leu15]-G17 binding correlated positively with the parietal cell (r = 0.98) and negatively with chief cell content (r = -0.96). In fractions enriched to 45-65% parietal cells, specific 125I-[Leu15]-G17 binding was rapid, reaching a steady state at 37 degrees C within 30 min. Dissociation was also rapid, with the rate similar after 100-fold dilution or dilution plus excess pentagastrin. At a tracer concentration from 10 to 30 pM, saturable binding was 7.8 +/- 0.8% per 10(6) cells (mean +/- SE) and binding in the presence of excess pentagastrin accounted for 11% of total binding. G17 and carboxyl terminal octapeptide of cholecystokinin (26-33) were equipotent in displacing tracer binding and in stimulating parietal cell function ( [14C]aminopyrine accumulation), whereas the tetrapeptide of gastrin (14-17) had a much lower potency. Proglumide inhibited gastrin binding and selectively inhibited gastrin stimulation of parietal cell function. Canine parietal cells have specific receptors for gastrin that mediate stimulation of parietal cell function. Gastrin receptors were undetectable on chief cells, and yet present on another smaller mucosal cell(s).

Aminopyrine↗
PubMed1984

Primary gastrin cell hyperplasia. Report of five cases and a review of the literature.

Primary gastrin cell hyperfunction of the gastric antrum as a clinical syndrome consists of basal hypergastrinemia, an exaggerated gastrin response to feeding, the absence of any ectopic source of gastrin secretion, and peptic ulcer disease. The number of G-cells were quantitated in the gastric antrum of five patients with clinically diagnosed primary G-cell hyperfunction, and the results were compared to controls with a variety of gastric diseases. Patients with the clinical diagnosis of primary G-cell hyperfunction had a significantly increased number of antral G-cells (p less than 0.05). The clinical syndrome of primary G-cell hyperplasia appears to be associated with hyperplasia of G-cells rather than with the hypersecretion of gastrin by a normal number of G-cells.

Adult↗
PubMed1984

Two-stage clinical trial stopping rules.

Two-stage stopping rules for clinical trials are considered. The nominal significance level needed for the second-stage test, for any choice of first-stage significance level, is derived for rules with overall significance levels of .01 and .05 and for studies with either half or two-thirds of the patients analyzed in the first stage. A graphical demonstration is given of the inherent tradeoff between power and expected sample size (or probability of early termination). A specific rule, intermediate to those advocated by Pocock (1977, Biometrika 64, 191-199) and O'Brien and Fleming (1979, Biometrics 5, 549-556), is recommended.

Biometry↗