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Biomedical subjects

H Petersen

Publications and source records attributed to H Petersen.

At least 91 records · Page 5Linked to original sources
PubMed1991

Combined single subject trials.

Randomized controlled single subject trials are designed as multiple crossovers between the treatments to be compared. Results from such independent trials may be combined and integrated for the purpose of extending the conclusions beyond the single subject. Unlike the conventional crossover group trial, the primary goal of the combined single subject study is not to demonstrate an overall clinical benefit of a drug, but to indicate the features typical for drug responders. The external validity of combined single subject trials depends on the same prerequisites as are employed in group trials: strict entry criteria, uniform treatment procedures, consensus targets for outcome measures, and acceptable statistical tests. In clinical research the main role of combined single subject trials should be to elucidate new insight and generate hypotheses that could optimize the design of subsequent group trials.

Data Interpretation, Statistical↗
PubMed1990

Statistical aspects of controlled single subject trials.

Randomized controlled trials in groups and single subjects differ in several statistical aspects. In group trials the experimental unit is a randomly selected subject from a predefined population and this subject is randomly assigned to a treatment. Outcome is confined to average effects which can be generalized to the specific population, but which do not necessarily apply to individual persons. In single subject trials the experimental unit is a treatment period and each treatment period is randomly allocated in a multiple cross-over sequence of periods. The single subject is only representative of itself, but similar responses in corresponding single subject trials may justify careful extrapolation of the results. Single subject trials have a high risk of Type II errors. However, the randomization procedure chosen and the type of statistical test applied may enhance the statistical power of such trials. Internal validity depends on modeling the trial design to the clinical features, drug properties and statistical requirements, while reliability is determined by the reproducibility of the trial response.

Humans↗
PubMed1990

Dependence of antigen expression on functional state of beta-cells.

Antigen expression corresponding to anti-islet cell surface monoclonal antibodies IC2 and A2B5 was studied. IC2 is a rat-rat hybridoma autoantibody produced from the BB rat; among islet cells, IC2 is beta-cell specific. A2B5 is an anti-ganglioside antibody described as labeling beta-cells. Islets of Langerhans from Lewis rats were isolated and cultured for 18 h in RPMI-1640 with five different glucose concentrations (2.2, 3.3, 5.5, 11.1, and 18.3 mM). In some experiments, islets were precultured for 2 or 3 days. After isolation of islet cells and antibody labeling, the percent of IC2+ beta-cells in the different groups increased from 33.3, 34.5, 40.9, and 57.2 to 58.6% (P less than 10(-6). For A2B5, the percent of labeled islet cells increased from 37.4, 41.8, 46.7, and 53.8 to 56.2% (P less than 10(-4). Thus, increasing glucose concentration leading to higher beta-cell activity implies an increase in antigen expression. Neither A2B5 nor IC2 reacts with insulin, as shown by absorption experiments and immune electron microscopy of binding sites. Electron microscopy of IC2-gold-labeled islet cells substantiated the beta-cell specificity of IC2. In conclusion, expression of the corresponding antigens to IC2 and A2B5 depends on the functional state of the beta-cells; because this has been shown to be an important factor in the development of insulin-dependent diabetes, our findings may be of potential pathogenetic interest.

Animals↗
PubMed1990

The predictive value of history in dyspepsia.

Symptomatic patients referred to an open-access upper gastrointestinal endoscopy completed a detailed, self-administered questionnaire aimed at assessing the predictive value of history in dyspepsia. Nine hundred and thirty patients were suitable for analysis. Of these, 29% were found to have organic dyspepsia. A substantial overlap of symptoms and demographic data was found among the various endoscopic diagnoses. Discriminating variables were identified by stepwise logistic regression analysis and included in predictive score models. Pain relieved by antacids, age above 40 years, previous peptic ulcer disease, male sex, symptoms provoked by berries, and night pain relieved by antacids and food were found to predict organic dyspepsia with a sensitivity and specificity of approximately 70%, when applied on the observed material. Similar probabilities were found for score models of peptic ulcer and esophagitis. In general, the low prevalence of organic diseases resulted in low positive and high negative predictive values. Accordingly, the main impact of the predictive models may be to reduce the number of negative endoscopies rather than to predict a precise diagnosis. Independent of disease category and age, 41% of the subjects expressed a fear of malignancy, emphasizing the value of reassurance from a negative endoscopy.

Adult↗
PubMed1990

The benefit of colonoscopy.

In a prospective study involving 833 consecutive outpatient and open-access colonoscopies, attempts were made to characterize the benefit of colonoscopy in terms of both predicted and unpredicted findings and therapeutic procedures. The endoscopist therefore predicted the endoscopic findings before the endoscopy. The results were compared for the different indications for colonoscopy. The overall agreement between the predictions and the colonoscopic findings was 61%. Clinically significant abnormalities were found in about half the examinations. The most frequent abnormal findings were benign polyps (24%), inflammatory bowel disease (17%), and malignancy (5%). In about half the patients with a malignancy the indication for colonoscopy was rectal bleeding, and half of the malignancies were not predicted. The greatest benefit of colonoscopy was found in patients referred because of overt rectal bleeding or occult faecal blood, and abnormal barium enema or endoscopy findings. The importance of complete colonoscopy in connection with operation for colorectal carcinoma is emphasized.

Colonic Polyps↗
PubMed1990

Influence of analytical quality and preanalytical variations on measurements of cholesterol in screening programmes.

In screening programmes one should distinguish between the traditional bimodal distributions of results and a unimodal distribution as the basis for interpretation. A model for evaluation of the effects of biological within-subject and preanalytical variation as well as analytical variation is described. It is concluded that bias from blood sampling and analytical performance influences the outcome of screening programs significantly. At least three blood specimens are needed for estimating the homeostatic set point of cholesterol in individuals.

Chemistry, Clinical↗
PubMed1990

Effect of pancreatic enzymes in non-ulcer dyspepsia. A pilot study.

The symptomatic effect of pancreatic enzymes was examined in 37 patients with non-ulcer dyspepsia (NUD) recruited from general practice by means of a 24-day multicrossover model (MCOM) including six treatment periods and five regular interchanges between pancreatic enzymes and placebo. The evaluation was based on a comparison of the enzyme- and placebo-associated symptoms and on the number of times pancreatic enzymes were associated with less symptoms than the preceding or following placebo period in individual patients. No evidence of a short-term effect of pancreatic enzymes in NUD was found.

Adult↗
PubMed1989

Differential effects of hyperoxia and hydrogen peroxide on DNA damage, polyadenosine diphosphate-ribose polymerase activity, and nicotinamide adenine dinucleotide and adenosine triphosphate contents in cultured endothelial cells and fibroblasts.

The effects of oxidative stress on DNA damage and associated reactions, increased polyadenosine diphosphate-ribose polymerase (PARP) activity and decreased nicotinamide adenine dinucleotide (NAD) and adenosine triphosphate (ATP) contents, have been tested in primary cultures of porcine aortic endothelial cells. The cells were treated with 50-500 microM H2O2 for 20 min or 100 microM paraquat for 3 days or were exposed to 95% O2 for 2 and 5 days. The administration of 250-500 microM H2O2 resulted in a marked increase in PARP activity and a profound depletion of ATP and NAD. Although hyperoxia had no effect on PARP activity and reduced only slightly the ATP and NAD stores, it markedly reduced the ability of endothelial cells to increase PARP activity upon exposure to DNase. Paraquat had a similar effect. Human dermal fibroblasts were also exposed to 50-500 microM H2O2 for 20 min or 95% O2 for 5 days. Their response to H2O2 differed from that of endothelial cells by their ability to maintain the ATP content at a normal level. Fibroblasts were also insensitive to the effect of hyperoxia. These results suggest that the oxidant-related DNA damage is a function of the type of oxidative stress used and may be cell-specific.

Adenosine Triphosphate↗
PubMed1989

Histamine and gastrin in plasma of patients with upper gastrointestinal diseases.

The etiology of peptic ulcer disease is completely unknown. However, gastric acid secretion plays an important role in the pathogenesis of the disease. Acetylcholine, gastrin and histamine are recognized as the main stimulators of the acid secretion. Extensive studies on blood gastrin have not incriminated this hormone in the pathogenesis of the disease. The present study was done to evaluate the role of circulating histamine in peptic ulcer disease using a sensitive and specific radioimmunoassay method. Since gastrin at least in some species seems to exert its stimulatory effect by releasing histamine, serum gastrin was also determined. There was no significant difference in plasma histamine between patients with duodenal or gastric ulcer, nonulcer dyspepsia or ulcer patients after proximal gastric vagotomy. However, patients taking a histamine-2 blocker (cimetidine or ranitidine) had significantly higher plasma histamine than those not taking these drugs. This effect was not due to interference in the histamine assay. There was no correlation between plasma histamine and plasma gastrin. Plasma gastrin was significantly increased in patients having been operated on with a proximal gastric vagotomy. In conclusion, plasma histamine is similar in patients with different upper gastrointestinal disorders. However, histamine-2 blockers may increase plasma histamine.

Blood Specimen Collection↗
PubMed1989

The effects of graded doses of a cholecystokinin-like peptide with and without secretin on pancreatic growth and synthesis of RNA and polyamines in rats.

The dose dependence of a cholecystokinin-like peptide (CCK-LP) on the trophic response in the rat pancreas was studied. Graded doses of Thr28Nle31CCK25-33 (0.02, 0.1, 0.5, 2.5, and 12.5 micrograms/kg/h) or saline were given as a continuous intravenous infusion to conscious and fed rats for 8 and 48 h. Secretin (5.0 micrograms/h) was given alone or combined with the three highest doses of CCK-LP for 48 h. CCK-LP showed a dose-dependent stimulating effect on pancreatic growth and synthesis of RNA and polyamines. The threshold dose ranged from 0.02 to 0.5 micrograms/kg/h and was lowest for stimulation of ornithine decarboxylase (ODC). The maximal effects on protein, RNA, and DNA contents were achieved with 2.5 micrograms/kg/h. These same variables markedly decreased with 12.5 micrograms/kg/h, whereas marked further increases were found for the activities of RNA polymerase, DNA polymerase, and thymidine kinase. This same dose of CCK-LP caused after 8 h of treatment a marked and transient increase in pancreatic weight, activity of ODC, and concentration of putrescine. When secretin was added to 0.5 and 2.5 micrograms/kg/h of CCK-LP, no additional effect (except for ODC) was found. When secretin was added to the highest dose of CCK-LP, the decreased contents of protein and RNA were significantly increased, and the markedly increased activities of RNA- and DNA-synthesizing enzymes were significantly decreased. The present study shows a clear dose-response relationship for the trophic effect of CCK-LP on the rat pancreas and indicates that the growth effect of a supramaximal dose includes components of regeneration secondary to damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Short- and long-term effects of secretin and a cholecystokinin-like peptide on pancreatic growth and synthesis of RNA and polyamines.

Little is known about the cellular mechanisms responsible for the trophic effects of cholecystokinin (CCK) and secretin on the rat pancreas, and controversy exists with regard to the interaction between these two peptides. In the present study attempts were made to elucidate the time course of events leading to pancreatic growth and to clarify the interaction between the peptides when given as continuous, long-term intravenous infusions to rats. A cholecystokinin-like peptide (CCK-LP) and secretin were given as a continuous intravenous infusion to conscious and unrestrained animals with free access to food and water for 0.5, 1, 2, 4, 6, 8, 12, 24, 48, and 96 h. The pancreas was quickly removed and analyzed for variables indicating synthesis and accumulation of DNA, RNA, and polyamines. CCK-LP increased the activity of RNA polymerase already after 1 h, whereas an increase in the activity of ornithine decarboxylase (ODC) and the level of putrescine was seen at 4 h. Spermidine was increased after 12 h. The activities of DNA polymerase and thymidine kinase were increased at 12 and 24 h, respectively, whereas the total contents of DNA and RNA were first increased at 48 h. Secretin alone showed a marked but short-lived effect on polyamine synthesis and a weak effect on the variables indicating protein synthesis and growth. When the two peptides were given together, a large but transient potentiation of ODC activity was observed, whereas no interaction was seen on polyamines, RNA synthesis, or pancreatic growth. The present study confirms the trophic effects of CCK and secretin on the rat pancreas but fails to confirm an interaction between the two peptides on growth. Both peptides stimulate polyamine synthesis, and ODC appears to be an early and sensitive indication of their trophic effect. The initiation of RNA synthesis appears to be independent of the ODC activity.

Animals↗
PubMed1989

Inhibition of polyamine synthesis by alpha-difluoromethylornithine and its effects on pancreatic secretion and growth in the rat.

The role played by the polyamines in mediating the pancreatic growth and secretory responses to hormonal stimulation is uncertain. The effect of an inhibitor of ornithine decarboxylase (ODC), alpha-difluoromethylornithine (DFMO), on rat pancreatic protein secretion and synthesis and on growth in response to hormonal stimulation was therefore studied. Anesthetized rats were given an intravenous injection of DFMO (50, 100, or 150 mg/kg), followed by a 7-h continuous infusion (15, 25, or 35 mg/kg/h, respectively). After a basal 1-h period an intravenous infusion of 2.5 micrograms/kg/h of the cholecystokinin-like peptide Thr28Nle31CCK25-33 (CCK-LP) was added and continued for 6 h. The control rats received CCK-LP only. The ODC activity in the pancreas was markedly reduced by DFMO, but DFMO did not affect pancreatic juice volume or protein output. In another series conscious rats were given a continuous intravenous infusion of 2.5 micrograms/kg/h of CCK-LP for 8, 24, and 48 h or 5.0 micrograms/kg/h of secretin for 8 and 48 h, with or without DFMO (100 mg/kg as an injection initially and thereafter 25 mg/kg/h). The ODC activity and putrescine concentration in the pancreas were significantly reduced by DFMO at 8 and 24 h but not at 48 h. DFMO also significantly reduced the activities of RNA polymerase, DNA polymerase, and thymidine kinase at 24 h, but not at 48 h. The present study thus indicates that polyamines play a role in the initiation of the growth response to hormonal stimulation but does not support a similar dependence for early pancreatic protein synthetic and secretory responses.

Animals↗
PubMed1988

Interaction between secretin and a cholecystokinin-like peptide on pancreatic protein secretion and synthesis in the rat.

The effects of secretin and a cholecystokinin-like peptide alone and in combination on pancreatic protein secretion and synthesis were examined in anesthetized rats. L-[75Se]selenomethionine was given as an i.v. shot (5 microCi) followed by a continuous infusion (1 microCi/h). Pancreatic juice was collected basally for 1 h and then during a 4-h i.v. infusion of 0.5, 2.5, and 12.5 micrograms/kg/h of Thr28Nle31CCK25-33 (CCK-LP) alone or combined with 5 micrograms/kg/h of secretin, as well as during an infusion of secretin alone. The protein-bound radioactivity in pancreatic juice was taken to indicate secretion of newly synthesized proteins. The free and protein-bound radioactivity remaining in the gland after 2 h of stimulation was also investigated. Secretin alone slightly increased both protein secretion and secretion of newly synthesized proteins. Considerably greater effects were found with CCK-LP. The two lowest doses behaved similarly, whereas the volume and protein responses to 12.5 micrograms/kg/h were significantly lower and associated with large amounts of free radioactivity in pancreatic juice, suggesting leakage and cell damage. The addition of secretin transiently potentiated protein discharge and secretion of newly synthesized proteins and permanently increased the amount of protein-bound radioactivity per milligram of protein in response to all doses of CCK-LP. Secretin markedly increased volume and reduced the amount of free radioactivity in pancreatic juice with the largest dose of CCK-LP. The peptides were not found to influence amino acid uptake or incorporation of radioactivity into tissue proteins. This study demonstrates an interaction between the effects of secretin and those of CCK-LP on pancreatic protein secretion and synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗