PubMed Health⌕ Search

Biomedical subjects

H Olson

Publications and source records attributed to H Olson.

15 recordsLinked to original sources
PubMed2000

Concordance of the toxicity of pharmaceuticals in humans and in animals.

This report summarizes the results of a multinational pharmaceutical company survey and the outcome of an International Life Sciences Institute (ILSI) Workshop (April 1999), which served to better understand concordance of the toxicity of pharmaceuticals observed in humans with that observed in experimental animals. The Workshop included representatives from academia, the multinational pharmaceutical industry, and international regulatory scientists. The main aim of this project was to examine the strengths and weaknesses of animal studies to predict human toxicity (HT). The database was developed from a survey which covered only those compounds where HTs were identified during clinical development of new pharmaceuticals, determining whether animal toxicity studies identified concordant target organ toxicities in humans. Data collected included codified compounds, therapeutic category, the HT organ system affected, and the species and duration of studies in which the corresponding HT was either first identified or not observed. This survey includes input from 12 pharmaceutical companies with data compiled from 150 compounds with 221 HT events reported. Multiple HTs were reported in 47 cases. The results showed the true positive HT concordance rate of 71% for rodent and nonrodent species, with nonrodents alone being predictive for 63% of HTs and rodents alone for 43%. The highest incidence of overall concordance was seen in hematological, gastrointestinal, and cardiovascular HTs, and the least was seen in cutaneous HT. Where animal models, in one or more species, identified concordant HT, 94% were first observed in studies of 1 month or less in duration. These survey results support the value of in vivo toxicology studies to predict for many significant HTs associated with pharmaceuticals and have helped to identify HT categories that may benefit from improved methods.

Animals↗
PubMed1998

The predictivity of the toxicity of pharmaceuticals in humans from animal data--an interim assessment.

This project was undertaken by the International Life Sciences Institute's Health and Environmental Sciences Institute (ILSI-HESI) to develop an improved understanding of the extent to which various types of human toxicities (HTs) manifested during clinical trials could be predicted from standard toxicology studies. A multi-company database of 131 pharmaceutical agents to-date was based on compounds with one or more demonstrated HTs identified during clinical development. These interim results support a true positive prediction rate of animal models for human toxicity of 69%, and also that study results from non-rodent (dog, primate) species have good potential to identify HTs from many therapeutic classes. The continuing assessment of a larger database may have impact on the identification of new toxicology methodologies, and may lead to optimization of non-clinical study designs and improved assessments.

Animals↗
PubMed1993

Reduction of animal use with improved procedure for acute tolerance assessment.

A retrospective evaluation of previously conducted acute tolerance tests in rats and mice, following oral and intravenous routes of administration, and a review of the literature indicated that a minimum of three animals per group was adequate to characterize acute tolerance. Limited exploratory testing, using six compounds for which classical LD50 tests had been performed previously, indicated that fewer numbers of rats gave comparable results. A method is proposed by which the acute tolerance of a compound may be adequately characterized in both sexes using approximately 30 animals instead of the 70 to 100 used in the classical LD50 test. The objective of the testing procedure is identification of the maximum nonlethal dose or the minimum lethal dose, rather than determination of the LD50.

Administration, Oral↗
PubMed1992

Computer probability estimates of angiographic coronary artery disease: transportability and comparison with cardiologists' estimates.

A computer algorithm for estimating probabilities of any significant coronary obstruction and triple vessel/left main obstructions was derived, validated, and compared with the assessments of cardiac clinician angiographers. The algorithm performed at least as well as the clinicians when the latter knew the identity of the patients whose angiograms they had decided to perform. The clinicians were more accurate when they did not know the identity of the subjects but worked from tabulated objective data. Referral and value induced bias may affect physician judgment in assessing disease probability. Application of computer aids or consultation with cardiologists not directly involved with patient management may assist in more rational assessments and decision making.

Adult↗
PubMed1991

Effects of long term 2% fish oil supplements on tissue fatty acids, phospholipids, cholesterol, and arterial histology in Japanese quail (Coturnix coturnix japonica).

The effects of 2% olive oil (OO) or fish oil (FO) (Super epa500) dietary supplementation (9 months) on Japanese "SEA" quail was investigated. The animals were examined for tissue biochemical changes and possible blood vessel fatty deposition. The fatty acids of blood and tissue extracts from heart, liver and fat were analyzed by gas-chromatography/mass spectrometry. The ratio of arachidonic acid to eicosapentaenoic or docosahexaenoic acid was markedly decreased in FO treated animals compared to OO or control diet treated animals. Tissue cholesterol and total phospholipids were present in elevated amounts in the heart and liver of FO treated animals. After the 9-month regimen many animals had residual atherosclerotic lesions but the FO treated birds had considerably more fatty streaks and fatty deposition in their large vessels compared to control or OO treated animals. Although the lipid composition of tissues of FO treated animals would indicate that the purported cardioprotective omega-3 fatty acids are enriched in the various tissues examined compared to olive oil and control diet treated animals, the possible detrimental effect of saturated fat, cholesterol, or some other component of the fish oil preparations is suggested from the histological appearance of fatty deposition in the blood vessels (aortae) of these inbred animals. These results in quail are strikingly similar to that seen in the omega-3 FA treated WHHL rabbit (15).

Adipose Tissue↗
PubMed1986

Hospital stay following biliary tract surgery. A comparison of two community hospitals.

An apparent difference in length of postoperative hospitalization following biliary tract surgery at two university-affiliated community hospitals led to a retrospective review of 200 consecutive patients at each hospital. Patient characteristics and surgical practices that potentially affected hospital stay were compared. A highly significant difference was identified in the length of hospitalization between the two institutions. Statistically significant differences in variables that seemed to affect length of stay included the use of nasogastric tubes and abdominal drains and the time interval to the institution of postoperative feedings. Cumulative hospitalization was 517 days shorter at one institution. This was accomplished despite a high percentage of emergent procedures and more frequent involvement of surgical residents. Since hospital stay accounts for the majority of expenditure for surgical treatment of biliary tract disease, shortening postoperative hospitalization can significantly reduce the overall costs.

Adolescent↗
PubMed1986

Stimulation of undermineralized matrix formation by 1,25 dihydroxyvitamin D3 in long bones of rats.

We previously reported that pharmacologic doses of 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) given for 2-3 days, inhibited osteoblastic collagen synthesis in young rats. In this study, we tested the effects of 5, 25, and 125 ng of 1,25(OH)2D3 injected subcutaneously into 6-week-old rats for 12 or 18 days. In rats given 125 ng, cortical bone of distal half femurs exhibited decreased calcium (Ca) content but dry weight and hydroxyproline (Hyp) content were no different from control. Trabecular bone Ca was not different from control but dry weight and Hyp were increased. When cortical and trabecular bone were combined, there was a decrease in Ca, an increase in Hyp, and a 50% decrease in Ca:Hyp. Fluorescent labels given after 8 days of treatment were either diffuse or absent in calcified sections from rats given 125 ng, indicating impaired mineralization. The 25 and 125 ng doses produced hypercalcemia with normal serum phosphate. There was a dose-related increase in serum immunoreactive bone gla protein (BGP) and serum 1,25(OH)2D3 and a decrease in serum 25(OH)D3. At the 5 ng dose, no adverse effects were seen on body growth. With 25 ng and 125 ng, growth was inhibited. Increased serum urea nitrogen and histologic evidence of nephrocalcinosis occurred at the 125 ng dose. When 125 ng was given for 12 days and then withdrawn for 6 days, systemic toxicity decreased and bone Hyp and Ca increased so that Ca:Hyp remained low and comparable to that of rats treated with 1,25(OH)2D3 continuously.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1982

Stress myocardial imaging in patients with mitral valve prolapse: evidence of a perfusion abnormality.

Twenty-four patients with mitral valve prolapse underwent cardiac catheterization, exercise testing, and exercise 201thallium scintigraphy. Of 10 patients with coronary artery disease, six had abnormal scintigrams. Two of these six had exercise-induced reversible defects, two had defects that persisted during redistribution, and two had both reversible and persistent defects. Of 14 patients with normal coronary arteries, five had negative scintigrams. Of the remaining nine patients, two had exercise-induced defects, and seven (50%) had defects involving the inferior or posterior wall that persisted during redistribution. Possible mechanisms for this latter finding are discussed. In contrast to previous reports, exercise 201thallium scintigraphy was not entirely successful in identifying patients with coronary artery disease in our patients with mitral valve prolapse.

Adult↗
PubMed1976

Intraventricular free wall dissection causing acute interventricular communication with intact septum in myocardial infarction.

This report delineates a previously unrecognized complication of acute myocardial infarction, an intraventricular wall dissection producing interventricular communication without septal perforation. The clinical, hemodynamic, and pathologic features of this unique condition are documented, as well as the factors important in the mechanism of its production.

Aged↗
PubMedDate not supplied

Production of a biologically active variant form of recombinant human secretin.

A biologically active variant form of recombinant human secretin was produced using a gene fusion system designed to facilitate the purification of the protein. The fusion protein was recovered from the culture medium of Escherichia coli by IgG affinity chromatography, and recombinant secretin was released by cyanogen bromide treatment. A novel approach involving addition of a C-terminal Gly-Lys-Arg extension, was used to overcome the lack of amidation of recombinant proteins in Escherichia coli. The biological activity of the recombinant variant of secretin was at least 80% of the porcine secretin standard.

Amino Acid Sequence↗
PubMedDate not supplied

Use of transgenic animals for carcinogenicity testing: considerations and implications for risk assessment.

Advances in genetic engineering have created opportunities for improved understanding of the molecular basis of carcinogenesis. Through selective introduction, activation, and inactivation of specific genes, investigators can produce mice of unique genotypes and phenotypes that afford insights into the events and mechanisms responsible for tumor formation. It has been suggested that such animals might be used for routine testing of chemicals to determine their carcinogenic potential because the animals may be mechanistically relevant for understanding and predicting the human response to exposure to the chemical being tested. Before transgenic and knockout mice can be used as an adjunct or alternative to the conventional 2-year rodent bioassay, information related to the animal line to be used, study design, and data analysis and interpretation must be carefully considered. Here, we identify and review such information relative to Tg.AC and rasH2 transgenic mice and p53+/- and XPA-/- knockout mice, all of which have been proposed for use in chemical carcinogenicity testing. In addition, the implications of findings of tumors in transgenic and knockout animals when exposed to chemicals is discussed in the context of human health risk assessment.

Animals↗
PubMedDate not supplied

The role of infection in atherosclerosis and coronary artery disease: a new therapeutic target.

There is growing evidence that inflammatory processes may be involved in the development of atherosclerosis and its complications. Viral and bacterial pathogens have been implicated as possible causative factors in the pathogenesis of coronary artery disease (CAD) and restenosis after angioplasty. Antibiotic trials are now in progress to examine whether treatment of infection can prevent the complications of CAD. Atherosclerosis, the primary pathologic process in coronary artery disease (CAD), carotid artery disease, abdominal aortic aneurysm, and peripheral vascular disease, is no longer considered to be an obscure, slowly progressive, degenerative disease. Indeed, recent molecular studies on the atherosclerotic plaque have shown that the initiation, progression, and acute sequelae of atherosclerosis can be explained in part by a low-grade inflammatory process. Studies show that mediators of inflammation can be found at all stages of the life cycle of the atherosclerotic plaque. These include activated macrophages and lymphocytes, cytokines, growth factors, matrix degenerating proteinases, and tissue factor. It is hypothesized that risk factors such as hypertension, smoking, or elevated levels of low-density lipoprotein (LDL) cholesterol result in injury to the endothelial cell of the artery, and this injury initiates the inflammatory process. However, many patients with vascular disease do not have these established risk factors, and this observation has galvanized efforts to find new risk factors. Because inflammation is now considered to be an operative paradigm for atherosclerosis, it is not a major leap to the hypothesis that infectious agents, such as viral or bacterial, may play a role. Certainly this is not a new concept, and with the recent discovery that peptic ulcer disease, heretofore considered a disease of excess acid and reduced mucosal resistance, is caused by the ubiquitous bacterium Helicobacter pylori, interest in finding an infectious etiology for atherosclerosis has increased. Accordingly, the purpose of this discussion is to review in a historical manner the evidence that infectious agents-including herpes simplex virus (HSV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), Enterovirus (adenovirus, Coxsackie virus), Chlamydia pneumoniae, and H. pylori-may play a role in atherosclerosis and its manifestations, especially as they relate to CAD.

Chlamydophila Infections↗