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Biomedical subjects

G Oster

Publications and source records attributed to G Oster.

At least 91 records · Page 5Linked to original sources

The mechanical basis of cell rearrangement. I. Epithelial morphogenesis during Fundulus epiboly.

Many morphogenetic processes are accomplished by coordinated cell rearrangements. These rearrangements are accompanied by substantial shifts in the neighbor relationships between cells. Here we propose a model for studying morphogenesis in epithelial sheets by directed cell neighbor change. Our model describes cell rearrangements by accounting for the balance of forces between neighboring cells within an epithelium. Cell rearrangement and cell shape changes occur when these forces are not in mechanical equilibrium. We will show that cell rearrangement within the epidermal enveloping layer (EVL) of the teleost fish Fundulus during epiboly can be explained solely in terms of the balance of forces generated among constituent epithelial cells. Within a cell, we account for circumferential elastic forces and the force generated by hydrostatic and osmotic pressure. The model treats epithelial cells as two-dimensional polygons where the mechanical forces are applied to the polygonal nodes. A cell node protrudes or contracts when the nodal forces are not in mechanical equilibrium. In an epithelial sheet, adjacent cells share common boundary nodes; in this way, mechanical force is transmitted from cell to cell, mimicking junctional coupling. These junctional nodes can slide, and nodes may appear or disappear, so that the number of polygonal sides is variable. Computer graphics allows us to compare numerical simulations of the model with time-lapse cinemicroscopy of cell rearrangements in the living embryo, and data obtained from fixed and silver stained embryos. By manipulating the mechanical properties of the model cells we can study the conditions necessary to reproduce normal cell behavior during Fundulus epiboly. We find that simple stress relaxation is sufficient to account for cell rearrangements among interior cells of the EVL when they are isotropically contractile. Experimental observations show that the number of EVL marginal cells continuously decreases throughout epiboly. In order for the simulation to reproduce this behavior, cells at the EVL boundary must generate protrusive forces rather than contractile tension forces. Therefore, the simulation results suggest that the mechanical properties of EVL marginal cells at their leading edge must be quite different from EVL interior cells.

Animals↗

Benzodiazepine tranquilizers and the risk of accidental injury.

To determine whether benzodiazepine tranquilizers increase the risk of accidental injury requiring medical attention, we used pharmacy claims submitted to a large third-party payer to identify 4,554 persons who had been prescribed these agents and a matched control group of 13,662 persons who had been prescribed drugs other than benzodiazepines. We then used diagnoses recorded on claims submitted by medical care providers to identify all accident-related care received by these persons during three months before their first-observed prescription for a benzodiazepine or nonbenzodiazepine agent, respectively, and six months subsequently. We found accident-related care was more likely among persons who had been prescribed benzodiazepines; among these persons, the probability of an accident-related medical encounter was higher during months in which a prescription for a benzodiazepine had recently been filled compared to other months; and persons who had filled three or more prescriptions for these agents in the six months following initiation of therapy had a significantly higher risk of an accident-related medical event than those who had filled only one such prescription. Approximately two-fold risks of accident-related care were found, after controlling for age, sex, and prior utilization.

Accidents↗

The economic costs of non-insulin-dependent diabetes mellitus.

Persons with diabetes experience elevated risks of a variety of other illnesses-- including circulatory, visual, neurological, renal, and skin disorders--relative to their nondiabetic peers. Previous estimates of the economic burden of diabetes, however, have not taken full account of this related morbidity and mortality and have therefore understated the cost to the nation due to this disease. Accordingly, we estimated the economic costs of type II, or non-insulin-dependent, diabetes mellitus, reflecting its contribution to the total burden of disease in the United States. In 1986, non-insulin-dependent diabetes mellitus was responsible for $11.6 billion in health care expenditures, including $6.8 billion for diabetic care and $4.8 billion attributable to an excess prevalence of related (principally cardiovascular) conditions. The human toll of non-insulin-dependent diabetes mellitus included 144,000 deaths -- about 6.8% of total US mortality -- and the total disability of 951,000 persons. The total economic burden of non-insulin-dependent diabetes mellitus in 1986, including health care expenditures and productivity forgone due to disability and premature mortality, was $19.8 billion.

Aged↗

The cost-effectiveness of counseling smokers to quit.

Cigarette smoking is the most important preventable cause of death in the United States. Surveys of patients, however, suggest that many physicians do not routinely counsel smokers to quit. Because physicians may not consider counseling against smoking to be as worthwhile as other medical practices, we examined its cost-effectiveness. We based our estimates of the effectiveness of physician counseling on published reports of randomized trials and our estimates of its cost on average charges for physician office visits. Our results indicate that the cost-effectiveness of brief advice during routine office visits ranges from $705 to $988 per year of life saved for men and from $1204 to $2058 for women. Follow-up visits about smoking appear to be similarly cost-effective. Physician counseling against smoking, therefore, is at least as cost-effective as several other preventive medical practices and should be a routine part of health care for patients who smoke.

Adult↗

Cimetidine and adverse reactions: a meta-analysis of randomized clinical trials of short-term therapy.

PURPOSE: We pooled data from randomized, double-blind, placebo-controlled trials to determine the frequency of adverse reactions among patients treated with cimetidine for acute acid-peptic disorders. METHODS: Meta-analysis was used to analyze data obtained from a search of English language reports of trials of cimetidine in the ambulatory treatment of acute acid-peptic disorders that were published between January 1982 and April 1987. RESULTS: Of 161 trials of cimetidine that we identified, 84 provided complete reporting of data on adverse reactions and, of these, 24 employed a randomized, double-blind, placebo-controlled design. Across these 24 trials, the overall rate of reported adverse reactions among 622 patients randomly assigned to receive cimetidine was 10.9%; the corresponding rate among 516 patients randomly assigned to receive placebo was 10.1%. This difference was not statistically significant (p greater than 0.10), nor were any significant differences noted in the frequencies of reported central nervous system or gastrointestinal adverse reactions (p greater than 0.10). Rates of adverse reactions also did not differ by dosage or trial duration. The overall rate of adverse reactions reported in the 60 trials that did not utilize a randomized, double-blind, placebo-controlled design was similar to the rate reported in those that did. CONCLUSIONS: Our findings suggest that the frequency of adverse reactions among patients receiving cimetidine for acute acid-peptic disorders is not significantly different from that of patients receiving placebo.

Acute Disease↗

An assessment of the role of 123I-N-isopropyl-p-iodoamphetamine with single-photon emission computed tomography in the diagnosis of stroke and Alzheimer's disease.

The role of 123I-N-isopropyl-p-iodoamphetamine (123I-IMP), a new agent used in brain imaging with single-photon emission computed tomography (SPECT), has been assessed in the early diagnosis of acute infarctive stroke and Alzheimer's disease (AD). The diagnosis of these conditions in their early stages has remained problematic, principally due to limitations of existing technologies. To more formally assess this new technology, we estimated the sensitivity and specificity of 123I-IMP SPECT scanning in the diagnosis of stroke and AD. We based our assessment on a review of all published studies that reported on 123I-IMP SPECT scans and which included three or more patients. The results from three major studies indicate that 123I-IMP SPECT scanning has a higher sensitivity (92% to 100%) than computerized tomography (55% to 86%) in the early diagnosis of acute cerebral infarction. Preliminary findings from studies using 123I-IMP SPECT in the diagnosis of early AD are promising and show a sensitivity of at least 69%. Furthermore, 123I-IMP SPECT scanning clearly discriminates patients with advanced AD from normals: sensitivity has ranged from 50% to 100%, while specificity has ranged from 97% to 100%. Studies also suggest that it can discriminate AD patients from those with multi-infarct dementia. Our review indicates that 123I-IMP SPECT may have an important future role in the early diagnosis and management of patients with acute infarctive stroke and AD.

Alzheimer Disease↗

Cell rearrangement and segmentation in Xenopus: direct observation of cultured explants.

We make use of a novel system of explant culture and high resolution video-film recording to analyse for the first time the cell behaviour underlying convergent extension and segmentation in the somitic mesoderm of Xenopus. We find that a sequence of activities sweeps through the somitic mesoderm from anterior to posterior during gastrulation and neurulation, beginning with radial cell intercalation or thinning, continuing with mediolateral intercalation and cell elongation, and culminating in segmentation and somite rotation. Radial intercalation at the posterior tip lengthens the tissue, while mediolateral intercalation farther anterior converges it toward the midline. This extension of the somitic mesoderm helps to elongate the dorsal side of intact neurulae. By separating tissues, we demonstrate that cell rearrangement is independent of the notochord, but radial intercalation - and thus the bulk of extension - requires the presence of an epithelium, either endodermal or ectodermal. Segmentation, on the other hand, can proceed in somitic mesoderm isolated at the end of gastrulation. Finally, we discuss the relationship between cell rearrangement and segmentation.

Animals↗

Economic aspects of clinical decision making: applications in patient care.

An overview of the techniques of cost-effectiveness analysis as they apply to clinical decision making is presented, and ways that the techniques can assist decision makers in a limited-resource environment are identified. Most applications of cost-effectiveness analysis concern a problem in which a choice must be made between different ways of accomplishing a given clinical goal, such as treating a particular illness. As such, these applications involve comparisons between competing and mutually exclusive strategies and attempt to identify those strategies that provide the greatest benefit for a given set of resource constraints. The need for these analyses continues to increase as a consequence of the growing importance of rate-based and capitated (as opposed to cost-based) methods of paying for patient care. Despite this growing need, most decision makers will not want or be able to conduct such analyses on a regular basis; they may nonetheless benefit from formal studies of clinical problems conducted and reported by others. The validity and quality of these reports, however, need to be carefully assessed before decisions can be based on such information. Properly done, cost-effectiveness analyses can be powerful tools in clinical decision making, particularly as the concern with providing quality care in a cost-constrained environment continues to grow.

Cost-Benefit Analysis↗

Cost-effectiveness of antihyperlipemic therapy in the prevention of coronary heart disease. The case of cholestyramine.

Using cholestyramine as a model, we considered the cost-effectiveness of antihyperlipemic therapy in the primary prevention of coronary heart disease among men between 35 and 74 years of age with elevated levels of total plasma cholesterol. Our findings indicate that the cost-effectiveness of treatment varies substantially, ranging from about $36,000 to over $1 million per year of life saved. Cost-effectiveness was highest for younger patients, for those with additional coronary risk factors (eg, smoking or hypertension), and for those whose course of therapy is of less-than-lifelong duration. Conversely, it is lowest for older patients, for those with no additional coronary risk factors, and for those who are treated for a lifetime. Our results suggest that pharmacologic therapy may not be cost-effective for all patients with elevated cholesterol levels, especially those over 65 years of age. For many younger patients, however--those with additional coronary risk factors and more severe elevations in cholesterol levels--the cost-effectiveness of therapy may be comparable with other accepted medical practices.

Adult↗

Cortical activity in vertebrate eggs. I: The activation waves.

We present a physical model for the propagation of chemical and mechanical waves on the surface of vertebrate eggs. As a first step we analyzed the propagation of the calcium wave observed to sweep over the surface of the Medaka egg (Gilkey et al., 1978). It has been assumed that this wave is driven by a mechanism of calcium-stimulated-calcium-release. By formulating this hypothesis mathematically we can use the observed wavefront data to obtain a map of cortical reactivity. This map indicates a gradient of reactivity along the egg: highest in the animal hemisphere and tapering off towards the vegetal hemisphere. The cortex of Xenopus eggs is also capable of propagating a calcium wave (Busa & Nuccitelli, 1985). At about the same time a wave of expansion followed by a wave of contraction sweeps across the egg surface (Takeichi et al., 1984). We have proposed a mechanism for this wave pair based on the physical chemistry of actomyosin gels. The calcium wave activates solation factors which sever some of the actin chains which leads to an osmotic swelling of the gel. Calcium also activates the contractile machinery of the actomyosin system which causes the gel to contract. The contraction lags the swelling because of the nature of the kinetics: solation and swelling is a more rapid process than contraction. By writing the equations for gel expansion and contraction we can mimic the mechanical and chemical wave propagation by a computer simulation. If the model is correct this provides a method for using the waves as a diagnostic of the mechanochemical properties of the egg cortex.

Actomyosin↗

A cost-effectiveness analysis of prophylaxis against deep-vein thrombosis in major orthopedic surgery.

A number of methods of prophylaxis can reduce the likelihood of postoperative deep-vein thrombosis in patients undergoing major orthopedic surgery. Using techniques of decision analysis, we examine the cost-effectiveness of several of these--warfarin sodium, low-dose subcutaneous heparin sodium, graduated compression stockings, intermittent pneumatic compression, heparin plus dihydroergotamine mesylate, and heparin plus stockings--compared with clinical diagnosis and treatment only. Our results show that 153 deaths per 10 000 patients occur when no prophylaxis is used; with most prophylaxis, this number is at least halved, and the most effective methods may reduce the number of deaths by three fourths. In addition, all of the prophylaxis considered are cost saving: average costs of care (including prophylaxis costs) are reduced by +19.40 to +181.60 per patient. Prophylaxis against deep-vein thrombosis in major orthopedic surgery therefore saves both lives and health care dollars.

Cost-Benefit Analysis↗

Prevention of venous thromboembolism after general surgery. Cost-effectiveness analysis of alternative approaches to prophylaxis.

A number of methods of prophylaxis can reduce the risk of postoperative venous thromboembolism in patients undergoing general surgery. The cost-effectiveness of several of these--low-dose subcutaneous heparin, intermittent pneumatic compression, graduated compression stockings, heparin plus dihydroergotamine, heparin plus stockings, and intermittent pneumatic compression plus stockings--was assessed by pooling data from published reports of randomized controlled trials. Using clinical protocols, costs for prophylaxis, diagnosis, and treatment of venous thromboembolism were determined. The expected outcomes and costs of each strategy were then calculated using techniques of decision analysis. The results indicate that stockings are the only prophylactic method that is actually cost-saving. Costs of care average $34 less per admission for patients using stockings than for those receiving no prophylaxis. Most other methods of prophylaxis further reduce thromboembolic risk, but increase costs by $50 to $88 per patient relative to costs for the use of stockings. Differences in the cost-effectiveness of these prophylaxis are more marked, ranging from about $50,000 to almost $500,000 per additional life saved.

Clothing↗

Accident- and injury-related health-care utilization among benzodiazepine users and nonusers.

Benzodiazepine tranquilizers have been found to cause psychomotor and cognitive impairment, and there is evidence of an increased rate of automobile accidents among users of these drugs. To determine whether benzodiazepine users are more likely than nonusers to experience accidental injury requiring medical attention, we examined health-care utilization among 7,271 such users and an age- and sex-matched sample of 65,439 nonusers, all of whom were enrolled in an "HMO-like" health insurance plan. Benzodiazepine users and nonusers were identified through a review of 4 months' prescription drug claims. Six months' health-care claims for each user and nonuser subsequent to the first observed claim for a benzodiazepine or nonbenzodiazepine agent, respectively, were compiled. Claims related to accidents were identified on the basis of physician-recorded diagnoses. Our results indicate that benzodiazepine users were significantly (p less than .01) more likely than nonusers to experience (1) at least one accident-related episode of care; (2) a greater number of accident-related hospital admissions; and (3) a greater number of accident-related inpatient days. Accident-related utilization was also significantly higher when users had recently filled a prescription for a benzodiazepine agent. Benzodiazepine users, however, also utilized significantly more non-accident-related health-care services than nonusers. The nature of the association between benzodiazepine use and a higher accident-related utilization is thus unclear. A pretest-posttest study is now being undertaken to ascertain the significance of these findings.

Accidents↗