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Biomedical subjects

J Dunbar

Publications and source records attributed to J Dunbar.

At least 55 records · Page 3Linked to original sources
PubMed1989

Tarsius delta- and beta-globin genes: conversions, evolution, and systematic implications.

Comparisons between duplicated genes have shown that gene conversions play an important role in the evolution of multigene families. Previous comparisons have documented in the recently duplicated gamma-fetal globin genes of catarrhine primates, over 15 separate conversions affecting extensive stretches of coding and noncoding sequences. In the present study, delta- and beta- globin genes from a lower primate Tarsius syrichta, and the delta-globin gene of the Asian great ape, Pongo pygmaeus, have been isolated and sequenced. Comparisons of these sequences with other primate delta and beta sequences confirmed a previously reported conversion in an anthropoid ancestor and revealed additional conversions in basal primate, stem haplorhine, tarsier, and early lemur lineages. Conversions found between primate delta- and beta-globin genes contrast with those found in the gamma-genes in that delta-beta conversions appear much less frequently and are more restricted to regions conserved by selection (i.e. coding and 5'-regulatory sequences). These differences indicate that soon after a duplication occurs, conversions can be quite frequent and encompass extensive portions of the duplicated region. With time, sequence differences accumulate, particularly in noncoding regions, and limit both the frequency and size of the conversions. Sequences conserved by selection accumulate differences more slowly and are therefore subject to gene conversions for a longer period of time. Both unconverted and converted sequences were consistent in supporting the placement of tarsier with anthropoids.

Animals↗
PubMed1989

Compliance measurement with arthritis regimen.

Rheumatoid arthritis affects nearly 6.5 million Americans, causing significant disability and suffering. Improvement of treatment efficacy is of considerable importance. Because adherence moderates treatment effects, efficacy studies need to account for the extent to which the patient complied. This paper reviews the methods of assessing adherence. These methods fall into four categories: (1) clinical measures (therapeutic outcome and clinician judgement); (2) self-report (interviews, questionnaires, and daily records); (3) direct measures (direct observation and biologic assays); and (4) indirect measures (pill counts, pharmacy refills, and electronic monitors). The most commonly used measure is some form of self-report. The clinical measures are problematic as compliance indicators and should not be used in this regard. Selections among the other categories should be made based upon the behavior being studied, the cost and resources available, the capabilities of the patient, the questions being asked, and the level of accuracy and detail desired. There are no perfect measures.

Activities of Daily Living↗
PubMed1988

Single-pump techniques for assisted circulation in cardiogenic shock: experimental evaluation and case report.

Acute cardiogenic shock or bridging to transplantation often involves the need for circulatory and cardiac support systems that are more effective than the intraaortic balloon pump. Biventricular failure, which is present in many cases, is generally treated with total cardiac replacement or with a complex of pumps and oxygenator that makes application difficult. With the goal of developing a universally applicable method of cardiac and circulatory support, we undertook a series of canine experiments designed to evaluate the effect of various treatment methods on survival, hemodynamics, and metabolic function. The series involved 123 dogs, in which cardiogenic shock was induced by means of multiple coronary artery ligations. The individual animals were then subjected to bypass, treated medically, or left untreated, depending on random selection. Each treatment lasted for 4 hours and was followed by a 2-hour period of observation. The following single-pump methods were tested: 1) left ventricular (LV) bypass, 2) left atrial (LA) bypass, 3) left ventricular and right atrial (LV + RA) bypass, 4) left atrial and right atrial (LA + RA) bypass, 5) LV + RA bypass, plus treatment with substrates (cysteine and ribose), and 6) LV + RA bypass, plus treatment with fluosol. Each bypass system incorporated a single reservoir and a centrifugal pump, and blood was returned to a femoral artery. Medical therapy consisted of either 1) treatment with sodium nitroprusside alone or 2) treatment with substrates alone. With respect to survival and hemodynamic effects (as reflected by oxygen consumption), LV + RA bypass and LA + RA bypass proved superior. During the posttreatment period, LV + RA bypass was associated with the highest survival rates and, therefore, with the most satisfactory recovery of myocardial or cardiac function. Despite the limited desaturation produced during venous shunting from the right atrium, perfusion of the entire body and consumption of oxygen were least in the LV + RA bypass group. The addition of substrates, or even of fluosol, caused a reduction in oxygen consumption. Our experience also includes one clinical case in which LA + RA bypass was used to support a 57-year-old man for 32 hours, after left atrial bypass alone proved inadequate. The dual-chamber technique brought about an improvement not only in hemodynamics but also in blood-gas values and pH. On the basis of this case and the canine experiments, we conclude that LV + RA and LA + RA bypass techniques offer safe, effective means of long-term temporary support for patients in severe cardiogenic shock.

Journal Article↗
PubMed1987

Computer-aided molecular modeling of a D2-agonist dopamine pharmacophore.

Using computer-aided molecular modeling techniques to analyze models recently proposed for the receptor binding sites of dopaminergic agonists, we superimposed the chemical structures of various compounds that mimic the pharmacological behavior of dopamine, as well as inactive enantiomers, on a postulated three-dimensional frame of reference. We analyzed the vector directionalities of the lone pairs of the nitrogen common to these molecules, and the acidic hydrogen of phenols (in aminoindanes, aminotetralins, apomorphines, p-phenol-piperazines, octahydrobenzo(g)quinolines, octahydrobenzo(f)quinolines, and benzazepines) or of nitrogen (in ergoline-type compounds and related structures). This model, when expressed as distances from that of the reference compound pergolide, correlates with the dopaminergic binding affinity observed in compounds previously reported to act on the dopaniergic system in the central nervous system (CNS). The regression analysis of log KD with respect to the distances of the vectors of the acidic hydrogen support the hypothesis that these compounds bind to the receptor as donors in hydrogen bond formation.

Computer Graphics↗
PubMed1986

Dissociation between pancreatic enzyme secretory and synthetic dose-responses to cholecystokinin in man.

The effect of varying the intensity of pancreatic stimulation on the synthesis of human pancreatic enzymes has not previously been studied. We have measured the secretion and synthesis of pancreatic enzymes in response to either secretin alone (1 CU.kg-1.h-1) or secretion plus increasing doses of cholecystokinin (CCK) (0.25, 0.5 or 1.0 IDU.kg-1.h-1). Enzyme synthesis was measured using the incorporation of 75Se-methionine (0.15 mCi (5.6 kBq).kg-1.h-1) into the trichloracetic acid-insoluble fraction of the duodenal aspirate. Outputs of trypsin, chymotrypsin, lipase and protein showed a bell-shaped dose response to increasing doses of cholecystokinin, with maximal outputs occurring in response to secretin plus cholecystokinin 0.5 IDU.kg-1.h-1. The rate of incorporation of 75Se-methionine increased with increasing doses of cholecystokinin and was maximal in response to secretion plus cholecystokinin 1.0 IDU.kg-1.h-1. There was therefore dissociation between the secretory and synthetic responses to increasing doses of cholecystokinin.

Cholecystokinin↗
PubMed1986

Practical aspects of dietary management of hypertension: compliance.

This paper addresses compliance issues that arise in the implementation of weight loss and other therapeutic diets prescribed for the individual with hypertension. Dietary compliance poses a significant problem. Studies suggest that dropout rates in both self-help and other weight loss programs range from 50 to 70% within 1-2 years. Further, just 50% of persons can be expected to comply with diets for cardiovascular disease. Assessment of adherence is confounded by the lack of precise measures that reflect adherence over time. Measures in general use include daily diaries, urinary chloride dip sticks, multiple 24-h or overnight urinary sodium, analysis of food samples, as well as 24-h recall and food histories. When poor compliance has been identified, it has been associated with a variety of factors. These include multicomponent regimens, conflicting lifestyle habits, skill in identifying and (or) preparing appropriate foods, the cost:benefit ratio of compliance, and social support. Limited investigation has been undertaken to directly improve compliance to diet. However, such strategies as tailoring, goal setting, self-monitoring, stimulus control, social support, cognitive restructuring, and a consistent approach between the care providers show promise.

Attitude↗
PubMed1986

Concepts in assisted circulation.

Assisted circulation by extracorporeal and extracardiac bypass techniques must be based on the requirements of the heart and of the total body, though these may differ. The cardiac problem in cardiogenic shock is more likely to be a biventricular problem demanding decompression of both sides. Extra pulmonary oxygenation should be avoided because of complexity in long-term use. Principles of assisted circulation may be applied in an extra-thoracic temporary manner or as an intracorporeal long-term device without removal of the heart. We have compared a number of extracorporeal mechanical bypass techniques (left ventricular bypass, left atrial bypass, right atrial plus left ventrical bypass, and right atrial plus left atrial bypass) in dogs at different flow rates with control groups (nitroprusside, metabolic substrates, and no therapy) for survival during and after 4-hour treatment periods in a standard severe myocardial infarction preparation with biventricular failure. The left ventricle was cannulated in a retrograde manner. Right atrial bypass was mixed with oxygenated left ventricular blood before return without oxygenation. Results in 50 dogs revealed that without treatment 20% survived; left ventricular plus right atrial bypass provided 100% survival during the 4-hour treatment, whereas left ventricular bypass and nitroprusside were intermediate with approximately 70% survival. Respiration and acid-base balance were not significantly altered by right atrial bypass, which provided adequate decompression of the right ventricle. Flow rates of 50% of control levels were adequate to provide normal or increased peripheral circulation as well as decompression of both ventricles and maintenance of sinus or nodal rhythm. Left atrial or left ventricular bypass alone was unable to support the heart or circulation in severe failure. Hemodynamics, including total body perfusion, atrial pressures, and dP/dt were improved significantly only by left ventricular plus right atrial bypass, even though reduced rates of flow were used. Similar findings were seen in lactic acid, CPK, and oxygen consumption. The addition of metabolic substrates currently does not improve survival though they appear to act as metabolic modulators. We conclude that the principle of a low flow left ventricular plus right atrial bypass without an oxygenator offers a technique for long- or short-term assistance.

Journal Article↗
PubMed1985

Pancreatic enzyme synthesis in pancreatic disease.

In a prospective evaluation of patients suspected of having chronic pancreatitis, synthesis of pancreatic enzymes was measured by means of the incorporation of selenium-75-labelled methionine into the proteins of duodenal aspirate during stimulation of pancreatic secretion with secretin (1 CU X kg-1 X h-1) plus cholecystokinin (CCK) (1 IDU X kg-1 X h-1). The rate of pancreatic enzyme synthesis was increased in patients with chronic pancreatitis. Measurement of pancreatic enzyme synthesis was more sensitive in the detection of chronic pancreatitis than either the bicarbonate or the trypsin secretory response to secretin plus CCK. A combination of the bicarbonate secretory response with measurement of the rate of enzyme synthesis provided a positive predictive power of 100% when both tests were abnormal and a negative predictive power of 100% when both tests were normal, so that the combined test can be recommended both for excluding and confirming the presence of chronic pancreatitis.

Adult↗
PubMed1984

A proposal for the metal geometry in yeast superoxide dismutase based on results from EXAFS spectroscopy.

Extended x-ray absorption fine structure (EXAFS) spectra have been recorded at the Cu edge and Zn edge in native yeast superoxide dismutase and at the Cu edge and Cd edge in the yeast superoxide dismutase derivative, where Zn has been substituted with Cd. Two different metal ligand distances in the range 1.9-2.0 A and 2.3-2.4 are determined for the Cu and Zn metals. For Cd in the Zn site two different metal ligand distances about 2.2 A and 2.6 A, respectively, were found. The striking feature is the similarity between the amplitude and radii determined for both the Cu and Zn sites. The increased distances for Cd can be explained by the increased ionic radius of Cd relative to Cu and Zn. Based on these EXAFS results and other relevant knowledge about the metal geometries, we propose that histidine 61 (63) positioned between the Cu and Zn metals are in one subunit bound to Zn and in the other to Cu. This model explains the recently observed difference between the two metal sites in each subunit.

Copper↗
PubMed1984

Adherence measures and their utility.

This article addresses the variety of adherence measures available to the researcher, with particular reference to the utility of markers. It is proposed that the generic nature of the research question will suggest both the adherence definition and the appropriate assessment methodology. Each measurement procedure offers somewhat different information and has unique advantages and disadvantages. It is suggested that markers are limited by the relatively short duration of the measurement period, the lack of quantitative data on adherence, and, with some, the potential for confounding influences on their specificity. The probable value of markers lies in validating the subject's recent self-report, determining recent medication ingestion, and estimating the probability of adherence over time.

Clinical Trials as Topic↗
PubMed1983

Oxygen and hydrogen isotopes in fruit and vegetable juices.

(18)O/(16)O ratios from the juices of a number of fruits and vegetables were measured and found to be isotopically more enriched than the water in which they grew. Fast-growing high-water-content vegetables exhibited less enrichment than slower growing fruits such as apples, pears, and plums. (18)O/(16)O measurements were also made on the water from various sections of several plants, and the enrichment was found to occur in the following order: leaves > fruit > stem >/= ground water.D/H and (18)O/(16)O measurements were made on a series of grape juice samples and, when plotted against each other, gave a slope of 3.9, indicating that the physical process causing this enrichment was probably evaporation, i.e. evapotranspiration.

Journal Article↗
PubMed1982

Organization and management of recruitment.

Recruitment of participants to a multicenter study is complex. Considerable attention must be given to management and organization. In either a multi- or single-center study, a data-based management system is a sensitive and responsive means of monitoring participant flow. This system gives rapid feedback, encourages ongoing evaluation of strategies and permits centers to mark their own progress. In a multicenter study, an effective organizational framework for recruitment should include the central functions of administration, data management, monitoring progress and providing consultation concerning recruitment strategies, and public relations activities; and the recruitment team at each center, composed of counterparts of these central functions at the local level and the screening staff. The central staff is responsible for developing strategies, monitoring recruitment performance and providing consultation at the collaborative level. Staff from the central functional areas and local center recruitment teams can communicate effectively by using a central coordinating committee composed of representatives of each major component. This system is effective and applicable to most multicenter clinical research studies. In a single-center study, coordination may be provided through the recruitment team with equivalent representation to that described for this component in multicenter studies.

Clinical Trials as Topic↗
PubMed1980

Inhaled powder compared with aerosol administration of fenoterol in asthmatic children.

Fenoterol as a powdered inhalation was shown to have a longer and stronger bronchodilator effect than the same dose inhaled from a standard metered dose aerosol in a double-blind double-placebo controlled cross-over study in 13 severely asthmatic children. The powder method of administration is free from many of the disadvantages of pressurised aerosols and may prove the method of choice in childhood.

Administration, Intranasal↗
PubMed1977

The temperature-dependent dissociation of spectrin.

Spectrin, isolated from both human and bovine erythrocyte membranes, was found to exist predominantly as a tetramer of 960 000 daltons when prepared at 4 degrees C, but as a dimer of 480 000 daltons when prepared at 37 degrees C. The purified tetramer from both species could be dissociated to dimers by low ionic strength incubation at 37 degrees C.

Animals↗