Biomedical subjects
Publications and source records attributed to J Dunbar.
Individualized care, resident assessment by a multidisciplinary team, and rehabilitation enhance functional independence in nursing home residents. Creativity in choosing alternatives to restraints was important in successful restraint reduction. Residents free of restraints had higher ADL levels, were more continent, and sustained fewer serious injuries, all of which are important quality of life indicators.
Brain edema is a major contributor to the brain swelling process and raised intracranial pressure, yet the specific pathways involved in clearance of brain edema (fluid and proteins) and their relative contribution to the resolution process remain unknown. The objective of this study was to document the temporal course of edema resolution from brain to cerebrospinal fluid (CSF) and by the brain vasculature. Radioiodinated (125I) cat serum albumin (RICSA) was infused continuously into the white matter of anesthetized adult cats for 8 h, and ventriculocisternal perfusion was used to monitor the RICSA activity in CSF at 15-min intervals and to compare with the blood taken at 15-min intervals. The RICSA that cleared from the brain in 8 h measured 29.8% of the amount infused. Of the amount of RICSA leaving the brain, we found that the CSF compartment accounted for 87.14% of the cleared RICSA volume, while only 10.96% of RICSA was found in the blood during the 8-h experiment. The amount of RICSA remaining in the brain when the animal was killed equaled 71.2 +/- 15.9% (mean +/- SD) of the RICSA infused. We conclude that vascular clearance during the acute stage of resolution is minimal and that clearance of RICSA occurs predominantly via the CSF pathways.
Assisted circulation in severe cardiogenic shock was evaluated using a reservoir and a single pump without an oxygenator in 88 dogs. Study groups included: no treatment, substrates only (cysteine, ribose), nitroprusside, left ventricular (LV) + right atrial (RA) bypass + substrates, LV + RA bypass, left atrial (LA) + RA bypass, LA bypass, LV bypass, LV + RA + fluosol. Metabolic studies of O2 consumption, acid and alkaline phosphatase, lactate, creatine phosphokinase (CPK), myocardial depressant factor (MDF), and tissue adenosine triphosphate (ATP) were done in the course of 4-hour treatment periods followed by 2-hour observation periods. Best survival at 4-hour and 6-hour levels were achieved in LV + RA bypass. Cysteine and ribose reduced survival when added to the pump supported (LV + RA bypass) group. Cysteine/ribose improved survival over the no treatment group. O2 consumption increased significantly in the groups with best survival but remained unchanged from control or shock levels when cysteine/ribose were added. Unusually high levels of CPK, acid and alkaline phosphatase, and MDF occurred in both groups receiving cysteine/ribose, indicating significant organ damage correlating with poor survival. Lactate levels were less predictive. Heart tissue ATP levels were higher in groups with good survival. Liver ATP levels were lower in high survival groups. Lung ATP did not differ between groups.
Streptozotocin (STZ)-induced diabetes mellitus is associated with decreased renal clearances of inulin and p-aminohippurate (PAH). The present experiments were designed to determine whether STZ-induced renal hemodynamic changes are due to the drug per se, rather than to the diabetic state that it induces. Isogenic Lewis rats with native right and transplanted left kidneys were studied. In one group, kidney donors received 50 mg STZ/kg body wt on day 1 and transplantation was performed on day 4 (untreated recipients). On day 29, the inulin and PAH clearances of these nondiabetic recipients were, respectively, 0.94 +/- 0.04 and 2.58 +/- 0.11 ml.min-1 x g-1 for the transplanted left kidney (previously exposed to STZ) and 0.95 +/- 0.07 and 2.54 +/- 0.14 ml.min-1 x g-1 for the native right kidney (never exposed to STZ). In another group, recipients received STZ on day 1 and transplantation was performed on day 4 (untreated donors). On day 29, the inulin and PAH clearances of these diabetic recipients were, respectively, 0.62 +/- 0.04 and 1.46 +/- 0.11 ml.min-1 x g-1 for the transplanted left kidney (never exposed to STZ) and 0.61 +/- 0.05 and 1.42 +/- 0.08 ml.min-1 x g-1 for the native right kidney (previously exposed to STZ). We conclude that the diabetic state, rather than STZ, is responsible for the decreased renal clearances of inulin and PAH in this experimental model.
2-(Aminoalkyl)-5-nitropyrazolo[3,4,5-kl]acridines were prepared from substituted anilines via the 1-chloro-4-nitroacridones followed by condensation with [(alkylamino)alkyl]hydrazines. Impressive activity was demonstrated for the 9-hydroxy, 9-alkoxy, and 9-acyloxy analogs in vitro on a L1210 leukemia line and in vivo against the P388 leukemia. Advanced studies led to the selection of 3bbb for clinical trial.
The application of pumps and other mechanical and physiologic aids for improving circulation and heart recovery must be based on physiologic requirements. The needs of circulation and cardiac recovery are different and depend on competence of the right ventricle as well as the left ventricle and the pattern of cannulation and decompression. Our studies of various bypass techniques and drugs in a standardized severe cardiogenic shock model lead us to believe that biventricular decompression can be accomplished with a single centrifugal pump without an oxygenator. Cardiogenic shock and severe biventricular failure was best treated by LV + RA bypass, based on survival, hemodynamics and metabolism. LA + RA bypass was the next best. LA bypass, LV bypass, substrates (cysteine and ribose) and nitroprusside were intermediate. Circulatory support is not enough unless appropriate cardiac decompression ensures myocardial recovery.
These results show that infusion edema produces a significant increase in brainstem tissue water similar to the distribution seen after traumatic injury. The increased brainstem water of 0.24 cc is equivalent to a brainstem volume rise of 7.26% and was sufficient to cause a marked reduction in the PVI and sustained elevation of the ICP. Despite the ICP rise, somatosensory and brainstem potentials are only mildly affected and return to normal within 8 hr. The fact that severe fluid percussion injury results in obliteration of BAER immediately after impact would suggest that the neurologic deterioration seen in the fluid percussion model of injury is due to direct structural damage of the tissue, which was received at the moment of impact, and not to the compressive effect of the developing brainstem edema at levels achieved in these experiments (7.62% swelling). As in other mechanical models, edema results in secondary compression of the tissue and contributes to the general brain swelling, which if unabated could lead to tentorial herniation and death. In these infusion studies, we must conclude that in some cases, mild secondary compression was sufficient to affect other control centers and produce systemic failure at levels of edema that do not result in alteration of evoked potentials. This might explain the deaths of those animals that occurred during the infusion period in which brainstem potentials remained intact.
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.
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.
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.
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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.
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.
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.
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.
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.