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Biomedical subjects

C Ryan

Publications and source records attributed to C Ryan.

At least 55 records · Page 3Linked to original sources

The effects of repeated treatment with 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) on the lever press responding of the rat under FI and DRL schedules of food reinforcement.

In general, the effects of 8-OH-DPAT on the body temperature of rats or in inducing the 5-HT syndrome show rapid tolerance. However, in contrast, the 8-OH-DPAT-induced increase in the activity of rats in a two-way active avoidance task only occurs after repeated administration, i.e. there is sensitisation. The present study was conducted to examine whether this developing hyperactivity may also be expressed as increased rates of lever press responding, and if so, under which conditions it occurs. Rats were trained to press levers under fixed interval 60-s (FI 60) or differential reinforcement of low rates 20-s or 72-s (DRL20, DRL72) schedules of food reinforcement. Groups of trained rats were then treated daily 5 min before testing with doses of 0.01, 0.1 and 1.0 mg/kg 8-OH-DPAT SC for 10-21 days. In all three procedures, in the first couple of days of drug treatment, 8-OH-DPAT generally suppressed lever pressing in a dose-dependent manner. Thereafter, tolerance to this effect was seen to a greater (DRL20, DRL72) or lesser (FI60) extent. Some evidence for stimulation of low rates of lever press responding was seen after 10 days treatment under FI60, but not in DRL20 or DRL72 during short 30 to 60 min long daytime tests although in the latter case, the rats responded to the stimulating effects of 0.8 mg/kg SC amphetamine administered once at the end of the experiment. However, when rats were allowed to respond under DRL72 testing for 12 h during the night, after 10 days treatment a clear stimulation of lever pressing was observed. This stimulation was not specific to lever pressing, however, since a stimulation of entries into the food tray and licking were also seen. From these results, it may be concluded that the stimulating effect of 8-OH-DPAT after repeated administration may be expressed as increased rates of lever pressing, but not under all conditions in which psychomotor stimulation by amphetamine is seen. The potential for 8-OH-DPAT and related compounds to stimulate motor responding in this way should be taken into account when interpreting the effects of these drugs in animal models of psychiatric disorders.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Effects of acute hyperglycemia on mental efficiency and counterregulatory hormones in adolescents with insulin-dependent diabetes mellitus.

OBJECTIVE: To determine whether acute hyperglycemia adversely affects mental efficiency to the same extent as acute mild hypoglycemia. STUDY DESIGN: We administered a battery of cognitive tests to adolescents studied at hyperglycemic (20 mmol/L (360 mg/dl)), hypoglycemic (3.3 mmol/L (60 mg/dl)), or euglycemic (5.5 mmol/L (100 mg/dl)) targets, which were maintained by an insulin-glucose clamp. The study included 36 children, 9 to 19 years of age (mean = 14.7 years), with diabetes duration more than 2 years (mean = 6.9 years). RESULTS: Cognitive test performance did not deteriorate during hyperglycemia. In contrast, there was a significant decline in performance on all cognitive tests during mild hypoglycemia. Autonomic symptoms did not change significantly during hyperglycemia or during the rapid return from hyperglycemia to euglycemia. Although significant increments in epinephrine and pancreatic polypeptide levels occurred during mild hypoglycemia, no changes in counterregulatory hormones occurred during hyperglycemia. An exploratory regression analysis demonstrated that changes in mental efficiency were best predicted by increases in pancreatic polypeptide, a marker of autonomic activation. CONCLUSION: These results confirm our previous finding that mild hypoglycemia causes transient decrements in cognitive function. In contrast, neither hyperglycemia, nor the rapid drop from acute hyperglycemia to euglycemia, affected symptoms, cognitive function, or counterregulatory hormone secretion.

Acute Disease↗

Unintentional weight loss in long-term care: predictor of mortality in the elderly.

We retrospectively reviewed the medical records of 153 long-term care residents. Of these, 24 had lost at least 5% of their body weight during a 1-month interval. An unmatched control group of 51 patients was randomly selected from the remaining patients. Subjects who lost at least 5% body weight in 1 month were 4.6 times more likely to die within 1 year. Using multiple logistic regression, the odds ratio for weight loss and mortality was 5.1 (95% confidence interval 1.5 to 17.1) after adjustment for potential confounding by age and sex. The relatively simple anthropometric measure of body weight could be used by a multidisciplinary team in long-term care settings to identify patients at increased risk of dying. Further work is needed to clarify the role that nutrition could play in decreasing mortality in long-term care facilities.

Aged↗

Rapid assay for mycobacterial growth and antibiotic susceptibility using gel microdrop encapsulation.

Effective control of tuberculosis transmission in vulnerable population groups is dependent on rapid identification of the infectious agent and its drug susceptibility. However, the slow growth rate of mycobacteria has undermined the ability to quickly identify antimicrobial resistance. These studies describe a mycobacterial growth assay based on microencapsulation technology used in conjunction with flow cytometric analysis. Mycobacteria were encapsulated in agarose gel microdrops approximately 25 microns in diameter, and colony growth was monitored by using flow cytometry to evaluate the intensity of auramine staining after culture for various times at 37 degrees C. By this method, colony growth of Mycobacterium bovis and M. smegmatis could be quantified within 1 to 3 days after encapsulation. Inhibition of growth by rifampin and isoniazid was also evaluated in this time period, and the presence of an isoniazid-resistant subpopulation representing 3% of the total microorganisms could be detected. This use of encapsulation and flow cytometry has the potential to facilitate rapid and automated evaluation of inhibition of growth by antimicrobial agents and shorten the time frame for analysis of clinical specimens.

Bacteriological Techniques↗

Distinguishable substrate pools for muscle glyconeogenesis in lactate-supplemented recovery from exercise.

The formation of muscle glycogen from substrates other than glucose (glyconeogenesis) has now been demonstrated 1) from circulating lactate when this lactate is elevated and 2) from intramuscular substrate, which equilibrates with the products of local glucose metabolism but not with circulating lactate [Am. J. Physiol. 267 (Endocrinol. Metab. 30): E210-E218, 1994]. The purpose of the present studies was to examine the interaction of recovery from low-intensity exercise (4-h swim) and supplementation with exogenous lactate in determining the distribution of carbon flux between these two pathways for the glyconeogenic process in the gastrocnemius muscles. Ten protocols were defined using [14C]bicarbonate (no local incorporation into glycogen), [U-14C]lactate (tracks circulating lactate), and recycled [1-14C]glucose (tracks local substrate formation and glyconeogenesis). During recovery, lactate was infused to increase circulating concentrations 15- to 20-fold. Glucose and saline infusions during recovery were used as controls. The results indicate that prior exercise primarily promotes the local incorporation of recycled glucose label produced within the muscle into glycogen. Exogenous lactate stimulates the incorporation of circulating lactate into muscle glycogen. The contribution of the two substrate pools to glycogen synthesis appears to be additive, indicating the independence of muscle glycogenesis from these two sources.

Animals↗

Dyslipoproteinemias in atherosclerosis, thrombosis and restenosis after coronary angioplasty.

Lipids play a vital role in normal metabolic function in mammals. However, dyslipoproteinemias have been implicated in the pathophysiologic process of atherogenesis, thrombogenesis and restenosis after interventional procedures. Lipoproteins provide important chemical linkages among these three complex phenomena. Lipoproteins participate in atherogenesis and play a major role in plaque fissuring, the pathophysiologic common denominator of acute ischemic syndromes. Thrombogenesis is majoraly affected by the action of lipids on platelets, coagulation and fibrinolysis. LDL tend to destabilize platelet membrane activity, macrophages, endothelial and smooth muscle cell function; HDL tend to reverse these abnormalities. The metabolism of arachidonic acid, a metabolite of the essential polyunsaturated lipoprotein, linoleic acid, is integral to platelet and endothelial cell membrane formation, via the cyclooxygenase-prostanoid pathway. Arachidonic acid also is metabolized by the lipoxygenase-leukotreine pathway in neutrophils and monocytes. The relationship of dyslipoproteinemias (increased LDL and Lp(a); decreased HDL) to restenosis after angioplasty has been reported, though there is not universal agreement about causality. Lipid lowering regimens and other pharmacotherapy have had favorable effect slowing the rate of atherogenesis, decreasing the frequency of cardiac events (perhaps by "stabilizing" vulnerable plaques) and causing regression in some atheromata. The salutary effect of lipid-lowering agents upon the incidence of restenosis after angioplasty is problematic. Some investigators have found a statistically significant correlation, while others have not; but studies have not been standardized. In conclusion, the study of lipid metabolism across a wide range of physiochemical activities and the interaction of these phenomena describe complex, genetically determined linkages which instruct (and often humble) investigators in their study of lipids in health and disease.

Angioplasty↗

Nutritional screening of older South Carolinians: a pilot study.

Malnutrition can be a major health care problem for older adults. Thirty-one percent of the participants in a pilot study, conducted in Newberry county, were determined to be at high risk for nutritional deficiencies and 26 percent were at moderate risk. All health care professionals who work with the elderly must become aware of the NSI and offer the Checklist to their clients. The solutions to malnutrition require multidisciplinary interventions and the physician is the central figure in this team approach to improving the quality and quantity of life for older adults.

Aged↗

Regulation of the 28 kDa heat shock protein by retinoic acid during differentiation of human leukemic HL-60 cells.

Dysregulation of hematopoietic cellular differentiation contributes to leukemogenesis. Unfortunately, relatively little is known about how cell differentiation is regulated. Considering that heat shock proteins (hsp) and specifically the small hsps have been increasingly linked to growth regulation, we sought to determine whether the mammalian small hsp (hsp28) is a growth-regulatory candidate during hematopoietic cell differentiation. Because of its effects on cell growth and differentiation and its increasing clinical use as a differentiating agent, we examined the effect of retinoic acid (RA) on hsp28 during differentiation of the human leukemic HL-60 cell line. Although hsp28 was constitutively expressed at low levels in untreated HL-60 cells, steady state hsp28 protein increased transiently, concomitant with the onset of G1 cell cycle arrest. Furthermore, hsp28 phosphorylation transiently increased within one hour following treatment with RA. Interestingly, in contrast to other differentiating agents the induction of hsp28 by RA was post-transcriptionally mediated with hsp28 protein and mRNA being discordantly regulated. These observations underscore the complex regulation of hsp28 by RA during granulocytic differentiation of human leukemic cells and indicate hsp28 as an intermediary in the pathway through which retinoids exert their growth and differentiative effects.

Cell Cycle↗

Studies of the epidemiology of dementia: comparisons between developed and developing countries.

By the year 2025, 68% of the world's population aged 65 and above, nearly 277 million people, will be residing in developing countries. The less industrialized nations have been the least studied to date, and may yield significant new information about the etiology and risk factors for Alzheimer's disease (AD) and other dementias. Although it is readily apparent that cross-national and cross-cultural comparisons are desirable, these can be meaningful only if based on comparable methodology. In this work we will discuss some general conceptual and methodological issues regarding epidemiological studies of dementia in developing countries. The topics discussed include community-based screening for dementia, screening instruments and their application in cross-cultural studies, steps in standardization of new or modified neuropsychological tests, and some special considerations in studying uneducated/illiterate populations.

Aged↗

Truly silent ischemia and the relationship of chest pain and ST segment changes to the amount of ischemic myocardium: evaluation by supine bicycle stress echocardiography.

OBJECTIVES: The objectives of this study were 1) to determine the relationship between the amount of exercise-induced ischemic myocardium and the presence or absence of chest pain and ST segment depression, and 2) to define the incidence and characteristics of "truly silent ischemia," that is, ischemia that is not manifested by symptoms or electrocardiographic (ECG) findings. BACKGROUND: There are no prior data relating ischemia to chest pain and ST depression. Thallium-201 imaging studies have evaluated perfusion but not ischemia. In contrast, supine bicycle stress echocardiography demonstrates exercise-induced ischemic dysfunction. METHODS: Supine bicycle stress echocardiography and arteriography were performed in 130 patients and the severity and geographic extent of ischemic myocardium were compared in three groups. On exercise, Group I patients had both chest pain and ST segment depression (symptomatic ischemia), Group II patients ST depression without chest pain (asymptomatic ischemia) and Group III patients had neither chest pain nor ST depression (truly silent ischemia). RESULTS: There were no differences among groups in arteriographic characteristics. The incidence of "truly silent ischemia" was 43%. The number of abnormally contracting ischemic segments, average score per segment and sum of scores were virtually identical in Groups I and II and significantly greater than in Group III for the patients (p < 0.01 to < 0.0001), for the vessels as a group (p < 0.01 to < 0.0001) and for the left anterior descending (p < 0.01 to < 0.0001) and right (p < 0.05) coronary arteries. By multivariate analysis, positive findings on the stress ECG was the single most significant variable in relation to the amount of ischemia (p < 0.001); exercise chest pain had no significant relationship. CONCLUSIONS: Exercise-induced ST segment depression is the single most significant variable in relation to the amount of ischemic myocardium; exercise-induced chest pain is not related to the amount of ischemia. Patients with "truly silent ischemia" constitute almost 50% of patients with coronary artery disease and have less ischemia than do patients with ECG indications of ischemia, with or without chest pain.

Coronary Angiography↗

National Lesbian Health Care Survey: implications for mental health care.

This article presents demographic, lifestyle, and mental health information about 1,925 lesbians from all 50 states who participated as respondents in the National Lesbian Health Care Survey (1984-1985), the most comprehensive study on U.S. lesbians to date. Over half the sample had had thoughts about suicide at some time, and 18% had attempted suicide. Thirty-seven percent had been physically abused as a child or adult, 32% had been raped or sexually attacked, and 19% had been involved in incestuous relationships while growing up. Almost one third used tobacco on a daily basis, and about 30% drank alcohol more than once a week, 6% daily. About three fourths had received counseling at some time, and half had done so for reasons of sadness and depression. Lesbians in the survey also were socially connected and had a variety of social supports, mostly within the lesbian community. However, few had come out to all family members and coworkers. Level of openness about lesbianism was associated with less fear of exposure and with more choices about mental health counseling.

Adolescent↗

Cue conflict and stereoscopic surface slant about horizontal and vertical axes.

The way in which a planar surface is defined or configured may affect its apparent slant about a given axis, and the magnitude of slant-axis anisotropies. The authors have previously suggested that (i) these within-axis and between-axis configuration effects may be attributable, in part at least, to the perspective-disparity conflict generated when geometrically frontoparallel configured surfaces are slanted stereoscopically; and (ii) that implicit contours, defined by line endings or conjunctions, may have effects analogous to those seen with explicit contours. These possibilities were directly examined in two experiments. In experiment 1, slant-axis anisotropy was progressively induced by adding horizontal lines to a vertical-line (zero anisotropy) grid under conditions of cue conflict; slants about the vertical (but not the horizontal) were attenuated-demonstrating a clear and systematic nexus between surface configuration and slant-axis anisotropy. The presence of regular implicit horizontals similarly and selectively attenuated the slant perceived about the vertical. In experiment 2, cue conflict was seen to exacerbate slant-axis anisotropy, but clearly could not fully account for it. There was an axis asymmetry in the effect of degrading implicit contours: degradation had a marked impact on perceived slant about the horizontal but not the vertical axis.

Adult↗

Verbal intellectual and verbal memory performance of youths with childhood-onset insulin-dependent diabetes mellitus.

Tested the hypothesis that memory dysfunction mediated the decline in verbal intellectual performance (as measured by the WISC-R Vocabulary test) that we detected previously in a prospective study of children who developed IDDM between the ages of 8 to 13 years. Three tests of verbal learning and memory were administered to 57 diabetic youths at end-of-study who had been followed for 8 years, on average. Memory performance at end-of-study was predicted only by Vocabulary test score at study entry. IDDM duration, long-term metabolic control, depression/anxiety, demographic variables, or blood glucose level at the time of assessment were not associated with memory test scores. Stepwise multiple regression revealed that level of performance on a test of short-term or working memory was associated with magnitude of decline in verbal intellectual performance over time, providing partial support for our hypothesis.

Age of Onset↗

Preclinical findings with new antipsychotic agents: what makes them atypical?

Many early antipsychotics such as haloperidol, while effective in treating the symptoms of schizophrenia, cause detrimental side effects and moreover induce nonspecific sedation in many patients. Newer drugs such as remoxipride are as effective as the classical antipsychotics but induce fewer debilitating side effects. These clinical properties are reflected to some extent in their preclinical pharmacology, with drugs such as remoxipride having effects on various preclinical behavioural and biochemical models that are quite different to those exerted by drugs such as haloperidol. This article reports some new behavioural data and discusses the various mechanisms that can underlie the effect of new atypical antipsychotics.

Animals↗

Muscle glyconeogenesis during recovery from a prolonged swim in rats.

Glyconeogenesis in muscle was assessed during a 3-h recovery period after prolonged submaximal exercise represented by a 4-h swim. Rats fasted for 12 h and previously catheterized underwent this protocol with the concomitant infusion of [6-3H]glucose and one of the following: 1) [14C]bicarbonate, 2) [U-14C]lactate, and 3) [1-14C]glucose. Rested rats served as controls. The incorporation of 14C label ([14C]bicarbonate and [U-14C]lactate) or its transfer to the sixth position of glucosyl units of glycogen, over and above that taken up from circulating glucose (and determined from [6-3H]glucose uptake), was used as an index of muscle glyconeogenesis. 14C from 14CO2 is not expected to be incorporated into glycogen in muscle, and any incorporation that is not from circulating glucose is used to define experimental error. [14C]lactate incorporation measures equilibration with circulating lactate, and label randomization in glucosyl units beyond that seen in plasma glucose is taken as evidence of glyconeogenesis from locally accumulated glycolytic products. The results of these studies demonstrate 1) no glyconeogenesis in the soleus; 2) in the red and white gastrocnemii, glyconeogenesis takes place only from glycolytic products within the muscle. Approximately 35-40% of the [6-14C]glucose in glycogen can only be accounted for by muscle glyconeogenesis. The substrate does not equilibrate with circulating lactate to a detectable extent. 3) Glyconeogenesis appears to persist throughout the recovery period and uses substrate at the level of pyruvate. This is consistent with a continuing elevation of glycolysis during this period.

Animals↗