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Biomedical subjects

C Ryan

Publications and source records attributed to C Ryan.

At least 37 records · Page 2Linked to original sources

Lesbian and Gay Youth: Care and Counseling.

Adolescents face many barriers in accessing appropriate primary care. Among the most underserved are lesbian, gay, and bisexual youth who are often neglected by traditional systems of care. This is a reference guide that provides background knowledge, substantive references, and detailed information on the stressors, health needs, experiences, and developmental challenges facing lesbian and gay youth. The first part focuses on experiences and needs of lesbian and gay adolescents-health challenges, identity development, their experiences, vulnerabilities, and risks, and confidentiality and legal issues that are of concern. The second part deals with primary care and disease prevention objectives in this group of adolescents-most frequent health concerns, issues of transgendered youth, special populations, primary interventions and anticipatory guidance, medical assessment, treatment, and prevention, and mental health concerns, assessment, and treatment. The third part presents an overview of HIV infection in all adolescents, with a focus on issues of concern for lesbians and gay males. It covers issues of HIV counseling, testing, and prevention as well as clinical care and prevention. Several appendices offer additional resources for primary care needs of lesbian and gay adolescents, resources for parents and youth, recommended reading for providers, adolescent HIV counseling and testing protocols and clinical care protocols.

Journal Article

Disruption of the erp/mkp-1 gene does not affect mouse development: normal MAP kinase activity in ERP/MKP-1-deficient fibroblasts.

Externally regulated phosphatase (ERP or MKP-1) is a dual specificity phosphatase that has been implicated in the dephosphorylation of mitogen activated protein kinases (MAP kinases). MAP kinase is activated in response to external signals and in turn phosphorylates proteins essential to the regulation of cell growth. To study the role of ERP/MKP-1 protein in mammalian development and its function in signal transduction we have generated mice, embryonic stem (ES), cells and mouse embryo fibroblasts (MEFs) that are deficient in the ERP/MKP-1 protein. ERP/MKP-1-deficient mice are born at normal frequency, are fertile and present no phenotypic or histologic abnormalities. MAP kinase activity and the induction of c-fos mRNA is unaltered in MEFs lacking the ERP/MKP-1 protein, indicating no alteration of the MAP kinase pathway. In addition, ERP/MKP-1 deficient MEFs grow and enter DNA synthesis at the same rate as control cells. Our results demonstrate that the activity of ERP/MKP-1 is not essential for embryo development and indicate that the lack of ERP/MKP-1 activity can be compensated by other phosphatases in vivo.

Animals

Testing the global-slowing hypothesis: are alcohol's effects on human performance process-specific or task-general?

In an interesting recent meta-analysis, Maylor and Rabbitt (1993) suggested that alcohol's effects on human performance may not be process- or stage-specific, but reflect a general, undifferentiated, cognitive slowing. According to this view, performance is globally slowed by a constant multiplicative fraction (b), such that the longer a process takes without alcohol on board (a -), the more it will be slowed by alcohol (a +). In summary: RTa+ = b b (RTa-). In this sense, the effects of alcohol are determined simply by the duration of a process or stage--not by its function or content--and attempts to map the effects of alcohol to specific cognitive operations are essentially futile. This global-slowing hypothesis entails, then, (i) that the function relating RTa+ to RTa- will be linear and increasing; (ii) that the value of b will be significantly greater than 1.0; and (iii) that all experimental factors which increase the complexity (hence, duration) of a task or stage will interact with alcohol. In this study we tested the global-slowing hypothesis directly using fixed set, varied set and concurrent sets item-recognition paradigms. All three tasks showed convincing additivity between alcohol and other key experimental factors which affect response latency (e.g., setsize, response type); there was no hint of any of the spectrum of significant interactions predicted by the global-slowing hypothesis. A meta-analysis of varied set latencies, analogous to Maylor and Rabbitt's, yielded a reasonably linear alcohol/no-alcohol function, but with a slope constant (b) less than 1.0. In all, the data provided little support for the global-slowing hypothesis.

Adolescent

Gender, type of treatment, dysfunctional attitudes, social support, life events, and depressive symptoms over naturalistic follow-up.

OBJECTIVE: The present study investigated gender differences in depressive symptoms during a naturalistic follow-up for outpatients with major depressive disorder in the National Institute of Mental Health Treatment of Depression Collaborative Research Program. Specifically, the study investigated whether gender interacted with type of treatment received, dysfunctional attitudes, life events, or social support to predict severity of depressive symptoms. In addition, aspects of these psychosocial factors (need for approval, interpersonal life events, and close friendships), hypothesized to be more salient for women, were examined to determine if they had a differential impact on level of depressive symptoms in men and women. METHOD: Assessments conducted 6, 12, and 18 months after treatment included measures of depressive symptoms, dysfunctional attitudes, current life events, and social support. Data were available for 188 subjects (134 women and 54 men). Regression analyses were conducted to examine whether gender as a main effect, or interacting with dysfunctional attitudes, life events, social support, or subtypes of these variables, predicted cross-sectional or longitudinal measures of depressive symptoms during follow-up. RESULTS: A consistent finding of the study was that over the 18 months of this naturalistic follow-up, there were no main effects for gender or any significant interactions involving gender and any of the variables of interest. The study demonstrated that life events and social support were related to severity of depressive symptoms for both genders. CONCLUSIONS: Despite differential prevalence rates of major depression for men and women, findings do not support a different process in outcome of illness for men and women.

Adult

Day case oral surgery: a review of 25 years experience at the Dublin Dental Hospital.

A retrospective analysis of the changing work-load at the Dublin Dental Hospital oral surgery day case unit was undertaken. This involved 26,697 operations performed during the 25-year period 1968-1992. The results show how the practice of oral surgery has changed over this time. Annual totals ranged from 766 to 1549 operations. While most categories of operations remained largely unchanged, the removal of impacted third molars increased from 10.5% of the annual total to 57.0%. Routine extractions of permanent teeth decreased from 53.9% of the annual total to 18.0%.

Ambulatory Surgical Procedures

28-kDa mammalian heat shock protein, a novel substrate of a growth regulatory protease involved in differentiation of human leukemia cells.

Because of their differentiating effects in neoplastic cells in vitro, the use of retinoids in the treatment of various malignant and premalignant conditions is under investigation. To date, signal transduction pathways involved in retinoid-induced differentiation remain poorly understood. Differentiation of HL-60 cells by all-trans-retinoic acid (tRA) is directly mediated by down-regulation of the serine protease myeloblastin (mbn). In this report, we investigate the possibility that the 28-kDa heat shock protein (hsp28), previously linked to differentiation of normal and neoplastic cells including HL-60, may be regulated by mbn. Using NB4 promyelocytic leukemic cells as a differentiative model, we show that tRA induces initial suppression and subsequent up-regulation of hsp28 protein, mirroring tRA-induced changes in mbn protein. The progressive reduction in hsp28 mRNA levels in response to tRA suggests that changes in hsp28 protein levels might be posttranscriptionally mediated, raising the possibility that hsp28 may be targeted by mbn. To address this, we developed an assay using purified mbn and recombinant hsp28 and now show that hsp28 is hydrolyzed by mbn but not its homologue, human neutrophil elastase. Moreover, mbn does not indiscriminately hydrolyze other proteins. Identifying hsp28 as a substrate of mbn strongly suggests that hsp28 may be a key component of the tRA signaling pathway involved in regulating cell differentiation.

Cell Differentiation

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