Biomedical subjects

D R O'Brien

Publications and source records attributed to D R O'Brien.

11 recordsLinked to original sources

PubMed1995

Randomized controlled trials in industrial low back pain relating to return to work. Part 1. Acute interventions.

Employers and insurers are interested in being able to use cost-effective interventions for returning injured workers to the workplace. Unfortunately, truly objective information is lacking. The purpose of this and two subsequent review articles was to perform thorough scrutiny and methodologic comparison among all obtainable, published randomized and controlled studies on low back pain (LBP) interventions leading to return to work. The study was confined to English language articles published from 1975 through 1993. Of more than 4,000 LBP citations, more than 500 were chosen for review. Of that number, 35 articles met the selection criteria of randomization, reasonable controls, and work return comparisons. This paper focuses on the 10 articles relating to interventions for acute (less than 4 weeks) LBP, and considers bed rest, exercise, spinal manipulation, back school, and case management. A 26-point quality system was used to compare the methodologic rigor of each article. This literature survey demonstrated the meager scientific foundations on which our industrial rehabilitation programs are based.

Bed Rest↗

PubMed1992

Eliminating human immunodeficiency virus (HIV) from infected individuals and cells: is it possible?

The literature from 1984 to 1991 has been searched for reports of patients who have eliminated human immunodeficiency virus (HIV) from their system. While such reports are scarce, it appears that a small number of HIV-positive patients have reverted to a negative state either spontaneously or following radical immunosuppressive regimens for neoplastic disease. Although no carefully planned animal experiments or clinical trials have been reported, it would appear that bone marrow ablation and replacement may eliminate HIV from healthy, asymptomatic HIV-positive individuals. Although much of the clinical experience to date suggests that radical immunosuppression is not indicated in advanced AIDS patients in whom the virus has likely spread beyond the immune system, such cases do not represent evidence that immunosuppression is not indicated in healthy, HIV-positive individuals.

Adult↗

PubMed1989

The effective agent in electroconvulsive therapy: convulsion or coma?

The ability of electrically-induced convulsions to alleviate at least some symptoms of mental illness was first reported in the literature 50 years ago; however, the cerebral mechanisms responsible for such therapeutic effects have thus far escaped elucidation. It is thus interesting to note that those seeking explanations for the therapeutic effects of electroconvulsive therapy (ECT) have focused their attention on the convulsion produced by ECT, as opposed to the coma. The present hypothesis emphasizes the coma following the convulsion as a potential explanation of the effectiveness of ECT and other convulsive therapies. It is postulated that the primary effect of the convulsion is to cause the release of adenosine (ARN) from neuronal tissue and that the subsequent depressant effect of ARN on neuronal activity results in the clinical effect observed. Thus hypothesis suggests that chemically-induced coma, particularly coma induced by benzodiazepines, may offer a safe, effective and more acceptable alternative to ECT.

Adenosine↗

PubMed1989

Child life services and persons with mental retardation.

We admitted an adult with mental retardation and an eating disorder to a pediatric inpatient unit. Child life services were a core feature in the assessment and treatment of the patient. The role of child life services in the care of persons with mental retardation should be expanded.

Adult↗

PubMed1989

Thyroid dysfunction in individuals with Down syndrome.

A group of 138 community-based patients with Down syndrome were examined for evidence of autoimmune thyroid dysfunction at the time of their referral for routine health care services provided as part of a model program. Twenty-eight patients (20.3%) were found to have previously unrecognized hypothyroidism, and 2 patients (1.4%) had previously unrecognized hyperthyroidism. In addition, 66 patients were tested for thyroid autoantibodies, and 26 were found to have positive antimicrosomal and/or antithyroglobulin antibody test results. There was no statistically significant association between age or sex and the mean thyrotropin value or the presence of thyroid autoantibodies. The relationship between the mean thyroxine level and sex was mildly significant. Of the patients with hypothyroidism, 78.5% were female, and most were between the ages of 30 and 50 years. However, a higher-than-expected number of patients with autoimmune hypothyroidism were under age 30 years. These findings highlight the lack of adequate health care services available to persons with Down syndrome who live in the community. All persons with Down syndrome must undergo regular clinical and laboratory screening for the presence of thyroid disease.

Adolescent↗

PubMed1988

The adenosine hypothesis of epilepsy.

The present communication summarizes a variety of diverse observations indicating that adenine ribo-nucleoside (ARN), or adenosine, may play an important role as an endogenous anti-epileptic compound in the central nervous system. From such observations has evolved an hypothesis which states that defects in the synthesis, release, action and/or degradation of ARN may be a causative factor in some forms of epilepsy. Of particular interest is the emerging realization that the adenosine system may be a common factor in the mechanism of action of many otherwise unrelated anticonvulsant compounds. Thus, a more detailed understanding of the ARN system and its role in the control of cerebral activity may lead to rational strategies for the development of efficacious therapeutic agents having greater specificity and fewer side effects.

Adenosine↗

PubMed1987

Accumulation of adenosine 3',5'-monophosphate in slices of rat cerebral cortex induced by alpha-adrenergic agonists. I. Responses to methoxamine and norepinephrine in adult and neonatal tissue.

The effects of adrenergic agonists and adenosine on the accumulation of adenosine 3',5'-monophosphate (cyclic AMP) were examined in cerebral cortical slices from adult and neonatal rats. Methoxamine (10 to 100 microM) produced up to a two-fold increase in tissue from adult animals only in the presence of optimal concentrations of adenosine (40 to 100 microM), but had no effect in neonatal tissue. Such responses were inhibited more readily by prazosin than by yohimbine, but the reverse was true for responses to norepinephrine; when tested without the addition of adenosine, however, responses to norepinephrine were somewhat more sensitive to prazosin. Under the latter conditions, norepinephrine induced about twice as much increase in cyclic AMP as did isoproterenol in adult tissue. While always prevented by alpha-adrenergic antagonists, the greater efficacy of norepinephrine was eliminated by methylxanthines only in some instances, but never in tissue from animals known to be less than 60 days of age. At 11 to 15 days of age, responses to norepinephrine were more than fourfold those to isoproterenol, even in the presence of methylxanthines, and were completely suppressed by propranolol. Responses to isoproterenol were enhanced when tested in the presence of adenosine, especially in neonatal tissue. The results suggest that both endogenous adenosine and age-related phenomena may account for some of the discrepancies among earlier studies. Moreover, they indicate that several populations of alpha-adrenergic receptors may be involved in responses to adrenergic agonists in rat cerebral cortical tissue.

Adenosine↗

PubMed1987

Accumulation of adenosine 3',5'-monophosphate in slices of rat cerebral cortex induced by alpha-adrenergic agonists. II. Studies on mechanisms underlying the interaction with adenosine.

Incubation of slices of rat cerebral cortex with the calcium ionophore A23187 produced small increases in the accumulation of adenosine 3',5'-monophosphate (cyclic AMP). While low concentrations of Ca2+ ions (e.g., 200 microM) were sometimes necessary, the presence of adenosine (e.g., 50 microM) was essential; no effect of ionophore was observed when isoproterenol or isobutylmethylxanthine was substituted for adenosine. These results are consistent with the previously advanced hypothesis that stimulation of alpha-adrenergic receptors in this issue may cause calcium mobilization and thereby produce a calmodulin-mediated stimulation of adenylate cyclase. However, there is no apparent explanation for the requirement for adenosine. In addition, the possibility that additional mechanisms may be operating was suggested by experiments in which the incorporation of 3H-adenine into cyclic AMP was examined under steady-state conditions. While brief exposure to 3H-adenine after maximal adenosine- or isoproterenol-induced accumulations had been achieved led to small increases in the specific activity of cyclic AMP, the combination of norepinephrine and adenosine (plus propranolol) produced substantial decreases in the specific activity of cyclic AMP. Since the rate of incorporation of radioactivity did not keep pace with the expansion of the cyclic AMP pool, it is possible that norepinephrine also caused some reduction in the rate of cyclic AMP degradation under these conditions. Other interpretations of these results are discussed.

Adenine↗

PubMed1987

The inverse relationship between drug affinity and effectiveness: prediction under rate theory, paradox under occupancy theory.

The two major theories of drug action are occupancy theory and rate theory. Although the two theories make a number of predictions that should serve to clearly distinguish one from the other, data generated over the last 25 years in intact muscle or organ systems have failed in this respect because the interpretation of those data has been confounded by unknown and unmeasurable factors such as the rates and extent of drug diffusion, uptake and metabolism. In the present communication rate theory and occupancy theory are discussed in the light of data obtained from a broken-cell system in which uncontrollable factors are minimized, the beta adrenergic-responsive adenylate cyclase of the S49 mouse lymphoma cell line. It is pointed out that rate theory predicts an inverse relationship between the affinity of isoproterenol (INE) for the beta adrenergic receptor and the magnitude of stimulation of adenylate cyclase. On the other hand, occupancy theory predicts that the affinity of INE and the magnitude of its effect will be directly related. By fitting data obtained in this system to the simple equations derived from the two theories it is demonstrated that the available data are in excellent agreement with the predictions of rate theory and diametrically opposed to the predictions of occupancy theory.

Adenylyl Cyclases↗

PubMed1986

Effects of D-aspartate on excitatory amino acid-induced release of [3H]GABA from goldfish retina.

The rate of release of [3H]GABA from isolated intact goldfish retinas was studied. Release of [3H]GABA is markedly stimulated by the inclusion in the incubation medium of the photoreceptor neurotransmitter candidates L-glutamate (L-Glu) and L-aspartate (L-Asp), and the glutamate analogs, kainate and quisqualate. At micromolar concentrations, kainate and quisqualate are effective releasers of [3H]GABA, whereas millimolar concentrations of L-Glu and L-Asp are required to release comparable amounts of [3H]GABA. The D-isomers of aspartate (D-Asp) and glutamate (D-Glu) are able to release [3H]GABA, but only when applied at high concentrations (3-30 mM). In the presence of 5 mM D-Asp, the effect of L-Glu in releasing [3H]GABA was markedly potentiated. This dose-response curve of L-Glu was shifted to the left in the presence of D-Asp, although the maximal amount of release was unchanged. D-Asp at 5 mM only slightly increased the GABA release induced by quisqualate, and it did not increase the GABA release induced by kainate. Finally, low concentrations of L-Asp were potentiated by D-Asp, but higher concentrations of L-Asp (3-10 mM) were clearly inhibited by this agent. This biphasic effect of D-Asp on L-Asp-induced release of [3H]GABA is a possible explanation for previously conflicting reports of D-Asp's effect on L-Asp action. Our data suggest that D-Asp has both pre- and postsynaptic sites of action.

Amino Acids↗

PubMed1985

Dopaminergic regulation of GABA release from the intact goldfish retina.

The rate of release of [3H]GABA from intact goldfish retinas was studied using a modified superfusion technique. Small, significant increases in the rate of GABA release were observed when the retinas were exposed to dopamine (DA) (100-1000 microM); however, when free Ca2+ was removed from the medium, the basal rate of GABA release was increased and DA became inhibitory. Forskolin, a non-specific stimulator of adenylate cyclase in intact cells, also inhibited GABA release in the absence of Ca2+. There was no significant effect of forskolin in the presence of Ca2+; however, (+)-butaclamol, a dopamine antagonist, increased basal GABA release under these conditions. L-glutamic acid (L-Glu) (1-10 mM) causes up to a 10-fold increase in GABA release. In the presence of Ca2+, DA did not significantly alter the effects of L-Glu; however, in the absence of Ca2+ a significant inhibition of the effects of L-Glu by DA was observed. Forskolin, on the other hand, inhibited the effects of L-Glu both in the presence and absence of Ca2+. Finally, EGTA (0.3-1 mM) produced a large release of GABA: this release was inhibited by DA, forskolin, theophylline, and 8-bromo cyclic AMP. These results suggest a model wherein DA stimulates Ca2+-dependent GABA release from one site and inhibits Ca2+-independent GABA release from another site via a cyclic AMP-mediated event.

Animals↗