Biomedical subjects

R A O'Brien

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

At least 19 recordsLinked to original sources

PubMed1996

Are alternative long-term-care programs needed for adults with chronic progressive disability?

Long-term care planning for middle-aged adults with progressive neurological impairment is a largely unexplored area. The purpose of this study was to examine factors that place individuals with progressive disability at risk for institutional placement and identify whether innovative long-term care preferences would be used if available. The sample of 102 clients with a diagnosis of multiple sclerosis (N = 92) or other progressive illnesses (N = 10) was mostly female, married and Caucasian, with an average age of 48 years. The social support network of family and friends was small; most tangible aid was provided by family members. Seventy percent of the participants used community services, the most common being a home-health aide (44%) and professional nursing services (21%). Medicaid insurance, severity of functional disability and lack of social support were associated with greater use of community services. Participants could foresee using long-term care alternatives such as a community residence (65%), adult day healthcare (63%) and family respite (46%), although these services were regarded with some ambivalence. With their knowledge of community resources, nurses are in a key position to make early assessments of clients' present and future care needs and to suggest needed modifications in living arrangements to avoid premature institutionalization.

Activities of Daily Living↗

PubMed1995

Correlates of the caregiving process in multiple sclerosis.

This study sought to identify predictors of general health, mood, family, and life satisfaction for spousal caregivers of persons with multiple sclerosis. Cross-sectional data were obtained through structured interviews with 34 husbands and 27 wives of the disabled individuals. Results of the hierarchical regression analyses indicated that objective burden, subjective burden, and perceived uncertainty about the illness situation accounted for the largest proportion of variance in caregivers' general health, mood, family and life satisfaction. Perceived social support explained an additional small, but significant proportion in caregivers' general health, mood, and family satisfaction. Contrary to expectation, family coping did not significantly explain any variance in caregiver outcome measures.

Adaptation, Psychological↗

PubMed1993

Reduction of spontaneous alcohol drinking and physical withdrawal by levemopamil, a novel Ca2+ channel antagonist, in rats.

Neuronal Ca2+ channels have been shown to be involved in both alcohol drinking behavior in rats and nonhuman primates and in the manifestation of alcohol withdrawal symptoms in rodents. Experiments were performed to determine the effect of a single injection of levemopamil, a novel Ca2+ channel antagonist with antiserotonergic [5-hydroxytryptamine2 (5-HT2)] properties, on alcohol preference and alcohol withdrawal symptoms in alcohol-preferring (P) and Wistar rats, respectively. P rats were individually housed and provided free access to food, water, and a solution of 10% (v/v) ethanol. Ethanol, food, and water intakes were measured daily. After establishing a stable baseline, P rats were injected with levemopamil (0, 3.3, 10, 15, and 20 mg/kg) and their food, water, and alcohol intakes measured 24 h later. In a separate experiment, the ability of acute and chronic (12 consecutive days) administrations of levemopamil to suppress alcohol withdrawal symptoms in chronically alcohol-treated rats was studied. In addition, the effects of levemopamil on the level of monoamines in different areas of the brain, as well as its action in alcohol metabolism, were examined. Our findings showed that a single administration of levemopamil (10, 15, and 20 mg/kg) significantly and dose-dependently attenuated alcohol intake and increased water intake in P rats. Both acute and chronic treatment with levemopamil reduced the alcohol withdrawal symptoms, overall seizure scores, and proportion of rats seizing. A single injection of levemopamil produced a clear, but not significant, trend to increase the 5-HT turnover rate in certain brain areas. This drug did not influence the pharmacokinetics of alcohol.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking↗

PubMed1993

Congruence in uncertainty between individuals with multiple sclerosis and their spouses.

The purpose of this study was to examine differences in the perception of illness uncertainty between husband and wife and to explore how these differences influence emotional well-being. Mood and family satisfaction were used as indicators of emotional well-being. The sample consisted of sixty-one married couples in which one spouse had multiple sclerosis. Results supported that both individual perceptions of illness uncertainty and congruence in perceived uncertainty between spouses may have negative effects on marital partners. For both spouses, those who reported higher levels of uncertainty were more likely to have lower moods and feel more dissatisfied with family life. However, the most crucial factor in determining family satisfaction for spouses with multiple sclerosis was their own perception of illness uncertainty, while for well spouses, it was the congruence between each partner's perception of the illness uncertainty.

Activities of Daily Living↗

PubMed1990

Deliberations on nursing administration practice.

Blair and O'Brien orient us to the conference where this issue's articles on nursing administration education originated. The authors stress the critical need for development of nursing administration theory.

Career Mobility↗

PubMed1989

Simultaneous administration of thromboxane A2- and serotonin S2-receptor antagonists markedly enhances thrombolysis and prevents or delays reocclusion after tissue-type plasminogen activator in a canine model of coronary thrombosis.

Dynamic changes of the thrombus after its formation due to platelet activation may affect the speed of thrombolysis. In the present study, we wanted to evaluate the role played by thromboxane A2 (TXA2) and serotonin (5HT) in mediating platelet activation during lysis of intracoronary thrombi with human recombinant tissue-type plasminogen activator (t-PA). Coronary thrombi were induced in 26 anesthetized, open-chest dogs by inserting a copper coil into the left anterior descending coronary artery (LAD). LAD blood flow was monitored throughout the experiment by means of a Doppler flow probe placed proximally to the coil. Presence of the thrombus was documented for 30 minutes. The dogs were then assigned to one of four groups as follows: group 1 dogs (n = 8), serving as controls, received a bolus of heparin (200 units/kg) and a bolus of t-PA (80 micrograms/kg) followed by a continuous infusion (8 micrograms/kg/min) for up to 90 minutes or until reperfusion was achieved; group 2 dogs (n = 10) received, immediately before heparin and t-PA, an intravenous bolus of SQ29548 (SQ) (0.4 mg/kg, a selective TXA2-receptor antagonist) and LY53857 (LY) (0.2 mg/kg, a selective serotonin S2-receptor antagonist); group 3 dogs (n = 7) received, before heparin and t-PA, an intravenous bolus of SQ alone (0.4 mg/kg); and group 4 dogs (n = 7) received, before heparin and t-PA, an intravenous bolus of LY alone (0.2 mg/kg). After thrombolysis, all dogs were monitored for 90 minutes or until a persistent reocclusion occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Metastatic anaplastic oligodendroglioma.

We report 7 patients, ages 21 to 49 years, with systemic metastasis from anaplastic oligodendroglioma. Metastases developed in the scalp, cervical lymph nodes, bone, and other organs 1 to 76 months after the most recent surgery and 18 to 86 months after diagnosis. Systemic metastases responded to focal radiotherapy or nitrosourea-based chemotherapy for 6 to 18 months. Five patients have died, 4 to 24 months after the appearance of systemic metastases, all with progressive cerebral and systemic tumor. We observed 2 distinct patterns of spread of oligodendroglioma. Pattern 1, initial scalp or regional lymph node involvement followed by distant metastasis, was associated with multiple craniotomies. Pattern 2, distant metastasis without scalp or regional lymph node spread, was associated with early radiotherapy and chemotherapy. Longer-than-expected survival was not essential to metastasis. We speculate that anaplastic oligodendrogliomas possess special characteristics favoring metastasis and that early aggressive treatment alters the biology of this disease.

Adult↗

PubMed1986

Reinnervation of fast and slow mammalian muscles by a superfluous number of motor axons.

In this study peripheral nerves from flexor digitorum longus, (alien nerve) as well as the deep branch of the muscle's own lateral popliteal nerve were cut and connected to the distal stump of the lateral popliteal nerve. Extensor digitorum longus and tibialis anterior muscles then became reinnervated to a similar extent by either nerve, showing no preference for its own nerve. A significant proportion of the endplates in these muscles remained permanently supplied by more than one axon, and a proportion of the muscle fibres was supplied by both nerves. No ectopic endplates were formed on fast muscle fibres. The same two nerves were also connected to the slow soleus muscle and this muscle became preferentially reinnervated by the nerve to flexor digitorum longus. In contrast to fast muscles, endplates of soleus muscle fibres were only rarely contacted by more than one axon, and ectopic endplates were often found in this muscle. In both types of muscles that had an excess of motor nerves, extensive sprouting persisted for many months. Thus, identical motor nerves induce different patterns of innervation in slow and fast muscles, and muscle fibres do not show a preference for their own nerve.

Animals↗

PubMed1985

The effect of altered peripheral field on motoneurone function in developing rat soleus muscles.

In soleus muscles of 4- to 5-day-old rats the quantum content of axon terminals from L4 spinal roots is less than half that from L5. With development the size of L4 motor units decreases and the quantum content of L4 nerves increases to become similar to that of L5 axons. During this time the overlap of territories of L4 and L5 axons is reduced from 46% at 4-6 days to 2% at 18-20 days. This reduction occurs entirely at the expense of L4 territory. Removal of the L5 ventral ramus (v.r.) at 4-6 days prevents the reduction of L4 territory so that at 18 days L4 motor units are about 4 X normal size. In spite of this enlarged peripheral field of L4 axons the quantum content of their terminals increases to normal levels. When L5 v.r. was removed at 16-18 days, i.e. when the reduction of the L4 peripheral field was complete, expansion of L4 motor units was also seen, but in this case the quantum content of L4 terminals was less than normal. Thus it appears that during early stages of development, before synaptic reorganization within the muscle is complete, motoneurones are able to adapt their function to increased peripheral demands more effectively than at later stages of post-natal development. Retrograde labelling of soleus motor pool with horseradish peroxidase (HRP) showed that removal of L5 v.r. either at 4 or 15 days of age reduced the number of motoneurones supplying soleus muscle to less than 20%. No change in size of the remaining motoneurones was seen, indicating that the adjustment of transmitter output at the neuromuscular junctions in the younger group had no effect on the size of the cell.

Animals↗

PubMed1984

Protease inhibitors reduce the loss of nerve terminals induced by activity and calcium in developing rat soleus muscles in vitro.

The end-plate of a mammalian skeletal muscle fibre is innervated by several axons at the time of birth but by only one axon in the adult. In the rat soleus muscle the transition from polyneuronal to single innervation occurs during the first 2-3 weeks after birth. While it is evident that the loss of the excess nerve terminals depends to some extent on neuromuscular activity, the mechanism involved is not known. In the present experiments neonatal rat soleus muscles were stimulated in vitro in the presence of a variety of combinations of calcium, the cholinesterase inhibitor edrophonium and the proteolytic enzyme inhibitors leupeptin, pepstatin and Ep-475. Electron microscopical examination revealed that stimulation alone had little effect on the morphology of the end-plate region but stimulation in the presence of raised levels of calcium caused severe disruption of the nerve terminals and a marked reduction in the number of intact nerve terminal profiles contacting each end-plate. Contraction measurements showed that, in spite of this, the muscles were not functionally denervated to any large extent. The addition of edrophonium potentiated the morphological alterations but caused no further reduction in the number of profiles. Conversely, the protease inhibitors wholly or partially (in the case of Ep-475) prevented the effects of stimulation and calcium on the nerve terminals. These results are consistent with the idea that neuromuscular activity induces the secretion of proteolytic enzymes into the end-plate region, where they digest the immature nerve terminals. The importance of calcium suggests that the calcium-dependent neutral protease may be involved, and is also consistent with a secretory mechanism. The possibility that the nerve terminals are digested by their own proteases is also discussed.

Acetylcholine↗

PubMed1983

A pharmacokinetic/pharmacodynamic/receptor binding model to predict the onset and duration of pharmacological activity of the benzodiazepines.

Ex vivo receptor binding as a function of time was determined in Charles River rats. The pharmacokinetic and protein binding parameters in man as well as the ex vivo receptor binding parameters in rat brain for three benzodiazepine induction agents, diazepam, lorazepam and midazolam, were used to develop and test a pharmacokinetic/pharmacodynamic/receptor binding model. The model was subsequently used to predict changes in receptor binding and pharmacodynamics as a function of changes in pharmacokinetics. The model was found to be a good predictor of the relative onset and duration of the sedative and amnesic properties in normal subjects as well as in the presence of certain patho-physiological conditions and certain drug interactions.

Animals↗

PubMed1982

[3H]CL 218,872, a novel triazolopyridazine which labels the benzodiazepine receptors in rat brain.

We examined the specific binding of [3H]CL 218,872, a novel triazolopyridazine to benzodiazepine receptors in the rat cerebral cortex. Two binding sites with KD values of about 10-30 nM and 200-600 nM were demonstrated. A number of benzodiazepine anxiolytics inhibited [3H]CL 218,872 binding in a manner which correlates with the potency of these drugs for inhibiting [3H]benzodiazepine binding. Our initial studies show that [3H]CL 218,872 can label the benzodiazepine receptors and may prove to be a useful probe for studying benzodiazepine heterogeneity and regulation.

Animals↗

PubMed1982

Abnormal brown adipose composition and beta-adrenoceptor binding in obese Zucker rats.

The composition, morphology, beta-adrenergic receptor binding, and in vitro lipolysis were examined in lean and obese, 5- to 6-mo-old male Zucker rat interscapular brown adipose tissue (IBAT). IBAT pads from obese rats were heavier (283%), had more lipid (700%), and more (75%)( and larger (83%) adipocytes than those from lean rats. Also, IBAT from obese rats had no multiloculated cells, and 50% of their IBAT adipocytes were the size of white fat cells. High affinity binding for (-)-[3H]dihydroalprenolol (KD, 15-18 nM), as well as the estimated KD values for binding and the 1/2 Vmax values for adrenergic agonist-induced lipolysis were similar in isolated IBAT cells from lean and obese rats. However, adipocytes from IBAT in obese rats had 75% fewer high affinity beta-adrenergic binding sites per cell (Bmax) compared to those in lean rats. These findings are most compatible with the infiltration of IBAT by white adipocytes. Such infiltration would be expected to reduce the overall thermogenic capacity of IBAT in obese Zucker rats and thereby contribute to the maintenance of their obesity.

Adipose Tissue, Brown↗

PubMed1982

Binding of a radiolabeled triazolopyridazine to a subtype of benzodiazepine receptor in the rat cerebellum.

The triazolopyridazine (TPZ) drugs, typified by CL218,872 (CL), have a relatively higher affinity for a subpopulation of benzodiazepine (BZ) receptors. The binding of radiolabeled CL to membranes from rat cerebellum, a region enriched in the TPZ-preferring ("Type 1") BZ receptor, was characterized and compared with that of [3H]flunitrazepam ([3H]FLU) in the same preparation. [3H]CL had clonazepam displaceable binding which was saturable. The Kd was approximately 21 nM and the Bmax was approximately 600 fmol/mg of protein. [3H]CL binding was similar to that for [3H]FLU in that exogenous gamma-aminobutyric acid (GABA) enhanced the binding; however, [3H]CL binding differed from that for [3H]FLU in that anions, cartazolate and pentobarbital did not enhance [3H]CL binding. These data suggest that [3H]CL binds to the Type 1 BZ receptor in a manner different from that of a BZ drug such as FLU. Inasmuch as GABA enhances [3H]CL binding, but anions, cartazolate and pentobarbital do not, [3H]CL may bind to the Type 1 BZ receptor in such a way that it interacts with the GABA site, but perhaps not directly with the ionophore or the postulated pyrazolopyridine-barbiturate site. Thus, TPZ drugs may affect the GABA receptor complex in a different or perhaps less extensive way than the BZs. This, in addition to the regional localization of the Type 1 receptor, may be an important part of the mechanism of action of the TPZs.

Animals↗

PubMed1982