PubMed Health⌕ Search

Biomedical subjects

R H Lenox

Publications and source records attributed to R H Lenox.

15 recordsLinked to original sources
PubMed1992

Increased motor activity and recurrent manic episodes: predictors of rapid relapse in remitted bipolar disorder patients after lithium discontinuation.

Ten patients with remitted bipolar illness on lithium maintenance therapy underwent placebo-controlled lithium discontinuation. Clinical ratings and recording of sleep-wake activity using wrist-worn actigraphs were carried out before and after lithium discontinuation. Seven patients experienced relapse into mania or hypomania within the first 3 months after lithium discontinuation. Actigraphic recordings revealed that patients who relapsed had higher baseline levels of daytime motor activity than patients without relapse. This may suggest that motor activity can be a sensitive marker of subclinical manic tendencies and early relapse following lithium discontinuation.

Adult↗
PubMed1992

Chronic lithium administration alters a prominent PKC substrate in rat hippocampus.

The therapeutic effect of lithium in the treatment of bipolar disorder exhibits a significant delay in the onset of action and a persistence of efficacy beyond abrupt discontinuation of treatment. Lithium is known to alter receptor-coupled phosphoinositide second messenger pathway in brain, resulting in indirect changes in an endogenous activator of protein kinase C (PKC). Such evidence has suggested that PKC may be involved in the mechanism of action of lithium in the brain. PKC represents a site wherein long-term regulatory changes in cell function occur through the phosphorylation of specific phosphoproteins involved in processes including neurotransmitter release and receptor activation. In studies of rats exposed to lithium, however, we have found no significant effects of chronic administration on the relative activity, subcellular distribution, or activation of PKC in hippocampus. We did find a major reduction in the in vitro PKC mediated phosphorylation of two major substrates, 83 kDa and 45 kDa, in hippocampus of rats exposed to chronic lithium and maintaining clinically relevant therapeutic levels in brain. Using immunoblot analysis we have identified a known myristoylated alanine-rich C kinase substrate (MARCKS) at 83 kDa. In vivo levels of MARCKS in hippocampus were found to be significantly reduced after chronic lithium exposure. These findings persist in animals withdrawn from lithium, but are not apparent following acute treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Peripheral noradrenergic function during chronic lithium treatment in the rat.

Noradrenergic function was evaluated in the rat vas deferens following chronic treatment with lithium (30 mM in the diet for 2 weeks followed by 50 mM for 1 week). No alteration could be detected in: a) 3H-noradrenaline release evoked by electrical field stimulation, b) alpha 1-adrenoceptor function as assessed by contractile response to noradrenaline, c) active neuronal uptake of 3H-noradrenaline, d) alpha 2-adrenoceptor activity, as assessed by yohimbine-enhancement of evoked release of 3H-noradrenaline. The data argue against a primary action of lithium on the noradrenergic nerve. On the other hand, these findings do not rule out the possibility that the function of CNS noradrenergic neurons could be altered as a result of the known effects of lithium on the phosphatidyl-inositol system, and the greater sensitivity of CNS neurons to depletion of the neuronal membrane inositol pool.

Animals↗
PubMed1992

Adjunctive treatment of manic agitation with lorazepam versus haloperidol: a double-blind study.

BACKGROUND: While lithium is effective in treating the majority of bipolar patients during a manic episode, the addition of neuroleptic during the early phase of treatment has been common clinical practice in inpatient settings. In an earlier open study, we demonstrated the utility of the short-acting benzodiazepine lorazepam as an adjunct to lithium for the clinical management of manic agitation. METHOD: We now present data from a randomized, double-blind clinical study of lorazepam versus haloperidol in 20 hospitalized patients with a DSM-III-R diagnosis of bipolar disorder who were being treated concomitantly with lithium. Patients were rated using the Mania Rating Scale, Brief Psychiatric Rating Scale, Physician Global Impression Scale, and side effects scales. Data were analyzed using standard group comparisons and survival analysis. RESULTS: There was no evidence for a significant difference between the two treatment groups in the magnitude of or time to response (5.0 +/- .82 days for haloperidol; 6.5 +/- .93 days for lorazepam). Of the patients who were terminated from the protocol early, nonresponse was the primary reason in the lorazepam group while side effects were the reason in the haloperidol group. CONCLUSION: Lorazepam may offer an efficacious and safe alternative to haloperidol as an adjunctive treatment to lithium in the clinical management of the early phase of manic agitation in a subgroup of bipolar patients.

Adult↗
PubMed1979

Changes in brain levels of cyclic nucleotides and gamma-aminobutyric acid in barbiturate dependence and withdrawal.

Rats exposed to chronic intake of sodium barbital maintained high circulating levels of barbital in blood and brain and exhibited increased sensitivity ot audiogenic convulsions during the withdrawal period. Levels of gamma-aminobutyric acid (GABA), glutamate, guanosine 3',5'-monophosphate (cyclic GMP) and adenosine 3',5'-monophosphate (cyclic AMP) were measured in selected brain regions after sacrifice with high power microwave inactivation. Cyclic GMP during chronic barbital administration was significantly lower than controls in most brain regions, especially the hindbrain. During the withdrawal period cyclic GMP in the cerebellum was significantly increased, while returning at least to control levels in all other regions. GABA throughout the brain tended to be reduced during barbital dependence, while cyclic AMP and glutamate levels remained unchanged in all groups. These results indicate a possible role for cyclic GMP in the mediation of the central nervous system response during barbiturate dependence and withdrawal.

Acoustic Stimulation↗
PubMed1979

Dopamine diffusion after microwave fixation at 986 MHz.

It has been previously demonstrated by us that microwave irradiation at 2450 MHz causes diffusion of dopamine from rat brain regions of high dopamine concentration to contiguous regions low in dopamine. Because we have found that the heating pattern at 986 MHz is opposite to that seen at 2450 MHz, we attempted in the present study to eliminate DA diffusion by heating at 986 MHz. However, dopamine levels were elevated in frontal and parietal cortex, remainder of cortex, and amygdala after sacrifice by microwave irradiation at 986 MHz. Norepinephrine levels were unaffected by sacrifice method. Microwave-induced diffusion of certain substances must be considered in the interpretation of regional neurochemical data.

Animals↗
PubMed1977

Regional levels of cyclic AMP in rat brain: pitfalls of microwave inactivation.

Techniques of in-vivo microwave irradiation to inactivate brain enzymes in rats were varied as to exposure configuration and output power. The rate at which metabolism was stopped was studied in various regions of the rat brain, using changes in levels of cyclic AMP and phosphodiesterase activity. Exposure times required to obtain stabilized levels of cyclic AMP varied in different brain regions, i.e., hypothalamus, cortex and cerebellum. Levels of cyclic AMP in selective regions of the brain decreased as more rapid inactivation was achieved. The authors identify important sources of variability of present microwave inactivation systems and the need for improved control of signficant microwave parameters.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1976

Statistical characterization of the random errors in the radioimmunoassay dose--response variable.

We have developed practical methods for evaluating the magnitude of the random errors in radioimmunoassay dose--response variables, and the relationship between this error and position on the dose--response curve. This is important: to obtain appropriate weights for each point on the dose--response curve when utilizing least-squares curve-fitting methods; to evaluate whether the standards and the unknowns are subject to error of the same magnitude; for quality-control purposes; and to study the sources of errors in radioimmunoassay. Both standards and unknowns in radioimmunoassays for cAMP and cGMP were analyzed in triplicate. The same mean (Y), sample standard deviation, sy, and variance (2-y) of the response variable were calculated for each dose level. The relationship between s 2-y and y was calculated utilizing several models. Results for standards and unknowns from several assays were pooled, and a curve smoothing procedure was used to minimize random sampling errors. This pooling increased the reliability of the analysis, and confirmed the presence of the theoretically predicted nonuniformity of variance. Thus, the calculation of results from these radioimmunoassays should utilize a weighted least-squares curve-fitting program. These analyses have been computerized, and can be used as a "pre-processor" for programs for routine analysis of results of radioimmunoassay.

Analysis of Variance↗