5-HT3 Receptor-independent Inhibition of the Depolarization-induced 86Rb Efflux from Human Neuroblastoma Cells,TE671, by Ondansetron

The 5-HT₃-receptor antagonist, ondansetron, has been shown to have positive effects in selected in-vivo models of memory impairment and anxiety. The exact mechanisms underlying such bioactivities are unknown. In the present work, an ⁸⁶Rb efflux bioassay was used to show that ondansetron has a unique ability to block voltage-gated potassium channels in TE671 human neuroblastoma cells. This intrinsic potassium-channel-blocking (KCB) property is relatively weak (IC50 20 (M), but is not shared by other 5-HT₃-receptor ligands including zatosetron, MDL 72222, LY 278, 584, zacopride, 1-phenylbiguanide, and ICS 205–930 (tropisetron). Pre-incubation of the target neuroblastoma cells with several 5-HT-receptor ligands including 5-hydroxytryptamine, 8-OH-DPAT, ketanserin, 2-methyl-5-HT, as well as a number of potent 5-HT₃ agonists and antagonists and two selective neurotoxins, failed to abolish the KCB action of ondansetron. A preliminary structure-activity relationship analysis indicates that the KCB activity of ondansetron is almost entirely attributable to its structural nucleus, 2,3-dihyro-9-methyl-4(lH)-carbazolone. It is hypothesized that the KCB action of ondansetron is mediated through receptors other than 5-HT₃ receptors. The KCB activity of ondansetron may be a significant factor in the in-vivo cognition-enhancing activities of this compound, conceivably due to depolarization of the hippocampal synaptic membranes and a consequent augmentation of neurotransmission.     

Elevated levels of acute phase plasma proteins in major depression.

Levels of acute phase and other plasma proteins were measured in 21 men with major depression, 28 men with alcohol dependence, and 12 men who acted as controls. The depressed men had significantly elevated levels of the acute phase proteins, haptoglobin and alpha-1-antichymotrypsin, and of immunoglobulin G. The elevations in haptoglobin and alpha-1-antichymotrypsin were highly correlated with each other, and were correlated with the severity of depression and negatively correlated with the thyroid stimulating hormone response to thyrotropin. The alcoholic men had elevated haptoglobin levels, but significantly decreased levels of immunoglobulin G. These findings provide further evidence for an inflammatory response during depression.     

Case study of a patient with severe nephrotic syndrome

M.T. battled SLE for 9 years before renal failure occurred. She is now free of extrarenal symptoms of lupus, as has been described elsewhere (Ziff & Hilderman, 1983). The patient has regained here appetite, lost 13 pounds, recovered some strength and reestablished her social network. Without the severe proteinuria, M.T. has a chance to improve her nutritional status and increase her albumin. Her pulmonary status may also improve if she can refrain from smoking. Although fatigue is a debilitating feature of lupus, M.T. has increased stamina and is learning energy conservation techniques. Immediately after surgery, she did experience problems with bleeding, pneumonia, and pleural effusions, but the medical and nursing management prevented serious adverse outcomes. Fluid balance is no longer problematic, and M.T. is approaching her ideal body weight as her nutritional status improves. Her serum albumin has increased to about 2.6 gm/dl with some decrease in her proteinuria.     

Advanced practice nurses in emergency care settings: A demographic profile.

INTRODUCTION: Very little is known about clinical nurse specialists and nurse practitioners (advance practice nurses [APNs]) who practice in emergency care settings. The Advanced Practice Committee of the ENA sought to determine a profile of these individuals. METHODS: Surveys were distributed to all registrants at 2 ENA conferences and posted on the ENA Web site. This survey asked 17 questions concerning the demographic characteristics of the APN respondents (eg, education, experience, certification, state recognition, and practice area). The survey was completed by 166 APNs. RESULTS: APNs had considerable experience as ED registered nurses before becoming an APN. They obtained their APN education at the master's degree or post-master's degree level. State recognition was required for 89.2% of the APNs. The majority of APNs (61.4%) obtained their certification through the American Nurses Credentialing Center. Nurse practitioners were predominantly family nurse practitioners (43%), and clinical nurse specialists were either critical care clinical nurse specialists (8.9%) or had other certifications (5.9%). APNs provided services in both the main emergency department and the fast track (45.7%) and were relatively new to their role as an APN. DISCUSSION: Consistent with current educational and certification requirements, the vast majority of APNs held a master's degree. Although relatively new to their role as APNs in emergency care, they were nonetheless very experienced as ED registered nurses. The majority of APNs were certified, even though that is not required for practice in all states. Continued research is needed to identify the most effective utilization of APNs, document their contributions to patient care outcomes, and develop strategies to meet their educational and practice needs.     

The Alcohol Beverage Warning Label: When Did Knowledge Increase?

This article presents data on the awareness of the alcohol beverage warning label among a sample of 5,169 inner city African-American gravidas seeking prenatal care. While the label law was implemented in November 1989, a significant increase in knowledge of the label did not occur until March 1990. Women who predominantly consumed wine coolers and beer, and those under age 30 were more likely to know about the label than their counterparts.     

Coordinated diagnostic approach for adult obstructive lung disease in primary care.

AIMS: To present an age-stratified approach to the diagnosis of obstructive lung disease based on asthma and COPD guidelines and epidemiology. METHODS: Asthma guidelines emphasize the role of the history and physical examination, with pulmonary function used primarily to confirm the diagnosis. COPD guidelines begin with symptoms and risk exposure, presenting spirometry as the primary diagnostic maneuver. Data from the National Health Interview Survey and the Third National Health and Nutrition Examination Survey illustrate relationships in prevalence of asthma and COPD in nationally representative samples. RESULTS: Asthma prevalence in adults declines with age from 5-10% at age 20-40 to 4-8% above age 60. COPD is uncommon in adults under age 40 but increases with age, surpassing asthma in older adults. CONCLUSIONS: These trends suggest that asthma screening is most useful in adults up to age 40, after which COPD screening and differential diagnosis are of comparable or greater utility.     

Physiological evaluation of gait disturbances post stroke.

A large proportion of stroke survivors have to deal with problems in mobility. Proper evaluations must be undertaken to understand the sensorimotor impairments underlying locomotor disorders post stroke, so that evidence-based interventions can be developed. The current electrophysiological, biomechanical, and imagery evaluations that provide insight into locomotor dysfunction post stroke, as well as their advantages and limitations, are reviewed in this paper. In particular, electrophysiological evaluations focus on the contrast of electromyographic patterns and integrity of spinal reflex pathways during perturbed and unperturbed locomotion between persons with stroke and healthy individuals. At a behavioral level, biomechanical evaluations that include temporal distance factors, kinematic and kinetic analyses, as well as the mechanical energy and metabolic cost, are useful when combined with electrophysiological measures for the interpretation of gait disturbances that are related to the control of the central nervous system or secondary to biomechanical constraints. Finally, current methods in imaging and transcranial magnetic stimulation can provide further insight into cortical control of locomotion and the integrity of the corticospinal pathways.     

Temazepam impairs effortful but not automatic processing of stimulus elements

The experiment investigated the effects in healthy volunteers of a single dose of temazepam (30 mg, oral) on effortful and automatic processing, by measuring memory for information and its context. Effortful processing was impaired, as shown by significant impairments in free recall of an 18-item list, but automatic processing was spared, as evidenced by no impairments in recall of the frequency of presentation, the colour, size or form of the items. In a second task, temazepam significantly impaired both recognition and recency memory of 30 items, although these scores were not correlated. Temazepam caused significant sedation, measured by an objective test and by subjective ratings, but this did not correlate with the memory impairments. The pattern of results is discussed with reference to the hypothesis that the memory impairments resulting from benzodiazepines are due to a reduction in information processing resources and thus affect effortful processing more than automatic processing.     

Organization of dopamine D1 and D2 receptors in human striatum: receptor autoradiographic studies in Huntington's disease and schizophrenia

The technique of quantitative autoradiography was used to examine the effects of Huntington's disease (HD) and schizophrenia on the organization of striatal dopamine (DA) D1 and D2 receptors. Whereas the striatum of HD cases showed a reduction in the density of D1 ([3H]SCH 23390) and D2 ([3H]spiroperidol) receptors, the patterning of D2 receptor loss did not match that of the D1 receptor loss. The HD loss of D1 D1 receptors (65%) is far greater than the loss of D2 receptors (28%). Whereas there was a dorsal-ventral gradient of effect on both receptor subtypes, the effects of HD on D2 receptors in the ventral putamen (PUT) and nucleus accumben septi (NAS) were minimal. Similarly, muscarinic M1 and M2 receptors demonstrate different patterns of alteration in HD. The M2 subtype, labeled with [3H]N-methylscopolamine (in the presence of excess pirenzepine to occlude M1 sites), was depleted far more than the M1 receptor subtype, labeled with [3H]pirenzepine. Although the effects of HD on [3H]mazindol labeling of DA terminals were more heterogeneous, there appeared to be a relative preservation of this afferent input to the striatum of the HD cases. In the schizophrenic cases, our autoradiographic studies confirm previous reports of an elevation of D2 receptor density in the striata of many schizophrenics. This increase was evident even though two of the three cases were known to have not been treated with neuroleptics, and the third case may also have been drug naive. However, the increase was far greater in the NAS (164%) and ventral PUT (173%) than more dorsally in the striatum (68%). The density of D1 receptors and DA terminals labeled with [3H]mazindol in the striatum of schizophrenics was not significantly different from that of control cases. Thus in both HD and schizophrenia, the ratio of D2/D1 receptors is altered in favor of the D2 population, particularly in the NAS.