Biomedical subjects
L Jacobson
Publications and source records attributed to L Jacobson.
Intrathecal fentanyl alleviates spasticity in the presence of tolerance to intrathecal baclofen.
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The use of oral mexiletine for the treatment of pain after peripheral nerve injury.
Neuropathic pain is often a difficult condition to treat. Clinical and laboratory studies using intravenously administered local anesthetics or antiarrhythmic agents support the use of these drugs for the treatment of neuropathic pain. The availability of the oral antiarrhythmic medication, mexiletine, has made it possible to study the effects of an orally administered medication on chronic neuropathic pain. The study used a double-blind placebo-controlled design to examine 11 subjects in whom treatment with conventional pain medications had been unsuccessful. Subjects had a history of peripheral nerve injury or dysfunction, and all complained of symptoms consistent with neuropathic pain. After baseline pain measurements, mexiletine or placebo was given in gradually increasing doses to a maximum daily dose of 750 mg mexiletine. After 1 month at steady state, the subject received the alternative medication. Mexiletine was found to produce a statistically significant reduction in reported pain when compared to baseline or placebo. Pain scores were rated on a scale from 0 (no pain) to 10 (unbearable pain). Median pain scores prior to mexiletine were 7, after placebo treatment 7, and while receiving mexiletine (750 mg/day) 4. Side effects were mild and well-tolerated. Mexiletine may be effective in reducing neuropathic pain for patients in whom alternative pain medications have been unsatisfactory.
Development of an acute withdrawal syndrome following the cessation of intrathecal baclofen in a patient with spasticity.
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Persistent low-back pain is real. However, diagnostic spinal injections are not helpful in its evaluation.
We endeavored to assess the short-term effects of intrathecal fentanyl and lidocaine in chronic-pain patients by ascertaining whether the opioid fentanyl, by virtue of its lack of sensory and motor paralysis, conferred any diagnostic advantages over lidocaine, a local anesthetic whose effects include sensory and motor paralysis. Neuraxial administration of fentanyl has been touted as an improved diagnostic tool to distinguish between peripheral and central pain, because the absence of sensory and motor effects may avert the patient's presumption of the onset of analgesia based on these cues. Twenty-two patients with persistent low-back pain, whose investigations had determined that they were not surgical candidates, were studied using a counter-balanced, placebo-controlled, and double-blinded crossover design. Each patient received three separate lumbar intrathecal injections of equal volume (1.4 ml): cerebrospinal fluid, fentanyl 25 micrograms, and lidocaine 70 mg. Pain and symptom assessments were performed preinjection (baseline), and at regular intervals up to and including 4 h postinjection. Pain was evaluated by verbal patient response using a numerical pain-rating system of 0 to 10. Duration of analgesia, sensation of warmth, and adverse effects were noted. Statistical analyses were performed using nonparametric tests. Subjects' average age was 56 years, with a median low-back pain duration of 16 years. There were no significant differences in the baseline median-pain scores among injection types. The baseline and best cerebrospinal fluid-pain scores were significantly different, suggesting a placebo effect. The best pain scores for fentanyl and lidocaine were superior to their own baseline levels and to the best cerebrospinal fluid scores.(ABSTRACT TRUNCATED AT 250 WORDS)
Hemodynamic interactions when combining verapamil, acute changes in extracellular ionized calcium concentration and enflurane, halothane or isoflurane in chronically instrumented dogs.
To assess the hemodynamic interactions when combining verapamil, acute changes in extracellular ionized calcium concentration [Ca2+] and enflurane (2.5%), halothane (1.2%) or isoflurane (1.6%), seven dogs were chronically instrumented to measure heart rate (HR), aortic, left atrial and left ventricular (LV) pressures, and cardiac output (CO). [Ca2+] was lowered 0.35 mmol.l-1 by citrate infusion and then increased 0.35 mmol.l-1 above control level by CaCl2 infusions. Verapamil was infused at 3 micrograms.kg-1 x min-1 (loading dose 200 (awake), 150 (isoflurane) or 100 (enflurane and halothane) micrograms.kg-1), giving mean verapamil concentrations around 75 (range of means: 66-84 ng.ml-1). Verapamil produced mostly minor changes in the cardiovascular effects of changing [Ca2+] in both awake and anesthetized dogs, indicating mostly additive effects. Verapamil induced a decrease in HR at high [Ca2+] and abolished an increase in mean aortic pressure at both low and high [Ca2+] awake. Verapamil exaggerated the decrease in CO and stroke volume (SV) induced by low [Ca2+] during enflurane anesthesia and abolished the increase in CO induced by low [Ca2+] and exaggerated the increase in SV and LV dP/dtmax induced by high [Ca2+] during halothane anesthesia.
Survey of nursing research in NYS: XIV.
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What is nursing research: evolving approaches to methods and content.
In addressing what constitutes nursing research in the 1990s, approaches to conducting nursing research and examples of studies are discussed in the context of historical forces. The early studies were characteristically educational in focus and quantitative by design. Nursing research has come a long way in regard to foci of the questions asked, diversity of approaches to knowledge development, and sophistication of research methods. Three approaches are described to illustrate the diversity in nursing research: quantitative, qualitative, and triangulation.
Acquired immune deficiency syndrome occurring within 5 years of infection with human immunodeficiency virus type-1: the Multicenter AIDS Cohort Study.
The objective of this study is to describe participants in the Multicenter AIDS Cohort Study (MACS) with incident infection due to the human immunodeficiency virus type-1 (HIV-1) in whom AIDS developed by March 1990 and within 5 years of seroconversion (group A). Secondly, behavioral, clinical, and immunologic characteristics of these men are compared to those of matched seroconverters remaining AIDS free (group B). Between entry into the MACS (April 1984-March 1985) and July 1989, 345 seronegative homosexual/bisexual men had HIV-1 antibody; of these men, AIDS developed in 32 by March 1990. The Kaplan-Meier estimates of the proportion of men with incident HIV-1 infection with AIDS were 6 months, 0%; 12 months, 1%; 24 months, 3%; and 48 months, 10%. These 32 men engaged in receptive anal intercourse with more partners before (p less than 0.005) and after seroconversion (p less than 0.005) and reported more sexually transmitted disease preseroconversion (p = 0.05) than did group B. These findings suggest that sexually transmitted co-factors, preseroconversion and/or postseroconversion, play a role in the progression of HIV-1 infection. Alternatively, greater sexual activity could increase the hazard of exposure to a more virulent HIV-1 strain.
Two isoforms of the muscle acetylcholine receptor alpha-subunit are translated in the human cell line TE671.
We have previously reported the existence of 2 forms of mRNA for the human muscle acetylcholine receptor (AChR) alpha-subunit, thought to be generated by alternate splicing of a primary transcript and to encode 2 alpha-subunit protein isoforms. The 2 predicted alpha-subunit isoforms, differing by the insertion of 25 amino acids at position 58/59, have been synthesized from cRNA transcripts using rabbit reticulocyte lysates; these protein isoforms could be differentiated by immunoprecipitation using antibodies raised against synthetic peptides. The antibodies were used to demonstrate translation of both AChR alpha-subunit isoforms in the rhabdomyosarcoma (muscle) cell line TE671, in an approximate 1:1 ratio.
A prospective study of intraoperative pulse oximetry failure.
Since pulse oximetry is now an ASA standard for intraoperative monitoring, we sought to determine the intraoperative failure rate for this device. We prospectively evaluated the intraoperative failure rate of our pulse oximeters at the four University of Washington Hospitals (University of Washington Medical Center, Veterans Affairs Medical Center [VAMC], Children's Hospital and Medical Center, and Harborview Medical Center [HMC]) recorded from April 1989 to August 1989. We defined failure as the inability to obtain any oximetry reading for a cumulative period of more than 30 minutes during any anesthetic procedure after all equipment malfunctions had been eliminated. Our puse oximeters failed in 124 of 11,046 cases studied; this is a failure rate of 1.12%, which ranged from 0.56% at HMC to 4.24% at VAMC. The failure rate at VAMC (4.24%) was significantly higher than the other hospitals (p less than 0.001). Those cases associated with the pulse oximeter failure had the following characteristics: (1) an ASA status of 3 or higher, (2) lengthy operations, and (3) elderly patients. When the device did fail in a patient, it did not function for 32% of the mean anesthesia time. We conclude that the intraoperative use of the pulse oximetry can provide information about blood oxygen saturation in most patients. However, in approximately 1% of the patients we studied in the operating room, mechanically functioning pulse oximeters failed to provide readings of blood oxygen saturations during routine operative use.
Regulation of basal ACTH secretion by corticosterone is mediated by both type I (MR) and type II (GR) receptors in rat brain.
The mechanisms involved in the physiology of the secretion of ACTH are reviewed. The secretion is regulated by the biological consequences of the occupancy of high affinity mineralocorticoid (MR) and lower affinity glucocorticoid receptors (GR) for corticosterone at specific sites of the rat brain. The regulation by this mechanism of basal secretion during the circadian rhythm, the effect of adrenalectomy and of corticosterone replacement is discussed. Experiments with RU486, a specific glucocorticoid antagonist, suggest that occupancy of both MR and GR is required for normal control of ACTH at the time of peak activity. The occupancy of the GR for a few hours per day apparently suffices to maintain steady levels of the products of GR-responsive genes throughout the body.
Comparison of oral and parenteral vitamin K prophylaxis for prevention of late hemorrhagic disease of the newborn.
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An objective comparison of intrathecal lidocaine versus fentanyl for the treatment of lower extremity spasticity.
The reduction of spasticity after administration of intrathecal fentanyl, 35 micrograms, and intrathecal lidocaine, 50 mg, was compared with preinjection spasticity levels in ten subjects with central nervous system disease or injury. Spasticity was objectively assessed by an electronic instrument that simultaneously measures degrees of extension and force during passive knee extension. Duration of spasticity relief and adverse effects were recorded. Both drugs equally reduced spasticity and increased the range of motion. There were no supraspinal side effects from the fentanyl, whereas three subjects became hypotensive after receiving lidocaine. The reduction of spasticity with intrathecal fentanyl lasted at least 3 h. The authors postulate that fentanyl reduced spasticity by an effect on spinal pathways. Intrathecal fentanyl should be considered as an alternative to lidocaine for diagnostic blocks in patients with spasticity.
The role of the hippocampus in feedback regulation of the hypothalamic-pituitary-adrenocortical axis.
There is considerable, although not entirely consistent, evidence that the hippocampus inhibits most aspects of HPA activity, including basal (circadian nadir) and circadian peak secretion as well as the onset and termination of responses to stress. Although much of the evidence for these effects rests only on the measurement of corticosteroids, recent lesion and implant studies indicate that the hippocampus regulates adrenocortical activity at the hypothalamic level, via the expression and secretion of ACTH secretagogues. Such inhibition results largely from the mediation of corticosteroid feedback, although more work is required to determine whether the hippocampus supplies a tonic inhibitory input in the absence of corticosteroids. It must be noted that the hippocampus is not the only feedback site in the adrenocortical system, since removal of its input only reduces, but does not abolish, the efficacy of corticosteroid inhibition, and since other elements of the axis appear eventually to compensate for deficits in feedback regulation. The importance of other feedback sites is further suggested not only by the presence of corticosteroid receptors in other parts of the brain and pituitary, but also by the improved prediction of CRF levels by combined hypothalamic and hippocampal receptor occupancy. The likelihood of feedback mediated by nonhippocampal sites underscores the need for future work to characterize hippocampal influence on HPA activity in the absence of changes in corticosteroid secretion. However, despite the fact that the hippocampus is not the only feedback site, it is distinguished from most potential feedback sites, including the hypothalamus and pituitary, by its high content of both type I and II corticosteroid receptors. The hippocampus is therefore capable of mediating inhibition over a wide range of steroid levels. The low end of this range is represented by corticosteroid inhibition of basal (circadian nadir) HPA activity. The apparent type I receptor specificity of this inhibition and the elevation of trough corticosteroid levels after hippocampal damage support a role for hippocampal type I receptors in regulating basal HPA activity. It is possible that basal activity is controlled in part through hippocampal inhibition of vasopressin, since the inhibition of portal blood vasopressin correlates with lower levels of hippocampal receptor occupancy, and the expression of vasopressin by some CRF neurons is sensitive to very low corticosteroid levels. At the high end of the physiological range, stress-induced or circadian peak corticosteroid secretion correlates strongly with occupancy of the lower affinity hippocampal type II receptors.(ABSTRACT TRUNCATED AT 400 WORDS)
Normative data for a brief neuropsychological screening battery. Multicenter AIDS Cohort Study.
This study reports normative data for a group of 733 homosexual/bisexual men stratified by age (range 25 to 54 years) and by education on the following six neuropsychological tests: (1) Digit Span (WAIS-R), (2) Rey Auditory Verbal Learning Test, (3) Symbol Digit Modalities Test, (4) Controlled Oral Word Association Test, (5) Grooved Pegboard, and (6) The Trail Making Test. Analysis demonstrates that both age and education are important determinants of performance for several of these measures.
An antagonist to vasoactive intestinal peptide affects cellular functions in the central nervous system.
A vasoactive intestinal peptide (VIP) antagonist was synthesized and used to investigate the interactions of VIP with its receptors present in the central nervous system (CNS). The VIP antagonist is a hybrid peptide consisting of a portion of VIP and a portion of neurotensin, designed to change the membrane permeability of the VIP portion. The hybrid antagonist displaced 80 to 90% of [125I]VIP binding to cell cultures from cerebral cortex, hippocampus or spinal cord. The displacement curve was biphasic, suggesting two binding sites. In the case of cortical astrocytes, the antagonist had a Ki of 45 pM at one site and a Ki of 74 nM at the other. At the lower affinity binding site, the antagonist was about 10-fold more potent than VIP in displacing radiolabeled VIP. The accumulation of cyclic AMP (cAMP) in VIP-stimulated cortical glia cultures was decreased by the new antagonist (EC50, 59 nM). This decrease in cAMP was greater than that achieved in the presence of other putative VIP antagonists. Finally, the addition of 1 nM hybrid antagonist to dissociated spinal cord cultures resulted in a 42% reduction in neuronal cell counts as compared with controls, and the EC50 of this effect was about 30 pM, which corresponded closely to the Ki of antagonist displacement of [125I]VIP binding at the high-affinity site. The antagonist appears to be a competitive blocker for both VIP-mediated increases in cAMP formation or VIP-associated maintenance of neuronal survival in spinal cord cultures. Thus, we describe a potent VIP antagonist which interacts with two functionally distinct VIP receptors in the CNS.
Cognitive skills & development competencies for conducting research critiques.
As the nursing profession expands its unique scientific body of knowledge, it is essential that all professional nurses become capable of evaluating the scientific and clinical merits of this information generated by nursing research. Three developmental levels of research critique skills are delineated by the nurse reader's competencies: novice, intermediate, and advanced. Each developmental level is described in relation to five cognitive skills which underlie the proposed competencies: knowledge, comprehension, analysis, evaluation, and synthesis.