Biomedical subjects
Publications and source records attributed to L L Davis.
Environmental heat-related deaths and illnesses in the United States are considered preventable. Through proper education, planning, and hydration, hundreds of individuals would not succumb to heat-related illness.
The overlap in clinical phenomenology and morbidity between post-traumatic stress disorder (PTSD) and such conditions as major depression, anxiety disorders and aggression, in which a serotonin dysfunction is implicated, suggests a role for serotonin in the pathophysiology of PTSD. In this paper, we review current knowledge concerning the role of serotonergic mechanisms and interventions in PTSD. Since there is no clearly effective pharmacologic intervention for this disorder, the underlying neurochemical dysfunction needs to be carefully defined so that more effective treatment can be developed. Preclinical and clinical studies of the serotonergic mechanisms in the pathophysiology of PTSD and treatment trials involving serotonergic agents are limited, but indicate considerable promise. Further investigation of a serotonergic dysfunction in PTSD and of its treatment with serotonergic agents is warranted.
Low levels of gamma-aminobutyric acid (GABA) in plasma have been associated with the presence of mood disorders in patients with major depressive disorder. We examined plasma GABA in patients with panic disorder, a disorder that is often comorbid with major depression, and in a group of control subjects. Patients with panic disorder had plasma GABA levels that did not differ significantly from levels in controls subjects. These data support the specificity of low plasma GABA as a marker for mood disorders.
Growth hormone (GH) response and baclofen levels were measured in seven healthy adult men following a 10-mg and a 20-mg dose of oral baclofen (gamma-aminobutyric acidB agonist) to determine the preferred dose in baclofen challenge studies. Multivariate analysis of variance (ANOVA) with repeated measures revealed no differences between the doses. However, when a univariate ANOVA with repeated measures was performed for each dose, the 10-mg dose showed no significant GH response over time, whereas the 20-mg dose showed a significant GH response over time. The average delta GH (change in GH from baseline) was 7.84 ng/ml (SD = 10.17) for the 10-mg dose and 3.34 ng/ml (SD = 3.64) for the 20-mg dose. The variability in the delta GH response to the 10-mg dose was significantly greater than the response to the 20-mg dose of baclofen. This variance in GH response was not explained by the differences in serum baclofen levels. Thus, a 20-mg baclofen dose appears to be preferable to a 10 mg-dose in baclofen challenge studies.
STUDY OBJECTIVE: The objective was to determine whether external chest wall oscillation (ECWO) during sleep (1) reduced spontaneous ventilation while maintaining adequate gas exchange over several hours, (2) influenced the quality and distribution of sleep, and (3) increased the number of respiratory events. DESIGN: Prospective controlled study with counterbalanced order of intervention. SETTING: Pulmonary function sleep laboratory. PARTICIPANTS: Seven healthy volunteers. INTERVENTION: One night of ECWO at 1 Hz (I:E = I:I; oscillation mean [SEM] from - 11.1 [0.7] to 6.0 [0.7] cm H2O) and a night during which the cuirass was applied without ECWO. MEASUREMENTS AND RESULTS: ECWO resulted in a significant decrease in spontaneous minute ventilation (VE) in all stages of sleep. ECWO was associated with a reduction in the total sleep time and a reduction in rapid eye movement (REM) sleep. The number of stage changes and the sleep efficiency did not change significantly. The mean PCO2 was similar between the control and cuirass nights (44 to 46 mm Hg). There was a significant decrease in the mean PCO2 during stage 1 (41 [2] mm Hg) and stage 2 (42 [2] mm Hg) sleep during the ECWO night. The mean arterial oxygen saturation (SaO2) was maintained at 96 to 97% throughout sleep during the control, cuirass, and ECWO nights. The apnea + hypopnea index increased (p < 0.05) during ECWO mostly due to an increase in the number of hypopneas in stage 2 sleep. During ECWO, 18 of 30 respiratory events were associated with an arousal, whereas only 2 events were associated with an arousal during the control night. CONCLUSIONS: ECWO can be tolerated for several hours and will assist ventilation while maintaining normal mean PCO2 and mean SaO2 during sleep. Monitoring of the apnea + hypopnea index and the SaO2 is recommended at the time of application. Clinical trials to define the most appropriate indications for ECWO are now necessary.
The spectrum of efficacy of the serotonin selective reuptake inhibitor (SSRI) antidepressant drugs continues to expand. In fact, no psychiatric syndrome seems to worsen with these agents, and few studies fail to demonstrate clinical improvement in some patients, regardless of any nosologic nicety, such as precise DSM diagnosis. This suggests that the biological rubric of psychopathology is dimensional rather than categorical. New research using in vivo microdialysis shows differences in neurochemistry among SSRIs, wherein fluoxetine blocks reuptake of dopamine and norepinephrine, as well as serotonin, in medial prefrontal cortex, and fluvoxamine has a relatively more selective neurochemical profile. In the animal model of learned helplessness, which is a biobehavioral model for stress-induced anxiety causing depression, the SSRIs including fluvoxamine prevent helplessness. From these and other data, a neurotransmitter balance theory of biopsychopathology is formulated. In this hypothetical construct, dopamine, norepinephrine, and GABA modulate thought, anxiety, and mood, respectively. Serotonin is a stabilizing agent, which assists in returning the mind to its homeostatic setpoint.
Thirty-three outpatients who met DSM-IV criteria for major depressive disorder (MDD) with no history of manic or hypomanic symptomatology were enrolled in an 8-week open trial of valproate. By Week 4, 15 of the 28 completers (54%) demonstrated a significant clinical response as defined by a score reduction of 50 percent or more or a total score of 9 or lower on the Hamilton Rating Scale for Depression (HRSD). Mean HRSD scores of the completers decreased 48.8 percent at Week 4 (p < .0001). At Week 8, 19 of the 22 completers (86%) showed a significant response. Mean HRSD scores decreased from 22 +/- 5 at baseline to 7 +/- 4 at Week 8 (p < .0001). With the intent-to-treat analysis at Week 8, 66 percent were responders, and total group mean HRSD scores decreased 55 percent (p < .0001). The data suggest that valproate may be an effective treatment for MDD. Double-blind, placebo-controlled trials are needed to further document its efficacy in the treatment of MDD.
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Growth hormone releasing peptide (GHRP, sequence His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) is a synthetic hexapeptide under consideration for transdermal iontophoretic drug delivery. Cyclic voltammetry, controlled-potential electrolysis, HPLC/UV analysis, LC/MS/MS analysis, and EPR spin-trapping studies indicate that the electrolysis-induced oxidative degradation of GHRP is likely to be mediated by electrogenerated oxygen radicals from the electrolysis of water. Within 2 h and up to 2.5 V versus an Ag/AgCl reference electrode, the peptide backbone remains largely intact. The chemical modifications are selectively on imidazole (histidine) and indole (tryptophan). Strategies for alleviating the electrolysis-induced degradation of GHRP are proposed.
Continuous-infusion prostacyclin improves symptom scores and decreases mortality in patients with primary pulmonary hypertension, but use of prostacyclin in patients with pulmonary veno-occlusive disease may precipitate pulmonary edema. A patient with pulmonary veno-occlusive disease received a graduated intravenous infusion of prostacyclin and pulmonary capillary pressures were calculated during prostacyclin dose ranging. Calculated capillary pressure increased with low-dose prostacyclin (< or = 6 ng/kg/min) but decreased with higher doses. These data suggest that the post-capillary pulmonary venules in our patient had reversible vasomotor tone, but required a higher dose of prostacyclin to vasodilate than did the precapillary arterioles.
Nine patients exposed to gentamicin ototoxicity were tested with active head movements to determine their high-frequency (2-6 Hz) horizontal and vertical vestibulo-ocular reflex (VOR) responses. Results showed a common pattern documenting patients' reports of oscillopsia during walking: gains of 0.5 or less, and phases less than 180 degrees. A subset of these patients undergoing exercise rehabilitation therapy were tested repeatedly during follow-up visits to monitor changes in their VORs. VOR improvements toward reduced oscillopsia were correlated with patients' reported reduction of symptoms. Each patient's VOR changes over time were monitored with a quantitative least-squares method which predicted results of the next test, based on trends from three or more previous tests. The method was tested by comparing predicted results with actual test results, following the next test. Preliminary results show relatively accurate predictions up to 6 weeks in advance of actual tests, at least when trends of recent, previous tests were in a consistent direction. We conclude that predictive monitoring of changing VOR states can be useful for continuing, or modifying, the course of vestibular rehabilitation therapy, by providing quantitative prediction estimates of future results.
Development of home health care programs for family caregivers is predicated on an understanding of problems caregivers encounter and ways in which they manage those problems. This article describes home care management strategies of family caregivers of stroke survivors. Qualitative analysis of interviews with a purposive sample of family caregivers indicated that caregivers of stroke survivors practice situational vigilance for the stroke survivor, create solutions for problems associated with functional losses of a stroke, construct the reality of recovery for themselves and the stroke survivor, and seek to find personal meaning in the caregiving experience. Implications for practice and future research are proposed.
A morbidly obese patient was emergently nasotracheally intubated using a fiberoptic bronchoscope. Simultaneous application of 20 cm H2O nasal continuous positive airway pressure (CPAP) to the contralateral naris using a nasal pillow helped maintain ventilation of the patient during intubation and greatly facilitated visualization of anatomic landmarks and translaryngeal passage of the bronchoscope. Fiberoptic video images of this patient's hypopharynx demonstrate the pharyngeal splinting action of nasal CPAP thus applied. This is a novel approach to difficult intubation of the obese patient.
Neurotransmitters activate a phospholipase D that is though to specifically hydrolyse phosphatidylcholine. This enzyme has a unique property known as transphosphatidylation: in the presence of an appropriate nucleophilic receptor such as an alcohol, phospholipase D will catalyse the production of phosphatidyl-alcohol. We have studied phospholipase D using an in vitro assay that uses [3H]butanol of high specific radioactivity (15 Ci/mmol) as an acceptor. In the presence of [3H]butanol and phosphatidylcholine, a microsomal membrane fraction from rat brain catalysed the production of phosphatidyl[3H]butanol. Phospholipase D activity was dependent upon the presence of a detergent; the optimal sodium oleate concentration was between 4 and 6 mM. The RF of the phosphatidyl[3H]butanol on t.l.c. was identical to the RF of the phosphatidylbutanol formed when [3H]phosphatidylcholine was incubated with 100 mM butanol. These data confirm the identity of phosphatidyl[3H]butanol. One important advantage of this assay is that the substrate does not need to be labelled. We have used this advantage to examine the substrate specificity of phospholipase D. Microsomal phospholipase D appears to hydrolyse phosphatidylcholine most efficiently. There is a relatively small but significant activity against phosphatidylethanolamine and phosphatidylserine, and there is no significant activity against phosphatidylinositol. As the head-group becomes more like choline, the phospholipid becomes a better substrate for phospholipase D. The addition of one methyl group leads to a large increase in activity. Fatty acid composition does not play a role in determining the substrate specificity. This assay should be useful in furthering our understanding of this important enzyme.
Consultation for measurement issues is an increasingly common expectation for many studies, yet there are few published guidelines on the use of psychometric consultants. The role of the psychometrician as research consultant is discussed and questions commonly asked of these measurement experts are identified. Consultation when selecting, revising, and developing data collection instruments is explored.
Clinicians of many health care disciplines provide health care services to the family unit. Because of the multiple perspectives that individual family members bring to the health care encounter, family-focused primary health care presents special challenges for providers. The need to reconcile multiple individual family member perspectives requires that clinicians develop increasingly more sophisticated, effective, family intervention skills that can be used in busy primary care settings. Social constructivism can provide a means through which clinicians can quickly engage families in creating a consensus on health issues, thus leading to effective, efficient problem solving. This paper reviews the origins and principles of social constructivist thought and describes assessment questions and therapeutic stances that can be used to empower families to become active participants in the process of initiating their own health-related life changes. These approaches are useful for episodic, brief, problem-focused encounters with families in many primary care practice settings.
To be useful, a frame of reference must enable an investigator to organize all components of a research study beginning with the literature review and problem statement and continuing through interpretation of findings. Careful conceptualization of the entire research process will move nurses closer to building an orderly system of scientific knowledge in which each investigation serves as a tool of nursing science.
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