Nonphysician clinicians in the health care workforce.
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Allied Health Personnel↗
Biomedical subjects
D Harper
Publications and source records attributed to D Harper.
Pathologic evaluation of the human suprachiasmatic nucleus in severe dementia.
Sleep disruption and other circadian rhythm disturbances are frequently seen in dementia patients. In this study, we examined the suprachiasmatic nucleus (SCN), the putative site of the hypothalamic circadian pacemaker, to determine the nature and degree of pathologic changes caused by severe dementia. Neuropathologic examination indicated that among 30 patients with a clinical history of severe dementia, 22 had Braak and Braak stage V-VI Alzheimer disease, 3 had combined Alzheimer and Parkinson disease, 3 had Pick disease and 2 had severe hippocampal sclerosis. Comparisons were made with a control group composed of 13 age-matched patients with no clinical or pathological evidence of dementia or other CNS disorders. To determine the pathologic involvement within the SCN, human hypothalami were stained with: Nissl, Bielchowsky silver, thioflavin S and specific antibodies directed against vasopressin (VP), neurotensin (NT), neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), beta-amyloid (B/A4) and glial fibrillary acidic protein (GFAP). Pathologic damage was primarily limited to neuronal loss and neurofibrillary tangle formation. Only rare diffuse plaques were noted. The pathologic changes within the SCN were less severe than in the other brain regions. Morphometric analysis was accomplished using a stereological approach to sample the average total number of positively stained neurons and astrocytes in 10 different 0.1mm2 microscopic fields in the dorsal subdivision of the SCN. Patients with Alzheimer disease exhibited a significant decrease in vasopressin (9.75 vs 16.7, p < 0.001) and neurotensin (6.82 vs 9.63, p < 0.002) neurons, as well as a corresponding increase in the GFAP-stained astrocyte/Nissl-stained neuron ratio (0.54 vs 0.10, p < 0.009). These studies provide evidence that both vasopressin and neurotensin neurons are lost in Alzheimer disease, and that the astrocyte/neuron ratio is a reliable indicator of disease-related pathology within the SCN. Taken collectively, our data support the hypothesis that damage to the SCN may be an underlying anatomical substrate for the clinically observed changes in circadian rhythmicity that have been observed in Alzheimer patients.
Case-Control Studies↗
Cybercases: an innovation in internet education.
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Computer-Assisted Instruction↗
Effect of hen production age on egg composition and embryo development in commercial Pekin ducks.
At 26, 31, 36, and 42 wk of age, eggs were collected from the same duck breeder flock to study the effects of hen production age on egg composition and embryo development. At each hen age, yolk and albumen measurements were made on a random subsample of unincubated eggs. Embryo and yolk sac measurements were made at 20, 22, 24, 26, 27, and 28 d of incubation. Egg weight was significantly affected by hen production age, but most of the observed age effects occurred between 26 and 31 wk with minimal age differences thereafter due to a quantitative feed restriction for egg weight. Yolk weight increased significantly with hen production age, with the largest increase, 6.6 g, also occurring between 26 and 31 wk of age. Yolk-free duckling weight increased with hen production age at 27 d of incubation. The yolk sacs of embryos from the 31-, 36-, and 42-wk-old hens were heavier at 20 and 22 d, before the differentiation in embryo weight. Differences in yolk sac weight were not consistently affected by hen production age between 26 and 28 d of incubation. The eggs from the 42-wk-old hens weighed 3.3 g less than those from the 31-wk-old hens, but yolk-free duckling weight at 27 d was 2.9 g heavier from the 42-wk-old hens.
Aging↗
T-lymphopoietic capacity of cord blood-derived CD34+ progenitor cells.
Umbilical cord blood contains an abundance of CD34+ hematopoietic progenitor cells and has been used in transplantation as an alternative to adult bone marrow or mobilized peripheral blood. Although efficient myelomonocytic, erythroid, and B lymphoid differentiation has been shown in highly purified cord blood CD34+ mononuclear cells lacking expression of lineage-specific antigens, generation of functional T cells has not been previously documented. Exploiting two recently developed, complementary thymic stromal monolayer systems, we show here that immature hematopoietic progenitor cells (CD34+lineage-) from human and rhesus monkey cord blood mononuclear cells undergo T lymphopoiesis in a manner that recapitulates T cell ontogeny in vivo. After 2 weeks of proliferation, cultures contained myeloid [corrected] cells and discrete populations of CD4+CD8+ (double-positive) immature T lymphocytes, followed after an additional 2 weeks by the appearance of single-positive CD4+CD8- and CD4-CD8+ T cells that coexpressed CD3. The T lymphoid phenotype was confirmed at the transcriptional level by the presence of the lymphoid-restricted genes RAG-2 and T cell receptor. T cells generated from cord blood progenitors in these systems exhibited immunofunction as assessed by alloreactive responses in mixed lymphocyte reactions. These findings were comparable between human and rhesus progenitor cells and closely resemble previous data using adult bone marrow CD34+ cells in these models. Together, these observations demonstrate that cord blood contains abundant lymphoid progenitors that undergo T lymphopoiesis in vitro, suggesting the full multipotentiality of this stem cell source and its validity in investigating T lymphoid differentiation.
Animals↗
Circadian rest-activity disturbances in seasonal affective disorder.
BACKGROUND: Previous studies hypothesized that seasonal affective disorder (SAD) was caused by a circadian rhythm abnormality. The purpose of this study was to ascertain whether rest-activity rhythms were phase delayed, diminished in amplitude, or more poorly entrained to the 24-hour day. METHOD: Twenty healthy adult controls and 25 outpatients meeting Rosenthal-National Institute of Mental Health criteria for SAD and DSM-III-R criteria for major or bipolar depression with seasonal pattern had their levels of activity recorded for 72 hours (weekdays) using wrist-worn actigraphs. RESULTS: Subjects with SAD had activity levels that were 11% lower than controls (P = .03), and their levels of activity were most attenuated during the first 2 hours after arising (P = .004). The relative amplitude of the circadian rhythm did not differ between groups. Patients with SAD were phase delayed by 50 minutes for the entire period (P = .02). Analysis of each individual day indicated that patients were delayed by up to 70 minutes (P = .007). Interdaily stability, an index of coupling between the rhythm and its zeitigeber was reduced in SAD (P = .01). Compared with controls, patients with SAD had best-fit circadian periods that were 92% more deviated from 24 hours (P = .007) and daily acrophase (time of the peak of the fit circadian rhythm) times that were 110% more variable between days (P < .001). CONCLUSIONS: Patients with SAD have circadian rest-activity rhythms that are significantly phase delayed and more poorly entrained to the 24-hour day.
Activity Cycles↗
The effects of hippocampal and area parahippocampalis lesions in pigeons: I. Delayed matching to sample.
Four experiments were conducted to determine the effects of bilateral damage to the hippocampus and area parahippocampalis (Hp-APH) on visual memory in pigeons using the delayed matching-to-sample (DMS) procedure. In Experiment 1, we generated visual retention gradients with delays of 0, 1.5, 3, 6, and 12 sec both preoperatively and postoperatively in three pigeons with considerable preoperative visual DMS experience. Bilateral Hp-APH lesions had no effect whatsoever on visual retention. In Experiment 2, we examined the effects of Hp-APH lesions on both the acquisition of a visual DMS task with a 0-sec delay, and the subsequent retention performance with delays of 0, 3, 6, 12, and 24 sec. There was no difference between unoperated control pigeons and Hp-APH pigeons either in terms of the number of sessions required to learn the visual DMS task or in terms of their subsequent visual retention performance levels. In Experiments 3 and 4, we examined whether Hp-APH pigeons might be more sensitive than control pigeons to the effects of proactive interference (by reducing the duration of the intertrial interval) and retroactive interference (by introducing delay-interval illumination). Although reducing the duration of the intertrial interval and increasing the level of delay-interval illumination both resulted in lower performance levels on the visual DMS task, there was no indication that the Hp-APH pigeons were any more affected by the changes in interference levels than were unoperated control pigeons. These findings support the view that the Hp-APH in pigeons plays little role in the processing and retention of purely visual information.
Animals↗
Oxalated pyridoxalated hemoglobin polyoxyethylene conjugate normalizes the hyperdynamic circulation in septic sheep.
OBJECTIVE: Excessive production of nitric oxide significantly contributes to the hyperdynamic state associated with sepsis. The ability of hemoglobin to scavenge nitric oxide may therefore be beneficial in the treatment of sepsis. In this study, we determined the effects of different doses of the modified human pyridoxalated hemoglobin polyoxyethylene conjugate in an ovine model of hyperdynamic sepsis. DESIGN: Prospective, experimental study. SETTING: Large animal research laboratory at a university medical center. INTERVENTIONS: Sheep (n = 23) were surgically prepared for chronic study. After a 5-day recovery period, all animals received a continuous infusion of live Pseudomonas aeruginosa (2.5 x 10(6) colony-forming units/min) for the next 48 hrs. After 24 hrs of sepsis, the animals were divided into four groups: a) six sheep were used as controls and received a bolus of 200-mL vehicle; b) three sheep received a bolus of 50 mg/kg hemoglobin; c) six sheep received 100 mg/kg of hemoglobin; d) six sheep received 200 mg/kg of hemoglobin. MEASUREMENTS AND MAIN RESULTS: All animals that survived the first 24 hrs of sepsis (n = 21) developed a hyperdynamic circulation. All three doses of hemoglobin reversed this hyperdynamic state by increasing mean arterial pressure and systemic vascular resistance while decreasing cardiac index. Pulmonary arterial pressure increased after hemoglobin infusion. Increased pulmonary arterial pressure did not affect arterial oxygen saturation nor result in the development of pulmonary edema. Infusion of hemoglobin also caused a 30-fold increase in endothelin-1 plasma concentrations and significantly decreased nitrate and nitrite plasma concentrations. CONCLUSIONS: The infusion of low doses of pyridoxalated hemoglobin polyoxyethylene conjugate in septic sheep reverses the hyperdynamic circulatory state. An increase in pulmonary arterial pressure was the only observed hemodynamic side effect; changes in the structure or function of other organ systems, or their biochemical correlates were not investigated in this study. In addition to a possible nitric oxide scavenging effect, pyridoxalated hemoglobin polyoxyethylene may affect the nitric oxide synthase and endothelin systems.
Animals↗
Typing of varicella zoster virus by amplification of DNA polymorphisms.
The polymerase chain reaction was used to amplify five variable regions of varicella zoster virus DNA from 20 samples of vesicle fluid. Two of the regions, R1 and R5, were found to be polymorphic, with the former having three alleles (A, B and C) and the latter, two (A and B). The R1 and R5 polymorphisms were stable up to passage five in tissue culture. The sensitivity of the PCR (down to six copies) enabled detection of virus from vesicle fluid dried on glass slides and overall the method was five times more sensitive than conventional tissue culture. The method described is simple, sensitive and informative and provides a means by which questions about the epidemiology and clinical biology of VZV infection may begin to be addressed.
Adult↗
Blessed are the flexible: the George Team.
Our educational efforts produced several intersecting interdisciplinary groups: faculty, students, faculty/students and our community sites, with faculty, clinical staff, and students. As we worked through the issues, these interdisciplinary teams found that commitment to change, caring for patients, and open, honest communication were essential to keeping the project teams on track. We have increased our understanding of both the complexity and value of interdisciplinary collaborative education. The LIT faculty provided the initial guidance and support, the students energized the process, and our community sites made our learning and our contributions readily available to our patient populations. It is not easy to learn and teach the language and tools of continuous improvement, but doing so infinitely improves the educational process and the clinical outcome. We must learn to carefully listen to each other so that our patients can fully reap the benefits of our interdisciplinary team efforts. As a result of what we learned, the members of the George Team have expanded our motto to "Blessed Are the Flexible--and the Perseverant!"
Community Health Services↗
Effects of inhaled nitric oxide and nebulized prostacyclin on hypoxic pulmonary vasoconstriction in anesthetized sheep.
OBJECTIVES: Inhaled nitric oxide has been shown to be a selective pulmonary vasodilator, leading to reduced pulmonary arterial pressure and improved ventilation/perfusion ratio in the acute respiratory distress syndrome. This local pulmonary vasodilation theoretically can be achieved by the airway application of a short-acting vasodilator, such as prostacyclin. We hypothesized that nebulized prostacyclin has the same properties for selective pulmonary vasodilation as inhaled nitric oxide. DESIGN: Prospective, experimental study in sheep. SETTING: Investigational intensive care unit in a university hospital. SUBJECTS: Six adult ewes of the Merino breed. INTERVENTIONS: Sheep (n = 6) were surgically prepared for chronic study. After 5 days of recovery, the sheep had tracheostomies performed under anesthesia. Intubation with a modified Robert-Shaw tube allowed side-separated ventilation. The entire left lung was ventilated with pure nitrogen, whereas the right lung was ventilated with pure oxygen. Nitric oxide and prostacyclin were added in different concentrations to the nitrogen, with which the left lung was ventilated. MEASUREMENTS AND MAIN RESULTS: The blood flows to the left and right lungs were measured with ultrasonic flow probes on the common and left pulmonary artery. Measurements were taken after each compound had been administered for 10 mins at a predefined dose. Both inhaled nitric oxide and nebulized prostacyclin caused effective, selective, dose-dependent pulmonary vasodilation. Inhaled nitric oxide was able to abolish hypoxic pulmonary vasoconstriction when insufflated into the animals at a concentration of 50 ppm of nitrogen, but 100 ppm of nitric oxide had no further effect. Prostacyclin, at a dosage of 10 micrograms/min, showed maximum pulmonary vasodilation, which could not be further increased by doubling the dosage. However, prostacyclin produced less dilation than high doses of nitric oxide, and its maximum pulmonary vasodilation was comparable with that effect obtained under ventilation with 20 ppm of nitric oxide. CONCLUSIONS: Both drugs selectively dilated the pulmonary vasculature in ventilated alveoli. Prostacyclin nebulization is an excellent tool to reduce pulmonary hypertension and to improve the ventilation/perfusion ratio. Prostacyclin nebulization can be used without the highly sophisticated technical equipment that is needed for controlled nitric oxide inhalation, and may therefore become a new, noninvasive therapeutic approach for treatment of adult respiratory distress syndrome in hospitals that cannot provide nitric oxide inhalation.
Administration, Inhalation↗
Effects of passive body heating on the sleep of older female insomniacs.
The purpose of this study was to evaluate passive body heating (PBH) as a treatment for insomnia in older adults. Polysomnographic recordings of older adults routinely show an increase in sleep fragmentation and a substantial decrease in slow-wave sleep (SWS) consistent with complaints of "lighter" more disturbed sleep. An increase in body temperature in young adults early in the evening by way of PBH has been shown to produce an increase in SWS in the early part of the sleep period. In a crossover design, nine female insomniacs (aged 60-72 yr) participated in two consecutive nights of PBH, involving hot (40-40.5 degrees C) and luke-warm (37.5-38.5 degrees C) baths 1.5 hours before bedtime. Significant improvement in sleep continuity and a trend toward an increase in SWS occurred after hot baths. Results of subjective measures showed that subjects experienced significantly "deeper" and more restful sleep after hot baths. In addition, hot baths resulted in a significant delay of temperature nadir in comparison to baseline nights.
Adult↗
An audit of percutaneous transluminal angioplasties in the treatment of lower limb ischaemia in a district general hospital over a period of 10 years.
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Adult↗
Designing the Optimal Health Assessment System: the Cleveland Quality Choice (CHQC) example.
Cleveland Health Quality Choice (CHQC) is an ongoing collaborative partnership between business, hospitals, and physicians designed to assess the performance of health care institutions in the greater Cleveland metropolitan area. CHQC coordinates the collection of data for analysis of intensive care unit outcomes; general medical, surgical and obstetric outcomes; and patient satisfaction. CHQC has documented improved outcomes in all measured spheres over a 4-year period. Its success can be attributed to a leadership strategy focused on providing rigorously tested analytic tools and a shared vision regarding the value of outcome information in assessing institutional performance. CHQC can serve as a model for communities interested in creating joint programs between purchasers and providers of health care to measure health outcomes.
Health Care Coalitions↗
Agonist-antagonist interactions at angiotensin receptors: application of a two-state receptor model.
Interactions between agonists and antagonists at angiotensin receptors are characterized by a number of features: variation of antagonist dynamics between apparent simple competition, insurmountable antagonism and, occasionally, augmentation; the tendency for insurmountable antagonism to be saturable; slow recovery of agonist responses following agonist-induced tachyphylaxis; and the ability of competitive antagonists to accelerate recovery from the latter intervention. Some of these phenomena have also been observed in studies of 5-HT2 receptors where they were attributed to the operation of a two-state model with an allosteric site. In this article, Mark Robertson and colleagues propose that the properties of angiotensin AT1 receptors may be explained by a similar model, but without the need to evoke an allosteric site.
Angiotensin II↗
The microbial degradation of thiocyanate.
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Acinetobacter↗
Modifying quiet room design enhances calming of children and adolescents.
OBJECTIVE: To determine whether altering design of a quiet room (QR) produced more rapid calming of agitated or aggressive hospitalized children. METHOD: One of five similar QRs was modified by painting the white walls tea rose, carpeting the vinyl floor, and painting a picturesque mural on one wall. The effects of these modifications were assessed in 19 patients (mean age = 9.6 years), using a within-subjects, repeated-measures design. Overt Aggression ratings were made at the time of placement, and at 5-minute intervals thereafter, until the child was dismissed. Children were blind to the fact that a study was being conducted; raters and staff were not. RESULTS: Total aggression ratings were 45% lower in the modified QR than in the standard QR (p < .03), and initial aggression scores fell by 50% during 5 minutes of placement in the modified QR, but only after 20 minutes of placement in the standard QR (p < .0001). Motor excitement and verbal aggression were the two component factors most strongly influenced by QR design. CONCLUSION: This preliminary report suggests that it may be possible to modify QRs to facilitate calming of aggressive, agitated children and provides preliminary support for redesign of QRs.
Acting Out↗
Locomotor activity in depressed children and adolescents: I. Circadian dysregulation.
OBJECTIVE: To determine whether circadian activity rhythms were altered in pediatric patients with depression. Evidence was sought for a shift in the timing of the rhythm, blunting of circadian amplitude, or emergence of noncircadian periodicities. METHOD: Locomotor activity was quantified in 57 patients with major depressive mood disorders (mean age 12.4 years) and 16 normal controls (9.9 years). Activity was measured in 5-minute epochs during 72 hours using belt-worn electronic activity monitors. RESULTS: Patients with mood disorders displayed a 15% decrease in the amplitude of their circadian rhythm, and a 52% increase in the magnitude of their twice-daily (hemicircadian) rhythm. No significant difference emerged in the timing of the circadian rhythm. Depressed inpatients and outpatients displayed comparable disturbances, which were most marked in adolescents. CONCLUSIONS: Circadian activity rhythms were dysregulated in pediatric patients with major depression. These findings may have etiological and diagnostic significance.
Adolescent↗