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Biomedical subjects

D Harper

Publications and source records attributed to D Harper.

At least 37 records · Page 2Linked to original sources
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1993

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↗
PubMed1993

Estimation of partial agonist affinity by interaction with a full agonist: a direct operational model-fitting approach.

1. The operational model of agonism (Black & Leff, 1983) has been extended to describe the interaction between a partial agonist and a full agonist at the same receptor. The derived equation explicitly describes the interaction and allows the affinity (and efficacy) of the partial agonist to be estimated by direct fitting of raw experimental agonist concentration-effect (E/[A]) curve data. 2. The model was used to analyse experimental E/[A] curve data generated for the interaction between pilocarpine (partial agonist) and carbachol (full agonist) at the M3-muscarinic receptor mediating contraction of the guinea-pig isolated trachea. Pilocarpine affinity estimates obtained by operational model-fitting were compared with those obtained by use of the null method (Stephenson, 1956). These analyses demonstrated that the two methods gave comparable results (mean pKB estimates were 5.79 and 5.86 for the operational model and null method respectively). 3. When multiple concentrations of partial agonist are used, simultaneous operational model-fitting of all the E/[A] curve data allows the competitive nature of the interaction to be studied. 4. We conclude that operational model-fitting is a valid and analytically simple alternative to the conventional null method of analysing full/partial agonist interactions.

Animals↗
PubMed1993

Increased prevalence of electrophysiological abnormalities in children with psychological, physical, and sexual abuse.

This retrospective study examined the association between abuse history and neurological abnormalities in 115 consecutive patients admitted to a child and adolescent psychiatric inpatient unit. Increased electrophysiological abnormalities were found in abused patients compared with non-abused patients (54.4% vs. 26.9%, P = 0.021), predominantly in the left side of the frontal, temporal, or anterior region (P = 0.036). This may support the hypothesis that early abuse alters brain development, particularly limbic structures. However, a large-scale prospective longitudinal assessment study is needed to interpret this association. Possible clinical consequences of relatively preserved right frontal function are discussed.

Adolescent↗
PubMed1992

Evaluation of implementation of a cholesterol management program in physicians' offices.

This article describes an evaluation of the implementation of a cholesterol management program in family physicians' offices as part of the Physician-Based Nutrition Program to Lower Coronary Heart Disease Risk (PBNP). The evaluation, conducted through a partnership evaluation model, used multiple case study methodology and combined the use of quantitative and qualitative methods. Data sources included office staff reports and interviews, records of contacts with study personnel, patient care data, and patient telephone interviews. Data from these sources revealed gradual program implementation and considerable variation in practitioner and clinic involvement in cholesterol management. Clinic staff reported that the support provided by PBNP in the form of training, operations materials, patient education materials and ongoing assistance was very useful. This formative evaluation has implications for refinement of the PBNP and for other prevention programs in primary care settings. It demonstrates the feasibility and acceptability of a systems approach to physicians, cholesterol/nutrition educators and clinic support staff. It also suggests ways in which researchers and clinicians can implement and evaluate health care innovations.

Adult↗
PubMed1992

Analysis of the agonist activity of fenoldopam (SKF 82526) at the vascular 5-HT2 receptor.

1. The 5-HT2 receptor agonist activity of fenoldopam (SKF 82526) was characterized in the rabbit isolated aorta preparation. 2. Fenoldopam was an agonist at the vascular 5-HT2 receptor with lower affinity and efficacy than the naturally occurring agonist 5-hydroxytryptamine (5-HT). Fenoldopam had an affinity (pKA) of 5.84 +/- 0.04 and efficacy (tau) of 0.57 +/- 0.04, whereas 5-HT had a pKA of 6.65 +/- 0.12 and tau of 2.66 +/- 0.41. 3. The constrictor effects of fenoldopam and 5-HT were competitively antagonized by the 5-HT2 antagonist, ketanserin, with pKB values of 8.81 +/- 0.11 and 8.83 +/- 0.10 respectively. 4. Prior incubation with fenoldopam produced a concentration-related rightward shift of a subsequent 5-HT concentration-response curve. This inhibition was specific for 5-HT since constrictor responses to angiotensin II were unaffected. 5. This study indicates that the D1 receptor agonist, fenoldopam, acts as an agonist at the vascular 5-HT2 receptor, but with an affinity and efficacy less than that of the naturally occurring agonist, 5-HT.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1992

e-PTFE ventricular shunt catheters.

The perfect polymer surface for implantation should resist the adhesion of bacteria while producing no reaction in surrounding tissues. Silicone elastomer is a common material used for medical implantation devices. This material is superior to most available for implantation because of its flexibility and low, but detectable, tissue reaction. We have evaluated a flexible, expanded polytetrafluoroethylene (e-PTFE) ventricular catheter for cerebrospinal fluid shunting and have found that although e-PTFE is safe for cerebral implantation, the porosity of the material allows tissue ingrowth that obstructs the lumen. Our limited clinical evaluation of 5-microns internodal distance e-PTFE revealed that this open-cell structure, allowing tissue ingrowth, apparently is a poor candidate to replace silicone elastomer in cerebrospinal fluid shunting devices. However, further investigation may provide a polymer superior to silicone elastomer to create a cerebrospinal fluid shunt.

Animals↗
PubMed1991

An outbreak of Legionnaires' disease in Gloucester.

Fourteen people living in or near the city of Gloucester fell ill with Legionnaires' disease caused by Legionella pneumophila serogroup (SG) 1 between 27 August and 27 October 1986. Another patient had fallen ill on 30 May. Nine of the 15 were diagnosed retrospectively during a case finding exercise. There were three deaths. Three cases of Pontiac fever were also diagnosed. The source was probably one or more wet cooling towers. Nineteen premises in the city with such towers were identified, and three just outside Gluocester. Samples from 11 of the 22 premises grew Legionella spp.; from nine of these L. pneumophila SG 1 (Pontiac) was isolated. The efficacy of regular addition of biocide in addition to hypochlorite added at the time of disinfection in inhibiting the growth of Legionella spp. was demonstrated. A survey of patients' movements during their likely incubation period showed that there was no single building that all patients had visited, but there were two areas of the city which nearly all had visited or passed through by car. A case-control study demonstrated an association with one of these areas. Cooling towers near both areas may have been sources but the evidence is insufficient to incriminate any single one. The unexpected finding of L. pneumophila SG 1 (Pontiac) in nine towers supports the hypothesis that there may have been multiple sources. Cooling towers may have been contaminated by mains water or by drift from other towers.

Adult↗
PubMed1991

Estimation of the efficacy and affinity of the beta 2-adrenoceptor agonist salmeterol in guinea-pig trachea.

1. We have attempted to estimate the affinity and efficacy of the new beta 2-adrenoceptor agonist salmeterol in the guinea-pig isolated trachea and to compare these estimates with those obtained for salbutamol. 2. The kinetics of the relaxation to salmeterol were considerably slower than those to salbutamol and the responses were poorly defined. Nevertheless, in experiments employing a cumulative curve design both salmeterol and salbutamol exhibited partial agonist behaviour. Operational model-fitting of these data indicated that the intrinsic efficacies of the two agonists were indistinguishable but that salmeterol had an affinity (pKA = 7.4) some 30 fold greater than salbutamol (pKA = 5.9). 3. Single dose experiments, using maximally effective concentrations of salmeterol or salbutamol were carried out in an attempt to quantify more reliably the relative efficacies of the two agonists. In these experiments salbutamol was found to have an efficacy (2.5) approximately 3 fold greater than that of salmeterol (0.8). 4. Full/partial agonist interaction studies were carried out to provide another estimate of the affinity of salmeterol. Isoprenaline and adrenaline were employed as full agonists in these experiments and the affinity (pKB) estimates obtained for salmeterol against these agonists were 7.3 and 7.4 respectively. These affinity estimates were similar to the pKA value (7.4) obtained by operational model-fitting. 5. Salmeterol has slightly lower efficacy (3 fold) but markedly greater affinity (30 fold) than salbutamol at beta 2-receptors. The slightly lower efficacy of salmeterol is unlikely to have clinical implications for this drug as a bronchodilator beta 2-adrenoceptor agonist in asthma.

Adrenergic beta-Agonists↗