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Biomedical subjects

S A Harvey

Publications and source records attributed to S A Harvey.

At least 19 recordsLinked to original sources

Skilled birth attendant competence: an initial assessment in four countries, and implications for the Safe Motherhood movement.

OBJECTIVES: Percentage of deliveries assisted by a skilled birth attendant (SBA) has become a proxy indicator for reducing maternal mortality in developing countries, but there is little data on SBA competence. Our objective was to evaluate the competence of health professionals who typically attend hospital and clinic-based births in Benin, Ecuador, Jamaica, and Rwanda. METHODS: We measured competence against World Health Organization's (WHO) Integrated Management of Pregnancy and Childbirth guidelines. To evaluate knowledge, we used a 49-question multiple-choice test covering seven clinical areas. To evaluate skill, we had participants perform five different procedures on anatomical models. The 166 participants came from facilities at all levels of care in their respective countries. RESULTS: On average, providers answered 55.8% of the knowledge questions correctly and performed 48.2% of the skills steps correctly. Scores differed somewhat by country, provider type, and subtopic. CONCLUSION: A wide gap exists between current evidence-based standards and current levels of provider competence.

Benin↗

Down-regulation and recovery of endothelin-1 binding and signaling in rat cardiomyocytes.

Down-regulation and recovery of endothelin (ET) receptors and of ET-dependent phosphoinositide-specific phospholipase C (PI-PLC) signaling was examined in cultured cardiomyocytes from neonatal rats. Three hours treatment with 5 nM ET-1 decreased surface receptors to 30%, and transduction to 19%, of their respective time-zero values. After extensive washing and a 3 h recovery period surface receptors returned to 74% of the time-zero value, with concomitant recovery of signal transduction to 75% of the time-zero value. The recovery of PI-PLC signaling in these cells is in contrast with a previous report, but consistent with recovery of the receptor complement.

Animals↗

A23187 causes release of inositol phosphates from cultured rat Kupffer cells.

The Ca2+ ionophore A23187 is routinely used to illustrate the extracellular Ca2+-dependence of a variety of cellular reactions. We found that A23187-induced hydrolysis of phosphoinositides to various inositol phosphates in rat Kupffer cells was accompanied by their release from the cells. The synthesis and release of inositol phosphates was A23187 concentration-dependent (0.5-10 microM), and was apparent at the lowest concentration tested. A23187-induced release of inositol phosphates increased time-dependently, was apparent at 5 s of stimulation and maximal at 20 min. The effects of A23187 were reversed by EGTA. The integrity of the cells was not affected by A23187 treatment as indicated by their exclusion of trypan blue and the lack of release of lactate dehydrogenase. We propose that such effects should be considered while evaluating the Ca2+-dependence of biological processes based on the actions of A23187.

Animals↗

S.C.A.L.E.--spiritual care at life's end: a multi-disciplinary approach to end-of-life issues in a hospital setting.

End-of-life care is a hot topic in many hospitals of late, in part due to an aging society, which is forcing health care professionals to address the issue. A culture that places enormous value on youth and avoids the topic of death also contributes to the discomfort many health care professionals feel discussing this topic with their patients and family members. Inpatient satisfaction survey scores at Thunderbird Samaritan Medical Center (TSMC) were very inconsistent on the question of how the institution was meeting the emotional and/or spiritual needs of patients. A staff survey and needs assessment was also conducted regarding end-of-life care, which pointed out communication issues among staff members. All of these factors led to the development of an inter-disciplinary team to examine the issue of end-of-life care at TSMC.

Arizona↗

Bone morphogenetic protein-9. An autocrine/paracrine cytokine in the liver.

Bone morphogenetic proteins (BMPs) occupy important roles during development serving to direct cells through specific differentiation programs. While several BMPs are essential for embryonic viability, their significance in mediating intercellular communication in the context of adult organ systems remains largely unknown. In the adult rat we characterized the tissue- and cell-specific transcription and translation of BMP-9. Utilizing a ribonuclease protection assay, we determined that in the adult animal, BMP-9 expression occurs predominantly in the liver. Furthermore, we determined that the non-parenchymal cells of the liver, i.e. endothelial, Kupffer, and stellate cells, are the major sources of this message. Western analyses corroborate the ribonuclease protection assay results, confirming that LEC and KC contain an abundance of immunoreactive BMP-9. Using [(125)I]BMP-9, a receptor with specific binding affinity for BMP-9 was characterized in primary cultures of hepatic endothelial cells and Kupffer cells. BMP-9 binding to these cell types was observed to be fully reversible and highly specific for this ligand. Additionally, we demonstrate that BMP-9 is specifically internalized upon binding to its receptor. This may represent a novel BMP receptor and is the first to be characterized in primary cultures of mature liver non-parenchymal cells. Our results depict BMP-9 as a potential autocrine/paracrine mediator in the hepatic reticuloendothelial system.

Animals↗

Nitric oxide synthase inhibitors do not substitute in rats trained to discriminate phencyclidine from saline.

Release of nitric oxide occurs as a consequence of glutamate stimulation of NMDA receptors and is dependent upon calcium-calmodulin activation of the enzyme nitric oxide synthase. Since nitric oxide may serve as an intracellular messenger for NMDA glutamatergic neurons, it could be hypothesized that blockade of its synthesis may produce pharmacological effects similar to those of NMDA receptor antagonists. The purpose of the present study was to compare the effects of nitric oxide synthase inhibitors to those of the high affinity NMDA open channel blocker phencyclidine in drug discrimination, a pharmacologically selective procedure in which phencyclidine produces distinctive effects. Rats were trained to discriminate 2 mg/kg phencyclidine from saline in a standard two-lever discrimination task with food reward. Whereas phencyclidine dose-dependently substituted for itself, 7-nitroindazole, L-NAME (N(G)-nitro-L-arginine methyl ester), and L-NOARG (N(G)-nitro-L-arginine) failed to substitute for phencyclidine when administered intraperitoneally. L-NAME and 7-nitroindazole were tested up to doses that disrupted responding, providing evidence that a behaviorally-relevant dosage range was evaluated. Although these results conflict with those of a previous study which found that nitric oxide synthase inhibitors substituted for phencyclidine and produced phencyclidine-like catalepsy in pigeons, they are consistent with research showing that these drugs did not produce phencyclidine-like pharmacological effects in behavioral procedures in rats.

Animals↗

Relevant issues in revision canal-wall-down mastoidectomy.

The role of canal-wall-down (CWD) versus intact-canal-wall (ICW) mastoidectomy in the treatment of chronic otitis media with or without cholesteatoma remains a debated issue. Although past conventional wisdom has held that CWD mastoid surgery leads to a "safe" ear and is technically less demanding than the more controversial ICW mastoidectomy, this is often not the case. Although our preference is an ICW technique when possible, 47 of 109 (43%) mastoid procedures for chronic otitis media performed between January 1993 and June 1996 involved a CWD mastoid cavity. More than two thirds of these procedures (32 of 47) represented revision surgery, the most common indication being a poorly contoured, preexisting CWD mastoidectomy with persistent otorrhea. A dry, well-epithelialized ear was obtained in 90% of cases. Our preferred method of ossicular reconstruction (double cartilage block ossiculoplasty) is detailed, and hearing results according to American Academy of Otolaryngology Head and Neck Surgery guidelines are reported.

Adolescent↗

Vestibular compensation in guinea pigs given intravenous lidocaine after unilateral labyrinthectomy.

Intravenous lidocaine has been reported to alleviate vertigo in Meniere's disease and suggested as a possible antivertigo agent after unilateral labyrinthectomy in a study of cats. To further evaluate the effects of intravenous lidocaine on the acute phase of postural compensation, we subjected 13 pigmented guinea pigs to unilateral labyrinthectomy. Seven received intravenous lidocaine (4 mg/kg) immediately after labyrinthectomy. The other six served as controls and received an equivalent-volume injection of normal saline solution. Total body curvature, trunk curvature, yaw head tilt, and roll head tilt were measured at frequent intervals for up to 30 hours after surgery. Both groups had immediate difficulties with posturing that gradually improved. The lidocaine group tended to exhibit delayed postural compensation, but this was only statistically significant for roll head tilt. These results do not show improvement in postural compensation from unilateral labyrinthectomy after the administration of intravenous lidocaine. A species-specific effect on the vestibular pathways is suggested, and we conclude that further evaluation of lidocaine and the vestibular system is warranted.

Animals↗

Pediatric fibromyalgia and dizziness: evaluation of vestibular function.

Twelve children with fibromyalgia and complaints of chronic dizziness were evaluated with both clinical office maneuvers of vestibular function and laboratory tests composed of electronystagmography and sinusoidal harmonic acceleration rotary chair testing. All test results were normal for spontaneous nystagmus with or without visual fixation, oculocephalic reflex, dynamic visual acuity, head-shaking nystagmus, Quix test, and Dix-Hallpike maneuver. Electronystagmography test results were essentially normal for saccades, gaze, Dix-Hallpike, pendular tracking, and caloric evaluation. Rotary chair testing was normal in all 12 patients. These findings suggest that central (brainstem) and peripheral vestibular (inner ear) mechanisms do not account for the complaints of dizziness in the pediatric patient with fibromyalgia. The common musculoskeletal abnormalities of fibromyalgia may affect their proprioceptive orientation, therefore giving them a sense of imbalance.

Adolescent↗

Double cartilage block ossiculoplasty in chronic ear surgery.

OBJECTIVES/HYPOTHESIS: Multiple techniques of ossicular reconstruction have been advocated for hearing rehabilitation in the setting of chronic otitis media No single method can adequately address the clinical spectrum of disease severity. In the situation of a severely diseased ear requiring a canal wall down (CWD) mastoidectomy in the presence of an intact stapes superstructure, the authors have employed a double cartilage block (DCB) ossiculoplasty. The technique and short-term results are reviewed. STUDY DESIGN: Retrospective chart review in a tertiary referral otologic practice. METHODS: Twenty-three patients underwent a CWD tympanomastoidectomy with DCB ossiculoplasty. Ages ranged from 6 to 85 years (mean, 36.1 y). The majority of ears were actively draining at the time of surgery (83%) and most procedures were revisions of prior mastoidectomies (74%). Audiometric data (mean postoperative follow-up, 19.5 mo) were calculated according to 1995 American Academy of Otolaryngology-Head and Neck Surgery guidelines. RESULTS: Audiometric results were available in 20 patients. The mean air-bone gap (ABG) was 23.8 dB after surgery. Closure of the ABG to within 20 dB was achieved in 10 of 20 patients (50%). No cases of DCB extrusion have occurred to date. CONCLUSIONS: The DCB represents an excellent alternative to biocompatible prostheses for ossicular reconstruction in the setting of severe chronic ear disease. As with all methods of ossiculoplasty, long-term follow-up will be necessary to determine if this technique remains stable in the hostile environment in which it has been employed.

Adolescent↗

Clinical yield and cost of exercise treadmill testing to screen for coronary artery disease in asymptomatic adults.

Exercise treadmill testing is frequently performed to screen for coronary artery disease (CAD) in asymptomatic individuals; however, its clinical value is unclear. We examined a consecutive cohort of asymptomatic adults undergoing exercise treadmill testing at the Cleveland Clinic Foundation between September 1990 and December 1993. End points included (1) identification of subjects with severe CAD and (2) performance of any second diagnostic study within 90 days of the index exercise treadmill test. Screening exercise treadmill testing was performed in 4,334 adults (median age 51, 89% men); only 34% had > or = 1 cardiac risk factor and 15% exhibited an abnormal response to exercise. A second test after treadmill testing was performed in 215 patients (in 110, coronary angiography; in 105, stress thallium scintigraphy, followed by coronary angiography in 16). The strongest predictor of referral for a second test was an ischemic ST-segment response (adjusted odds ratio [OR] 34, 95% confidence intervals [Cl] 24 to 47, p < 0.0001). The only clinical variable independently associated with referral for a second test was female gender (adjusted OR 0.35, 95% CI 0.21 to 0.60, p <0.0001). Of the 126 patients who underwent coronary angiography, severe CAD was identified in only 19 individuals (10.44% of the original cohort, 95% CI 0.26% to 0.62%); coronary artery bypass grafting was performed in 14 of these patients. The estimated cost of exercise treadmill testing to identify 1 case of severe CAD for which surgical revascularization may provide a survival benefit was $39,623. The estimated cost per year of life saved was at least $55,274. Thus, as used in actual practice in 1 center, screening exercise treadmill testing has a low yield and is costly. This is perhaps in part because of the low-risk population that was selected and the failure to incorporate pretest variables, increasing probability of disease into post-test clinical decision making.

Adult↗

Endothelin association with cultured rat hepatic endothelial cells: functional characterization.

Endothelin is a potent vasoactive peptide whose concentration increases in a number of pathophysiological states. In the intact animal, the liver is known to sequester approximately 12% of an injected bolus of [125I]endothelin-1 ([125I]ET-1). Endothelial cells (ECs) isolated from rat liver were maintained in culture in order to examine their role in ET sequestration. LECs were shown to express predominantly ET(B) receptors both by association assays and by Northern blot analysis. In these cells the reaction between [125I]ET-1 and its receptor was essentially irreversible. Ligand binding experiments performed at 4 degrees C showed that LECs in early culture (approximately 3 h) had 4.3 +/- 0.8 fmol of ET receptors per 10(6) cells; this number fell progressively to < or = 1 fmol/10(6) cells during 24 h of culture. The decrease in receptor numbers could be blocked by maintaining the cells at 4 degrees C. Northern blot analysis showed that relative to freshly isolated cells, mRNA for the ET(B) receptor decreased 4-fold in early culture, and recovered somewhat at 24 h. At 37 degrees C [125I]ET-1 bound by the cells was rapidly internalized, with concomitant down-regulation of ET receptors. Recovery of down-regulated ET receptors was sensitive to cycloheximide, making short-term receptor recycling unlikely. Metabolism of [125I]ET-1 was low at short (< 4 h) exposure times, and at 24 h showed a concentration dependence similar to that of ligand association, suggesting that ET-1 metabolism primarily was intracellular. ET stimulation of Kupffer cells and other hepatic cell types is known to activate phosphoinositide signaling, but no such activation was seen in LECs. Moreover, ET did not appear to stimulate protein tyrosine kinase activity in LECs. While hepatic LECs may lack some of the ET-dependent responses seen in other cell types, they likely contribute substantially to the liver's previously reported ability to sequester systemically administered ET.

Animals↗

Age and referral to coronary angiography after an abnormal treadmill thallium test.

This study investigated the association between age and referral to coronary angiography among ambulatory adults with an abnormal treadmill thallium scan. The subjects studied were 416 consecutive adults who were > or = 30 years old, under the care of cardiologists, and had an abnormal treadmill thallium scan between 1990 and 1993 at the Cleveland Clinic Foundation. The primary end point was performance of coronary angiography within 90 days of the treadmill test. Coronary angiography was performed in 163 subjects. Coronary angiography was performed in 46% of patients aged 30-49 years, in 53% of those aged 50 to 64 years, in 33% of those aged 65 to 74 years, and in only 18% of those aged > or = 75 years (chi2 test for trend, p < 0.0001). After adjustment for potential confounders, age remained associated with a lower rate of referral to angiography (p < 0.0001). During 2 years of follow-up 34 deaths occurred (14 cardiac), with particularly high mortality rates among those aged >74 years (cumulative rate 31%, 95% confidence interval 16% to 47%). The number of abnormal thallium scan segments was predictive of death (p = 0.02). These data suggest that increasing age is associated with a lower rate of referral to coronary angiography after an abnormal treadmill thallium test.

Adult↗

Sex and diagnostic evaluation of possible coronary artery disease after exercise treadmill testing at one academic teaching center.

Controversy exists as to whether a sex bias exists that affects the diagnostic approach to suspected coronary artery disease: previous studies have used coronary angiography, but not other noninvasive testing, as a primary end point. This investigation examined posttest sex differences in diagnostic evaluation after exercise treadmill testing according to a broader end point than just coronary angiography alone. The design was a cohort analytic study with a 90-day follow-up. The study was done at the Cleveland Clinic Foundation, an academic group practice. Patients included consecutive adults (1023 men and 579 women) with chest pain but no documented coronary disease who were referred for symptom-limited exercise treadmill testing without adjunctive imaging; none had undergone prior invasive cardiac procedures. Main outcome measures included (1) performance of any subsequent diagnostic study (invasive or noninvasive) and (2) performance of coronary angiography as the next diagnostic study. During follow-up, 89 (8.7%) men and 48 (8.3%) women underwent a second diagnostic study (odds ratio 0.95; 95% confidence interval 0.66 to 1.37; p > 0.8), whereas 64 (6.3%) men and 21 (3.6%) women went straight to coronary angiography (odds ratio 0.56; 95% confidence interval 0.34 to 0.93; p = 0.02). In multivariable logistic regression analyses, which considered baseline clinical characteristics, the ST-segment response, and other prognostically important exercise responses, women tended to be less likely than men to be referred to any second test (adjusted odds ratio 0.70; 95% confidence interval 0.42 to 1.19; p > 0.1) but were markedly and significantly less likely to be referred straight to coronary angiography (adjusted odds ratio 0.33; 95% confidence interval 0.17 to 0.65). After exercise treadmill testing, women were only slightly less likely than men to be referred for subsequent diagnostic testing; they were, however, much less likely to be referred straight to coronary angiography as opposed to another noninvasive study.

Academic Medical Centers↗

Importance of estimated functional capacity as a predictor of all-cause mortality among patients referred for exercise thallium single-photon emission computed tomography: report of 3,400 patients from a single center.

OBJECTIVES: We sought to determine the relative influence of estimated functional capacity and thallium-201 (Tl-201) single-photon emission computed tomographic (SPECT) findings on prediction of short-term all-cause and cardiac-related mortality. BACKGROUND: Decreased functional capacity and abnormal Tl-201 SPECT findings are predictive of increased cardiovascular risk and mortality. However, the relative importance of these variables as predictors of all-cause mortality is not well established. METHODS: Analyses were based on 3,400 consecutive adults undergoing symptom-limited exercise Tl-201 SPECT testing at the Cleveland Clinic Foundation between September 1990 and December 1993; none had previous invasive procedures, heart failure or valve disease. Estimated functional capacity, classified by age and gender, and thallium perfusion defects, expressed as a stress extent thallium score on a 12-segment scale, were analyzed to determine their relative prognostic importance during 2 years of follow-up. RESULTS: Of 3,400 patients, 108 (3.2%) died during follow-up; 32 deaths were identified as cardiac related. On univariable analysis, estimated functional capacity was a strong predictor of death, with 62 (57%) deaths occurring in patients achieving < 6 metabolic equivalents (METs) (log-rank chi-square 86, p < 0.0001). On multivariable analysis, the strongest independent predictors of all-cause mortality were fair or poor functional capacity (adjusted relative risk [RR] 3.96, 95% confidence interval [CI] 2.36 to 6.64, chi-square 27, p < 0.0001) and age (adjusted RR for 10 years 2.25, 95% CI 1.80 to 2.80, chi-square 27, p < 0.0001). The presence of SPECT thallium perfusion defects was a less powerful predictor of death (for each two additional segments with defects, adjusted RR 1.21, 95% CI 1.03 to 1.43, chi-square 5, p = 0.02). Cardiac mortality was predicted by both fair or poor functional capacity (adjusted RR 4.37, 95% CI 1.59 to 12.00, chi-square 8, p = 0.004) and by stress extent thallium score (adjusted RR 1.62, 95% CI 1.25 to 2.11, chi-square 13, p = 0.0003). CONCLUSIONS: In this clinically low risk group, estimated functional capacity was a strong and overwhelmingly important independent predictor of all-cause mortality among patients undergoing exercise Tl-201 SPECT testing. The extent of myocardial perfusion defects was of comparable importance for the prediction of cardiac mortality.

Adult↗

Skin grafting in otology.

Proper healing after surgery of the external auditory canal and open-cavity mastoid depend on epithelialization of exposed surfaces. This may be retarded by the formation of abundant granulation tissue or cicatrix, which can be dealt with by the use of thin, split-thickness skin grafts. This technique, which has received little attention in the literature, is described in detail and nine cases treated for various disorders are illustrated. Patient ages ranged from 5 to 80 years and the mean follow-up was 17.2 years. Results, complications, and caveats for successful grafting are presented.

Adult↗

Thermal effects of laser stapedectomy in an animal model: CO2 versus KTP.

Although use of the laser for stapedectomy has become common in recent years, controversy remains regarding whether the CO2 or visible-spectrum lasers (argon and KTP) are best suited for this operation. The main concern has been the potential for thermal injury to the inner ear with the visible-spectrum lasers attributable to their absorption characteristics. To further investigate this issue, the author performed 20 laser stapedectomies on adult chinchillas. Following placement of a 0.127-mm-diameter copper/constantan thermocouple (sampling at 12 Hz) beneath the footplate on the medial wall of the vestibule via a distant fenestration site, thermal changes with a micromanipulator-based CO2 and fiberoptic KTP system were compared. This was the first live animal model comparison of these two lasers. There was no statistical difference in the mean temperature elevation between the two systems (P = 0.395).

Animals↗

Osteogenic protein-1 downregulates endothelin A receptors in primary rat osteoblasts.

Osteogenesis is a complex process whereby growth factors and mediators from both local and systemic sources modulate the bone-forming activities of osteoblasts. In the present study we utilized primary cultures of fetal rat calvarial cells to characterize osteoblast responsiveness to the vascular mediator endothelin-1 (ET-1) and to investigate whether ET-1 responses are regulated by osteogenic protein-1 (OP-1). We found that a 1- to 2-day exposure to OP-1 diminished ET-1 receptor ligand binding and signal transduction by downregulating ET-1 receptor mRNA expression. ET-1-mediated calcium signaling and ligand binding were completely abolished by the ETA receptor antagonist BQ-123, suggesting that ET-1 effects are mediated by this receptor. Northern analysis of total RNA revealed that ETA mRNA expression was inhibited approximately 50% by OP-1 treatment, whereas ETB receptor mRNA was not detected by this method of analysis. In OP-1-treated cultures, the magnitude and duration of ET-1 calcium signals varied among individual cells. This finding may be related to a heterogeneous OP-1 response, indicated by alkaline phosphatase induction in only a subpopulation of cells. These results suggest that modulation of osteoblast function by ET-1 occurs during distinct periods of phenotypic development and imply that downregulation of ET-1 responsiveness may be necessary for optimal bone formation in vivo.

Alkaline Phosphatase↗