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Biomedical subjects

S K Miller

Publications and source records attributed to S K Miller.

At least 19 recordsLinked to original sources

Characterization of a human plasma membrane heme transporter in intestinal and hepatocyte cell lines.

Heme is the most bioavailable form of dietary iron and a component of many cellular proteins. Controversy exists as to whether heme uptake occurs via specific transport mechanisms or passive diffusion. The aims of this study were to quantify cellular heme uptake with a fluorescent heme analog and to determine whether heme uptake is mediated by a heme transporter in intestinal and hepatic cell lines. A zinc-substituted porphyrin, zinc mesoporphyrin (ZnMP), was validated as a heme homolog in uptake studies of intestinal (Caco-2, I-407) and hepatic (HepG2) cell lines. Uptake experiments to determine time dependence, heme inhibition, concentration dependence, temperature dependence, and response to the heme synthesis inhibitor succinylacetone were performed. Fluorescence microscope images were used to quantify uptake and determine the cellular localization of ZnMP; ZnMP uptake was seen in intestinal and hepatic cell lines, with cytoplasmic uptake and nuclear sparing. Uptake was dose- and temperature dependent, inhibited by heme competition, and saturated over time. Preincubation with succinylacetone augmented uptake, with an increased initial uptake rate. These findings establish a new method for quantifying heme uptake in individual cells and provide strong evidence that this uptake is a regulated, carrier-mediated process.

Carrier Proteins↗

Exposures of geotechnical laboratory workers to respirable crystalline silica.

Geotechnical laboratory testing involves the determination of the physical properties of soil, rock, and other building materials for engineering purposes. Individuals working in these laboratories are exposed to airborne soil, rock, and other dusts during the preparation and testing of these materials. Crystalline silica as quartz is a common constituent of these materials and represents a potential hazard to geotechnical laboratory workers when airborne as a respirable dust. The authors conducted an examination of the potential for geotechnical laboratory workers to be exposed to respirable dust and respirable quartz during the performance of three routine laboratory tasks. A task-based exposure assessment strategy was used. Although respirable dust was generated during the performance of each of these tasks, its impact on exposures was generally overridden by the presence of respirable quartz in the dust. Quartz content in the respirable dust ranged from below the detection limit to greater than 50 percent. Mean exposure to respirable quartz, based on the duration of the task and assuming no other exposures for the rest of the 8-hour day, exceeded the National Institute for Occupational Safety and Health (NIOSH) "action level" (the exposure level at which certain actions must be taken) of 0.025 mg/m3. If exposure was assumed to continue for the rest of the 8-hour day at the measured concentration, mean exposure to respirable quartz exceeded the American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value (TLV) time-weighted average (TWA), the Occupational Safety and Health Administration (OSHA) PEL, and the NIOSH REL. Seven percent of 57 individual task exposure measurements exceeded the TLV-TWA and the PEL, 18 percent exceeded the REL, and another 12 percent exceeded excursion limits as defined by ACGIH. The results of this study support the conclusion that geotechnical laboratory workers are potentially exposed to respirable crystalline silica as quartz at levels that may be harmful. Because the quartz content of the materials being tested in these laboratories is highly variable and is almost never determined prior to testing, all materials being tested in the geotechnical laboratory should be assumed to contain quartz. Appropriate controls should be used to protect workers from inhaling dusts generated from these materials.

Geological Phenomena↗

Hypertension update.

Explore the source record for details and available documents.

Antihypertensive Agents↗

Nurse practitioners in the county correctional facility setting: unique challenges and suggestions for effective health promotion.

The correctional facility practice setting is among the newer practice specialties emerging for nurse practitioners (NPs). As with any new setting, a variety of unique challenges continues to emerge. Because there is a relative paucity of literature regarding NP practice in this particular specialty, those practicing now do not have adequate resources to assist in the development of their practice. This article discusses some of the challenges unique to this area of practice and offers suggestions for incorporating theory-based health promotion interventions. This article is also an effort to begin development of a body of knowledge for NPs providing primary, secondary, and tertiary care to the inmate population of jails and prisons. Hopefully, nurse practitioners in this unique setting will be encouraged to share their own anecdotal and research-based suggestions for improving correctional facility practice.

Forensic Medicine↗

Identifying barriers to the administration of HIV medications to county correctional facility inmates.

The purpose of this study was to investigate the process of HIV medication administration at a county correctional facility. Anecdotal data suggested serious barriers to the process. Professional and licensed practical nursing staff practicing at a New Jersey county correctional facility participated in focus group interviews designed to discuss the process of medication administration and potential barriers to that process. Analysis of data revealed five contextual themes: uniqueness of the county correctional facility setting, barriers perceived by nursing staff, inmates' perceptions of HIV infection, internal systems' barriers, and the role of systems external to the correctional facility.

Anti-HIV Agents↗

Defining the acute in acute care nurse practitioner.

The role of the nurse practitioner in the tertiary care or hospital setting has become well established during the course of this decade. With the introduction of a national certifying examination for acute care nurse practitioners in 1995, it is important that the word acute be defined in a way that is acknowledged universally. Should an examination certifying acute care nurse practitioners contain critical care content? Are the terms acute care and critical care synonymous? The existing examination contains critical care content, but a review of relevant literature suggests a conflict. At times acute care and critical care are used interchangeably, and at other times they are discussed in a way that suggests they are two distinct specialties. This article presents the conflicting use of these two terms in the literature and provides a rationale for recognizing the differences. It is suggested that the definition of the word acute, as it is used in the title acute care nurse practitioner, be reexamined, and that either the content or the title of the certifying examination for acute care nurse practitioners be reconsidered.

Acute Disease↗

Impact of a gerontological nurse practitioner on the nursing home elderly in the acute care setting.

A retrospective analysis of the length of stay of nursing home elderly patients admitted to the hospital demonstrates a significant decrease when patients are comanaged by a nurse practitioner and attending physicians. A comparison of the 20 most heavily populated diagnostic groups between 1993 and 1994 reveals a shorter average length of stay in 17 of the 20 diagnostic groups, and an overall mean decrease of 2.78 days for all groups. This article discusses the impact of the gerontological nurse practitioner on hospital length of stay of the nursing home elderly with acute illness. Research is needed to document advanced practices that decrease length of stay, as well as to control for extraneous variables.

Aged↗

The effects of octreotide on healing of small bowel anastomosis.

Octreotide (OCT) is a somatostatin analog used for its inhibitory action on multiple GI functions. Although octreotide has numerous clinical benefits, it has also been shown to inhibit postresectional hyperplasia of small bowel and hepatic regeneration. Because octreotide inhibits both trophic and anabolic hormones, we hypothesize that the use of octreotide may be detrimental in patients with a recent bowel anastomosis. To test this hypothesis, 60 male rats were randomized to four equal groups following small bowel anastomosis. Group I = control; Group II = 10 mg/day of hydrocortisone succinate; Group III = 2.5 micrograms/kg/day octreotide (equivalent of a clinical dose); Group IV = 25 micrograms/kg/day octreotide. Hydrocortisone was used as a negative control because it is known to have inhibitory effects on small bowel anastomotic healing. On postoperative Day 7, bursting pressures were measured. Serum T-kininogen levels, as a marker for systemic inflammation, and hydroxyproline content from the anastomotic segments were obtained. These results indicate that in the rat small bowel model, octreotide did not have any deleterious effect on anastomotic strength, systemic inflammation, and collagen content, even at high doses. Hydrocortisone, as expected, showed significant detrimental effects on bursting strength, as well as decreasing systemic inflammation. These findings have significant clinical implications, as octreotide could be used without jeopardizing the intestinal anastomosis.

Anastomosis, Surgical↗

Cardiac staircase and NMR-determined intracellular sodium in beating rat hearts.

Isolated, perfused rat hearts (30 degrees C, n = 13) were paced from 218 +/- 4 beats/min to 433 +/- 4 beats/min while systolic and diastolic pressure were recorded and intracellular Na+ concentration ([Na+]i) was monitored by 23Na nuclear magnetic resonance (NMR) spectroscopy. [Na+]i increased progressively with increasing stimulation frequency. In seven hearts (group I) an initial, progressive increase in systolic pressure was observed followed by a decrease in pressure with further increase in frequency. From the onset, a progressive decrease in systolic pressure was observed in group II (n = 6) in response to increased frequency. In group I an [Na+]i increase of up to 134 +/- 7% of control (P < 0.001) was observed, whereas in group II the gain in [Na+]i with increasing pacing rate was attenuated, reaching a maximum of 120 +/- 3% of control (P < 0.02). The differential pressure response between group I and group II hearts may reflect an enhanced sensitivity of rat hearts to the shortening of the restitution period of the sarcoplasmic reticulum, outweighing the positive inotropic effect induced by an increased [Na+]i. Only in rat hearts whose [Na+]i-induced increase in pressure outweights the restitution deficit would a complete positive inotropic effect be anticipated.

Animals↗

Effect of leukotriene inhibitor on cochlear blood flow in salicylate ototoxicity.

Our previous studies showed that salicylate ototoxicity is associated with decreased levels of vasodilating prostaglandins (PGs) and increased vasoconstricting leukotrienes (LTs) in the perilymph and reduced cochlear blood flow (CoBF). The purpose of this study was to test the hypothesis that leukotriene inhibitor prevents salicylate ototoxicity by preventing abnormal elevation of LT levels in the inner ear, thus averting a decrease in CoBF resulting from abnormal levels of arachidonic acid metabolites in the inner ear. Ototoxicity was induced in chinchillas by either local round window membrane (RWM) application or systemic treatment with salicylate both with and without pretreatment with leukotriene inhibitor (Sch 37224). A moderate reduction in CoBF was documented with both local RWM and systemic treatment with salicylate. Salicylate induced hearing loss and reduction in CoBF were prevented by pretreatment with a leukotriene inhibitor. This study suggests that leukotriene inhibitor prevents salicylate ototoxicity by averting a decrease in CoBF mediated by abnormal levels of arachidonic acid metabolites in the inner ear.

Animals↗

The effect of postinfarction intramyocardial hemorrhage on transverse relaxation time.

1H NMR imaging has been used to define zones of myocardial infarction (MI), which appear as areas of relatively increased signal intensity (SI). However, zones of decreased SI have been observed within or around the areas of infarction in NMR images acquired at high magnetic fields. To determine the cause of these areas of reduced SI, ex vivo spin-echo 1H NMR imaging at 1.5 T was performed in eight dogs following 72 h of coronary artery occlusion. In all dogs, a zone of increased SI (122 +/- 7% compared to control myocardium; P less than 0.01) was observed in the territory of the occluded coronary artery. In seven of the dogs, additional zones were also seen, within or around the central zone of increased SI, which displayed SI that was reduced in comparison with the local enhanced intensity, but was similar to the intensity of normal myocardium (97 +/- 7% compared to control; P = NS). Gross inspection and histological assessment of sliced myocardium disclosed hemorrhage in these regions characterized by locally decreased NMR SI. Image-derived calculation of T2 in the various infarct regions revealed a significant shortening of T2 in the hemorrhagic infarct zones characterized by decreased SI, in comparison with the nonhemorrhagic infarct zones characterized by increased SI (59 +/- 7 ms vs 73 +/- 10 ms, P less than 0.05). No difference was found, however, between the observed T2's of hemorrhagic infarct and of control tissue (57 +/- 4 ms). Using a biexponential analysis of T2 from the hemorrhagic infarct zones, the intrinsic T2 of water protons affected by hemorrhage was determined to be 43 +/- 9 ms, significantly reduced in comparison with the values obtained with the standard monoexponential fit. The reduction in T2 in the hemorrhagic zone is consistent with the paramagnetic effects of deoxyhemoglobin associated with intramyocardial hemorrhage. Thus the apparent T2, measured in hemorrhagic infarct tissue, represents the result of an averaging effect of infarct and hemorrhage on T2 relaxation times. These observations improve our understanding of the changes in NMR SI within the infarcted regions, and may provide a noninvasive method for the detection and quantitative assessment of intramyocardial hemorrhage.

Animals↗

The longitudinal relaxation time (T1) of the intracellular 23Na NMR signal in the isolated perfused rat heart during hypoxia and reoxygenation.

Each of six perfused rat hearts was subjected to 30 min of hypoxia followed by 60 min of reoxygenation. Inversion-recovery data on the intracellular Na NMR signal, differentiated by a shift reagent, 6 mM Dy(PPP)2, were obtained every 5 min, and T1 values were calculated. The T1 of the intracellular Na signal did not show any significant change either during hypoxia or upon reoxygenation, although the level of Nai increased about 50%. Such an increase of total Nai is expected to reduce the observed relaxation rate by diluting the fraction of Nai ions that interact with intracellular polyelectrolytes. The observed constancy of T1 in our study is explained on the basis of the typical values of the dissociation constants of sodium ions, in aqueous solutions, in interaction with polyelectrolytes. Although the constancy of intracellular sodium T1 during hypoxia may preclude the utilization of T1 weighting for the monitoring of pathology, its determination could be important for setting optimal acquisition times in high time-resolution experiments.

Animals↗

Amiloride in ouabain-induced acidification, inotropy and arrhythmia: 23Na & 31P NMR in perfused hearts.

The increase in intracellular sodium (Nai), resulting from inhibition of the Na/K ATPase by cardiac glycosides, is known to increase calcium influx via Na(+)-Ca2+ exchange, and thereby increase contractility. This increase in intracellular Ca2+ has been related to the development of intracellular acidification and enhanced activity of the Na(+)-H+ exchanger as a measure by the cell to prevent further acidification. Thus, the efflux of the H+ ions results in an additional increase in Nai. This may subsequently lead to an increased rate of Ca2+ influx and therefore to the potentiation of the effects of cardiac glycosides. To assess the role of Na(+)-H+ exchange in the mechanism of ouabain action in the beating heart we used amiloride, a known inhibitor of Na(+)-H+ exchange. Isolated rat hearts were perfused with either ouabain (50 microM) alone (n = 8, Group I), amiloride (1.0 mM) + ouabain (50 microM) (n = 8, Group II), or amiloride (1.0 mM) alone as a control group (n = 4, Group III). 23Na and 31P NMR spectroscopy were used to assess the changes in Nai and intracellular pH (pHi), respectively, while simultaneous and continuous monitoring of left ventricular pressure was carried out. Perfusion with both ouabain alone (Group I) or ouabain + amiloride (Group II), resulted in a time dependent increase in Nai levels, reaching (within 25 mins) a maximum of 200 +/- 7% of control in Group I, and 170 +/- 10% of control in Group II. Concurrently, a mild but significant decrease in pHi was observed in both groups. This decrease, however, was significantly higher in Group II compared to Group I (0.34 pH units vs. 0.19 pH units, respectively; P less than 0.05), suggesting that inhibition of Na(+)-H+ exchange by amiloride limits the recovery from ouabain-induced intracellular acidification. While developed pressure gradually increased in Group I to a maximum of 268 +/- 52% of control, the addition of amiloride in Group II substantially reduced the positive inotropic effect. Ventricular fibrillation (VF) developed in three of the eight hearts in Group I within 10-13 mins after the addition of ouabain. Interestingly, the rate of Nai increase in hearts that sustained VF was significantly higher compared to those without VF (mean slope 10.1 +/- 2.11 vs. 3.9 +/- 1.0, respectively; P less than 0.0001). Ventricular fibrillation did not develop in Group II or III.(ABSTRACT TRUNCATED AT 400 WORDS)

Amiloride↗