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Biomedical subjects

K Nichols

Publications and source records attributed to K Nichols.

At least 19 recordsLinked to original sources

Stress experiences of occupational therapists in mental health practice arenas: a review of the literature.

The experience of job stress and burnout in occupational therapy has received only scant attention in the literature, although occupational therapists (OTs) share a number of important characteristics with other health care professionals that leave them vulnerable to the experience of stress. In addition, this group has a number of unique personal and work-related characteristics that could serve to increase its risk profile. Little effort has been directed at delineating work-related stressors or experienced levels of stress within different practice arenas of occupational therapy, even though some specialisms (e.g. mental health, forensic psychiatry, learning disabilities or paediatrics) are likely to be more emotionally demanding than others. There are a number of indicators which confirm that job stress is an issue for OTs, although some of the empirical data suggests that, on average, this occupational group experience less burnout than other human service professionals.

Adaptation, Psychological

Localization of GABAA receptor immunoreactivity in NO synthase positive myenteric neurones.

GABAA receptors were localized within laminar preparations of the rat distal colon myenteric plexus using a monoclonal antibody (mAb 62-3G1) to the affinity purified GABAA receptor/benzodiazepine receptor/Cl- channel complex. The immunofluorescence procedure showed that approximately half of the myenteric ganglion cells displayed extensive GABAA receptor labelling of their soma. This population was further characterised by treating some GABAA-receptor-labelled laminar preparations for the histochemical demonstration of nitric oxide (NO) synthase-related NADPH-dependent diaphorase activity. A subpopulation of the GABAA-receptor-immunoreactive cells (35%) were also found to display intense NO-synthase-related activity. These findings extend our understanding of the GABAA-receptor-related innervation of the rat gut wall herein referred to as 'A-GABAergic' and provides an anatomical basis for the pharmacologically-identified GABA-nitrergic pathway in the mammalian gut.

Animals

Immunopositive GABAergic neural sites display nitric oxide synthase-related NADPH diaphorase activity in the human colon.

In the enteric nervous system, gamma-aminobutyric acid (GABA) is a transmitter of interneurons which are proposed to innervate excitatory and inhibitory motor neurons. Nitric oxide (NO) is a putative transmitter of enteric inhibitory motor nerves targeted by GABA. In addition, NO is synthesized by a variety of enteric nerves throughout the gut wall indicative of its potential to be a transmitter of other nerve types, including interneurons. We sought to determine if some populations of nitrergic neurons are interneurons in human infant colon. As enteric neural GABA is exclusive to interneurons, colocalization with NO synthase-related NADPH diaphorase was examined. GABA-transaminase (GABA-T) immunohistochemistry was used to identify GABAergic neurons and a histochemical protocol was used as a marker of neuronal NO synthase-related NADPH diaphorase activity in enteric layers. GABA-T immunoreactive neurons were seen in the ganglionated nerve networks of the myenteric and submucosal layers. GABA-T immunoreactive fibres were also present in the longitudinal and circular muscle layers. A subpopulation of GABA-T immunoreactive neurons within both the myenteric and submucosal ganglia express NO synthase-related activity. This colocalization extends further to a subpopulation of fibers within the muscle layers. These findings strongly suggest that in addition to its role in inhibitory motor neurons, NO may also be a transmitter of enteric interneurons.

Amino Acid Oxidoreductases

Update on implantable cardioverter defibrillators: knowing the differences in devices and their impact on patient care.

Sudden cardiac death, a common cause of cardiac mortality, can be treated with either pharmacologic therapy or implantation of an implantable cardioverter defibrillator. Tremendous technologic advances have changed implantable cardioverter defibrillator therapy from shock-only therapy to multiprogrammable, tiered-therapy devices with backup pacing. Methods of implantation have changed from open chest to non-thoracotomy procedures. To provide optimal patient care, the critical care nurse is challenged to be knowledgeable about the different devices. In this article, the authors examine the commonalities and differences in device function in the seven currently available implantable cardioverter defibrillators and their impact on patient care.

Critical Care

Demonstration of benzodiazepine receptors in submucosal neurons of the gastrointestinal tract.

Benzodiazepine (BZ) receptors were visualized in laminar preparations of the rat colon submucosa, using a fluorescent derivative of the benzodiazepine receptor ligand desdiethyl fluorazepam, Bodipy RO-1986 (50 nM). Collateral confirmation of the results obtained were sought through immunohistochemistry, using a monoclonal antibody (62-3GI) for benzodiazepine cell receptors. Both procedures showed that a large proportion of ganglia in the colon submucosa displayed cells with extensive labelling of their soma. Nerve fibres and processes, blood vessels and vascular nerve bundles were not labelled. Fluorescent ligand-labelling could be reduced, using the BZ receptor ligand diazepam (5 microM). These findings provide an anatomical basis for the previously described neuropharmacology of BZ in the gut.

Animals

Neural sites of the human colon colocalize nitric oxide synthase-related NADPH diaphorase activity and neuropeptide Y.

BACKGROUND/AIMS: Nitric oxide and neuropeptide Y (NPY) exert similar biological actions in the mammalian intestine including modulation of food intake, blood flow, motility, and secretion. In addition, these substances coexist in submucosal secretomotor neurons of the rodent intestine. The aim of this study was to determine the relative disposition of elements displaying NPY immunoreactivity and NO synthase-related nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase activity in the nerve networks of the human infant colon. METHODS: Transverse and longitudinal sections, treated for immunohistofluorescent detection of NPY and then processed for NO synthase-related NADPH diaphorase histochemistry, were examined. RESULTS: Neural elements containing NPY immunoreactivity and NO synthase-related activity were identified in the external muscle layers, myenteric plexus, and all nerve layers of the submucosa, including Henle's plexus, the intermediate nerve layer, and Meissner's plexus. Perivascular NPY-immunoreactive nerve fibers did not contain NO synthase activity. There were no nitrergic perivascular nerve fibers. NPY-immunoreactive endocrine cells in the mucosa did not display NO synthase-related activity. CONCLUSIONS: These findings provide anatomical data indicating that NPY immunoreactivity and NO synthase-related activity are extensively colocalized in all layers of the human infant gut wall.

Amino Acid Oxidoreductases

[3H]GABA uptake and GABA localization in mucosal endocrine cells of the rat stomach and colon.

The aim of this study was to characterize the distribution of GABAergic cells in the rat gut mucosa. Thin and/or thick serial sections of segments of rat antrum and distal colon were treated for autoradiographic localization of sites of [3H]GABA (50 nM) high-affinity uptake, or GABA immunoreactivity. Dense accumulations of silver grains were localized to a discrete population of granulated mucosal cells. These appeared to be D-type endocrine cells. These gut regions also displayed strongly GABA-immunoreactive mucosal cells. These results confirm the presence of GABAergic cells in the rat antral mucosa, and reveal that [3H]GABA is accumulated by mucosal endocrine cells in the rat colon.

Animals

Distribution of nitric oxide synthase activity in arterioles and venules of rat and human intestine.

NO is produced within peripheral blood vessels through the action of the differentially distributed constitutive and inducible NO synthase isoforms in the vessel wall. As in other sites in the periphery, NO exerts local vasodilatory actions in the gastrointestinal microvasculature and is proposed to play a role in enteric vasomotor regulation. Using NO synthase histochemistry and endothelial cell immunohistochemistry, we provide the first anatomic evidence of NO synthesis in both endothelial and smooth muscle cells of submucosal blood vessels in the rat and human intestine. The findings of this study indicate that 1) as in the periphery, both the endothelial and vascular smooth muscle cells of the microvessels irrigating the rat and human intestinal wall possess NO synthesis potential, 2) NO synthase activity is predominantly localized to discrete subcellular patches, and 3) the source of NO within the vascular wall, either intimal or medial, should be a consideration in future studies in terms of the relative contribution of these sources of vasomotor tone in the rat and human gut wall.

Amino Acid Oxidoreductases

First-pass ventricular ejection fraction using a single-crystal nuclear camera.

UNLABELLED: The purpose of the study was to evaluate the reliability of ejection fractions obtained from first-pass radionuclide ventriculography with a large field-of-view tomographic single-crystal gamma camera. METHODS: A SPECT camera had its electronics redesigned to improve counting efficiency and was equipped with an experimental ultra-high sensitivity collimator. Left ventricular ejection fraction (LVEF) was measured in 28 patients by 30 degrees RAO first-pass imaging and by "best septal view" LAO planar equilibrium radionuclide ventriculography on a conventional small field of view Anger camera. For 28 other patients, first-pass ejection fractions were compared to multicrystal gamma camera values. Visual analysis was performed to judge clinical acceptability of first-pass images for identification of wall-motion abnormalities. RESULTS: Linear regression analysis of first-pass against equilibrium ejection fraction demonstrated good correlation (r = 0.92; slope = 0.90; intercept = 3.8; s.e.e. = 6.4%). First-pass ejection fraction values also correlated linearly with multicrystal camera values for the left ventricle (r = 0.94; slope = 1.05; intercept = 1.3; s.e.e. = 5.3%). For a subgroup of 19 patients, single-crystal camera right ventricle ejection fraction demonstrated good correlation with multicrystal camera values (r = 0.82; slope = 1.15; intercept = 1.3; s.e.e. = 6.1%). Interobserver variability correlated as r = 0.99 for LVEF ejection fraction and r = 0.92 for RVEF. Chi-square analysis of single-crystal first-pass image visual scores versus those from the gated equilibrium acquisitions showed close agreement (p < 10(-8)). CONCLUSIONS: The evaluated camera/collimator system measured left and right ventricular ejection fraction accurately. Lung frame correction and dual regions were superior to paraventricular background correction and a fixed end-diastolic region.

Feasibility Studies

Nitric oxide synthase distribution in the rat intestine: a histochemical analysis.

BACKGROUND: Nitric oxide is an inhibitory transmitter of nonadrenergic, noncholinergic neurons and is purported to be an endothelium-derived relaxant-type factor in the mammalian gut. This study aimed to provide a complete report on the distribution of NO synthase in the rat small and large intestine. METHODS: NO synthase was visualized histochemically through this enzyme's reduced nicotinamide adenine dinucleotide phosphate diaphorase activity and the distribution of staining within the gut wall. RESULTS: The presence of NO synthase activity in myenteric neurons and their efferents to the circular muscle was confirmed. The largest proportion of stained cells per ganglion was found in the ileum, and the smallest proportion was in the colon. Stained neural elements were also found within the submucosa throughout the intestine. Stained cells within the myenteric and submucous nerve plexi displayed both type I and type II morphologies, with the latter being more numerous. In addition to neural staining, submucosal arterioles showed a regular pattern of small patches of staining unrelated to any perivascular innervation. CONCLUSIONS: These findings indicate an extensive neural and vascular localization of NO generation potential throughout the wall of the rat intestine, thus providing a structural basis for the functional diversity of NO.

Amino Acid Oxidoreductases

Left ventricular ejection fraction assessed from gated technetium-99m-sestamibi SPECT.

By means of ECG gating of tomographic (SPECT) 99mTc-sestamibi (MIBI) images, myocardial perfusion and wall thickening have been evaluated after a single tracer injection. To determine if left ventricular ejection fraction (LVEF) can also be measured from gated MIBI SPECT, 30 patients 1 wk to 6 mo after myocardial infarction (MI) received 22-30 mCi 99mTc-MIBI during treadmill exercise. Eight frame per cardiac cycle gated MIBI 180 degrees SPECT was performed 60 min thereafter. Using 6.4-mm thick mid-ventricular vertical and horizontal long-axis slices from R-wave triggered end-diastolic and end-systolic frames, two independent observers manually drew endocardial borders at a count level of 34% of the maximum. LVEF was computed by the Simpson's rule method, corrected for the average point spread function of the SPECT camera. Results were correlated with LVEF determined from planar gated 99mTc-blood-pool studies performed within 4 days. LVEFs calculated from gated MIBI SPECT ranged from 0.21 to 0.73 and correlated linearly with gated blood-pool values (correlation coefficients ranged from 0.79 to 0.88; interobserver variability r = 0.75; intraobserver reproducibility r = 0.75). We conclude that in patients with MI resting LVEF can be determined from gated MIBI SPECT, thereby considerably augmenting the technique's diagnostic and prognostic value.

Adult

Histochemical localization of nitric oxide-synthesizing neurons and vascular sites in the guinea-pig intestine.

Laminar preparations of fixed segments of the guinea-pig intestine were examined for nitric oxide synthase activity using reduced nicotinamide adenine dinucleotide phosphate and nitroblue tetrazolium salt as substrates. Under conditions specific for detecting nitric oxide synthase-related diaphorase activity, a subpopulation of neural elements in the myenteric plexus, deep muscular plexus and submucosa were intensely stained. Intensely stained nerve fibres were distributed throughout the meshworks of the myenteric plexus and its innervation of the circular muscle, and in the submucosa within Henle's plexus. Intensely stained nerve cells and their processes were evident in most myenteric ganglia but were rare in ganglia of Henle's plexus. Stained ganglion cells comprised types I, II and VI of the morphologically defined enteric nerve cells. Stained neural elements were increasingly prevalent within successively more caudal segments of the intestine. In addition to neuronal staining, arterioles of the submucosal vascular network displayed distinct, punctate patches of staining distributed over their surface. Perivascular nerve fibre staining was absent. These results show nitric oxide synthase activity to be present within neurons and fibres of the major enteric nerve layers and within submucosal blood vessels throughout the guinea-pig small and large intestine.

Amino Acid Oxidoreductases

Pulsatile ACTH and cortisol in goats: effects of insulin-induced hypoglycemia and dexamethasone.

Insulin-induced hypoglycemia is a metabolic stress that stimulates secretion of adrenocorticotropic hormone (ACTH) and cortisol in a number of animal species. Dexamethasone is a potent synthetic glucocorticoid that suppresses the secretion of ACTH and cortisol. Both ACTH and cortisol exhibit complex secretory patterns demonstrating ultradian and circadian rhythms. This work investigated the pattern of ACTH and cortisol response to hypoglycemia in goats and the effect of dexamethasone on this response. Five goats were pretreated with dexamethasone (0.1 mg/kg) and 5 with saline. Blood samples were taken every 2 min for 60 min before and 60 min after administration of insulin (2.5 IU/kg, i.v.). Immunoreactive ACTH and cortisol were measured in all samples and glucose in selected samples. Data sets were analyzed for significant pulses with the Cluster Analysis program. Complete data sets were compared as well as those for each 30-min interval. Plasma glucose was lower than preinsulin levels at 10 min, declined rapidly between 10 and 30 min, and remained low 30-60 min after insulin injection in both treatment groups. Controls showed a rapid rise in ACTH and cortisol beginning 30 +/- 10 min postinsulin. The increase in mean plasma hormone levels during hypoglycemia was predominantly due to an increase in amplitude of secretory pulses for ACTH and cortisol compared with the 30 min before insulin. Dexamethasone significantly lowered mean ACTH and cortisol levels and prevented alteration in plasma ACTH and cortisol secretion during hypoglycemia but did not totally ablate pulsatile activity of either hormone. The amplitude of ACTH and cortisol pulses was significantly decreased by dexamethasone treatment. The frequency of cortisol but not ACTH pulses was also significantly decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone

Myocardial perfusion imaging with technetium-99m sestamibi SPECT in the evaluation of coronary artery disease.

Technetium-99m (Tc-99m) sestamibi is a new myocardial perfusion imaging agent that offers significant advantages over thallium-201 (Tl-201) for myocardial perfusion imaging. The results of the current clinical trials using acquisition and processing parameters similar to those for Tl-201 and a separate (2-day) injection protocol suggest that Tc-99m sestamibi and Tl-201 single photon emission computed tomography (SPECT) provide similar information with respect to detection of myocardial perfusion defects, assessment of the pattern of defect reversibility, overall detection of coronary artery disease (CAD) and detection of disease in individual coronary arteries. Tc-99m sestamibi SPECT appears to be superior to Tc-99m sestamibi planar imaging because the former provides a higher defect contrast and is more accurate for detection of disease in individual coronary arteries. Research is currently under way addressing optimization of acquisition and processing of Tc-99m sestamibi studies and development of quantitative algorithms for detection and localization of CAD and sizing of transmural and nontransmural myocardial perfusion defects. It is expected that with the implementation of the final results of these new developments, further significant improvement in image quality will be attained, which in turn will further increase the confidence in image interpretation. Development of algorithms for analysis of end-diastolic myocardial images may allow better evaluation of small and nontransmural myocardial defects. Furthermore, gated studies may provide valuable information with respect to regional myocardial wall motion and wall thickening. With the implementation of algorithms for attenuation and scatter correction, the overall specificity of Tc-99m sestamibi SPECT should improve significantly because of a substantial decrease in the occurrence of attenuation-related image artifacts.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Disease

Development and prospective application of quantitative 2-day stress-rest Tc-99m methoxy isobutyl isonitrile SPECT for the diagnosis of coronary artery disease.

The clinical diagnostic accuracy of 2-day stress/rest quantitative Technetium-99m (Tc-99m) methoxy-isobutyl-isonitrile (Tc-sestamibi) single photon emission computerized tomography (SPECT) was assessed in a validation population of 61 patients from two different sites using two different camera/computer systems. The study population was made up of 53 catheterized patients, 29 from Cedars-Sinai Medical Center (CSMC) and 24 from the University of Texas Southwestern Medical Center (UTSMC), and eight UTSMC patients with a less than 5% pre-test likelihood of coronary artery disease. Interpretation employed gender-specific normal limits developed in an additional 15 men and 8 women at CSMC with less than a 5% likelihood of significant coronary artery disease. The results from CSMC compared with those from UTSMC were not different from each other. The overall sensitivity for detection of patients with coronary artery disease (greater than or equal to 50% stenosis) was 94% (CSMC: 92%, UTSMC: 95%). Overall specificity in the five patients with normal coronary arteriograms was 80% (CSMC: 67%, UTSMC: 100%). The normalcy rate in patients with a low likelihood of coronary artery disease was 88%. Vessel sensitivity was 85% (CSMC: 84%, UTSMC: 85%), while vessel specificity was 71% (CSMC: 72%, UTSMC: 69%). There was also no significant difference in the sensitivities and specificities between male and female populations. In addition, the agreement with coronary angiography for assessment of disease extent (normal coronary arteriogram, single or multivessel disease) was 75% (kappa = 0.6 +/- 0.1). This study demonstrated that Tc-sestamibi SPECT by quantitative analysis is accurate for the detection and localization of coronary artery disease. Furthermore, the CSMC quantitative method was shown to provide similar diagnostic accuracy when applied to data acquired at a different site using a different camera/computer system.

Adult

Non-interventional background corrections for scintigrams.

A method is presented for the interpolation of optimally 'smooth' background correction matrices within arbitrarily shaped boundaries. Practical means of implementing this technique are discussed, along with series expansions for the special cases of square and round boundaries. This class of interpolation methods has the advantages over previous techniques of providing a unique mathematical solution, connecting exactly to count rates on the boundary, and containing no singularities. Clinical scintigraphic images and mathematically generated surfaces are used to test the different cases of the method, and it is shown that confining the boundary to a circle produces the most rapid convergence with the minimum deviation from ideal surfaces. Under common clinical conditions, these techniques lend themselves well to automated, non-interventional computer processing.

Humans