Self-disclosure disincentives. Feds must offer stronger protections to encourage providers to voluntarily report misconduct.
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Biomedical subjects
Publications and source records attributed to S Burke.
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To further understand the functions of the orexin/hypocretin system, we examined the expression and regulation of the orexin/hypocretin receptor (OX1R and OX2R) mRNA in the brain by using quantitative in situ hybridization. Expression of OX1R and OX2R mRNA exhibited distinct distribution patterns. Within the hypothalamus, expression for the OX1R mRNA was largely restricted in the ventromedial (VMH) and dorsomedial hypothalamic nuclei, while high levels of OX2R mRNA were contained in the paraventricular nucleus, VMH, and arcuate nucleus as well as in mammilary nuclei. In the amygdala, OX1R mRNA was expressed throughout the amygdaloid complex with robust labeling in the medial nucleus, while OX2R mRNA was only present in the posterior cortical nucleus of amygdala. High levels of OX2R mRNA were also observed in the ventral tegmental area. Moreover, both OX1R and OX2R mRNA were observed in the hippocampus, some thalamic nuclei, and subthalamic nuclei. Furthermore, we analyzed the effect of fasting on levels of OX1R and OX2R mRNA in the hypothalamic and amygdaloid subregions. After 20 h of fasting, levels of OX1R mRNA were significantly increased in the VMH and the medial division of amygdala. An initial decrease (14 h) and a subsequent increase (20 h) in OX1R mRNA levels after fasting were observed in the dorsomedial hypothalamic nucleus and lateral division of amygdala. Levels of OX2R mRNA were augmented in the arcuate nucleus, but remained unchanged in the dorsomedial hypothalamic nucleus, paraventricular hypothalamic nucleus, and amygdala following fasting. The time-dependent and region-specific regulatory patterns of OX1R and OX2R suggest that they may participate in distinct neural circuits under the condition of food deprivation.
Ectopia cordis is a rare congenital defect in which the heart is placed externally on the surface of the chest. This article describes the embrylogic events that lead to the various classifications of the defect and how they possibly explain the process of its unusual occurrence in children. While survival in some cases is possible, the ultimate repair is difficult and survival is rare. The most extreme forms of ectopia cordis, especially those with intracardiac defects, have a poor prognosis. Several cases of this rare anomaly with primary repair and staged repair are discussed.
STUDY DESIGN: A retrospective analysis of radiographic reports of 161 consecutive patients with idiopathic scoliosis at the authors' institution. OBJECTIVES: To compare various radiographic findings that directly affect surgical decision-making and the evaluation of postsurgical outcomes to determine the usefulness of information gathered from radiologists' multiple duplicate reading of films. SUMMARY OF BACKGROUND DATA: To the authors' knowledge, there are no previous studies on the readings of scoliosis films by radiologists and surgeons. METHODS: The patient pool was drawn from the private practices of two board-certified orthopaedic surgeons. Each set of radiographs was read by one of seven board-certified radiologists and by one of the two surgeons. The two reports of each radiograph were compared. The factors included in the reports were scoliosis deformity, scoliosis type, curve progression, curve magnitude, levels of the curve, kyphosis, lordosis, the presence of instrumentation, and the presence of a fusion. RESULTS: The radiologists and orthopedic surgeons mentioned the presence of scoliosis in 95% and 99.4% of their reports, respectively. The type of scoliosis was mentioned in 5% of reports by radiologists and in 99.4% by orthopedists. Progression of the curve was documented in 16.7% of the radiologists' reports and in 98.4% of orthopedists' reports. The magnitude of the curve was stated in 12.6% of the radiologists' reports, compared with 98.1% of the orthopaedists' reports. The levels of the curve were documented in 10.6% and 95.6% of reports by the radiologists and orthopedists, respectively. Radiologists mentioned kyphosis and lordosis in 28% and 26.5% of reports, respectively. These same two entities were mentioned in 98.2% and 79.4% of reports by the orthopedists. Finally, the radiologists noted the presence of instrumentation and of a fusion in 77.8% and 68.3% of reports, respectively. Orthopedists mentioned these same two entities in 84.4% and 100% of reports, respectively. In the radiologists' reports on the presence of instrumentation, 20% were mislabeled or improperly identified. Seven percent of the fusions documented by the radiologists were incorrect because they were recorded before biologic fusion could have taken place. In all these categories, the radiologists provided information in excess of the orthopedic reports a total of 1.9% of the time. Of this 1.9% additional information, 36.8% was incorrectly read or mislabeled. The other 63.2% of the additional information (1.9% of the total) did not elucidate anything of real clinical significance that was missed by the orthopedic surgeons (e.g., a tumor in the lung). CONCLUSIONS: These findings show that the attending orthopedic spine surgeons gained little useful information from the radiologists' multiple duplicate reading of films.
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The aim of the current investigation was to study the effects of sevelamer hydrochloride (RenaGel) on serum phosphate, intact parathyroid hormone levels (iPTH), and lipid profiles in stable hemodialysis patients. Hemodialysis patients maintained on calcium containing phosphate binders were enrolled in this study. Following two weeks of washout of the phosphate binders, serum phosphate rose from 6.4 +/- 0.6 to 10.5 +/- 0.7 mg/dl (p <0.001). After 8 weeks of titration with sevelamer hydrochloride, serum phosphate fell by 4.5 +/- 0.3 to 6.3 +/- 0.7 mg/dl (p <0.0001). Serum calcium levels fell during washout (9.8 +/- 0.4 to 8.9 +/- 0.3 mg/dl, p <0.004) and were unaffected by sevelamer hydrochloride. Sevelamer hydrochloride administration was associated with a 23.0 +/- 3.1% fall in total cholesterol, a 35.9 +/- 3.0% fall in LDL cholesterol, and a 35.2 +/- 5.3% fall in the LDL:HDL cholesterol ratio (p <0.001). There was no change in HDL cholesterol, triglycerides or the concentration of fat soluble vitamins. Sevelamer hydrochloride is a well tolerated alternative to calcium or aluminum containing phosphate binders and may offer an advantage to patients who become hypercalcemic on calcium-containing antacids and vitamin D supplementation. Furthermore, sevelamer hydrochloride lowers LDL cholesterol without affecting HDL cholesterol. The potential usefulness of the lipid lowering effects of sevelamer hydrochloride needs to be determined in additional prospective studies.
We evaluated the cost-effectiveness of routine dilated fundus examination in improving visual outcomes. The cost of routine dilated fundus examination was related to the number of preventable cases of vision-threatening peripheral retinal disease. Patients with these diseases who had no risk factors were ascertained in a population of 1.75 million adults for a period of 6 months. Those whose last examination had been undilated were identified because only for them could routine dilated examination (RDE) have been substituted for undilated examination. The number of preventable cases was calculated for multiples of a 10% probability of prevention. The cost of RDE was determined from the number of undilated examinations in the same population and period and the cost of a single RDE. The number of patients who underwent undilated examination was estimated by random medical record review. The additional cost of a single RDE was determined from estimated examination times and payroll costs. Among patients without risk factors, 38 were identified for whom undilated examination rather than RDE had been performed. If prevention had been 10% effective, the substitution of 50,000 RDEs for undilated examinations costing the provider $433,000 would have been required per prevented case. These results suggest that most peripheral retinal diseases cannot be prevented by RDE. Routine dilated examination is an expensive test per prevented case. Published clinical guidelines lack evidence to recommend its use.
A 6-month retrospective self-administered questionnaire study of 482 doctors and 380 midwives in two NHS Trusts was undertaken. The response rate was 384 (80%) and 293 (77%) respectively. The study revealed that only nine per cent of doctors and 46% of midwives had reported the contamination incidents they had received. The doctors' main reason for non-reporting was 'too time consuming' and midwives' was 'did not consider anything could be done', although their awareness of the active management of contamination incidents by occupational health departments was good. Seventy-seven per cent of doctors and 69% of midwives underestimated the risk of contracting hepatitis B virus from a needlestick injury, whilst 52% of doctors and 36% of midwives underestimated the risks of acquiring infection with HIV (human immunodeficiency virus) infection following such an injury. Strategies for improving the knowledge of the potential risks of contamination incidents and methods for facilitating ease of reporting are discussed.
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Several lines of evidence have demonstrated the presence of three opioid receptor types in the CNS and periphery. These receptors are referred to as mu, delta and kappa, and have been implicated in a wide variety of functions. The present study examines the localization of the kappa 1 receptor, a region of the receptor that has little homology with mu and delta receptors. Immunohistochemical studies in Zamboni-fixed rat tissue demonstrate immunoreactive perikarya and/or fibers in such regions as the deep layers of the parietal, temporal and occipital cortex, parasubiculum, central and medial amygdala, bed nucleus stria terminalis, nucleus accumbens, olfactory tubercle, endopiriform nucleus, claustrum, hypothalamic nuclei, median eminence, midline thalamic nuclei, zona incerta, central gray, caudal linear and dorsal raphe, substantia nigra, pars reticulata, ventral tegmental area, parabrachial nucleus, spinal trigeminal nucleus, nucleus of the solitary tract, spinal cord and the dorsal root ganglia. Specific kappa 1 receptor-like immunohistochemical staining is also observed in the pituitary, where immunoreactive perikarya and fibers are localized in the neural and intermediate lobes. Transfection and preabsorption controls suggest that the antibody is selective for the cloned kappa 1 receptor, and does not recognize mu or delta. This immunohistochemical localization corresponds well to previously described kappa 1 receptor mRNA and binding distributions and provides new insights into the cellular localization and pre- and postsynaptic organization of the kappa 1 receptor-like proteins in the rat brain and pituitary. The functional implications of these results are discussed in light of the kappa 1 receptors play in hormonal regulation, antinociception and reward.
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Three opioid receptor types have recently been cloned that correspond to the pharmacologically defined mu, delta and kappa 1 receptors. In situ hybridization studies suggest that the opioid receptor mRNAs that encode these receptors have distinct distributions in the central nervous system that correlate well with their known functions. In the present study polyclonal antibodies were generated to the C terminal 63 amino acids of the cloned mu receptor (335-398) to examine the distribution of the mu receptor-like protein with immunohistochemical techniques. mu receptor-like immunoreactivity is widely distributed in the rat central nervous system with immunoreactive fibers and/or perikarya in such regions as the neocortex, the striatal patches and subcallosal streak, nucleus accumbens, lateral and medial septum, endopiriform nucleus, globus pallidus and ventral pallidum, amygdala, hippocampus, presubiculum, thalamic and hypothalamic nuclei, superior and inferior colliculi, central grey, substantia nigra, ventral tegmental area, interpeduncular nucleus, medial terminal nucleus of the accessory optic tract, raphe nuclei, nucleus of the solitary tract, spinal trigeminal nucleus, dorsal motor nucleus of vagus, the spinal cord and dorsal root ganglia. In addition, two major neuronal pathways, the fasciculus retroflexus and the stria terminalis, exhibit densely stained axonal fibers. While this distribution is in excellent agreement with the known mu receptor binding localization, a few regions, such as neocortex and cingulate cortex, basolateral amygdala, medial geniculate nucleus and the medial preoptic area fail to show a good correspondence. Several explanations are provided to interpret these results, and the anatomical and functional implications of these findings are discussed.
The mu, delta, and kappa opioid receptors are the three main types of opioid receptors found in the central nervous system (CNS) and periphery. These receptors and the peptides with which they interact are important in a number of physiological functions, including analgesia, respiration, and hormonal regulation. This study examines the expression of mu, delta, and kappa receptor mRNAs in the rat brain and spinal cord using in situ hybridization techniques. Tissue sections were hybridized with 35S-labeled cRNA probes to the rat mu (744-1,064 b), delta (304-1,287 b), and kappa (1,351-2,124 b) receptors. Each mRNA demonstrates a distinct anatomical distribution that corresponds well to known receptor binding distributions. Cells expressing mu receptor mRNA are localized in such regions as the olfactory bulb, caudate-putamen, nucleus accumbens, lateral and medial septum, diagonal band of Broca, bed nucleus of the stria terminalis, most thalamic nuclei, hippocampus, amygdala, medial preoptic area, superior and inferior colliculi, central gray, dorsal and median raphe, raphe magnus, locus coeruleus, parabrachial nucleus, pontine and medullary reticular nuclei, nucleus ambiguus, nucleus of the solitary tract, nucleus gracilis and cuneatus, dorsal motor nucleus of vagus, spinal cord, and dorsal root ganglia. Cellular localization of delta receptor mRNA varied from mu or kappa, with expression in such regions as the olfactory bulb, allo- and neocortex, caudate-putamen, nucleus accumbens, olfactory tubercle, ventromedial hypothalamus, hippocampus, amygdala, red nucleus, pontine nuclei, reticulotegmental nucleus, motor and spinal trigeminal, linear nucleus of the medulla, lateral reticular nucleus, spinal cord, and dorsal root ganglia. Cells expressing kappa receptor mRNA demonstrate a third pattern of expression, with cells localized in regions such as the claustrum, endopiriform nucleus, nucleus accumbens, olfactory tubercle, medial preoptic area, bed nucleus of the stria terminalis, amygdala, most hypothalamic nuclei, median eminence, infundibulum, substantia nigra, ventral tegmental area, raphe nuclei, paratrigeminal and spinal trigeminal, nucleus of the solitary tract, spinal cord, and dorsal root ganglia. These findings are discussed in relation to the physiological functions associated with the opioid receptors.
A major histocompatibility complex class Ib protein, CD1d, is expressed by human intestinal epithelial cells (IECs) and is a ligand for CD8+ T cells. CD1d was found to be expressed on the surface of human IECs as a 37-kilodalton protein that was beta 2-microglobulin (beta 2M) independent with no N-linked carbohydrate. Transfection into a beta 2M- cell line confirmed that CD1d could be expressed at the cell surface in the absence of beta 2M. These data indicate that IECs use a specialized pathway for CD1d synthesis and that a beta 2M-independent class Ib protein may be the normal ligand for some intestinal T cells.
BACKGROUND/AIMS: Cluster of differentiation 1 (CD1) is a family of nonpolymorphic, major histocompatibility complex class I-like molecules with prominent expression in the liver and intestinal epithelium of humans and mice. Models of intestinal and hepatobiliary inflammation and experimental liver transplantation are conducted in the rat, yet nothing is known of CD1 expression in this species. METHODS: Monoclonal antibodies against murine CD1 were used to identify a rat CD1 homologue. Tissue messenger RNA expression was confirmed by Northern blot analysis with a murine CD1 complementary DNA probe. RESULTS: Immunoperoxidase staining detected CD1 in intestinal epithelial and liver cells but not in the thymus. Immunofluorescence of isolated hepatocytes and a rat fetal intestinal cell line, SLC-44, showed cell surface expression of CD1. Metabolic labeling and immunoprecipitation of the SLC-44 cell line and a mouse intestinal epithelial cell line, MODE-K, showed a protein of 55 kilodaltons. Immunoblotting of CD1 in isolated intestinal epithelial cells and hepatocytes showed a molecule of 55 kilodaltons. Northern blot analysis showed a single message of approximately 2.2 kilobases in hepatocytes. CONCLUSIONS: A CD1 homologue exists in the rat. Expression in the rat intestine and liver are similar to those in the human and mouse. The rat may be useful as a model for the study of CD1 function.
The cysteine lysosomal proteases comprise a large family of highly conserved enzymes which are essential for intracellular protein turnover. These proteases are very efficient in their ability to degrade components of the extracellular matrix, and have been implicated in processes of cell growth, malignant transformation and inflammation. There is also a growing body of evidence for their involvement in the metabolism of the amyloid precursor protein. The production of insoluble beta A4 amyloid peptide is thought to be one of the key events that lead to the development of Alzheimer's pathology. To see the physiological role these enzymes play in the brain, we studied the relative abundance and distribution of the messenger RNAs for three lysosomal cysteine proteases, cathepsins B and L and cathepsin S, by in situ hybridization histochemistry in rat brain. All three enzymes are capable of degrading components of the extracellular matrix but they have different substrate preferences and resistances to neutral pH. We found that the mRNAs for cathepsins B, L, and S have different expression patterns in brain. Cathepsin B mRNA shows the highest level of expression. It has a wide distribution, and is preferentially expressed in neurons. The expression patterns of cathepsin B and cathepsin L mRNA overlap in many brain regions; in some areas they complement each other. Cathepsin B and L mRNAs are highly expressed in the choroid plexus, a structure that is instrumental in brain development. Both transcripts are also abundant in the neuropeptide synthesizing hypothalamic nuclei. Cathepsin S mRNA has wide expression pattern throughout brain, in grey and white matter. A great number of cells that express cathepsin S have microglial morphology. Regions that are known to contain the highest amounts of the amyloid precursor protein express highest levels of cathepsin B and cathepsin L mRNA. Also, all three transcripts are highly represented in regions that are most prone to degeneration in Alzheimer's disease. These results suggest a role for these lysosomal hydrolases released from degenerating cells in the development of Alzheimer's pathology.