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Distinct genetic alterations and luminal molecular subtype in nested variant of urothelial carcinoma
3.
This paper analyses the methodological issues inherent in evaluating healthcare education and considers approaches for addressing these.Recent policies have exhorted practitioners to base their practice on evidence; however in healthcare education the evidence base is not extensive. Whilst educational evaluation has advanced in the last decades, standardised designs and toolkits are not available. Each evaluation has different aims and occurs in specific contexts, thus the design has to fit the circumstances, yet meet the challenge of scientific credibility. Indicators of educational processes and outcomes are not scientifically verified; no toolkit of standardised ‘off-the-shelf’ valid, reliable and sensitive measures exists. The evidence base of educational practice is largely derived from small-scale, single case studies; the majority of measures are self-devised, unvalidated tools of unproven reliability, thus meta-synthesis is not appropriate and results are not generalisable. Healthcare educational evaluators need valid and reliable assessments of both knowledge acquisition and its application to practice. The need to establish and explain attribution, i.e. the relationship between educational inputs and outcomes is complex and requires experimental/quasi-experimental design. In addition, educational evaluators face the pragmatic challenge of practice in healthcare contexts, where confounding variables are hard to control and resources are scarce. 相似文献
4.
The effects of adrenergic activation on aggressiveness and the aggression induced endocrine changes were tested in rats. α2 adrenoceptor blockers were used for enhancing activation of the adrenergic system, and changes in aggressiveness were tested in resident-intruder contests. Three experiments were conducted. In experiment 1, saline injected rats responded to the presence of an opponent by aggression and the increase in plasma ACTH and corticosterone. Intraperitoneal administration of 1 mg/kg CH-38083 (an α2 adrenoceptor antagonist) produced a several fold increase in clinch fighting and mutual upright scores, and also further enhanced the plasma ACTH and corticosterone response. In experiment 2, the effect of three doses (0.5, 1 and 2 mg/kg) of three different α2 adrenoceptor blockers CH-38083, idazoxan and yohimbine were tested. All the substances increased aggression at 0.5 and 1 mg/kg; at 2 mg/kg the effect of idazoxan and yohimbine disappeared, while with CH-38083 an additional increase was obtained. In yohimbine treated animals the enhancement of aggression was reduced already at 1 mg/kg. In experiment 3, indomethacin, a potent inhibitor of the catecholamine-induced ACTH release completely abolished the effects of the α2 adrenoceptor antagonist CH-38083: the intensity of agonistic interactions, as well as ACTH and corticosterone plasma concentrations, returned to control levels. The possible role of catecholamines and the stress hormones in the activation of aggression is discussed. 相似文献
5.
Chairat Shayakul Petr Jarolim Marie Zachlederova Daniel Prabakaran Dionisio Cortez-Campeao Dana Kalabova Alan K Stuart-Tilley Hiroshi Ideguchi Christlieb Haller Seth L Alper 《Nephrology, dialysis, transplantation》2004,19(2):371-379
BACKGROUND: Mutations in the human SLC4A1 (AE1/band 3) gene are associated with hereditary spherocytic anaemia and with distal renal tubular acidosis (dRTA). The molecular diagnosis of AE1 mutations has been complicated by the absence of highly polymorphic genetic markers, and the pathogenic mechanisms of some dRTA-associated AE1 mutations remain unclear. Here, we characterized a polymorphic dinucleotide repeat close to the human AE1 gene and performed an immunocytochemical study of kidney tissue from a patient with inherited dRTA with a defined AE1 mutation. METHODS: One CA repeat region was identified in a phage P1-derived artificial chromosome (PAC) clone containing most of the human AE1 gene and the upstream flanking region. We determined its heterozygosity value in multiple populations by PCR analysis. Genotyping of one family with dominant dRTA identified the AE1 R589H mutation, and family member genotypes were compared with the CA repeat length. AE1 and vH(+)-ATPase polypeptides in kidney tissue from an AE1 R589H patient were examined by immunocytochemistry for the first time. RESULTS: This CA repeat, previously reported as D17S1183, is approximately 90 kb upstream of the AE1 gene and displayed considerable length polymorphism, with small racial differences, and a heterozygosity value of 0.56. The allele-specific length of this repeat confirmed co-segregation of the AE1 R589H mutation with the disease phenotype in a family with dominant dRTA. Immunostaining of the kidney cortex from one affected member with superimposed chronic pyelonephritis revealed vH(+)-ATPase-positive intercalated cells in which AE1 was undetectable, and proximal tubular epithelial cells with apparently enhanced apical vH(+)-ATPase staining. CONCLUSIONS: The highly polymorphic dinucleotide repeat adjacent to the human AE1 gene may be useful for future studies of disease association and haplotype analysis. Intercalated cells persist in the end-stage kidney of a patient with familial autosomal dominant dRTA associated with the AE1 R589H mutation. The absence of detectable AE1 polypeptide in those intercalated cells supports the genetic prediction that the AE1 R589H mutation indeed causes dominant dRTA. 相似文献
6.
Atul K. Sharma Moira S. Mills Vijay L. Grey Keith N. Drummond 《Pediatric nephrology (Berlin, Germany)》1997,11(6):711-713
Accurate, timed urine collections for the measurement of glomerular filtration rate (GFR) may be impractical in infants or
in patients with urological abnormalities. GFR may be measured without urine collection using a constant subcutaneous infusion
of iothalamate. We compare the infusion clearance with conventional renal clearance in 14 children and young adults. The mean
clearance ratio (infusion clearance/renal clearance ± 1 SD) was 0.99±0.1 and the mean discrepancy between the two methods
was 8.5%±4.7%. The 95% limits of agreement for the ratio of the two methods are 0.83–1.23. These data indicate that subcutaneous
infusion of iothalamate is a practical method for measuring GFR in children without a urine collection.
Received March 18, 1996; received in revised form February 12, 1997; accepted March 26, 1997 相似文献
7.
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Previous studies of sonograms in premenarchal girls have reported the typical ovary to be homogeneous in echogenicity, with cysts an uncommon finding, particularly in children less than 6 years old. These studies found no macrocysts (cysts greater than 9 mm in greatest length) in patients less than 11 years old. This information contradicts published pathology studies and our sonographic experience. The goal of this study was to determine the prevalence of cysts in the ovaries of premenarchal girls. The pelvic sonograms of 101 consecutive premenarchal girls between 2 and 12 years old, without known gynecologic or endocrinologic disease, were prospectively studied. One hundred fifty-five ovaries were adequately imaged in three dimensions. Ovaries were evaluated for the presence or absence of cysts (as defined by sonographic criteria), and the length of the cyst or of the largest cyst, if several were noted, was measured. Cysts were identified in 106 ovaries (68%). Cysts were seen in patients of all ages, particularly in the younger children (2-6 years old). Thirteen of the cysts, noted in 11 patients between 2 and 10 years old, were macrocysts. The typical sonographic appearance of the ovary in premenarchal girls is not homogeneous. Cysts are common in premenarchal girls between 2 and 12 years old and are the cause of the typical heterogeneous image. Macrocysts can be seen in healthy girls less than 11 years old. 相似文献
9.
10.
A 13-year old boy presented with a three-year history of slowly progressive proximal muscle weakness, particularly involving the lower extremities. Chronic renal failure was uncovered in the course of his evaluation. Urologic investigation showed small and poorly functioning kidneys with a BUN of 118 mg/dL and a creatinine of 10.7 mg/dL. There were no anomalies of the proximal or distal collecting systems or history suggestive of recurrent urinary tract infection. The neurologic examination revealed proximal muscle weakness primarily of the lower extremities and especially of the proximal musculature of the pelvic girdle. Nerve conduction studies were normal. The electromyogram (EMG) showed high-voltage polyphasic potentials consistent with neurogenic muscle disease. A biopsy of the right quadriceps muscle demonstrated type II muscle fiber atrophy with histochemical staining. The patient's clinical findings, EMG studies, and muscle biopsy were not specific for either neurogenic or myopathic disease. Following a period of home peritoneal dialysis and renal transplantation, there was significant clinical improvement of the muscle weakness. 相似文献