21 research outputs found
Expression of estrogen and progesterone receptors in vestibular schwannomas and their clinical significance
<p>Abstract</p> <p>Objective</p> <p>The objective was to determine the expression of estrogen and progesterone receptors in vestibular schwannomas as well as to determine predictive factors for estrogen and progesterone receptor positivity.</p> <p>Materials and methods</p> <p>The study included 100 cases of vestibular schwannomas operated from January 2006 to June 2009. The clinical details were noted from the medical case files. Formaldehyde-fixed parafiin-embedded archival vestibular schwannomas specimens were used for the immunohistochemical assessment of estrogen and progesterone receptors.</p> <p>Results</p> <p>Neither estrogen nor progesterone receptors could be detected in any of our cases by means of well known immunohistochemical method using well documented monoclonal antibodies. In the control specimens, a strongly positive reaction could be seen.</p> <p>Conclusion</p> <p>No estrogen and progesterone receptor could be found in any of our 100 cases of vestibular schwannomas. Hence our study does not support a causative role of estrogen and progesterone in the growth of vestibular schwannoma as well as hormonal manipulation in the treatment of this tumor.</p
Pan-cancer analysis of whole genomes
Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe
Thoracoscopic resection of mediastinal parathyroids: current status and future perspectives
Multicenter Study of 19 Aortopulmonary Window parathyroid Tumors : The callenge of Embryologic origin
Background Ectopic abnormal parathyroid glands are relatively
common in the superior mediastinum but are rarely
situated in the aortopulmonary window (APW). The embryological
origin of these abnormal parathyroid glands is controversial.
The purpose of this investigation was to investigate
the embryological origin and the surgical management of
abnormal parathyroid glands situated in the APW.
Methods The databases of patients operated on for primary,
secondary, and tertiary hyperparathyroidism at eight
European medical centers with a special interest in endocrine
surgery were reviewed to identify those with APW adenomas.
Demographic features, localization procedures, and
perioperative and pathology findings were documented. The
embryological origin was determined based on the number
and position of identified parathyroid glands.
Results Nineteen (0.24%) APW parathyroid tumors were
identified in 7,869 patients who underwent an operation for
hyperparathyroidism (HPT) and 181 patients (2.3%) with
mediastinal abnormal parathyroid glands. Ten patients had
primary, eight had secondary, and one had tertiary HPT.
Sixteen patients had undergone previous unsuccessful cervical
exploration. In three patients, an APW adenoma was
suspected by preoperative localization studies and was cured
at the initial operation. Sixteen patients had persistent HPTof
whom 15 were reoperated, resulting in 6 failures. Evaluation
of 17 patients who had bilateral neck exploration allowed us
to determine the most probable origin of the APW parathyroid
tumors: 12 were supernumerary, 4 appeared to originate
from a superior, and 1 from an inferior gland.
Conclusions Abnormal parathyroid glands situated in the
APW are rare and usually identified after an unsuccessful
cervical exploration. Preoperative imaging of the mediastinum
and neck are essential. The origin of these ectopically
situated tumors is probably, as suggested by our data, from a
supernumerary fifth parathyroid gland or from abnormal
migration of a superior parathyroid gland during the
embryologic development
Parathyroid Glands in CKD: Anatomy, Histology, Physiology and Molecular Biology in CKD
Chronic kidney disease is a condition in which parathyroid are affected by a combination of elevated extracellular phosphate concentration, decreased extracellular ionized calcium concentration, and markedly reduced serum calcitriol, leading to increased PTH synthesis and release. At early stages in the development of hyperparathyroidism, these changes are compounded of variable down-regulation of the calcium-sensing receptor (CaSR) and vitamin D receptor (VDR), making the parathyroid cells unable to respond appropriately to calcium and/or calcitriol. The resulting increase in proliferative activity in the parathyroid glands leads to parathyroid hyperplasia
Time-dependent effects of parathyroid hormone and prostaglandin E2 on DNA synthesis by periosteal cells from embryonic chick calvaria
Taking the lead from our colleagues in medical education: the use of images of the in-vivo setting in teaching concepts of pharmaceutical science
Preferences for Analgesic Treatments Are Influenced by Probability of the Occurrence of Adverse Effects and the Time to Reach Maximal Therapeutic Effects
Using a learning health system to understand the mismatch between medicines supply and actual medicines use among adults with cystic fibrosis
Background
Studies in separate cohorts suggest possible discrepancies between inhaled medicines supplied (median 50-60%) and medicines used (median 30-40%). We performed the first study that directly compares CF medicine supply against use to identify the cost of excess medicines supply.
Methods
This cross-sectional study included participants from 12 UK adult centres with ≥1 year of continuous adherence data from data-logging nebulisers. Medicine supply was measured as medication possession ratio (MPR) for a 1-year period from the first suitable supply date. Medicine use was measured as electronic data capture (EDC) adherence over the same period. The cost of excess medicines was calculated as whole excess box(es) supplied after accounting for the discrepancy between EDC adherence and MPR with 20% contingency.
Results
Among 275 participants, 133 (48.4%) were females and mean age was 30 years (95% CI 29-31 years). Median EDC adherence was 57% (IQR 23-86%), median MPR was 74% (IQR 46-96%) and the discrepancy between measures was median 14% (IQR 2-29%). Even with 20% contingency, mean potential cost of excess medicines was £1,124 (95% CI £855-1,394), ranging from £183 (95% CI £29-338) for EDC adherence ≥80% to £2,017 (95% CI £1,507-2,526) for EDC adherence <50%.
Conclusions
This study provides a conservative estimate of excess inhaled medicines supply cost among adults with CF in the UK. The excess supply cost was highest among those with lowest EDC adherence, highlighting the importance of adherence support and supplying medicine according to actual use. MPR provides information about medicine supply but over-estimates actual medicine use