Immunodetection of nmt55/p54(nrb) isoforms in human breast cancer

BACKGROUND: We previously identified and characterized a novel 55 kDa nuclear protein, termed nmt55/p54(nrb), whose expression was decreased in a subset of human breast tumors. The objective of this study was to determine if this reduced expression in human breast tumors was attributed to the regulation of mRNA transcription or the presence of altered forms of this protein. RESULTS: Northern blot analysis and ribonuclease protection assay indicated that nmt55/p54(nrb) mRNA is expressed at varying levels in estrogen receptor positive (ER+) and estrogen receptor negative (ER-) human breast tumors suggesting that reduced expression of nmt55/p54(nrb) protein in ER- tumors was not due to transcriptional regulation. To determine if multiple protein isoforms are expressed in breast cancer, we utilized Western blot and immunohistochemical analyses, which revealed the expression of an nmt55/p54(nrb) protein isoform in a subset of ER+ tumors. This subset of ER+ human breast tumors expressed an altered form of nmt55/p54(nrb) that was undetectable with an amino-terminal specific antibody suggesting that this isoform contains alterations or modifications within the amino terminal domain. CONCLUSIONS: Our study indicates that nmt55/p54(nrb) protein is post-transcriptionally regulated in human breast tumors leading to reduced expression in ER- tumors and the expression of an amino terminal altered isoform in a subset of ER+ tumors. The potential involvement of nmt55/p54(nrb) in RNA binding and pre-mRNA splicing may be important for normal cell growth and function; thus, loss or alteration of protein structure may contribute to tumor growth and progression

Collision sellar lesions: experience with eight cases and review of the literature

The concomitant presence of a pituitary adenoma with a second sellar lesion in patients operated upon for pituitary adenoma is an uncommon entity. Although rare, quite a great variety of lesions have been indentified coexisting with pituitary adenomas. In fact, most combinations have been described before, but an overview with information on the frequency of combined pathologies in a large series has not been published. We present a series of eight collision sellar lesions indentified among 548 transsphenoidally resected pituitary adenomas in two Neurosurgical Departments. The histological studies confirmed a case of sarcoidosis within a non-functioning pituitary adenoma, a case of intrasellar schwannoma coexisting with growth hormone (GH) secreting adenoma, two Rathke’s cleft cysts combined with pituitary adenomas, three gangliocytomas associated with GH-secreting adenomas, and a case of a double pituitary adenoma. The pertinent literature is discussed with emphasis on pathogenetic theories of dual sellar lesions. Although there is no direct evidence to confirm the pathogenetic relationship of collision sellar lesions, the number of cases presented in literature makes the theory of an incidental occurrence rather doubtful. Suggested hypotheses about a common embryonic origin or a potential interaction between pituitary adenomas and the immune system are presented

Negotiating the risks of computed tomography in primary care

Computed tomography (CT) is one of the most frequently used imaging modalities. Over 5 million scans were performed in the UK in 2017/2018, a 6.9% increase from 2016/2017. One in ten scans performed for initial cancer investigations were referred directly from GPs.1 Versatility of scanners, an ageing population, patient knowledge, and improved access are some factors that have led to an increase in demand; however, there is regional variation in direct-access radiology for GPs in the UK. When GPs have direct access to cancer investigations, they diagnose cancer in a similar proportion of patients to specialists with the same test. The risks of ionising radiation from CT conflict with the demand for earlier cancer diagnosis creating a risk/benefit dilemma. GPs who frequently refer to CT may come under pressure from commissioners for their use of radiology, but if slow to refer they may be criticised for late diagnoses following repeat patient attendances. This piece aims to improve understanding of the risks of ionising radiation and who is responsible for them.</p

Metabolomic biomarkers in blood samples identify cancers in a mixed population of patients with nonspecific symptoms

Purpose: Early diagnosis of cancer is critical for improving patient outcomes, but cancers may be hard to diagnose if patients present with nonspecific signs and symptoms. We have previously shown that nuclear magnetic resonance (NMR) metabolomics analysis can detect cancer in animal models and distinguish between differing metastatic disease burdens. Here, we hypothesized that biomarkers within the blood metabolome could identify cancers within a mixed population of patients referred from primary care with nonspecific symptoms, the so-called “low-risk, but not no-risk” patient group, as well as distinguishing between those with and without metastatic disease. Experimental Design: Patients (n = 304 comprising modeling, n = 192, and test, n = 92) were recruited from 2017 to 2018 from the Oxfordshire Suspected CANcer (SCAN) pathway, a multidisciplinary diagnostic center (MDC) referral pathway for patients with nonspecific signs and symptoms. Blood was collected and analyzed by NMR metabolomics. Orthogonal partial least squares discriminatory analysis (OPLS-DA) models separated patients, based upon diagnoses received from the MDC assessment, within 62 days of initial appointment. Results: Area under the ROC curve for identifying patients with solid tumors in the independent test set was 0.83 [95% confidence interval (CI): 0.72–0.95]. Maximum sensitivity and specificity were 94% (95% CI: 73–99) and 82% (95% CI: 75–87), respectively. We could also identify patients with metastatic disease in the cohort of patients with cancer with sensitivity and specificity of 94% (95% CI: 72–99) and 88% (95% CI: 53–98), respectively. Conclusions: For a mixed group of patients referred from primary care with nonspecific signs and symptoms, NMR-based metabolomics can assist their diagnosis, and may differentiate both those with malignancies and those with and without metastatic disease

Revision hip arthroplasty using a cementless modular tapered stem

Here we report the short-term clinical and radiological results of the ProfemurA (R)-R cementless modular revision stem. Between June 2002 and May 2006, 68 revision hip arthroplasties were consecutively performed using this stem. Survival at a mean follow-up of 5.2 years was 94%. According to the Paprosky classification, the femoral defect was classified as type 1 in 39 hips (57.3%), type 2 in 18 hips (26.5%), type 3A in ten hips (14.7%) and type 3B in one hip (1.5%). The Harris Hip Score was 49.57 before surgery and averaged 78.28 at the latest follow-up. The Merle d'Aubigne score improved from 9.15 preoperatively to 14.30 postoperatively. Stem stability rated according to the Agora Roentgenographic Assessment (ARA) scoring system averaged 5.22, suggesting a high likelihood of a durable implant. The revision prosthesis examined in this study can be considered a viable and useful option in revision hip arthroplasty, even in patients with bony femoral defects

The UniSpacer™: correcting varus malalignment in medial gonarthrosis

While options for operative treatment of leg axis varus malalignment in patients with medial gonarthrosis include several established procedures, such as unicompartmental knee arthroplasty (UKA), total knee arthroplasty (TKA) or high tibial osteotomy (HTO), there has been little focus on a less invasive option introduced more recently: the UniSpacer™ implant, a self-centering, metallic interpositional device for the knee. This study evaluates clinical and radiological results of the UniSpacer™, whether alignment correction can be achieved by UniSpacer™ arthroplasty and alignment change in the first five postoperative years. Anteroposterior long leg stance radiographs of 20 legs were digitally analysed to assess alignment change: two relevant angles and the deviation of the mechanical axis of the leg were analysed before and after surgery. Additionally, the change of the postoperative alignment was determined one and five years postoperatively. Analysing the mechanical tibiofemoral angle, a significant leg axis correction was achieved, with a mean valgus change of 4.7 ± 1.9°; a varus change occurred in the first postoperative year, while there was no significant further change of alignment seen five years after surgery. The UniSpacer™ corrects malalignment in patients with medial gonarthrosis; however, a likely postoperative change in alignment due to implant adaptation to the joint must be considered before implantation. Our results show that good clinical and functional results can be achieved after UniSpacer™ arthroplasty. However, four of 19 knees had to be revised to a TKA or UKA due to persistent pain, which is an unacceptably high revision rate when looking at the alternative treatment options of medial osteoarthritis of the knee