Lynch syndrome-associated breast cancers: clinicopathologic characteristics of a case series from the colon cancer family registry

Purpose: The recognition of breast cancer as a spectrum tumor in Lynch syndrome remains controversial. The aim of this study was to explore features of breast cancers arising in Lynch syndrome families. Experimental Design: This observational study involved 107 cases of breast cancer identified from the Colorectal Cancer Family Registry (Colon CFR) from 90 families in which (a) both breast and colon cancer co-occurred, (b) families met either modified Amsterdam criteria, or had at least one early-onset (<50 years) colorectal cancer, and (c) breast tissue was available within the biospecimen repository for mismatch repair (MMR) testing. Eligibility criteria for enrollment in the Colon CFR are available online. Breast cancers were reviewed by one pathologist. Tumor sections were stained for MLH1, PMS2, MSH2, and MSH6, and underwent microsatellite instability testing. Results: Breast cancer arose in 35 mutation carriers, and of these, 18 (51%) showed immunohistochemical absence of MMR protein corresponding to the MMR gene mutation segregating the family. MMR-deficient breast cancers were more likely to be poorly differentiated (P = 0.005) with a high mitotic index (P = 0.002), steroid hormone receptor–negative (estrogen receptor, P = 0.031; progesterone receptor, P = 0.022), and to have peritumoral lymphocytes (P = 0.015), confluent necrosis (P = 0.002), and growth in solid sheets (P < 0.001) similar to their colorectal counterparts. No difference in age of onset was noted between the MMR-deficient and MMR-intact groups. Conclusions: MMR deficiency was identified in 51% of breast cancers arising in known mutation carriers. Breast cancer therefore may represent a valid tissue option for the detection of MMR deficiency in which spectrum tumors are lacking

The effect of injury diagnosis on expected Postconcussion Syndrome (PCS) symptom reporting and illness perception

Objective: To determine if systematic variation of diagnostic terminology (i.e. concussion, minor head injury [MHI], mild traumatic brain injury [mTBI]) following a standardized injury description produced different expected symptoms and illness perceptions. We hypothesized that worse outcomes would be expected of mTBI, compared to other diagnoses, and that MHI would be perceived as worse than concussion. Method:108 volunteers were randomly allocated to conditions in which they read a vignette describing a motor vehicle accident-related mTBI followed by: a diagnosis of mTBI (n=27), MHI (n=24), concussion (n=31); or, no diagnosis (n=26). All groups rated: a) event ‘undesirability’; b) illness perception, and; c) expected Postconcussion Syndrome (PCS) and Posttraumatic Stress Disorder (PTSD) symptoms six months post injury. Results: On average, more PCS symptomatology was expected following mTBI compared to other diagnoses, but this difference was not statistically significant. There was a statistically significant group effect on undesirability (mTBI>concussion & MHI), PTSD symptomatology (mTBI & no diagnosis>concussion), and negative illness perception (mTBI & no diagnosis>concussion). Conclusion: In general, diagnostic terminology did not affect anticipated PCS symptoms six months post injury, but other outcomes were affected. Given that these diagnostic terms are used interchangeably, this study suggests that changing terminology can influence known contributors to poor mTBI outcome.

A comparison of new and existing mild traumatic brain injury vignettes : recommendations for research into post-concussion syndrome

OBJECTIVE: To review and compare the mild traumatic brain injury (mTBI) vignettes used in postconcussion syndrome (PCS) research, and to develop 3 new vignettes. METHOD: The new vignettes were devised using World Health Organization (WHO) mTBI diagnostic criteria [1]. Each vignette depicted a very mild (VM), mild (M), or severe (S) brain injury. Expert review (N = 27) and readability analysis was used to validate the new vignettes and compare them to 5 existing vignettes. RESULTS: The response rate was 44%. The M vignette and existing vignettes were rated as depicting a mTBI; however, the fit-to-criteria of these vignettes differed significantly. The fit-to-criteria of the M vignette was as good as that of 3 existing vignettes and significantly better than 2 other vignettes. As expected, the VM and S vignettes were a poor fit-to-criteria. CONCLUSIONS: These new vignettes will assist PCS researchers to test the limits of important etiology factors by varying the severity of depicted injuries.

Irritable bowel syndrome : the role of gut neuroendocrine peptides

Irritable bowel syndrome (IBS) is a common chronic disorder with a prevalence ranging from 5 to 10 % of the world's population. This condition is characterised by abdominal discomfort or pain, altered bowel habits, and often bloating and abdominal distension. IBS reduces quality of life in the same degree of impairment as major chronic diseases such as congestive heart failure and diabetes and the economic burden on the health care system and society is high. Abnormalities have been reported in the neuroendocrine peptides/amines of the stomach, small- and large intestine in patients with IBS. These abnormalities would cause disturbances in digestion, gastrointestinal motility and visceral hypersensitivity, which have been reported in patients with IBS. These abnormalities seem to contribute to the symptom development and appear to play a central role in the pathogenesis of IBS. Neuroendocrine peptides/amines are potential tools in the treatment and diagnosis of IBS. In particular, the cell density of duodenal chromogranin A expressing cells appears to be a good histopathological marker for the diagnosis of IBS with high sensitivity and specificity.

Quality of life in chronic fatigue syndrome

Whilst the debilitating fatigue experienced in patients suffering from Chronic Fatigue Syndrome (CFS) results in a subjective marked impairment in functioning, little research has investigated the impact of this disorder on quality of life. Forty-seven subjects with a confirmed diagnosis of CFS and 30 healthy controls were compared using the Sickness Impact Profile (SIP). A subgroup of subjects were interviewed regarding the impact CFS has had on their social and family relationships, work and recreational activities. Results from both the SIP and the interview revealed that CFS subjects had significantly impaired quality of life, especially in areas of social functioning. These findings highlight the importance of addressing the social isolation and loss of role functioning experienced by CFS sufferers.

Reining in equine metabolic syndrome : a gluttony of challenges

We humans are complicated creatures. Despite remarkable intellect, a fearsome ability to push boundaries and superior survival mechanisms, we are at times our own worst enemy. Metabolic syndrome continues to be a premier health problem in developed, and now increasingly in undeveloped, nations. It is spreading across the planet like an infectious disease and is costing us millions. Metabolic disease remains an important focus both for medical research and for governments desperate to ease the burden on already over-taxed health systems. Unlike some previous worldwide health epidemics, obesity-related diseases will require more than a single, silver bullet. A simple vaccine or treatment cannot overcome a lack of education, awareness and in some cases sheer determination; the human element of these diseases. Undeniably, these ‘human elements’ also complicate our ability, as veterinarians, to effectively manage the growing incidence of equine obesity and metabolic disease...

Changes in Knee Biomechanics After a Hip-Abductor Strengthening Protocol for Runners With Patellofemoral Pain Syndrome

Context: Very few authors have investigated the relationship between hip-abductor muscle strength and frontal-plane knee mechanics during running. Objective: To investigate this relationship using a 3-week hip-abductor muscle-strengthening program to identify changes in strength, pain, and biomechanics in runners with patellofemoral pain syndrome (PFPS). Design: Cohort study. Setting: University-based clinical research laboratory. Patients or Other Participants: Fifteen individuals (5 men, 10 women) with PFPS and 10 individuals without PFPS (4 men, 6 women) participated. Intervention(s): The patients with PFPS completed a 3-week hip-abductor strengthening protocol; control participants did not. Main Outcome Measure(s): The dependent variables of interest were maximal isometric hip-abductor muscle strength, 2-dimensional peak knee genu valgum angle, and stride-to-stride knee-joint variability. All measures were recorded at baseline and 3 weeks later. Between-groups differences were compared using repeated-measures analyses of variance. Results: At baseline, the PFPS group exhibited reduced strength, no difference in peak genu valgum angle, and increased stride-to-stride knee-joint variability compared with the control group. After the 3-week protocol, the PFPS group demonstrated increased strength, less pain, no change in peak genu valgum angle, and reduced stride-to-stride knee-joint variability compared with baseline. Conclusions: A 3-week hip-abductor muscle-strengthening protocol was effective in increasing muscle strength and decreasing pain and stride-to-stride knee-joint variability in individuals with PFPS. However, concomitant changes in peak knee genu valgum angle were not observed.

Stockholm Syndrome : architecture, politics and the human body

The exchange between the body and architecture walks a fine line between violence and pleasure. It is through the body that the subject engages with the architectural act, not via thought or reason, but through action. The materiality of architecture is the often the catalyst for some intense association; the wall that defines gender or class, the double bolted door that incarcerates, the enclosed privacy of the bedroom to the love affair. Architecture is the physical manifestation of Lefebvre’s inscribed space. It enacts the social and political systems through bodily occupation. Architecture, when tested by the occupation of bodies, anchors ideology in both space and time. The architect’s script can be powerful when rehearsed honestly to the building’s intentions and just as beautiful when rebuked by the act of protest or unfaithful occupation. This research examines this fine line of violence and pleasure in architecture through performance, in the work of Bryony Lavin’s play Stockholm and Revolving Door by Allora & Calzadilla as part of the recent Kaldor Public Art Projects exhibition 13 Rooms in Sydney. The research is underpinned by the work of Architect and theorist, Bernard Tschumi in his two essays, Violence of Architecture and The Pleasure of Architecture. Studying architecture through the lens of performance shifts the focus of examination from pure thought to the body; because architecture is occupied through the body and not the mind.

Postoperative pain relief using intermittent intrapleural analgesia following thoracoscopic anterior correction for progressive adolescent idiopathic scoliosis

Background Thoracoscopic anterior scoliosis instrumentation is a safe and viable surgical option for corrective fusion of progressive adolescent idiopathic scoliosis (AIS) and has been performed at our centre on 205 patients since 2000. However, there is a paucity of literature reporting on or examining optimum methods of analgesia following this type of surgery. A retrospective study was designed to present the authors’ technique for delivering intermittent local anaesthetic boluses via an intrapleural catheter following thoracoscopic scoliosis surgery; report the pain levels that may be expected and any adverse effects associated with the use of intrapleural analgesia, as part of a combined postoperative analgesia regime. Methods Records for 32 patients who underwent thoracoscopic anterior correction for AIS were reviewed. All patients received an intrapleural catheter inserted during surgery, in addition to patient-controlled opiate analgesia and oral analgesia. After surgery, patients received a bolus of 0.25% bupivacaine every four hours via the intrapleural catheter. Patient’s perceptions of their pain control was measured using the visual analogue pain scale scores which were recorded before and after local anaesthetic administration and the quantity and time of day that any other analgesia was taken, were also recorded. Results 28 female and four male patients (mean age 14.5 ± 1.5 years) had a total of 230 boluses of local anaesthetic administered in the 96 hour period following surgery. Pain scores significantly decreased following the administration of a bolus (p < 0.0001), with the mean pain score decreasing from 3.66 to 1.83. The quantity of opiates via patient-controlled analgesia after surgery decreased steadily between successive 24 hours intervals after an initial increase in the second 24 hour period when patients were mobilised. One intrapleural catheter required early removal due to leakage; there were no other associated complications with the intermittent intrapleural analgesia method. Conclusions Local anaesthetic administration via an intrapleural catheter is a safe and effective method of analgesia following thoracoscopic anterior scoliosis correction. Post-operative pain following anterior thoracic scoliosis surgery can be reduced to ‘mild’ levels by combined analgesia regimes. Keywords: Adolescent idiopathic scoliosis; Thoracoscopic anterior spinal fusion; Anterior fusion; Intrapleural analgesia; Endoscopic anterior surgery; Pain relief; Scoliosis surgery

Segmental torso masses and gravity-induced coronal plane joint moments in adolescent idiopathic scoliosis

Introduction: Calculating segmental (vertebral level-by-level) torso masses in Adolescent Idiopathic Scoliosis (AIS) patients allows the gravitational loading on the scoliotic spine during relaxed standing to be estimated. This study used supine CT scans of AIS patients to measure segmental torso masses and explored the joint moments in the coronal plane, particularly at the apex of a scoliotic major curve. Methods: Existing low dose CT data from the Paediatric Spine Research Group was used to calculate vertebral level-by-level torso masses and joint moments occurring in the spine for a group of 20 female AIS patients with right sided thoracic curves. The mean age was 15.0 ± 2.7 years and all curves were classified Lenke Type 1 with a mean Cobb angle 52 ± 5.9°. Image processing software, ImageJ (v1.45 NIH USA) was used to create reformatted coronal plane images, reconstruct vertebral level-by-level torso segments and subsequently measure the torso volume corresponding to each vertebral level. Segment mass was then determined by assuming a tissue density of 1.04x103 kg/m3. Body segment masses for the head, neck and arms were taken from published anthropometric data (Winter 2009). Intervertebral joint moments in the coronal plane at each vertebral level were found from the position of the centroid of the segment masses relative to the joint centres with the segmental body mass data. Results and Discussion: The magnitude of the torso masses from T1-L5 increased inferiorly, with a 150% increase in mean segmental torso mass from 0.6kg at T1 to 1.5kg at L5. The magnitudes of the calculated coronal plane joint moments during relaxed standing were typically 5-7 Nm at the apex of the curve, with the highest apex joint torque of 7Nm. The CT scans were performed in the supine position and curve magnitudes are known to be 7-10° smaller than those measured in standing, due to the absence of gravity acting on the spine. Hence, it can be expected that the moments produced by gravity in the standing individual will be greater than those calculated here.

Mastery Motivation in Children with Down Syndrome : Promoting and Sustaining Interest in Learning

Motivation is central to children’s learning. Without persistent effort, especially in the face of failure, and an eagerness to engage in challenging tasks, individuals are unlikely to learn as effectively as they might. Because of their cognitive impairments, children with Down syndrome will almost certainly have difficulties with learning. These difficulties will be ameliorated somewhat by strong engagement with learning activities whereas problems with motivation are likely to further jeopardise their academic progress as well as potentially limiting achievements in other areas of life. In this chapter we begin with a general overview of motivation. Using the framework of mastery motivation, we review the relatively small amount of research about children with Down syndrome. We identify the individual characteristics and features of children’s environments that are likely to be related to lower or higher levels of mastery motivation. In the final section, we consider implications for educators and then draw together the findings to provide a set of recommendations for future research.

Chemotherapy induced reversible posterior leukoencephalopathy syndrome

The reversible posterior leukoencephalopathy syndrome (RPLES) is a condition characterised by reversible neurological and radiological findings that has been associated with use of immunosuppressive, chemotherapeutic and more recently novel targeted therapies. We describe the case of a 50-year-old woman with advanced non-small cell lung cancer who developed status epilepticus shortly after receiving cisplatin and gemcitabine chemotherapy. The clinical, radiological and EEG findings during and post event are presented and are in keeping with a diagnosis of RPLES. Early recognition of this rare syndrome, supportive management and withdrawal of the offending agent appear to result in a reversal of the manifestations described. © 2007 Elsevier Ireland Ltd. All rights reserved.

A metastatic neuroendocrine anaplastic small cell tumor in a patient with multiple endocrine neoplasia type 1 syndrome : assessment of disease status and response to doxorubicin, cyclophosphamide, etoposide chemotherapy through scintigraphic imaging with 111In-pentetreotide

Extrapulmonary small cell and small cell neuroendocrine tumors of unknown primary site are, in general, aggressive neoplasms with a short median survival. Like small cell lung cancer (SCLC), they often are responsive to chemotherapy and radiotherapy. Small cell lung cancer and well differentiated neuroendocrine carcinomas of the gastrointestinal tract and pancreas tend to express somatostatin receptors. These tumors may be localized in patients by scintigraphic imaging using radiolabeled somatostatin analogues. A patient with an anaplastic neuroendocrine small cell tumor arising on a background of multiple endocrine neoplasia type 1 syndrome is reported. The patient had a known large pancreatic gastrinoma and previously treated parathyroid adenopathy. At presentation, there was small cell cancer throughout the liver and skeleton. Imaging with a radiolabeled somatostatin analogue, 111In- pentetreotide (Mallinckrodt Medical B. V., Petten, Holland), revealed all sites of disease detected by routine biochemical and radiologic methods. After six cycles of chemotherapy with doxorubicin, cyclophosphamide, and etoposide, there was almost complete clearance of the metastatic disease. 111In-pentetreotide scintigraphy revealed uptake consistent with small areas of residual disease in the liver, the abdomen (in mesenteric lymph nodes), and posterior thorax (in a rib). The primary gastrinoma present before the onset of the anaplastic small cell cancer showed no evidence of response to the treatment. The patient remained well for 1 year and then relapsed with brain, lung, liver, and skeletal metastases. Despite an initial response to salvage radiotherapy and chemotherapy with carboplatin and dacarbazine, the patient died 6 months later.

A preliminary study of the effects of Tai Chi and Qigong medical exercise on indicators of metabolic syndrome, glycaemic control, health-related quality of life, and psychological health in adults with elevated blood glucose

Objectives To evaluate the feasibility, acceptability and effects of a Tai Chi and Qigong exercise programme in adults with elevated blood glucose. Design, Setting, and Participants A single group pre–post feasibility trial with 11 participants (3 male and 8 female; aged 42–65 years) with elevated blood glucose. Intervention Participants attended Tai Chi and Qigong exercise training for 1 to 1.5 h, 3 times per week for 12 weeks, and were encouraged to practise the exercises at home. Main Outcome Measures Indicators of metabolic syndrome (body mass index (BMI), waist circumference, blood pressure, fasting blood glucose, triglycerides, HDL-cholesterol); glucose control (HbA1c, fasting insulin and insulin resistance (HOMA)); health-related quality of life; stress and depressive symptoms. Results There was good adherence and high acceptability. There were significant improvements in four of the seven indicators of metabolic syndrome including BMI (mean difference −1.05, p<0.001), waist circumference (−2.80 cm, p<0.05), and systolic (−11.64 mm Hg, p<0.01) and diastolic blood pressure (−9.73 mm Hg, p<0.001), as well as in HbA1c (−0.32%, p<0.01), insulin resistance (−0.53, p<0.05), stress (−2.27, p<0.05), depressive symptoms (−3.60, p<0.05), and the SF-36 mental health summary score (5.13, p<0.05) and subscales for general health (19.00, p<0.01), mental health (10.55, p<0.01) and vitality (23.18, p<0.05). Conclusions The programme was feasible and acceptable and participants showed improvements in metabolic and psychological variables. A larger controlled trial is now needed to confirm these promising preliminary results.

Epidemiologic features of severe fever with Thrombocytopenia Syndrome in China, 2011-2012

Severe fever with thrombocytopenia syndrome (SFTS), an emerging vector-borne disease, is caused by a novel bunyavirus belonging to the genus Phlebovirus [1, 2]. SFTS infections can be life-threatening and are characterized by sudden onset of fever, thrombocytopenia, gastrointestinal symptoms, and leukocytopenia. The tick Haemaphysalis longicornis is generally considered to be the vector of SFTS, which is widely distributed in China [2]. Person-to-person transmission through direct contact with contaminated blood has also been reported as a possible means of SFTS transmission [3–5]. Currently, there is no specific treatment other than supportive care [6]...