Σάββατο 6 Μαΐου 2017
Boi-ogi-to (TJ-20), a Kampo Formula, Suppresses the Inflammatory Bone Destruction and the Expression of Cytokines in the Synovia of Ankle Joints of Adjuvant Arthritic Rats
TJ-20 is a formula consisting of 6 herbs that has been used in the clinical treatment of rheumatoid arthritis (RA) in China and Japan for centuries. However, scientific evidence of the effects of TJ-20 has not been established. In the present study, we focused on the therapeutic effects and investigated the main function of TJ-20 on adjuvant arthritis (AA), an animal model of RA, which was induced with complete Freund's adjuvant (CFA). TJ-20 was administered orally at 600 mg/kg once a day from 0, 7, and 10 days to 8 weeks after the CFA treatment. TJ-20 significantly ameliorated inflammatory progression and bone destruction in AA in a time-dependent manner. Furthermore, TJ-20 significantly reduced the increased changes in a number of macrophages and helper T cells. Moreover, TJ-20 suppressed the expression of TNF-α whereas it augmented the expression of IL-10 and attenuated Th1 cells responses in the synovia of the ankle joint. Therefore, TJ-20 regulated the expression of proinflammatory and anti-inflammatory cytokines in macrophages and Th1/Th2 balance in the synovia of ankle joints in AA rats. These results suggest the positive anti-inflammatory effect of TJ-20 and provide a scientific basis for the clinical use of TJ-20 for RA.
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Exogenous Expressions of FTO Wild-Type and R316Q Mutant Proteins Caused an Increase in HNRPK Levels in 3T3-L1 Cells as Demonstrated by DIGE Analysis
Fat mass and obesity-associated protein is an enzyme that oxidatively demethylates DNA. Although there are numerous studies regarding the catalytic function of FTO, the overall existence or absence of FTO on cellular proteome has not been investigated. This study investigated the changes in the soluble proteome of 3T3-L1 cells upon expression of the WT and the mutant (R316Q) FTO proteins. Protein extracts prepared from 3T3-L1 cells expressing either the WT or the mutant FTO proteins were used in DIGE experiments. Analysis of the data revealed the number of spots matched to every member and there were 350 ± 20 spots with 30.5% overall mean coefficient of variation. Eleven regulated protein spots were excised from the gels and identified by MALDI-TOF/TOF. One of the identified proteins was heterogeneous nuclear ribonucleoprotein K, which displayed more than 2.6- and 3.7-fold increases in its abundance in the WT and the mutant FTO expressing cells, respectively. Western blot analysis validated these observations. This is the first study revealing the presence of a parallel increase in expressions of FTO and HNRNPK proteins. This increase may codictate the metabolic changes occurring in the cell and may attribute a significance to HNRNPK in FTO-associated transformations.
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Helicobacter pylori from Peptic Ulcer Patients in Uganda Is Highly Resistant to Clarithromycin and Fluoroquinolones: Results of the GenoType HelicoDR Test Directly Applied on Stool
Background. Around 70–90% of peptic ulcer disease (PUD) is due to Helicobacter pylori and requires treatment with antimicrobials to which these bacteria are susceptible. Common H. pylori diagnostic tests do not provide drug susceptibility data. Using the GenoType HelicoDR PCR test designed for gastric biopsies for simultaneous detection of H. pylori and its resistance to clarithromycin (CLA)/fluoroquinolones (FLQ), we present evidence for stool as an optional test specimen and also provide data on prevalence of H. pylori resistance to CLA and FLQ in Uganda. Methods. Stool from 142 symptomatic PUD patients at three hospitals in Kampala was screened for H. pylori using a rapid antigen test. The GenoType HelicoDR test was run on all H. pylori antigen positives to determine PCR positivity and resistance to CLA/FLQ. Results. Thirty-one samples (22%) were H. pylori antigen positive, and 21 (68%) of these were H. pylori PCR positive. Six of the 21 (29%) were resistant to CLA and eight to FLQ (42%), while two gave invalid FLQ resistance results. Conclusion. Stool is a possible specimen for the GenoType HelicoDR test for rapid detection of H. pylori and drug resistance. In Uganda, Helicobacter pylori is highly resistant to CLA and FLQ.
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Novel Insights into the Treatment of Imatinib-Resistant Gastrointestinal Stromal Tumors
Abstract
Gastrointestinal stromal tumors (GIST) have emerged as a compelling clinical and biological model for the rational development of therapeutic strategies targeting critical oncogenic events over the past two decades. Oncogenic activation of KIT or PDGFRA receptor tyrosine kinases is the crucial driver for GIST tumor initiation, transformation, and cancer cell proliferation. Three tyrosine kinase inhibitors (TKIs) with KIT inhibitory activity – imatinib, sunitinib, and regorafenib – are approved to treat advanced GIST and have successfully exploited this addiction to KIT oncogenic signaling, demonstrating remarkable activity in a disease that historically had no successful systemic therapy options. However, GIST refractory to approved TKIs remain an unmet clinical need, as virtually all patients with metastatic GIST eventually progress on any given therapy. The main and best-established mechanism of resistance is the polyclonal expansion of multiple subpopulations harboring different secondary KIT mutations. The present review aims at summarizing current and forthcoming treatment directions in advanced imatinib-resistant GIST supported by a strong biological rationale.
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META-ANALYSIS OF THE IMPACT OF SPINK1 p.N34S GENE VARIATION IN CAUCASIC PATIENTS WITH CHRONIC PANCREATITIS. AN UPDATE.
SPINK1 p.N34S gene variation is one of the endogenous factors which seem to be associated with chronic pancreatitis (CP). However, in literature there is no clear agreement regarding its contribution in different ethnicity and CP etiologies.
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(P070) Malignant Glossopharyngeal Neuralgia, a Painful Syncope
Glossopharyngeal neuralgia is a rare disorder of the ninth cranial nerve in which paroxysms of severe pain are associated with excessive vagal outflow. This can result in debilitating bradycardia, hypotension, syncope, and cardiac arrest. Treatment depends on the etiology of the neuralgia. We describe a case of glossopharyngeal neuralgia secondary to a head and neck cancer that resolved with concurrent chemotherapy and radiation.
http://ift.tt/2qbNXp4
(P072) Prospective Validation of Bioelectrical Impedance Analysis for Clinically Applicable Monitoring of Body Composition in Head and Neck Cancer Patients Treated With Radiotherapy
Weight loss is common in patients with head and neck cancer (HNC) both prior to and during radiotherapy. Recent data indicate that low lean mass is more predictive of poor outcomes than weight loss. The objective of this study is to validate the use of bioelectrical impedance analysis (BIA) for in-clinic measurement of body composition in HNC patients during radiotherapy.
http://ift.tt/2qNi42P
(P067) Survival Outcomes With Adjuvant Chemoradiation Versus Adjuvant Radiation Alone for Elderly Patients With Resected Head and Neck Squamous Cell Carcinoma With Positive Surgical Margins or Extra-Capsular Extension
Randomized trials have demonstrated that adjuvant chemoradiotherapy (CRT) confers an overall survival (OS) benefit over adjuvant radiation (RT) alone in patients with resected head and neck squamous cell carcinoma (HNSCC) with adverse pathologic features (positive surgical margins [SM+] and/or extra-capsular extension [ECE]). Whether this OS benefit exists in an elderly population (age ≥65 years) remains unknown.
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Sushi repeat-containing protein 1: a novel disease-associated molecule in cerebral amyloid angiopathy
Abstract
Sporadic cerebral amyloid angiopathy (CAA) is characterized by cerebrovascular amyloid beta (Aβ) deposits and causes cerebral hemorrhage and dementia. The exact molecules that co-accumulate with cerebrovascular Aβ deposits are still not fully known. In our study here, we performed proteomic analyses with microdissected leptomeningeal arteries and cerebral neocortical arterioles from 8 cases with severe CAA, 12 cases with mild CAA, and 10 control cases without CAA, and we determined the levels of highly expressed proteins in cerebral blood vessels in CAA. We focused on sushi repeat-containing protein 1 (SRPX1), which is specifically expressed in CAA-affected cerebral blood vessels. Because SRPX1, which is known as a tumor suppressor gene, reportedly induced apoptosis in tumor cells, we hypothesized that SRPX1 may play an important role in Aβ-induced apoptosis in CAA. Immunohistochemical studies revealed that SRPX1 co-accumulated with Aβ deposits in cerebral blood vessels of all autopsied cases with severe CAA. In contrast, no SRPX1 co-accumulated with Aβ deposits in senile plaques. Furthermore, we demonstrated that both Aβ40 and Aβ42 bound to SRPX1 in vitro and enhanced SRPX1 expression in primary cultures of cerebrovascular smooth muscle cells. SRPX1 enhanced caspase activity induced by Aβ40. Knockdown of SRPX1, in contrast, reduced the formation of Aβ40 accumulations and the activity of caspase in cultured cerebrovascular smooth muscle cells. SRPX1 may thus be a novel molecule that is up-regulated in cerebrovascular Aβ deposits and that may increase Aβ-induced cerebrovascular degeneration in CAA.
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Young adult cancer survivors and work: a systematic review
Abstract
Context
Sixty-three percent of cancer survivors continue to work, or return to work after treatment. Among this population, work ability and challenges encountered in the workplace by young adult cancer survivors have not been well established.
Purpose
The purposes of the study are to describe what is currently known about work-related issues for young adult cancer survivors diagnosed between ages 15 and 39, to identify gaps in the research literature, and to suggest interventions or improvements in work processes and occupational settings.
Methods
A narrative review of articles using PubMed, CINAHL, and PsychInfo was conducted without date limitations. Search phrases included young adult cancer survivors, long-term cancer survivors, young adults affected by cancer, further combined with key terms employment, work, and occupationally active. Inclusion criteria for publications were young adult cancer survivors initially diagnosed between the ages of 15 and 39, data about work or employment was presented, and articles written in English.
Results
Twenty-three publications met the inclusion criteria. Work-related issues included the potential for reduced work productivity from cancer-changed physical and cognitive functional ability that affected income, and resulted in distress. Coping style, support systems, and changing perspectives about work and life in general were also influential on career decisions among young adult cancer survivors.
Conclusions
More research is needed to study interventions to better manage health changes in young adult cancer survivors within the context of the workplace. Since financial hardship has been shown to be especially high among young cancer survivors, employment is essential to ensure payment of cancer-associated costs and continued medical care.
Implications for Cancer Survivors
While young adult cancer survivors may initially grapple with cancer-related physical and psychosocial changes that impact work productivity or influence choice of occupation, employment appears to enhance overall quality of life.
http://ift.tt/2qbZ6WC
Safety and efficacy of radium-223 dichloride in Japanese patients with castration-resistant prostate cancer and bone metastases
Abstract
Background
Radiation therapy with radium-223 dichloride improves overall survival, reduces symptomatic skeletal events in Caucasian patients with castration-resistant prostate cancer (CRPC) and bone metastases, and is well tolerated. We report here the results of the first efficacy and safety study of radium-223 dichloride in a Japanese population.
Methods
In this open-label, uncontrolled, non-randomized, phase I trial, radium-223 dichloride was given to Japanese patients with CRPC and ≥2 bone metastases in 4-week cycles. The patients were divided into three cohorts, with cohort 1 and the expansion cohort receiving injections of radium-223 dichloride [55 kBq/kg body weight (BW)] every 4 weeks (Q4W) for up to six injections, and cohort 2 receiving an initial single radium-223 dichloride injection of 110 kBq/kg BW followed by up to five injections of 55 kBq/kg BW Q4W. Safety was determined via adverse event (AE) reporting, and biochemical bone markers were assessed for treatment efficacy.
Results
In total 19 patients received at least one dose of radium-223 dichloride and 18 patients experienced at least one treatment-emergent AE (TEAE) of which the most common were anemia, thrombocytopenia, and lymphocytopenia. Serious AEs were reported in three patients but none were drug-related. In the patients of cohort 1 + expansion cohort (55 kBq/kg BW Q4W treatment; n = 16), prostate-specific antigen levels remained stable or slightly increased while the bone alkaline phosphatase (ALP) level significantly decreased. The response rates of bone ALP (≥30 and ≥50% reductions) were 81.8 and 36.4% at week 12, and 81.3 and 50.0% at the end of treatment.
Conclusions
Radium-223 dichloride was well tolerated in these Japanese patients and, at a dose of 55 kBq/kg BW, efficacy on biomarkers was as expected. The outcomes in Japanese patients were consistent with those reported in other non-Japanese populations.
Trial registration
ClinicalTrials.gov record NCT01565746.
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Online adjustments of leg movements in healthy young and old
Abstract
Online movement adjustments are crucial for daily life. This is especially true for leg movements in relation to gait, where failed adjustments can lead to falls, especially in elderly. However, most research has focused on reach adjustments following changes in target location. This arm research reports two categories of online adjustments (see Gaveau et al., Neuropsychologia 55:25–40, 2014 for review). Small, frequently undetected, target location shifts invoke fast, automatic adjustments, usually without awareness. In contrast, large target location shifts can lead to slow, voluntary adjustments. These fast and slow adjustments presumably rely on different neural networks, with a possible role for subcortical pathways for the fast responses. Do leg movement adjustments also fall into these two categories? We review the literature on leg movement adjustments and show that it is indeed possible to discern fast and slow adjustments. More specifically, we provide an overview of studies showing adjustments during step preparation, initiation, unobstructed, and obstructed gait. Fast adjustments were found both during stepping and gait. In the extreme case, even step adjustments appear to be further modifiable online, e.g., when avoiding obstacles during tripping. In older adults, movement adjustments are generally slower and of smaller magnitude, consistent with a greater risk of falling. However, fast responses seem less affected by aging, consistent with the idea of independent parallel mechanisms controlling movement adjustments (Gomi, Curr Opin Neurobiol 18:558–567, 2008). Finally, putative neural pathways are discussed.
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Long-term Live Imaging of Drosophila Eye Disc
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A Review of Autologous Stem Cell Transplantation in Lymphoma
Abstract
Purpose of Review
Chemotherapy remains the first-line therapy for aggressive lymphomas. However, 20–30% of patients with non-Hodgkin lymphoma (NHL) and 15% with Hodgkin lymphoma (HL) recur after initial therapy. We want to explore the role of high-dose chemotherapy (HDT) and autologous stem cell transplant (ASCT) for these patients.
Recent Findings
There is some utility of upfront consolidation for-high risk/high-grade B-cell lymphoma, mantle cell lymphoma, and T-cell lymphoma, but there is no role of similar intervention for HL. New conditioning regimens are being investigated which have demonstrated an improved safety profile without compromising the myeloablative efficiency for relapsed or refractory HL.
Summary
Salvage chemotherapy followed by HDT and rescue autologous stem cell transplant remains the standard of care for relapsed/refractory lymphoma. The role of novel agents to improve disease-related parameters remains to be elucidated in frontline induction, disease salvage, and high-dose consolidation or in the maintenance setting.
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Fracture healing: A review of clinical, imaging and laboratory diagnostic options
Publication date: Available online 5 May 2017
Source:Injury
Author(s): Brian P. Cunningham, Sloane Brazina, Saam Morshed, Theodore Miclau
A fundamental issue in clinical orthopaedics is the determination of when a fracture is united. However, there are no established "gold standards," nor standardized methods for assessing union, which has resulted in significant disagreement among orthopaedic surgeons in both clinical practice and research. A great deal of investigative work has been directed to addressing this problem, with a number of exciting new techniques described. This review provides a brief summary of the burden of nonunion fractures and addresses some of the challenges related to the assessment of fracture healing. The tools currently available to determine union are discussed, including various imaging modalities, biomechanical testing methods, and laboratory and clinical assessments. The evaluation of fracture healing in the setting of both patient care and clinical research is integral to the orthopaedic practice. Weighted integration of several available metrics must be considered to create a composite outcome measure of patient prognosis.
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The relationship between physical and psychological complaints and quality of life in severely injured patients
Publication date: Available online 5 May 2017
Source:Injury
Author(s): Katinka van Delft-Schreurs, C.C.H.M. van Delft-Schreurs, M.A.C. van Son, M.A.C. de Jongh, K.W.W. Lansink, J. de Vries, M.H.J. Verhofstad
PurposeThe purpose of this study was two-fold. The first goal was to investigate which variables were associated with the remaining physical limitations of severely injured patients after the initial rehabilitation phase. Second, we investigated whether physical limitations were attributable to the association between psychological complaints and quality of life in this patient group.MethodsPatients who were 18 years or older and who had an injury severity score (ISS)>15 completed a set of questionnaires at one time-point after their rehabilitation phase (15-53 months after their trauma). The Short Musculoskeletal Function Assessment (SMFA) questionnaire was used to determine physical limitations. The Hospital Anxiety and Depression Scale, the Dutch Impact of Event Scale and the Cognitive Failure Questionnaire were used to determine psychological complaints, and the World Health Organization Quality of Life assessment instrument-BREF was used to measure general Quality of Life (QOL).Differences in physical limitations were investigated for several trauma- and patient-related variables using non-parametric independent-sample Mann-Whitney U tests. Multiple linear regression was performed to investigate whether the decreased QOL of severely injured patients with psychological complaints could be explained by their physical limitations.ResultsOlder patients, patients with physical complaints before the injury, patients with higher ISS scores, and patients who had an injury of the spine or of the lower extremities reported significantly more physical problems. Additionally, patients with a low education level, patients who were living alone, and those who were unemployed reported significantly more long-term physical problems.Severely injured patients without psychological complaints reported significantly less physical limitations than those with psychological complaints. The SMFA factor of Lower extremity dysfunction was a confounder of the association between psychological complaints and QOL in all QOL domains.ConclusionsLong-term physical limitations were mainly reported by patients with psychological complaints. The decreased QOL of severely injured patients with psychological complaints can partially be explained by physical limitations, particularly those involving lower extremity function. Experienced physical limitations were significantly different for some trauma and patient characteristics. These characteristics may be used to select patients for whom a rehabilitation programme would be useful.
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Treatment of aseptic non-union after intramedullary nailing without removal of the nail
Publication date: Available online 6 May 2017
Source:Injury
Author(s): Christos Garnavos
Failure of bone healing after intramedullary nailing of a diaphyseal long bone fracture is a severe complication that requires an effective management to ensure the best chances for successful bone-union and termination of a long period of incapacity and morbidity for the sufferers. Traditional procedures require removal of the existing nail and re-fixation with wider nail, plate or external fixation constructs. The concept that bone union can be obtained with the existing nail in situ is gaining popularity as its removal adds trauma and potential complications and prolongs the operating time. This article reviews all techniques that have been proposed for the management of aseptic diaphyseal long bone non-unions that stimulate bone healing without removing the existing nail.
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Maturation of Human Stem Cell-derived Cardiomyocytes in Biowires Using Electrical Stimulation
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Diaphragmatic Surgery and Related Complications In Primary Cytoreduction for Advanced Ovarian, Tubal, and Peritoneal Carcinoma
Abstract
Background
To evaluate the procedures and complications of diaphragm peritonectomy (DP) and diaphragm full-thickness resection (DFTR) during primary cytoreduction for advanced stage epithelial ovarian cancer.
Methods
All the patients with epithelial ovarian carcinoma who underwent diaphragm procedures at our institution between January 2009 and August 2015 were identified. Clinicopathological data were retrospectively collected from the patients' medical records. Postoperative morbidities were assessed according to the Memorial Sloan-Kettering Cancer Center (MSKCC) grading system.
Results
A total of 150 patients were included in the study. The majority of the patients had ovarian cancer (96%), stage IIIC disease (76%) and serous histology (89.3%). DP and DFTR were performed in 124 (82.7%) and 26 (17.3%) patients, respectively. A total of 142 upper abdominal procedures in addition to the diaphragmatic surgery were performed in 77 (51.3%) patients. No macroscopic residual disease was observed in 35.3% of the patients, while 84% of the total patient cohort had residual disease ≤1 cm. The overall incidence of at least one major morbidity (MSKCC grades 3–5) was 18.0%, whereas pleural effusions (33.3%), pneumonia (15.3%) and pneumothorax (7.3%) were the most commonly reported morbidities. The rate of postoperative pleural drainage was 14.6% in total, while half the patients in the DFTR group received drainage intraoperatively (11.5%) and postoperatively (38.5%). The incidence of postoperative pleural effusion was associated with stage IV disease (hazard ratio [HR], 17.2; 95% confidence interval [CI]: 4.5–66.7; P < 0.001), DFTR (HR, 4.9; 95% CI: 1.2–19.9; P = 0.028) and a long surgery time (HR, 15.4; 95% CI: 4.3–55.5; P < 0.001).
Conclusions
Execution of DP and DFTR as part of an extensive upper abdominal procedure resulted in an acceptable morbidity rate. Pleural effusion, pneumonia and pneumothorax were the most common pulmonary morbidities. The pleural drainage rate was not high enough to justify prophylactic chest tube placement for all the patients. However, patients who underwent DFTR merited special consideration for intraoperative prophylactic drainage.
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The Pharmacokinetic Interaction between Ivacaftor and Ritonavir in Healthy Volunteers
Aim
The aim of this study was to determine the pharmacokinetic interaction between ivacaftor and ritonavir.
Methods
A liquid chromatography mass spectrometry (LC-MS) method was developed for the measurement of ivacaftor in plasma. An open-label, sequential, cross-over study was conducted with 12 healthy volunteers. Three pharmacokinetic profiles were assessed for each volunteer: ivacaftor 150 mg alone (study A) ivacaftor 150 mg plus ritonavir 50 mg daily (study B) and ivacaftor 150 mg plus ritonavir 50 mg daily after two weeks of ritonavir 50 mg daily (study C).
Results
Addition of ritonavir 50 mg daily to ivacaftor 150 mg resulted in significant inhibition of the metabolism ivacaftor. Area under the plasma concentration–time curve from time 0 to infinity (AUC0-inf obv) was significantly increased in both studies B and C compared to study A (GMR [95% CI] 19.71 [13.18–31.33] and 19.74 [14.0–27.93] respectively). Elimination half-life (T1/2) was significantly longer in both studies B and C compared to study A (GMR [95% CI] 11.14 [8.72-13.62] and 9.72 [6.68–12.85] respectively). There was no significant difference in any of the pharmacokinetic parameters between study B and study C.
Conclusion
Ritonavir resulted in significant inhibition of the metabolism of ivacaftor. These data suggest that ritonavir may be used to inhibit the metabolism of ivacaftor in patients with cystic fibrosis (CF). Such an approach may increase the effectiveness of ivacaftor in 'poor responders' by maintaining higher plasma concentrations. It also has the potential to significantly reduce the cost of ivacaftor therapy.
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Meningocele manque
Description
A 53-year-old man presented with right-sided sciatic-like pain. He was otherwise asymptomatic with no weakness, sphincter disturbances or gait problems. On examination, upper motor neuron signs were elicited in both lower limbs and an MRI of the whole spine was requested.
MRI showed dorsal tethering of the spinal cord secondary to a fibrous band, associated with two midline lipomas (figure 1). The affected cord segment was triangular in cross section (figure 2), and a syrinx was also observed at the affected level. Radiological appearances were compatible with meningocele manqué (MM).
Figure 1
Sagittal T2-weighted (A) and T1-weighted (B) MRI of the cervical spine shows a thin band of tissue tethering the dorsal cord to the dura at T1–2 level (arrow) with resultant formation of a syrinx. At T2–3 level, there is a focal lesion at the dorsal aspect of the thoracic cord...
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A curious cause of pseudo-haematuria: a neglected vaginal pessary
Description
Vaginal pessaries represent a valid therapeutic option for the management of female pelvic organ prolapse in elderly women with significant comorbidities. Although leading to good functional and quality of life outcomes, when neglected, they can cause significant and severe complications.1
An 87-year-old woman semidependent and uncooperative due to progressive Alzheimer's dementia, who has lived in a nursing home for the last 5 years, presented to our outpatient clinic for 'intermittent hematuria'. She carried a pelvic ultrasound documenting a 'polypoid formation with 23 mm on the posterior bladder wall suggesting a bladder tumour'.
The blood loss had been detected intermittently in the diaper that she uses for hygienic purposes.
There were no analytical abnormalities except for leucoerythrocyturia with positive Escherichia coli urine culture. The hypothesis of a urothelial lesion led to the scheduling of a cystoscopy under anaesthesia and an abdominopelvic CT scan.
The abdominopelvic CT scan documented...
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You are what you eat: ophthalmological manifestations of severe B12 deficiency
Severe B12 vitamin deficiency due to diminished dietary intake is a known cause of severe pancytopenia with bleeding diathesis. The authors report a case with sudden-onset bilateral vision loss, severe pancytopenia and multiple organ failure secondary to B12 vitamin deficiency in a patient with a strict vegetarian diet. On funduscopic examination the patient had multiple bilateral exuberant haemorrhages in all retinal layers. Five months after presentation, he had a complete visual recovery without ophthalmological intervention.
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Unilateral infective sacroiliitis in a boy presenting with a limp
A 9-year-old boy admitted to a district general hospital with a 1-week history of fever and a 2-day history of right hip pain. Initial workup revealed raised inflammatory markers and unremarkable imaging studies. After clinical review, there was minimal improvement of the patient's condition 5 days after presentation; therefore, an MRI of the pelvis/hips was carried out, which supported a clinical diagnosis of right-sided infective sacroiliitis. Infective sacroiliitis is rare and only represents 1%–2% of septic arthritis in children. The condition still remains a diagnostic challenge first due to poor localisation of symptoms with referred pain to the hip, thigh and lower back and second due to a lack of awareness by non-specialist clinicians. Early diagnosis is a key to avoid sequelae such as an abscess, degenerative changes of the sacroiliac joint and can be achieved by a thorough clinical examination, monitoring inflammatory markers and MRI.
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Management of a cutaneous squamous cell carcinoma overlying an AV fistula
Cutaneous squamous cell carcinoma (cSCC) currently affects over 700 000 patients per year in the USA alone, and its incidence continues to rise in recent years. A known risk factor for cSCC is chronic inflammation; a cSCC that develops at a site of chronic inflammation is known as Marjolin's ulcer. We present the case of a 76-year-old man with end-stage renal disease requiring chronic haemodialysis who developed an invasive cSCC at the cannulation site of an underlying arteriovenous (AV) fistula. In this instance, treatment with standard surgical excision or Mohs surgery would pose unique risks associated with injury to an otherwise functional AV fistula. Thus, the lesion was treated with electron beam radiation therapy, which offers a similar efficacy to surgery while minimising risk to the fistula. This resulted in a successful oncological outcome with no complications.
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Myeloneuropathy due to multiple giant plexiform neurofibromas - an unusual presentation of neurofibromatosis type 1
Description
A man aged 33 years presented with a 10-year progressive history of difficulty in walking with poor gripping of flip-flops on feet. It was further associated with foot drop and weakened handgrip. There was a recent history of multiple falls and difficulty in climbing stairs or standing from a squatting position. Family history was suggestive of neurofibromatosis type 1 (NF-1) in grandfather, father, paternal aunt and cousin. Physical examination revealed multiple café-au-lait spots, axillary freckling, Lisch nodules with cutaneous and subcutaneous neurofibromas. On neurological examination, there was spastic quadriparesis with foot drop, distal sensory loss and absent ankle reflexes, which were suggestive of myeloneuropathy. MRI of the cervical spine and whole spine showed characteristic dumbbell-shaped neurofibromas, extending along the Intraspinal and extraspinal areas at multiple cord levels and also along various nerves of the upper and lower limb involving plexuses and roots (figure 1 and
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Radiological, pathological and gross correlation of an isolated renal cell carcinoma metastasis to the stomach
Description
A 59-year-old asymptomatic woman presented for follow-up CT thorax, abdomen and pelvis (CT-TAP). Fifteen months previously she underwent a left radical nephrectomy for a T1bN0MO, 5.5 cm Fuhrman grade 4 clear cell renal cell carcinoma (CCRCC) (figure 1).
Figure 1
Portal venous phase coronal image CT-TAP. The 6.8 cm expansile, heterogenous lesion is centred in the renal cortex of the mid/upper pole of the left kidney (yellow circle). It appears well encapsulated (red arrows) and abuts the renal sinus with no clear invasion. The low attenuation may be due to necrosis or cystic components. CT-TAP, CT thorax, abdomen and pelvis.
The CT-TAP revealed a new 3.6 cm peripherally enhancing, centrally necrotic, intramural lesion in the fundus of the stomach (figure 2). It was decided to biopsy the lesion via oesophago-gastro duodenoscopy (OGD). It was not apparent on direct visualisation of the stomach mucosa, thus...
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Fever without a source: evolution of a diagnosis from Kawasaki disease to acute myelogenous leukaemia
A previously healthy 11-month-old male patient presented with fever, abdominal pain and irritability. As part of an extensive evaluation for the cause of his fevers, an echocardiogram was performed and showed mildly dilated coronary arteries, leading to a diagnosis of incomplete Kawasaki disease (KD). He was treated with intravenous immunoglobulin (IVIG), defervesced and was discharged home. Two weeks later, he presented with anaemia initially attributed to haemolytic anaemia secondary to IVIG and received a red blood cell transfusion. However, his anaemia recurred 2 weeks later with leucocytosis, prompting a bone marrow aspirate 4 weeks after his diagnosis of KD. This demonstrated acute myelogenous leukaemia most consistent with acute megakaryocytic leukaemia. This case highlights the potentially subtle presentation of acute leukaemia and the need to keep an open mind and reconsider the initial diagnosis as new information comes to light in the care of an ill child.
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(Lack of) Corticospinal facilitation in association with hand laterality judgments
Abstract
In recent years, mental practice strategies have drawn much interest in the field of rehabilitation. One form of mental practice particularly advocated involves judging the laterality of images depicting body parts. Such laterality judgments are thought to rely on implicit motor imagery via mental rotation of one own's limb. In this study, we sought to further characterize the involvement of the primary motor cortex (M1) in hand laterality judgments (HLJ) as performed in the context of an application designed for rehabilitation. To this end, we measured variations in corticospinal excitability in both hemispheres with motor evoked potentials (MEPs) while participants (n = 18, young adults) performed either HLJ or a mental counting task. A third condition (foot observation) provided additional control. We hypothesized that HLJ would lead to a selective MEP facilitation when compared to the other tasks and that this facilitation would be greater on the right than the left hemisphere. Contrary to our predictions, we found no evidence of task effects and hemispheric effects for the HLJ task. Significant task-related MEP facilitation was detected only for the mental counting task. A secondary experiment performed in a subset of participants (n = 6) to further test modulation during HLJ yielded the same results. We interpret the lack of facilitation with HLJ in the light of evidence that participants may rely on alternative strategies when asked to judge laterality when viewing depictions of body parts. The use of visual strategies notably would reduce the need to engage in mental rotation, thus reducing M1 involvement. These results have implications for applications of laterality tasks in the context of the rehabilitation program.
http://ift.tt/2qM0AUC
Why Women Take Fewer Risk Than Men Do: The Mediating Role of State Anxiety
Abstract
Gender studies have showed that women take fewer risks than men do. Previous research has also provided evidence for a link between negative affect (anxiety and depressive mood) and risk-taking. Little is known about the relationships among these factors. We examined the role of state anxiety in the relationship between gender and risk-taking. Fully 149 undergraduate students filled out the State-Trait Anxiety Inventory (STAI) and the Beck Depression Inventory–II (BDI) before playing the hot version of the Columbia Card Task (hot CCT), which is designed to measure emotionally based risk-taking behavior. Hierarchical regression analysis showed that gender and state anxiety were associated with risk-taking even when controlling for age, depressive mood, and trait anxiety. Moreover, results pointed out that gender is related to risk-taking through state anxiety. These results offer insights into gender research, as well as affective and decision science. Implications for future studies and applied interventions are discussed.
http://ift.tt/2qatxfR
Women’s Ideals for Masculinity Across Social Contexts: Patriarchal Agentic Masculinity is Valued in Work, Family, and Romance but Communal Masculinity in Friendship
Abstract
The present study explores women's ideals for masculinity in different social contexts (work, family/romance, and friendship) and compares how traditional (agentic) and non-patriarchal (communal) masculinity are valued in each context. Survey data were collected from one international (N = 159) and three South African samples (Ns = 86, 100, 161) of women. Results show that although women value patriarchal ideals for masculinity, agentic and communal versions of masculinity are valued differently across contexts. Specifically, traditional agentic versions of masculinity were most valued in the contexts most important to the long-term production of viable identity (family/romance and work). It was only in friendship that non-patriarchal communal masculinity was consistently idealized over traditional agentic masculinity. The results are discussed in relation to hegemonic masculinity (HM) and system justification theory (SJT). Congruent with SJT, women idealized versions of masculinity that may not be in their own or their group's best interests, but in line with HM, the results emphasized the fluidity of masculinity and that the same individual can simultaneously idealize different versions of masculinity depending on the context. Because stereotypes are both explanations for the status quo and warrants for behaving in one way or another, these collective ideals for masculinity and contextual boundaries may be important obstacles to achieving gender equity.
http://ift.tt/2qLZAjk
Epidemiology of Candida albicans and non-C.albicans of neonatal candidemia at a tertiary care hospital in western China
Although the majority of Candida infections occur in the developing world, candidemia epidemiology is poorly understood in these countries. The aim of this study was to investigate the epidemiology of non-Candida...
http://ift.tt/2pkP2q8
Copenhagen Airport Cohort: air pollution, manual baggage handling and health
Purpose
Copenhagen Airport Cohort 1990–2012 presents a unique data source for studies of health effects of occupational exposure to air pollution (ultrafine particles) and manual baggage handling among airport employees. We describe the extent of information in the cohort and in the follow-up based on data linkage to the comprehensive Danish nationwide health registers. In the cohort, all information is linked to the personal identification number that also is used in Denmark Statistics demographic and socioeconomic databases and in the nationwide health registers.
ParticipantsThe cohort covers 69 175 men in unskilled positions. The exposed cohort includes men in unskilled jobs employed at Copenhagen Airport in the period 1990–2012 either as baggage handlers or in other outdoor work. The reference cohort includes men in unskilled jobs working in the greater Copenhagen area.
Findings to dateThe cohort includes environmental Global Positioning System (GPS) measurements in Copenhagen Airport, information on job function/task for each calendar year of employment between 1990 and 2012, exposure to air pollution at residence, average weight of baggage lifted per day and lifestyle. By linkage to registers, we retrieved socioeconomic and demographic data and data on healthcare contacts, drug subscriptions, incident cancer and mortality.
Future plansThe size of the cohort and the completeness of the register-based follow-up allow a more accurate assessment of the possible health risks of occupational exposure to ultrafine particles and manual baggage handling at airports than in previous studies. We plan to follow the cohort for the incidence of ischaemic heart diseases, cerebrovascular disease, lung and bladder cancer, asthma and chronic obstructive pulmonary disease, and further for associations between heavy manual baggage handling and musculoskeletal disorders.
Trial registrationnumber 2012–41–0199.
http://ift.tt/2qCWH7i
Medicine authentication technology as a counterfeit medicine-detection tool: a Delphi method study to establish expert opinion on manual medicine authentication technology in secondary care
Objectives
This study aims to establish expert opinion and potential improvements for the Falsified Medicines Directive mandated medicines authentication technology.
Design and interventionA two-round Delphi method study using an online questionnaire.
SettingLarge National Health Service (NHS) foundation trust teaching hospital.
ParticipantsSecondary care pharmacists and accredited checking technicians.
Primary outcome measuresSeven-point rating scale answers which reached a consensus of 70–80% with a standard deviation (SD) of <1.0. Likert scale questions which reached a consensus of 70–80%, a SD of <1.0 and classified as important according to study criteria.
ResultsConsensus expert opinion has described database cross-checking technology as quick and user friendly and suggested the inclusion of an audio signal to further support the detection of counterfeit medicines in secondary care (70% consensus, 0.9 SD); other important consensus with a SD of <1.0 included reviewing the colour and information in warning pop up screens to ensure they were not mistaken for the 'already dispensed here' pop up, encouraging the dispenser/checker to act on the warnings and making it mandatory to complete an 'action taken' documentation process to improve the quarantine of potentially counterfeit, expired or recalled medicines.
ConclusionsThis paper informs key opinion leaders and decision makers as to the positives and negatives of medicines authentication technology from an operator's perspective and suggests the adjustments which may be required to improve operator compliance and the detection of counterfeit medicines in the secondary care sector.
http://ift.tt/2qCVOvl
Cancers, Vol. 9, Pages 45: Metformin in Lung Cancer: Review of in Vitro and in Vivo Animal Studies
Cancer cells display enhanced growth rates and a resistance to apoptosis. The ability of cancer cells to evade homeostasis and proliferate uncontrollably while avoiding programmed cell death/apoptosis is acquired through mutations to key signaling molecules, which regulate pathways involved in cell proliferation and survival and these mutations allow them to develop resistance to many chemotherapeutic agents, highlighting the need for development of new potent anti-cancer agents. Metformin has long been used as a treatment for type 2 diabetes and has recently attracted attention as a potential agent to be used in the treatment of cancer. The present review summarizes the existing in vitro and in vivo animal studies focusing on the anti-lung cancer effects of metformin and its effects on key proliferative and anti-apoptotic signaling pathways.
http://ift.tt/2pMhWCr
Why is colon cancer survival improving by time? A nationwide survival analysis spanning 35 years
Abstract
There is limited information present to explain temporal improvements in colon cancer survival. This nationwide study investigates the temporal changes in survival over a 35-year period (1970-2004) in Iceland and uses incidence, mortality, surgery rate, stage distribution, lymph node yield, tumor location and histological type to find explanations for these changes. Patients diagnosed with colon cancer in Iceland 1970-2004 were identified (n=1962). All histopathology was reassessed. Proportions, age-standardized incidence and mortality, relative, cancer-specific and overall survival and conditional survival were calculated. When comparing first and last diagnostic periods (1970-1978 and 1997-2004), 5-year relative survival improved by 12% for men and 9% for women. At the same time surgery rate increased by 12% and the proportion of stage I increased by 9%. Stage-stratified, improved 5-year relative survival was mainly observed in stage II and III and coincided with higher lymph node yields, proportional reduction of stage II cancers and proportional increase of stage III cancers, indicating stage migration between these stages. Improvement in 1-year survival was mainly observed in stage III and IV. Five-year survival improvement for patients living beyond 1 year was minimum to none. There were no changes in histology that coincided with neither increased incidence nor possibly influencing improved survival. Concluding, as a novel finding, 1-year mortality, which previously has been identified as an important variable in explaining international survival differences, is in this study identified as also being important in explaining temporal improvements in colon cancer survival in Iceland. This article is protected by copyright. All rights reserved.
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Serology of Streptococcus gallolyticus subspecies gallolyticus and its association with colorectal cancer and precursors
Abstract
Streptococcus gallolyticus subspecies gallolyticus (SGG) is potentially associated with colorectal cancer (CRC) and its precursors. A previous case-control study measured antibody responses to SGG pilus proteins Gallo2178 and Gallo2179 and identified significant associations with a small fraction of CRC cases. We aimed at replicating and expanding these findings in an independent study including additional SGG antigens and explored the association with precancerous lesions.
We applied multiplex serology to measure antibodies to eleven SGG proteins in serum samples of a screening colonoscopy trial (BliTz study) including participants diagnosed with either non-advanced adenoma (NAA, n=30), advanced adenoma (AA, n=100), CRC (n=50) or controls (n=228). In addition, we analysed CRC samples (n=318) from patients recruited in a clinical setting (DACHSplus study).
The association of antibody responses to SGG pilus proteins Gallo2178 and Gallo2179 with CRC was replicated with 4% positive DACHSplus cases compared to 0% positive BliTz controls. Positivity to two or more proteins of a newly defined panel of six SGG markers was significantly associated with CRC in the DACHSplus study (OR: 1.81, 95% CI: 1.07-3.06). Odds for CRC, AA and NAA in the BliTz study were also increased with antibody responses to SGG, and the association was significant for NAA (OR: 2.98, 95% CI: 1.18-7.57).
Antibody responses to SGG are associated with CRC and its precursors. The newly identified SGG 6-marker panel and associations found with precancerous lesions should be further explored. This article is protected by copyright. All rights reserved.
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ADCC employing an NK cell line (haNK) expressing the high affinity CD16 allele with avelumab, an anti-PD-L1 antibody
Abstract
NK-92 cells, and their derivative, designated aNK, were obtained from a patient with non-Hodgkin lymphoma. Prior clinical studies employing adoptively transferred irradiated aNK cells have provided evidence of clinical benefit and an acceptable safety. aNK cells have now been engineered to express IL-2 and the high affinity (ha) CD16 allele (designated haNK). Avelumab is a human IgG1 anti‒PD-L1 monoclonal antibody, which has shown evidence of clinical activity in a range of human tumors. Prior in vitro studies have shown that avelumab has the ability to mediate antibody-dependent cell-mediated cytotoxicity (ADCC) of human tumor cells when combined with NK cells. In the studies reported here, the ability of avelumab to enhance the lysis of a range of human carcinoma cells by irradiated haNK cells via the ADCC mechanism is demonstrated; this ADCC is shown to be inhibited by anti-CD16 blocking antibody and by concanamycin A, indicating the use of the granzyme/perforin pathway in tumor cell lysis. Studies also show that while NK cells have the ability to lyse aNK or haNK cells, the addition of NK cells to irradiated haNK cells does not inhibit haNK-mediated lysis of human tumor cells, with or without the addition of avelumab. Avelumab-mediated lysis of tumor cells by irradiated haNK cells is also shown to be similar to that of NK cells bearing the V/V Fc receptor high affinity allele. These studies thus provide the rationale for the clinical evaluation of the combined use of avelumab with that of irradiated adoptively transferred haNK cells. This article is protected by copyright. All rights reserved.
http://ift.tt/2pQBDcv
RAD51 as a potential surrogate marker for DNA repair capacity in solid malignancies
Abstract
Targeting deficient mechanisms of cellular DNA repair still represents the basis for the treatment of the majority of solid tumors, and increased DNA repair capacity is a hallmark mechanism of resistance not only to DNA-damaging treatments such as cytotoxic drugs and radiotherapy, but also to small molecule targeted drugs such as inhibitors of poly-ADP ribose polymerase (PARP). Hence, there is substantial medical need for potent and convenient biomarkers of individual response to DNA-targeted treatment in personalized cancer care. RAD51 is a highly conserved protein that catalyzes DNA repair via homologous recombination, a major DNA repair pathway which directly modulates cellular sensitivity to DNA-damaging treatments. The clinical and biological significance of RAD51 protein expression is still under investigation. Pre-clinical studies consistently show the important role of nuclear RAD51 immunoreactivity in chemo- and radioresistance. Validating data from clinical trials however is limited at present, and some clinical studies show controversial results. This review gives a comprehensive overview on the current knowledge about the prognostic and predictive value of RAD51 protein expression and genetic variability in patients with solid malignancies. This article is protected by copyright. All rights reserved.
http://ift.tt/2qNB1Sr
Direct Observation of Cell-Cycle-Dependent Interactions between CTCF and Chromatin
The three-dimensional arrangement of chromatin encodes regulatory traits important for nuclear processes such as transcription and replication. Chromatin topology is in part mediated by the architectural protein CCCTC-binding factor (CTCF) that binds to the boundaries of topologically associating domains. Whereas sites of CTCF interactions are well characterized, little is known on how long CTCF binds to chromatin and how binding evolves during the cell cycle. We monitored CTCF-chromatin interactions by live cell single molecule tracking in different phases of the cell cycle.
http://ift.tt/2pR0o6F
Optimal Affinity Enhancement by a Conserved Flexible Linker Controls p53 Mimicry in MdmX
MdmX contains an intramolecular binding motif that mimics the binding of the p53 tumor suppressor. This intramolecular binding motif is connected to the p53 binding domain of MdmX by a conserved flexible linker that is 85 residues long. The sequence of this flexible linker has an identity of 51% based on multiple protein sequence alignments of 52 MdmX homologs. We used polymer statistics to estimate a global KD value for p53 binding to MdmX in the presence of the flexible linker and the intramolecular binding motif by assuming the flexible linker behaves as a wormlike chain.
http://ift.tt/2pLzpem
Direct Observation of Cell-Cycle-Dependent Interactions between CTCF and Chromatin
The three-dimensional arrangement of chromatin encodes regulatory traits important for nuclear processes such as transcription and replication. Chromatin topology is in part mediated by the architectural protein CCCTC-binding factor (CTCF) that binds to the boundaries of topologically associating domains. Whereas sites of CTCF interactions are well characterized, little is known on how long CTCF binds to chromatin and how binding evolves during the cell cycle. We monitored CTCF-chromatin interactions by live cell single molecule tracking in different phases of the cell cycle.
http://ift.tt/2pR0o6F
Optimal Affinity Enhancement by a Conserved Flexible Linker Controls p53 Mimicry in MdmX
MdmX contains an intramolecular binding motif that mimics the binding of the p53 tumor suppressor. This intramolecular binding motif is connected to the p53 binding domain of MdmX by a conserved flexible linker that is 85 residues long. The sequence of this flexible linker has an identity of 51% based on multiple protein sequence alignments of 52 MdmX homologs. We used polymer statistics to estimate a global KD value for p53 binding to MdmX in the presence of the flexible linker and the intramolecular binding motif by assuming the flexible linker behaves as a wormlike chain.
http://ift.tt/2pLzpem
A de novo missense mutation in SLC12A5 found in a compound heterozygote patient with epilepsy of infancy with migrating focal seizures
Abstract
Epilepsy of infancy with migrating focal seizures (EIMFS) is an infantile epileptic encephalopathy characterized by refractory seizures, severe psychomotor delay, and multiple moving epileptic discharges. The genetic etiology of EIMFS is relatively homogeneous with the majority of causative mutations found in KCNT1. Currently, gene panel or whole-exome sequencing is used for testing. To verify the pathogenicity of a variant, co-segregation of the variant and the disorder in a pedigree is important; hence, de novo mutations that are judged to be deleterious may be considered pathogenic because the patients are isolated. In contrast, in cases from non-consanguineous families, genes that cause disorders in a recessive manner should remain as potential candidates. Herein, we performed gene panel sequencing of a patient with EIMFS from a non-consanguineous family, and found a compound heterozygous constellation consisting of a maternally inherited p.Ser399Leu and a de novo p.Arg880Leu in SLC12A5, which encodes the neuronal KCC2 co-transporter. These unique mutations demonstrate gene variants that act in a recessive manner may be pathogenic for patients from non-consanguineous families.
Graphical Abstract
Identification of a novel compound heterozygous constellation (c.[1196C > T(;) 2639G > T]:p.[p.Ser399Leu(;) p.Arg880Leu]) in SLC12A5, which consisted of a maternally inherited mutation (p.Ser399Leu) and a de novo mutation (p.Arg880Leu), in a patient with epilepsy of infancy with migrating focal seizures from a non-consanguineous family.
http://ift.tt/2qCNhbR
Case of disseminated histoplasmosis in a HIV-infected patient revealed by nasal involvement with maxillary osteolysis
Disseminated Histoplasmosis (DH) is a rare manifestation of Acquired Immune Deficiency Syndrome (AIDS) in European countries. Naso-maxillar osteolysis due to Histoplasma capsulatum var. capsulatum (Hcc) is unusua...
http://ift.tt/2pjZ2jA
Cataplexy and Its Mimics: Clinical Recognition and Management
Opinion statement
This review describes the diagnosis and management of cataplexy: attacks of bilateral loss of muscle tone, triggered by emotions and with preserved consciousness. Although cataplexy is rare, its recognition is important as in most cases, it leads to a diagnosis of narcolepsy, a disorder that still takes a median of 9 years to be diagnosed. The expression of cataplexy varies widely, from partial episodes affecting only the neck muscles to generalized attacks leading to falls. Moreover, childhood cataplexy differs from the presentation in adults, with a prominent facial involvement, already evident without clear emotional triggers ('cataplectic facies') and 'active' motor phenomena especially of the tongue and perioral muscles. Next to narcolepsy, cataplexy can sometimes be caused by other diseases, such as Niemann-Pick type C, Prader Willi Syndrome, or lesions in the hypothalamic or pontomedullary region. Cataplexy mimics include syncope, epilepsy, hyperekplexia, drop attacks and pseudocataplexy. They can be differentiated from cataplexy using thorough history taking, supplemented with (home)video recordings whenever possible. Childhood narcolepsy, with its profound facial hypotonia, can be confused with neuromuscular disorders, and the active motor phenomenona resemble those found in childhood movement disorders such as Sydenham's chorea. Currently, the diagnosis of cataplexy is made almost solely on clinical grounds, based on history taking and (home) videos. Cataplexy shows remarkable differences in childhood compared to adults, with profound facial hypotonia and complex active motor phenomena. Over time, these severe symptoms evolve to the milder adult phenotype, and this pattern is crucial to recognize when assessing the outcome of uncontrolled case series with potential treatments such as immunomodulation. Symptomatic treatment is possible with antidepressants and sodium oxybate. Importantly, management also needs to involve sleep hygiene advice, safety measures whenever applicable and guidance with regard to the social sequelae of cataplexy.
http://ift.tt/2qLjDOM
Phenotypic and molecular differences between giant cell tumor of soft tissue and its bone counterpart
Abstract
Aims
Giant cell tumor of soft tissue (GCT-ST) is a primary soft tissue neoplasm histologically similar to GCT of bone (GCT-B). Recently, it has been reported that >90% of GCT-B have a driver mutation in H3F3A gene. Since the relationship between GCT-ST and GCT-B is unclear, we compared a series of GCT-ST and GCT-B for the presence of H3F3A mutations and for several immunophenotypic markers.
Methods and Results
Eight cases of GCT-ST were retrieved from our institutional archives. Fifteen GCT-B served as controls. Direct sequencing for H3F3A mutations in coding regions between codons 1 and 42, including the hot spot codons (28, 35 and 37) was performed on DNA extracted from formalin-fixed paraffin-embedded tissue. Tumors were studied immunohistochemically for the expression of CD14, CD33, RANKL, RANK, P63 and for the osteoblastic markers SATB2 and RUNX2. None of the 7 cases of GCT-ST that could be analyzed presented H3F3A mutations, whereas 14 GCT-Bs (93.3%) were mutated. All 8 cases of GCT-ST were positive for RANK and RUNX2, while RANKL and SATB2 were detected only in 2 cases (25%). CD14 was detected only in mononuclear elements, while multinucleated giant cells and part of the mononuclear population expressed CD33. Few mononuclear cells of GCT-ST expressed P63. In comparison, GCT-B showed higher expression of p63 (14/15 cases with >50% of positive mononuclear cells), RANKL and SATB2, while CD14, CD33, RANK and RUNX2 were similarly expressed.
Conclusions
Although similar in the histologic appearance, our results indicate that GCT-ST is immunophenotypically and genetically distinct from GCT-B.
This article is protected by copyright. All rights reserved.
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High grade serous carcinoma (HGSC) of tubo-ovarian origin: recent developments
Abstract
Extra-uterine high-grade serous carcinoma (HGSC) accounts for most of the morbidity and mortality associated with ovarian carcinoma, and is one of the leading causes of cancer death in women. Until recently our understanding of HGSC was very limited, compared to other common cancers, and it has only been in the last 15 years that we have learned how to accurately diagnose this ovarian carcinoma histotype. Since then, however, there has been rapid progress, with identification of a precursor lesion in the fallopian tube, development of prevention strategies for both those with inherited susceptibility (Hereditary Breast and Ovarian Cancer Syndrome) and without the syndrome, and elucidation of the molecular events important in oncogenesis. This molecular understanding has led to new treatment strategies for HGSC, with the promise of more to come in the near future. In this review we focus on these recent changes, including diagnostic criteria/differential diagnosis, primary site assignment, precursor lesions, and the molecular pathology of HGSC.
This article is protected by copyright. All rights reserved.
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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Alimentary Pharmacology &Therapeutics, EarlyView. https://ift.tt/2qECBIJ
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
