Fabiola Osorio | Bart N Lambrecht | Sophie Janssens
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Σάββατο 12 Μαΐου 2018
Antigen presentation unfolded: identifying convergence points between the UPR and antigen presentation pathways
Peptic Ulcer Disease
Peptic ulcer disease is when painful sores form in the lining of the stomach, duodenum (start of the small intestine), or bowels. Ulcers can cause belly pain, and sometimes bleeding or a hole in the stomach or bowel.
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Prognostic factors in primary anorectal melanoma: a Clinicopathologic study of 60 cases in China
To investigate the clinicopathologic features and prognostic factors of primary anorectal melanoma, we described the clinical presentations, histopathology, and prognosis of 60 cases in China. Patients' age ranged from 17 to 86years with a female-to-male ratio of 2.33:1. The prevalent anatomic site of tumor was anorectum. The mean tumor thickness was 11.5mm and mean tumor size was 2.9cm. Abdominoperineal resection was performed on 38 (63.3%) patients, while wide local excision on 22 (36.7%) patients.
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New insights into hypoxia-related mechanisms involved in different microvascular patterns of bronchopulmonary carcinoids and poorly differentiated neuroendocrine carcinomas. Role of ribonuclease T2 (RNASET2) and HIF-1 alpha
Ribonuclease T2 (RNASET2) is a pleiotropic and polyfunctional protein, which exerts several different activities in neoplastic cells since the early steps of tumor development. Besides having an antitumorigenic activity, RNASET2 inhibits both bFGF-induced and VEGF-induced angiogenesis and has a role as a stress-response, alarmin-like, protein. In this study, we investigated RNASET2 expression in well-differentiated and poorly differentiated neuroendocrine neoplasms of the lung (Lu-NENs), which are known to show clear-cut differences in morphology, biology and clinical behavior.
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Small cell carcinoma of the urinary bladder: a Clinicopathologic and Immunohistochemical analysis of 81 cases
Small cell carcinoma (SmCC) of the bladder is a rare disease. We retrospectively studied a large series of bladder SmCC from a single institution. The patients included 69 men and 12 women with a mean age of 68years. Most bladder SmCC were presented at advanced stage with tumors invading the muscularis propria and beyond (n=77). SmCC was pure in 27 cases and mixed with other histologic types in 54 cases, including urothelial carcinoma (UC) (n=32), UC in situ (n=26), glandular (n=14), micropapillary (n=4), sarcomatoid (n=4), and squamous (n=3), and plasmacytoid (n=1) features.
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TPL2 expression is correlated with distant metastasis and poor prognosis in colorectal cancer
Tumor progression locus 2 (TPL2) is a mitogen-activated protein kinase (MAPK) kinase kinase (MAP3K). The present study aimed to elucidate the clinicopathological significance and prognostic role of TPL2 expression in colorectal cancer (CRC) through immunohistochemistry. In the present study, the correlations between TPL2 expression and clinicopathological parameters, including survival rate, were investigated using 262 archival paraffin-embedded CRC tissue samples. In addition, the correlation between TPL2 expression and tumor-infiltrating lymphocytes was evaluated using immunoscore.
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Hepatic micrometastases are associated with poor prognosis in patients with liver metastases from neuroendocrine tumors of the digestive tract
Pathologic examination of hepatic metastasectomies from patients with metastatic small intestinal or pancreatic neuroendocrine tumor frequently reveals micrometastases undetectable by radiologic or macroscopic gross examination. This finding raises the possibility that undetectable micrometastases remain in these patients after metastasectomy. Here we examined liver resections for micrometastases and assessed their impact on prognosis. Hepatic metastasectomies from 65 patients with neuroendocrine tumor of the small intestine (N=43) or pancreas (N=22) were reviewed for the presence of micrometastases, which were defined as microscopic tumor foci ≤1mm in greatest dimension.
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BAP1 loss is unusual in well-differentiated papillary mesothelioma and may predict development of malignant mesothelioma
Literature on BRCA1-associated protein 1 (BAP1) expression status in well-differentiated papillary mesothelioma (WDPM) is limited. In the present study, we examined the prevalence of BAP1 loss in WDPM by immunohistochemistry with clinical correlation, along with CDKN2A deletion status by fluorescence in situ hybridization (FISH). Eight patients diagnosed as WDPM were identified from the surgical pathology file. Adenomatoid tumors (n=8) and malignant mesothelioma (MM) (n=39) were included for comparison.
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Impact of non-brain anatomy and coil orientation on inter- and intra-subject variability in TMS at midline
Transcranial magnetic stimulation (TMS) is an established neuromodulation technology that utilizes strong, transient magnetic fields generated by an electromagnetic coil placed on the scalp to induce electric fields in underlying brain tissues (Barker et al. 1985; Walsh and Cowey 2000; Pascual-Leone et al. 1994; Berlim et al. 2014). The strength and distribution of the time-varying magnetic fields are dependent on both the geometry and the amount of current traveling through the TMS coil (Deng et al.
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Patient-Identified Needs Related to Seeking a Diagnosis in the Emergency Department
Although diagnosis is a valuable tool for health care providers, and often the reason patients say they are seeking care, it may not serve the same needs for patients as for providers. The objective of this study is to explore what patients specifically want addressed when seeking a diagnosis at their emergency department (ED) visit. We propose that understanding these needs will facilitate a more patient-centered approach to acute care delivery.
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Micromanipulation Techniques Allowing Analysis of Morphogenetic Dynamics and Turnover of Cytoskeletal Regulators
We describe how micro- and photomanipulation techniques such as FRAP and photoactivation enable the determination of motility parameters and the spatiotemporal dynamics of proteins within migrating cells. Experimental readouts include subcellular dynamics and turnover of motility regulators or of the underlying actin cytoskeleton.
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Painful stimulation of a sensitized site in the forearm inhibits ipsilateral trigeminal nociceptive blink reflexes
Abstract
Exposure to moderate levels of ultraviolet B radiation (UVB) is painless but nevertheless induces an inflammatory response that sensitizes primary afferent nociceptors. Subsequently, heating the UVB-treated site can sensitize spinal nociceptors. We used a repeated-measures design to determine whether heating the UVB-treated site also triggers ipsilateral inhibitory controls. Specifically, a 2-cm diameter site on the forearm of 20 participants was exposed to UVB at twice the minimum erythema dose. 48 h later mechanical and thermal sensitivity had increased at the UVB-treated site, indicating primary hyperalgesia. In addition, sensitivity to blunt pressure had increased in the ipsilateral forehead, implying activation of an ipsilateral supra-spinal pro-nociceptive mechanism. Despite this, the area under the curve of the ipsilateral nociceptive blink reflex decreased when the UVB-treated site was heated to induce moderate pain. Together, these findings suggest that the UVB treatment sensitized primary nociceptive afferents and generated an ipsilateral supra-spinal pro-nociceptive mechanism. In addition, sensitization to heat induced by the UVB treatment strengthened an ipsilateral anti-nociceptive process elicited by heat-pain. Infrequent but enduring discharge of sensitized primary nociceptive afferents, driven by inflammation after UVB exposure, might initiate a lateralized supra-spinal pro-nociceptive influence that heightens awareness of impending harm on the sensitized side of the body. In addition, a lateralized anti-nociceptive response triggered by an intense barrage of nociceptive signals may help to differentiate stronger from weaker sources of pain.
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Adaptation of Microelectrode Array Technology for the Study of Anesthesia-induced Neurotoxicity in the Intact Piglet Brain
This study explores the novel use of enzyme-based microelectrode array (MEA) technology to monitor in vivo neurotransmitter activity in piglets. The hypothesis was that glutamate dysregulation contributes to the mechanism of anesthetic neurotoxicity. Here, we present a protocol to adapt MEA technology to study the mechanism of anesthesia-induced neurotoxicity.
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Heterozygous missense variants of LMX1A lead to nonsyndromic hearing impairment and vestibular dysfunction
Abstract
Unraveling the causes and pathomechanisms of progressive disorders is essential for the development of therapeutic strategies. Here, we identified heterozygous pathogenic missense variants of LMX1A in two families of Dutch origin with progressive nonsyndromic hearing impairment (HI), using whole exome sequencing. One variant, c.721G > C (p.Val241Leu), occurred de novo and is predicted to affect the homeodomain of LMX1A, which is essential for DNA binding. The second variant, c.290G > C (p.Cys97Ser), predicted to affect a zinc-binding residue of the second LIM domain that is involved in protein–protein interactions. Bi-allelic deleterious variants of Lmx1a are associated with a complex phenotype in mice, including deafness and vestibular defects, due to arrest of inner ear development. Although Lmx1a mouse mutants demonstrate neurological, skeletal, pigmentation and reproductive system abnormalities, no syndromic features were present in the participating subjects of either family. LMX1A has previously been suggested as a candidate gene for intellectual disability, but our data do not support this, as affected subjects displayed normal cognition. Large variability was observed in the age of onset (a)symmetry, severity and progression rate of HI. About half of the affected individuals displayed vestibular dysfunction and experienced symptoms thereof. The late-onset progressive phenotype and the absence of cochleovestibular malformations on computed tomography scans indicate that heterozygous defects of LMX1A do not result in severe developmental abnormalities in humans. We propose that a single LMX1A wild-type copy is sufficient for normal development but insufficient for maintenance of cochleovestibular function. Alternatively, minor cochleovestibular developmental abnormalities could eventually lead to the progressive phenotype seen in the families.
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Resveratrol analogue, (E)- N -(2-(4-methoxystyryl) phenyl) furan-2-carboxamide induces G 2 /M cell cycle arrest through the activation of p53–p21 CIP1/WAF1 in human colorectal HCT116 cells
Abstract
Resveratrol, a naturally occurring polyphenolic antioxidant, is a potential chemoprophylactic agent for various cancers, including colorectal cancer. Although emerging evidence continually suggests that a number of resveratrol derivatives may be better cancer chemopreventive candidates than resveratrol, studies on the mechanism of action of these derivatives are limited. This is the first study which investigates the mechanism underlying the cytotoxic effect of a synthesized resveratrol analogue, (E)-N-(2-(4-methoxystyryl) phenyl) furan-2-carboxamide (CS) on colorectal cancer. Previously, our group reported a series of synthesized resveratrol analogues, which showed cytotoxicity against a panel of cancer cell lines, in particular on colon cancer cells. In this study, we further discovered that CS also exerts a potent suppressive effect on HCT116 colorectal cancer cells. In contrast, normal colon cells (CCD-112 Con) were not sensitive to CS up to 72 h post treatment. CS caused cytotoxicity in HCT116 cells through several apoptotic events including activation of the Fas death receptor, FADD, caspase 8, caspase 3, caspase 9, and cleaved PARP, which occurred alongside cell cycle arrest from the up-regulation of p53 and p21. The results show that CS causes apoptosis via the activation of an extrinsic pathway leading to caspase activation and cell cycle arrest from activated p53. These findings suggest that CS may be a potential candidate for development as an anti-tumor agent in the future.
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Adeno-associated Virus-mediated Transgene Expression in Genetically Defined Neurons of the Spinal Cord
Intraspinal injection of recombinase dependent recombinant adeno-associated virus (rAAV) can be used to manipulate any genetically labelled cell type in the spinal cord. Here we describe how to transduce neurons in the dorsal horn of the lumbar spinal cord. This technique enables functional interrogation of the manipulated neuron subtype.
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Predictive value of early magnetic resonance imaging measures is differentially affected by the dose of interferon beta-1a given subcutaneously three times a week: an exploratory analysis of the PRISMS study
On-treatment magnetic resonance imaging lesions may predict long-term clinical outcomes in patients receiving interferon β-1a. This study aimed to assess the effect of active T2 and T1 gadolinium-enhancing (Gd...
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Convective influx/glymphatic system: tracers injected into the CSF enter and leave the brain along separate periarterial basement membrane pathways
Abstract
Tracers injected into CSF pass into the brain alongside arteries and out again. This has been recently termed the "glymphatic system" that proposes tracers enter the brain along periarterial "spaces" and leave the brain along the walls of veins. The object of the present study is to test the hypothesis that: (1) tracers from the CSF enter the cerebral cortex along pial-glial basement membranes as there are no perivascular "spaces" around cortical arteries, (2) tracers leave the brain along smooth muscle cell basement membranes that form the Intramural Peri-Arterial Drainage (IPAD) pathways for the elimination of interstitial fluid and solutes from the brain. 2 μL of 100 μM soluble, fluorescent fixable amyloid β (Aβ) were injected into the CSF of the cisterna magna of 6–10 and 24–30 month-old male mice and their brains were examined 5 and 30 min later. At 5 min, immunocytochemistry and confocal microscopy revealed Aβ on the outer aspects of cortical arteries colocalized with α-2 laminin in the pial-glial basement membranes. At 30 min, Aβ was colocalised with collagen IV in smooth muscle cell basement membranes in the walls of cortical arteries corresponding to the IPAD pathways. No evidence for drainage along the walls of veins was found. Measurements of the depth of penetration of tracer were taken from 11 regions of the brain. Maximum depths of penetration of tracer into the brain were achieved in the pons and caudoputamen. Conclusions drawn from the present study are that tracers injected into the CSF enter and leave the brain along separate periarterial basement membrane pathways. The exit route is along IPAD pathways in which Aβ accumulates in cerebral amyloid angiopathy (CAA) in Alzheimer's disease. Results from this study suggest that CSF may be a suitable route for delivery of therapies for neurological diseases, including CAA.
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Three different motor task strategies to assess neuromuscular adjustments during fatiguing muscle contractions in young and older men
Abstract
Healthy aging is associated with a marked decline in motor performance. The functional consequences of applying varying novel or unexpected motor stimuli during intermittent isometric prolonged (fatiguing) motor tasks for lower limb neuromuscular fatigability and steadiness, perception of effort, and blood markers of stress in healthy aged men compared with young men have not been investigated. The participants in this study were 15 young men (aged 22 ± 4 years) and 10 older men (aged 67 ± 6 years). They performed 100 intermittent isometric knee extensions under three experimental conditions involving intermittent isometric contraction tasks according to constant, predictable, and unpredictable torque target sequences. The variability in maximal voluntary contraction averaged 50%, and was 25, 50, and 75% for the three strategies. All included a 5-s contraction and 20-s rest. The main variables were measured before exercise, after 100 repetitions, and 1 h after exercise. In all experimental trials, the decreases in the maximal voluntary contraction and central activation ratio, and the increases in effort sensation and muscle temperature, were smaller in older men than in younger men. The coefficient of variation during the motor performance did not differ between age groups. However, in all three strategies, the dopamine concentration was significantly higher in older than in younger men. The prolactin concentration did not differ significantly between age groups or conditions, although its decrease during loading correlated negatively with the central activation ratio.
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Antioxidant and Antiapoptotic effect of aqueous extract of Pueraria tuberosa (Roxb. Ex Willd.) DC. On streptozotocin-induced diabetic nephropathy in rats
Oxidative stress and renal apoptosis play a significant role in the progression of diabetic nephropathy. The tubers of Pueraria tuberosa (Roxb. ex Willd.) DC. has been traditionally used as anti-ageing and health...
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A fatal case associated with respiratory syncytial virus infection in a young child
Respiratory syncytial virus (RSV) is the most common viral cause of pediatric bronchiolitis and pneumonia worldwide. Risk factors for high mortality and prolonged morbidity after RSV infection include prematur...
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What causes teeth to turn black?
Teeth are vulnerable to discoloration, which can happen due to staining from foods and drinks such as coffee or red wine. Black teeth can also be a sign of underlying decay or cavities, however. A dentist can provide tips on prevention and suggest the best method of treatment, which typically depends on the cause.
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Met is involved in TIGAR-regulated metastasis of non-small-cell lung cancer
Abstract
TIGAR is a p53 target gene that is known to protect cells from ROS-induced apoptosis by promoting the pentose phosphate pathway. The role of TIGAR in tumor cell invasion and metastasis remains elusive. Here we found that downregulation of TIGAR reduced the invasion and metastasis of NSCLC cells in vitro and in vivo. Immunohistochemical analysis of 72 NSCLC patients showed that TIGAR and Met protein expression was positively correlated with late stages of lung cancer. Besides, patients with high co-expression of TIGAR and Met presented a significantly worse survival. In addition, we found that Met signaling pathway is involved in TIGAR-induced invasion and metastasis. Our study indicates that TIGAR/Met pathway may be a novel target for NSCLC therapy. It is necessary to evaluate the expression of TIGAR before Met inhibitors are used for NSCLC treatment.
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Long noncoding RNA DANCR, working as a competitive endogenous RNA, promotes ROCK1-mediated proliferation and metastasis via decoying of miR-335-5p and miR-1972 in osteosarcoma
Abstract
Background
Accumulating evidences indicate that non-coding RNAs (ncRNAs) including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) acting as crucial regulators in osteosarcoma (OS). Previously, we reported that Rho associated coiled-coil containing protein kinase 1 (ROCK1), a metastatic-related gene was negatively regulated by microRNA-335-5p (miR-335-5p) and work as an oncogene in osteosarcoma. Whether any long non-coding RNAs participate in the upstream of miR-335-5p/ROCK1 axial remains unclear.
Methods
Expression of differentiation antagonizing non-protein coding RNA (DANCR) and miR-335-5p/miR-1972 in osteosarcoma tissues were determined by a qRT-PCR assay and an ISH assay. Osteosarcoma cells' proliferation and migration/invasion ability changes were measured by a CCK-8/EDU assay and a transwell assay respectively. ROCK1 expression changes were checked by a qRT-PCR assay and a western blot assay. Targeted binding effects between miR-335-5p/miR-1972 and ROCK1 or DANCR were verified by a dual luciferase reporter assay and a RIP assay. In vivo experiments including a nude formation assay as well as a CT scan were applied to detect tumor growth and metastasis changes in animal level.
Results
In the present study, an elevated DNACR was found in osteosarcoma tissue specimens and in osteosarcoma cell lines, and the elevated DNACR was closely correlated with poor prognosis in clinical patients. Functional experiments illustrated that a depression of DANCR suppressed ROCK1-mediated proliferation and metastasis in osteosarcoma cells. The results of western blot assays and qRT-PCR assays revealed that DANCR regulated ROCK1 via crosstalk with miR-335-5p and miR-1972. Further cellular behavioral experiments demonstrated that DNACR promoted ROCK1-meidated proliferation and metastasis through decoying both miR-335-5p and miR-1972. Finally, the outcomes of in vivo animal models showed that DANCR promoted tumor growth and lung metastasis of osteosarcoma.
Conclusions
LncRNA DANCR work as an oncogene and promoted ROCK1-mediated proliferation and metastasis through acting as a competing endogenous RNA (ceRNA) in osteosarcoma.
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Discovery of a Potent and Mutant-Selective EGFR Inhibitor that Overcomes T790M-Mediated Resistance in Lung Cancer
Abstract
Background
Despite remarkable activity in epidermal growth factor receptor (EGFR)-mutant lung cancer patients, the clinical efficacy of EGFR tyrosine kinase inhibitors (TKIs) is limited by the emergence of acquired resistance, which is mostly caused by a secondary T790M mutation. Fortunately, newly developed, mutant-selective EGFR-TKIs against T790M have been proven as an effective therapeutic approach although only osimertinib has received the FDA approval until now.
Objective
To determine the in vitro and in vivo efficacy of a new EGFR TKI, OBX1-012 in cells with mutant EGFR.
Methods
Effects of OBX1-012 on cellular viability and EGFR-related signaling were determined in EGFR-mutant non-small cell lung cancer (NSCLC) cells, including cells harboring T790M mutations. In addition, in vivo efficacy of OBX1-012 was evaluated in xenograft models.
Results
We report the discovery and preclinical assessment of another novel, mutant-selective EGFR-TKI, OBX1-012. Compared with other mutant-selective EGFR-TKIs such as olumitinib and osimertinib, it showed similar potency and selectivity for mutant EGFR. OBX1-012 treatment was highly effective against human EGFR-mutant lung cancer models with or without EGFR T790M, not only in vitro but also in vivo. However, OBX1-012 like other EGFR-TKIs failed to exhibit efficacy for the exon 20 insertion mutation or C797S mutation, which was generated by site-directed mutagenesis and stable transfection of Ba/F3 cells.
Conclusions
These results identify OBX1-012 as a highly effective, mutant-selective EGFR-TKI for the treatment of T790M-mediated resistance in NSCLC.
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Fibrosing mediastinitis-related pulmonary artery and vein stenosis-limiting chemotherapy
Description
A 74-year-old woman presented for second opinion of dyspnoea management. Her medical history included breast cancer treated with mastectomy, doxorubicin, cyclophosphamide and tamoxifen. She developed recurrent metastatic disease in the mediastinum, managed with 89 six-week cycles of paclitaxel over 10 years that was well tolerated and effective in stabilising the disease initially but eventually discontinued due to new sternal metastasis diagnosed on imaging and increasing dyspnoea. Examination revealed diminished left-sided breath sounds. Routine labs were normal. Echocardiogram showed normal left ventricular function and dilated right chambers. Repeat chest CT demonstrated: (1) extensive calcification and soft tissue mass in the anterior mediastinum consistent with fibrosing mediastinitis (FM); (2) severe left pulmonary artery stenosis (PAS, figure 1); and (3) an infiltrating soft tissue density in the pericardium. Subsequent pericardial tissue biopsy showed non-specific fibrosis. Pulmonary angiography showed bilateral PAS. Angiographic and surgical interventions were deferred due to...
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Cholestatic jaundice: a unique presentation leading to the diagnosis of HLH with Hodgkin lymphoma, HIV and EBV
Haemophagocytic lymphohistiocytosis (HLH) is a syndrome of dysregulated immune activity with macrophage activation that can manifest as pancytopenia, coagulopathy and other laboratory abnormalities, usually progressing to multiorgan failure and death. This report documents the rarely reported association between HLH and Hodgkin's lymphoma (HL) with simultaneous HIV and Epstein-Barr virus (EBV) and complete resolution with chemotherapy. The patient initially presented with cholestatic jaundice. He was then found to have HL associated with HLH with coexistent HIV and EBV viraemia. A-Brentuximab-VD regimen for the lymphoma was initiated, resulting in rapid resolution of HLH and ultimately remission of HL. HLH is a syndrome known to have high mortality; thus, early diagnosis and prompt treatment are crucial. Usual presentation includes non-specific symptoms and can easily be overlooked. This case highlights the importance of diagnosing the condition in unusual settings and attempting treatment by targeting the cause of HLH, HL in our case.
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Lateral semicircular canal osteoma presenting as chronic postaural fistula
Temporal bone osteoma is an unusual pathology which can occur by birth or can be acquired and mostly involves the tympanomastoid segment of the temporal bone. Osteomas arising from the otic capsule are extremely rare, and there has been only one other report of a lateral semicircular canal osteoma in the literature. We report a similar case of an acquired lateral canal osteoma which presented as a chronic postaural fistula in an ear previously operated for paediatric cholesteatoma.
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Granuloma formation associated with patellar tendon necrosis in response to Ethibond confirmed by histopathological examination
The aim of this study is to describe a case of delayed granuloma formation associated with tendon necrosis in response to Ethibond confirmed by histopathological examination and to review and discuss the related literature. A 40-year-old woman underwent a patellar tendon repair with Krakow-like #5 Ethibond sutures. Four years after the repair, she noticed progressive soreness with knee extension and swelling. An ultrasound examination revealed a proximal partial patellar tendon rupture. Based on these findings, the patient was advised to undergo surgical intervention due to a diagnosis of re-rupture. Tendinosis, fibrosis and necrosis scar tissue surrounding the previous suture were observed and excised, and samples were sent for histopathological and microbiological examination. Stripping of the patellar paratenon was performed. Surprisingly, a giant cell foreign body reaction surrounding the synthetic refringent material, as well as polymorphonuclear cells surrounding the necrotic tendon, was reported.
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Unravelling the NERDS syndrome
A 22-year-old man presented with symmetric polyarthritis, pruritus and deviation of angle of mouth to the right side since the last 7 years. His symptoms were persistent despite receiving ayurvedic medications and symptomatic therapy. Examination revealed dry skin, cutaneous nodules, xanthelasma, periarticular non-tender swellings, pitting oedema of hands and feet and lower motor neuron type right facial palsy. Haematological investigations revealed eosinophilia and skin biopsy had cutaneous eosinophilic infiltration. The constellation of above findings comprises the nodules, eosinophilia, rheumatism, dermatitis and swelling syndrome. It a rare syndrome with few reported cases in literature. The patient was started on oral corticosteroids which was subsequently tapered and methotrexate therapy. His polyarthritis and skin rashes resolved with therapy. He has been followed-up for 2 years and is presently asymptomatic for the last 1 year.
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Urothelial carcinoma of an allograft ureter 10 years after deceased donor kidney transplantation
The incidence of urothelial carcinoma (UC; formerly transitional cell carcinoma) is higher among renal transplant recipients compared with the general population. Upper urinary tract UC (UUT-UC) of allograft urothelium is a rare event with approximately 40 cases reported in the literature. Herein, we describe the clinical presentation and management of UUT-UC in a transplant ureter 10 years after deceased donor kidney transplantation.
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Improvement of primary biliary cholangitis (PBC) under treatment with sulfasalazine and abatacept
Description
A 51-year-old female patient was diagnosed with primary biliary cholangitis (PBC) in 2012 and rheumafactor-positive, Anti-citrullinated protein antibodies (ACPA)-positive rheumatoid arthritis (RA) in 2013. The diagnosis of a PBC was confirmed by liver biopsy showing portal inflammatory infiltrates with non-suppurative inflammatory lesions of the biliary duct (figure 1). PBC has been treated with ursodeoxycholic acid since 2012.
Figure 1
Dense lymphocytic infiltrates in portal tracts affecting small portal bile ducts, moderate lobular infiltrates.
After diagnosis of RA (initial Disease Activity Score 28 (DAS 28)=6.43), therapy was initiated with leflunomide 20 mg/day and low-dose oral glucocorticoids, tapered from 20 mg/day to zero over 12 weeks. Remission was reached within 4 months (DAS 28=1.84). However, elevated transaminases were detected. As a consequence, leflunomide was switched to sulfasalazine in September 2013. After an increase of activity of RA under sulfasalazine, abatacept 750 mg every 4 weeks was...
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Cavernous sinus meningioma presenting as third nerve palsy in pregnancy
A 33-year-old female patient presented with diplopia and left eye ptosis 26 weeks into her first pregnancy. No investigation was conducted at the time and her symptoms subsided 4 weeks post partum. This same phenomenon occurred during second pregnancy at 20 weeks of gestation, with patient becoming symptom-free again 6 weeks after giving birth. MRI revealed a lesion in the left cavernous sinus in keeping with a meningioma. Due to the surgically challenging location, the lesion was treated with gamma knife radiosurgery. To date, the patient remains asymptomatic with no progression on follow-up imaging 9 years on.
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Recovery of brain abscess-induced stuttering after neurosurgical intervention
Stuttering occurs in approximately 5% of all children and 1% of adults. One type, neurogenic stuttering, is usually attributable to strokes or other structural damages to the brain areas that are responsible for language fluency. Here, we present the first case of neurogenic stuttering caused by a brain abscess. The patient was a 60-year-old man admitted for a seizure and administered an anticonvulsant, after which he began stuttering. MRI revealed a brain abscess in the left frontal lobe that extended to the dorsolateral prefrontal cortex (BA (Brodmann's area) 9 and 46), frontal eye field (BA 8) and premotor cortex and supplementary motor area (BA 6). After neurosurgical drainage and antibiotic treatment, the symptoms had resolved. This case is unique in that the therapeutic effects and localisation of the cause of stuttering were rapidly identified, allowing for a more accurate description of the neural circuitry related to stuttering.
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Unusual cause of brachial palsy with diaphragmatic palsy
We report a preterm neonate born with respiratory distress. The neonate was found to have diaphragmatic palsy and brachial palsy. The neonate was born by caesarean section and there was no history of birth trauma. On examination, there was bilateral congenital talipes equinovarus and a scar was present on the forearm. The mother had a history of chickenpox during the 16 weeks of pregnancy for which no treatment was sought. On investigation, PCR for varicella was found to be positive in the neonate.
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Solitary calvarial haemangioma presenting as metastatic renal cell carcinoma
Renal cell carcinoma is the most common renal tumour in adult that often metastasises to the lung, liver or bone. Head and neck lesions are uncommon with no early warning signs and presents with overt metastases at primary presentation in 25%–30% of reported cases. The incidence of haemangiomas that suggest malignancy are similar to that of bone metastasis. Calvarial haemangiomas usually present as asymptomatic and discovered incidentally on imaging or postmortem examination. We report a case where an initial diagnosis of benign tumour of the skull was made based on clinical presentation and calvarial haemangioma on CT head but was confirmed as metastatic clear cell carcinoma of the kidney after histopathological results. Skull metastases are rare and present late in the course of the disease. It is unusual for metastatic lesion to be the primary presentation in a clinically silent renal cell carcinoma.
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Dichorionic twins discordant for body-stalk anomaly: a management challenge
Body-stalk anomaly is a sporadic and rare maldevelopment disorder characterised by large abdominal wall defect, spinal deformity and rudimentary umbilical cord. It is considered a lethal condition as there are only few reports of survival but there was at least one case of long-term survival after neonatal surgery.
Differential diagnosis includes isolated omphalocele or gastroschisis, short umbilical cord, amniotic band, limb body-wall complex and other polymalformative syndromes.
There are few reports about the expectant prenatal management of the body stalk anomaly as the majority of prenatal diagnosed cases undergo early elective termination. Twin pregnancies discordant for the anomaly represent a challenge to prenatal management as a healthy fetus should also be considered.
We describe a case of dichorionic-diamniotic twins discordant for body stalk anomaly which underwent selective feticide of the affected fetus late in pregnancy, in accordance with parents' decision focused on the neonatal well-being of the unaffected twin.
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Surprising pathological and clinical manifestations of miliary tuberculosis
We report a surprising pathological finding of miliary tuberculosis (TB) in a 49-year-old Chuukese, immunocompetent woman who was initially admitted to the hospital for a 1-month duration of chronic abdominal pain and intermittent fevers. Her clinical symptoms did not improve despite treatment with vancomycin and piperacillin–tazobactam. Based on the primary abdominal CT findings suggesting advanced ovarian cancer with omental metastatic disease, further workup with omental core biopsy was performed and demonstrated acute neutrophilic necrosis without malignant cells or granulomata. Within the omental tissue, however, many organisms stained positive for acid-fast bacilli despite lack of typical granulomata. The diagnosis of genitourinary TB was confirmed by urine Mycobacterium tuberculosis/rifampin automated molecular rapid nucleic acid amplification test. The chest CT showed a millet seed pattern of infiltration which is a hallmark for miliary TB. After initiation of multidrug TB therapy, her fever and abdominal pain drastically improved.
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Unilateral lung agenesis, hiatal hernia and atrioventricular septal defect: a rare combination of congenital anomalies
Unilateral lung agenesis is a relatively rare congenital anomaly with a reported incidence of 1 in 15 000 births. It is frequently associated with other congenital malformations. Some of the sequelae of lung agenesis are potentially life-threatening. Here, we report a case of left lung agenesis in association with hiatal hernia and atrioventricular septal defect, a rare combination of anomalies which have not been described previously in the literature.
https://ift.tt/2IgAu4G
Disseminated cryptococcosis in HIV negative patient
A 52-year-old white diabetic male with 4-weeks history of persistent cough followed by headache, drenching night sweats, low-grade fever, worsening photophobia, nausea and vomiting was presented. Examination was significant for photophobia and diminution of vision. His spinal fluid and blood cultures were positive for Cryptococcus neoformans. Intravenous fluconazole were given for 2 weeks followed by oral fluconazole. There was significant improvement in systemic and ocular symptoms. HIV serology was negative, but his CD4 counts were low with inverted CD4:CD8 ratio.
https://ift.tt/2jSUJLc
An interesting case of lymphadenopathy
Description
A 43-year-old man, a known case of diabetes mellitus and hypertension (both well controlled), with no history suggestive of high-risk sexual behaviour, presented with a painless swelling over the left side of the neck since 30 days which was insidious in onset and gradually progressive; fever since 15 days which was of sudden onset, intermittent, relieved with medications and was associated with generalised bodyache; diarrhoea since 3 days which was sudden in onset, foul smelling, watery, non-bloody, 7–8 episodes per day. He had lost 4 kg of weight in 15 days. He was a vegetarian, did not keep cats as pets and was not known to be having an immunocompromised state.
On clinical examination, only the lymph nodes in the posterior triangle of the left side of the neck were palpable. These were non-tender and were not matted.
Investigations showed anti-toxoplasma antibodies IgM and IgG (done by ELISA...
https://ift.tt/2Ifu4CP
Genetic variants in the HLA class II region associated with risk of cutaneous squamous cell carcinoma
Abstract
Background
The immune system has been implicated in the pathophysiology of cutaneous squamous cell carcinoma (cSCC) as evidenced by the substantially increased risk of cSCC in immunosuppressed individuals. Associations between cSCC risk and single nucleotide polymorphisms (SNPs) in the HLA region have been identified by genome-wide association studies (GWAS). The translation of the associated HLA SNPs to structural amino acids changes in HLA molecules has not been previously elucidated.
Methods
Using data from a GWAS that included 7238 cSCC cases and 56,961 controls of non-Hispanic white ancestry, we imputed classical alleles and corresponding amino acid changes in HLA genes. Logistic regression models were used to examine associations between cSCC risk and genotyped or imputed SNPs, classical HLA alleles, and amino acid changes.
Results
Among the genotyped SNPs, cSCC risk was associated with rs28535317 (OR = 1.20, p = 9.88 × 10− 11) corresponding to an amino-acid change from phenylalanine to leucine at codon 26 of HLA-DRB1 (OR = 1.17, p = 2.48 × 10− 10). An additional independent association was observed for a threonine to isoleucine change at codon 107 of HLA-DQA1 (OR = 1.14, p = 2.34 × 10− 9). Among the classical HLA alleles, cSCC was associated with DRB1*01 (OR = 1.18, p = 5.86 × 10− 10). Conditional analyses revealed additional independent cSCC associations with DQA1*05:01 and DQA1*05:05. Extended haplotype analysis was used to complement the imputed haplotypes, which identified three extended haplotypes in the HLA-DR and HLA-DQ regions.
Conclusions
Associations with specific HLA-DR and -DQ alleles are likely to explain previously observed GWAS signals in the HLA region associated with cSCC risk.
https://ift.tt/2IAip4F
Genetic variants in the HLA class II region associated with risk of cutaneous squamous cell carcinoma
Abstract
Background
The immune system has been implicated in the pathophysiology of cutaneous squamous cell carcinoma (cSCC) as evidenced by the substantially increased risk of cSCC in immunosuppressed individuals. Associations between cSCC risk and single nucleotide polymorphisms (SNPs) in the HLA region have been identified by genome-wide association studies (GWAS). The translation of the associated HLA SNPs to structural amino acids changes in HLA molecules has not been previously elucidated.
Methods
Using data from a GWAS that included 7238 cSCC cases and 56,961 controls of non-Hispanic white ancestry, we imputed classical alleles and corresponding amino acid changes in HLA genes. Logistic regression models were used to examine associations between cSCC risk and genotyped or imputed SNPs, classical HLA alleles, and amino acid changes.
Results
Among the genotyped SNPs, cSCC risk was associated with rs28535317 (OR = 1.20, p = 9.88 × 10− 11) corresponding to an amino-acid change from phenylalanine to leucine at codon 26 of HLA-DRB1 (OR = 1.17, p = 2.48 × 10− 10). An additional independent association was observed for a threonine to isoleucine change at codon 107 of HLA-DQA1 (OR = 1.14, p = 2.34 × 10− 9). Among the classical HLA alleles, cSCC was associated with DRB1*01 (OR = 1.18, p = 5.86 × 10− 10). Conditional analyses revealed additional independent cSCC associations with DQA1*05:01 and DQA1*05:05. Extended haplotype analysis was used to complement the imputed haplotypes, which identified three extended haplotypes in the HLA-DR and HLA-DQ regions.
Conclusions
Associations with specific HLA-DR and -DQ alleles are likely to explain previously observed GWAS signals in the HLA region associated with cSCC risk.
https://ift.tt/2IAip4F
An extract of Synedrella nodiflora (L) Gaertn exhibits antidepressant properties through monoaminergic mechanisms
Abstract
Synedrella nodiflora (SNE) has been used traditionally for many neurological conditions and some of these neuroactive effects have been scientifically substantiated. The usefulness of SNE in depression has however not been investigated despite the availability of data in other disease models indicating it may be useful. The present study therefore examined the effect of SNE in acute murine models of depression and the possible mechanisms mediating its activities in these models. Preliminary qualitative phytochemical and high performance liquid chromatography (HPLC) screening were conducted on SNE. The behavioural effects of SNE (100, 300 and 1000 mg/kg) pre-treated mice were examined in the forced swimming (FST) and tail suspension (TST) tests. Behavioural events such as mobility (swimming, climbing, curling and climbing), and immobility, were scored. The possible involvement of monoamines in the effects of SNE was assessed in the TST by pre-treating mice with α-methyldopa, reserpine and para-chlorophenylalanine (pCPA) in separate experiments. Flavonoids, tannins, saponins, alkaloids, cardiac glycosides, coumarins, triterpenes, sterols, anthraquinones and phenolic compounds were present in SNE. HPLC analysis revealed the presence of two major constituents observed at retention times 42.56 and 46.51 min, with percentage composition of 45.72% and 36.88% respectively. SNE significantly reduced immobility scores in both FST and TST, suggesting antidepressant effects. The antidepressant properties of SNE were reversed by the pre-treatment of α-methyldopa, reserpine and pCPA, suggesting a possible involvement of monoamines (noradrenaline and serotonin) in its mechanism(s) of actions. SNE exhibits antidepressant effects, possibly mediated through an interplay of enhancement of noradrenergic and serotoninergic mechanisms.
https://ift.tt/2G83zNJ
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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...
