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[PMID]: 25528358
[Au] Autor:Narisety SD; Frischmeyer-Guerrerio PA; Keet CA; Gorelik M; Schroeder J; Hamilton RG; Wood RA
[Ad] Address:Department of Pediatrics, Division of Allergy, Immunology and Infectious Diseases, New Jersey Medical School, Rutgers University, Newark, NJ....
[Ti] Title:A randomized, double-blind, placebo-controlled pilot study of sublingual versus oral immunotherapy for the treatment of peanut allergy.
[So] Source:J Allergy Clin Immunol;135(5):1275-1282.e6, 2015 May.
[Is] ISSN:1097-6825
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:BACKGROUND: Although promising results have emerged regarding oral immunotherapy (OIT) and sublingual immunotherapy (SLIT) for the treatment of peanut allergy (PA), direct comparisons of these approaches are limited. OBJECTIVE: This study was conducted to compare the safety, efficacy, and mechanistic correlates of peanut OIT and SLIT. METHODS: In this double-blind study children with PA were randomized to receive active SLIT/placebo OIT or active OIT/placebo SLIT. Doses were escalated to 3.7 mg/d (SLIT) or 2000 mg/d (OIT), and subjects were rechallenged after 6 and 12 months of maintenance. After unblinding, therapy was modified per protocol to offer an additional 6 months of therapy. Subjects who passed challenges at 12 or 18 months were taken off treatment for 4 weeks and rechallenged. RESULTS: Twenty-one subjects aged 7 to 13 years were randomized. Five discontinued therapy during the blinded phase. Of the remaining 16, all had a greater than 10-fold increase in challenge threshold after 12 months. The increased threshold was significantly greater in the active OIT group (141- vs 22-fold, P = .01). Significant within-group changes in skin test results and peanut-specific IgE and IgG4 levels were found, with overall greater effects with OIT. Adverse reactions were generally mild but more common with OIT (P < .001), including moderate reactions and doses requiring medication. Four subjects had sustained unresponsiveness at study completion. CONCLUSION: OIT appeared far more effective than SLIT for the treatment of PA but was also associated with significantly more adverse reactions and early study withdrawal. Sustained unresponsiveness after 4 weeks of avoidance was seen in only a small minority of subjects.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1505
[Cu] Class update date: 150509
[Lr] Last revision date:150509
[Js] Journal subset:AIM; IM
[St] Status:In-Data-Review

  2 / 612741 MEDLINE  
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[PMID]: 25609352
[Au] Autor:Bourke J; Pavlos R; James I; Phillips E
[Ad] Address:Department of Clinical Immunology, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia; Department of Clinical Immunology, Royal Perth Hospital, Perth, Western Australia, Australia....
[Ti] Title:Improving the Effectiveness of Penicillin Allergy De-labeling.
[So] Source:J Allergy Clin Immunol Pract;3(3):365-374.e1, 2015 May-Jun.
[Is] ISSN:2213-2201
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:BACKGROUND: Approximately 10-20% of hospitalized patients are labeled as penicillin allergic, and this is associated with significant health and economic costs. OBJECTIVES: We looked at the effectiveness of penicillin allergy de-labeling in clinical practice with the aim of deriving risk stratification models to guide testing strategies. METHODS: Consecutive patients aged 15 years or more, referred to a Western Australian public hospital drug allergy service between 2008 and 2013 for beta-lactam allergy, were included. Follow-up surveys were conducted. Results of skin prick testing and intradermal testing (SPT/IDT) and oral challenge (OC), and follow-up of post testing antibiotic usage were the main outcomes. RESULTS: SPT/IDT was performed in 401 consecutive patients with immediate (IMM) (≤1 hour) (n = 151) and nonimmediate (NIM) (>1 hour) (n = 250) reactions. Of 341 patients, 42 (12.3%) were SPT/IDT+ to ≥1 penicillin reagents, including 35/114 (30.4%) in the IMM group and 7/227 (3.1%) in the NIM group (P < .0001). Of 355 SPT/IDT patients, 3 (0.8%), all in the IMM group, had nonserious positive OC reactions to single dose penicillin VK (SPT/IDT negative predictive value [NPV] 99.2%). Selective or unrestricted beta-lactam was recommended in almost 90% overall, including 238/250 (95.2%) in the NIM group and 126/151 (83.4%) in the IMM group (P = .0001). Of 182 patients, 137 (75.3%) were following the allergy label modifications (ALM) at the time of follow-up. CONCLUSIONS: Penicillin SPT/IDT/OC safely de-labels penicillin-allergic patients and identifies selective beta-lactam allergies; however, incomplete adherence to ALM recommendations impairs effectiveness. Infrequent SPT/IDT+ and absent OC reactions in patients with NIM reactions suggest OC alone to be a safe and cost-effective de-labeling strategy that could improve the coverage of penicillin allergy de-labeling in lower risk populations.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1505
[Cu] Class update date: 150509
[Lr] Last revision date:150509
[Js] Journal subset:IM
[St] Status:In-Data-Review

  3 / 612741 MEDLINE  
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[PMID]: 24567524
[Au] Autor:Adamopoulos IE; Suzuki E; Chao CC; Gorman D; Adda S; Maverakis E; Zarbalis K; Geissler R; Asio A; Blumenschein WM; Mcclanahan T; De Waal Malefyt R; Gershwin ME; Bowman EP
[Ad] Address:Discovery Research, Merck Research Laboratories, Palo Alto, California, USA Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, USA Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children Northern California....
[Ti] Title:IL-17A gene transfer induces bone loss and epidermal hyperplasia associated with psoriatic arthritis.
[So] Source:Ann Rheum Dis;74(6):1284-92, 2015 Jun.
[Is] ISSN:1468-2060
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: Psoriatic arthritis (PsA) is a chronic inflammatory disease characterised by clinical features that include bone loss and epidermal hyperplasia. Aberrant cytokine expression has been linked to joint and skin pathology; however, it is unclear which cytokines are critical for disease initiation. Interleukin 17A (IL-17A) participates in many pathological immune responses; however, its role in PsA has not been fully elucidated. OBJECTIVE: To determine the role of IL-17A in epidermal hyperplasia and bone destruction associated with psoriatic arthritis. DESIGN: An in vivo gene transfer approach was used to investigate the role of IL-17A in animal models of inflammatory (collagen-induced arthritis) and non-inflammatory (receptor activator of NF-κB ligand (RANKL)-gene transfer) bone loss. RESULTS: IL-17A gene transfer induced the expansion of IL-17RA(+)CD11b(+)Gr1(low) osteoclast precursors and a concomitant elevation of biomarkers indicative of bone resorption. This occurred at a time preceding noticeable joint inflammation, suggesting that IL-17A is critical for the induction of pathological bone resorption through direct activation of osteoclast precursors. Moreover, IL-17A induced a second myeloid population CD11b(+)Gr1(high) neutrophil-like cells, which was associated with cutaneous pathology including epidermal hyperplasia, parakeratosis and Munro's microabscesses formation. CONCLUSIONS: Collectively, these data support that IL-17A can play a key role in the pathogenesis of inflammation-associated arthritis and/or skin disease, as observed in PsA.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1505
[Cu] Class update date: 150509
[Lr] Last revision date:150509
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1136/annrheumdis-2013-204782

  4 / 612741 MEDLINE  
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[PMID]: 24442880
[Au] Autor:Banka S; Cain SA; Carim S; Daly SB; Urquhart JE; Erdem G; Harris J; Bottomley M; Donnai D; Kerr B; Kingston H; Superti-Furga A; Unger S; Ennis H; Worthington J; Herrick AL; Merry CL; Yue WW; Kielty CM; Newman WG
[Ad] Address:Faculty of Medical and Human Sciences, Manchester Centre for Genomic Medicine, Institute of Human Development, University of Manchester, Manchester Academic Health Science Centre (MAHSC), Manchester, UK Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Tr...
[Ti] Title:Leri's pleonosteosis, a congenital rheumatic disease, results from microduplication at 8q22.1 encompassing GDF6 and SDC2 and provides insight into systemic sclerosis pathogenesis.
[So] Source:Ann Rheum Dis;74(6):1249-56, 2015 Jun.
[Is] ISSN:1468-2060
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:OBJECTIVES: Leri's pleonosteosis (LP) is an autosomal dominant rheumatic condition characterised by flexion contractures of the interphalangeal joints, limited motion of multiple joints, and short broad metacarpals, metatarsals and phalanges. Scleroderma-like skin thickening can be seen in some individuals with LP. We undertook a study to characterise the phenotype of LP and identify its genetic basis. METHODS AND RESULTS: Whole-genome single-nucleotide polymorphism genotyping in two families with LP defined microduplications of chromosome 8q22.1 as the cause of this condition. Expression analysis of dermal fibroblasts from affected individuals showed overexpression of two genes, GDF6 and SDC2, within the duplicated region, leading to dysregulation of genes that encode proteins of the extracellular matrix and downstream players in the transforming growth factor (TGF)-ß pathway. Western blot analysis revealed markedly decreased inhibitory SMAD6 levels in patients with LP. Furthermore, in a cohort of 330 systemic sclerosis cases, we show that the minor allele of a missense SDC2 variant, p.Ser71Thr, could confer protection against disease (p<1×10(-5)). CONCLUSIONS: Our work identifies the genetic cause of LP in these two families, demonstrates the phenotypic range of the condition, implicates dysregulation of extracellular matrix homoeostasis genes in its pathogenesis, and highlights the link between TGF-ß/SMAD signalling, growth/differentiation factor 6 and syndecan-2. We propose that LP is an additional member of the growing 'TGF-ß-pathies' group of musculoskeletal disorders, which includes Myhre syndrome, acromicric dysplasia, geleophysic dysplasias, Weill-Marchesani syndromes and stiff skin syndrome. Identification of a systemic sclerosis-protective SDC2 variant lays the foundation for exploration of the role of syndecan-2 in systemic sclerosis in the future.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1505
[Cu] Class update date: 150509
[Lr] Last revision date:150509
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1136/annrheumdis-2013-204309

  5 / 612741 MEDLINE  
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[PMID]: 25925987
[Au] Autor:Raghunath A; Sambarey A; Sharma N; Mahadevan U; Chandra N
[Ad] Address:Molecular Connections Private Limited, Bangalore, 560004, India. arathi@molecularconnections.com....
[Ti] Title:A molecular systems approach to modelling human skin pigmentation: identifying underlying pathways and critical components.
[So] Source:BMC Res Notes;8(1):170, 2015.
[Is] ISSN:1756-0500
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: Ultraviolet radiations (UV) serve as an environmental stress for human skin, and result in melanogenesis, with the pigment melanin having protective effects against UV induced damage. This involves a dynamic and complex regulation of various biological processes that results in the expression of melanin in the outer most layers of the epidermis, where it can exert its protective effect. A comprehensive understanding of the underlying cross talk among different signalling molecules and cell types is only possible through a systems perspective. Increasing incidences of both melanoma and non-melanoma skin cancers necessitate the need to better comprehend UV mediated effects on skin pigmentation at a systems level, so as to ultimately evolve knowledge-based strategies for efficient protection and prevention of skin diseases. METHODS: A network model for UV-mediated skin pigmentation in the epidermis was constructed and subjected to shortest path analysis. Virtual knock-outs were carried out to identify essential signalling components. RESULTS: We describe a network model for UV-mediated skin pigmentation in the epidermis. The model consists of 265 components (nodes) and 429 directed interactions among them, capturing the manner in which one component influences the other and channels information. Through shortest path analysis, we identify novel signalling pathways relevant to pigmentation. Virtual knock-outs or perturbations of specific nodes in the network have led to the identification of alternate modes of signalling as well as enabled determining essential nodes in the process. CONCLUSIONS: The model presented provides a comprehensive picture of UV mediated signalling manifesting in human skin pigmentation. A systems perspective helps provide a holistic purview of interconnections and complexity in the processes leading to pigmentation. The model described here is extensive yet amenable to expansion as new data is gathered. Through this study, we provide a list of important proteins essential for pigmentation which can be further explored to better understand normal pigmentation as well as its pathologies including vitiligo and melanoma, and enable therapeutic intervention.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1505
[Cu] Class update date: 150509
[Lr] Last revision date:150509
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1186/s13104-015-1128-6

  6 / 612741 MEDLINE  
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[PMID]: 25948977
[Au] Autor:Thakur DS; Khot R; Joshi PP; Pandharipande M; Nagpure K
[Ad] Address:Department of Medicine, Indira Gandhi Government Medical College, Nagpur, Maharashtra, India....
[Ti] Title:Glyphosate poisoning with acute pulmonary edema.
[So] Source:Toxicol Int;21(3):328-30, 2014 Sep-Dec.
[Is] ISSN:0971-6580
[Cp] Country of publication:India
[La] Language:eng
[Ab] Abstract:GlySH-surfactant herbicide (GlySH), one of the most commonly used herbicides worldwide, has been considered as minimally toxic to humans. However, clinical toxicologists occasionally encounter cases of severe systemic toxicity. The US Environmental Protection Agency (EPA) states that 'GlySH' is of relatively low oral and acute dermal toxicity. It does not have anticholinesterase effect and no organophosphate-like central nervous system (CNS) effects. The clinical features range from skin and throat irritation to hypotension and death. Severe GlySH-surfactant poisoning is manifested by gastroenteritis, respiratory disturbances, altered mental status, hypotension refractory to the treatment, renal failure, and shock.[1] GlySH intoxication has a case fatality rate 3.2-29.3%. Pulmonary toxicity and renal toxicity seem to be responsible for mortality. Metabolic acidosis, abnormal chest X-ray, arrhythmias, and elevated serum creatinine levels are useful prognostic factors for predicting GlySH mortality.[2] There is no antidote and the mainstay of treatment for systemic toxicity is decontamination and aggressive supportive therapy. We report a case of acute pulmonary edema, which is a rare but severe manifestation of oral GlySH poisoning, where patient survived with aggressive supportive therapy.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1505
[Cu] Class update date: 150509
[Lr] Last revision date:150509
[Da] Date of entry for processing:150507
[St] Status:PubMed-not-MEDLINE
[do] DOI:10.4103/0971-6580.155389

  7 / 612741 MEDLINE  
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[PMID]: 25948974
[Au] Autor:Venugopal K; Reddy MM; Bharathraj MY; Jaligidad K; Kushal DP
[Ad] Address:Department of General Medicine, Vijayanagara Institute of Medical Sciences, Bellary, Karnataka, India....
[Ti] Title:Pheniramine Maleate-Induced Rhabdomyolysis and Aki: Is it Fatal?
[So] Source:Toxicol Int;21(3):319-21, 2014 Sep-Dec.
[Is] ISSN:0971-6580
[Cp] Country of publication:India
[La] Language:eng
[Ab] Abstract:Pheniramine maleate is an easily accessible, over-the-counterantihistaminic, which is frequently involved in overdoses. Pheniramine has antimuscarinic effect causing tachycardia, dilated pupils, urinary retention, and dry flushed skin, and decreased bowel sounds, confusion, mild increase in body temperature, cardiac arrhythmias, and seizures at lethal doses. It has not been implicated as an important cause of rhabdomyolysis and acute kidney injury (AKI). Rhabdomyolysis causing AKI is rarely reported in the literature. This case report emphasizes the occurrence of nontraumatic rhabdomyolysis in pheniramine maleate overdose which required hemodialysis. Since there is a lack of a specific antidote, treatment is mainly symptomatic and supportive. We report a fatal case of a young male with a very high dose of consumption of pheniramine maleate (4.077 g), which was complicated by seizures, respiratory depression, nontraumatic rhabdomyolysis, and AKI. Despite hemodialysis, ventilator support, and other intensive supportive care, patient could not survive and death ensued due to multiorgan dysfunction syndrome.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1505
[Cu] Class update date: 150509
[Lr] Last revision date:150509
[Da] Date of entry for processing:150507
[St] Status:PubMed-not-MEDLINE
[do] DOI:10.4103/0971-6580.155384

  8 / 612741 MEDLINE  
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[PMID]: 25949230
[Au] Autor:Szewczyk M; Pazdrowski J; Golusinski P; Golusinski W
[Ad] Address:Department of Head and Neck Surgery, Poznan University of Medical Sciences Greater Poland Cancer Centre, Garbary 15, 61-866 Poznan, Poland....
[Ti] Title:Delayed reconstruction of the upper digestive tract in a patient following total pharyngolaryngectomy with resection of the cervical oesophagus.
[So] Source:Rep Pract Oncol Radiother;20(3):243-7, 2015 May-Jun.
[Is] ISSN:1507-1367
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Carcinoma of the hypopharynx is an uncommon disease, with an annual incidence of approximately 1 in 100,000. Post-cricoid carcinoma is more common in women and is not usually associated with tobacco and alcohol abuse. Reconstruction of large pharyngeal defects following surgery for squamous cell carcinoma is complex and often requires microvascular free tissue transfer to achieve the best oncological and functional outcomes. The most common complications of such procedures include fistulas and strictures of the neopharynx. Here, we describe a case of a female patient admitted to the Head and Neck Department at our hospital to undergo delayed reconstruction following pharyngolaryngectomy and removal of the cervical oesophagus. Several complications occurred during post-operative care, including stricture and skin dehiscence. At present, the patient is able to swallow saliva and is currently being prepared to return to a normal diet.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1505
[Cu] Class update date: 150509
[Lr] Last revision date:150509
[Da] Date of entry for processing:150507
[St] Status:PubMed-not-MEDLINE
[do] DOI:10.1016/j.rpor.2014.11.009

  9 / 612741 MEDLINE  
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[PMID]: 25949090
[Au] Autor:Turk U; Turk BG; Yilmaz SG; Tuncer E; Alioglu E; Dereli T
[Ad] Address:Department of Cardiology, Central Hospital, Bayrakli, Izmir, Turkey....
[Ti] Title:Amiodarone-induced multiorgan toxicity with ocular findings on confocal microscopy.
[So] Source:Middle East Afr J Ophthalmol;22(2):258-60, 2015 Apr-Jun.
[Is] ISSN:0975-1599
[Cp] Country of publication:India
[La] Language:eng
[Ab] Abstract:Amiodarone is an antiarrhythmic medication that can adversely effect various organs including lungs, thyroid gland, liver, eyes, skin, and nerves. The risk of adverse effects increases with high doses and prolonged use. We report a 54-year-old female who presented with multiorgan toxicity after 8 months of low dose (200 mg/day) amiodarone treatment. The findings of confocal microscopy due to amiodarone-induced keratopathy are described. Amiodarone may cause multiorgan toxicity even at lower doses and for shorter treatment periods.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1505
[Cu] Class update date: 150509
[Lr] Last revision date:150509
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.4103/0974-9233.154411

  10 / 612741 MEDLINE  
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[PMID]: 25949980
[Au] Autor:Nair PA
[Ad] Address:Department of Dermatology and Venereology, Pramukshwami Medical College, Karamsad, Gujarat, India.
[Ti] Title:Ciprofloxacin induced bullous fixed drug reaction: three case reports.
[So] Source:J Family Med Prim Care;4(2):269-72, 2015 Apr-Jun.
[Is] ISSN:2249-4863
[Cp] Country of publication:India
[La] Language:eng
[Ab] Abstract:Cutaneous adverse drug reactions (ADRs) are seen in about 1-2% cases. Fixed drug reaction (FDR) is responsible for about 10% of all ADRs. It is a delayed type of hypersensitivity reaction that occurs as lesions recurs at the same skin site due to repeated intake of an offending drug. The most common drugs causing fixed drug eruption (FDE) are analgesics, antibiotics, muscle relaxants and anticonvulsants. FDE due to ciprofloxacin has been reported earlier also, but bullous variant of FDR is rare. We hereby report three case reports of bullous FDR caused due to ciprofloxacin.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1505
[Cu] Class update date: 150509
[Lr] Last revision date:150509
[Da] Date of entry for processing:150507
[St] Status:PubMed-not-MEDLINE
[do] DOI:10.4103/2249-4863.154673


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