86 research outputs found

    Autoimmune Neuromuscular Disorders in Childhood

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    Autoimmune neuromuscular disorders in childhood include Guillain-Barré syndrome and its variants, chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), juvenile myasthenia gravis (JMG), and juvenile dermatomyositis (JDM), along with other disorders rarely seen in childhood. In general, these diseases have not been studied as extensively as they have been in adults. Thus, treatment protocols for these diseases in pediatrics are often based on adult practice, but despite the similarities in disease processes, the most widely used treatments have different effects in children. For example, some of the side effects of chronic steroid use, including linear growth deceleration, bone demineralization, and chronic weight issues, are more consequential in children than in adults. Although steroids remain a cornerstone of therapy in JDM and are useful in many cases of CIDP and JMG, other immunomodulatory therapies with similar efficacy may be used more frequently in some children to avoid these long-term sequelae. Steroids are less expensive than most other therapies, but chronic steroid therapy in childhood may lead to significant and costly medical complications. Another example is plasma exchange. This treatment modality presents challenges in pediatrics, as younger children require central venous access for this therapy. However, in older children and adolescents, plasma exchange is often feasible via peripheral venous access, making this treatment more accessible than might be expected in this age group. Intravenous immunoglobulin also is beneficial in several of these disorders, but its high cost may present barriers to its use in the future. Newer steroid-sparing immunomodulatory agents, such as azathioprine, tacrolimus, mycophenolate mofetil, and rituximab, have not been studied extensively in children. They show promising results from case reports and retrospective cohort studies, but there is a need for comparative studies looking at their relative efficacy, tolerability, and long-term adverse effects (including secondary malignancy) in children

    Prospective evaluation of the impact of sonography on the management and surgical intervention of neonates with necrotizing enterocolitis

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    Background/aimEstablished indications for surgery in necrotizing enterocolitis (NEC) are pneumoperitoneum and failure to improve or clinical deterioration with medical treatment alone. It has been proposed that infants with intestinal necrosis may benefit from surgery in the absence of one of these indications yet the diagnosis of definitive intestinal necrosis is challenging. Recent data suggest that abdominal ultrasound (US) examination focused on the gastrointestinal tract and the peritoneal cavity may be of utility in this regard. The aim of this study was to evaluate the ability of abdominal US to detect intestinal necrosis in infants with radiographically confirmed NEC.MethodsTwenty-six consecutive infants with Bell stage II or III NEC were prospectively included in the study between September 2013 and July 2014. Infants with a pre-existing indication for surgery were excluded. At least one abdominal US examination was performed in each patient using a standardized previously described method. Surgery was performed at the discretion of the attending surgeon based on clinical and imaging findings. Clinical, radiographic, US, and intra-operative data were recorded to allow comparison between US findings, surgical findings and outcome.ResultsUS demonstrated signs of intestinal necrosis in 5 of the 26 patients. All of these five had laparotomy. Intestinal necrosis requiring resection was confirmed in four and the other was found to have NEC but no necrosis was identified. In 21 patients US did not suggest intestinal necrosis. Of these, only one had surgery in whom NEC but no necrosis was identified. The remaining 20 responded to medical treatment for NEC and were assumed not to have had intestinal necrosis based on improvement without surgical intervention. The sensitivity, specificity, positive predictive value and negative predictive values of US for the detection of bowel necrosis were calculated as 100, 95.4, 80.0, and 100 %, respectively.ConclusionOur prospective findings suggest that abdominal US can identify those infants with NEC who may need surgery by detecting bowel necrosis (prior to the development of perforation or medical deterioration) with high sensitivity and specificity. Early surgical intervention in the clinical pathway of NEC may lead to improved outcomes

    Male sex and tumor diameter are independent risk factors for relapse or persistent disease in differentiated thyroid cancer

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    Background. Differentiated thyroid cancer (DTC) is one of the most frequently observed neoplasms today. Recurrence of DTC has been previously reported to be dependent on tumor characteristics, the tumor size, the presence of lymph node metastasis, the presence of extra thyroid invasion, the presence of distant metas‑ tasis, oncogenes such as B‑RAF proto‑oncogene, ad‑ vanced age and male sex. However, many studies have failed to associate many of these data with relapse. The objective of the study was to evaluate the re‑ lationship between some histopathological and mor‑ phological findings with thyroid cancer relapse or per‑ sistent disease in a cohort of 393 DTC patients. Methods. We retrospectively analyzed 393 subjects with DTC, diagnosed in our institution between January 2000 and December 2010. Results. Histopathological analysis indicated papil‑ lary carcinoma in 362 (92.1%) subjects and follicular carcinoma in 31 (7.9%) subjects. Eighty‑two (20.9%) of the subjects relapsed or had persistent disease. Male subjects had a higher trend for relapse (RR 1.739 %95 CI: 1.059‑2.856) p=0.029). 18.8% of female sub‑ jects relapsed or had persistent disease, whereas the relapse rate was 30.4% in male subjects. Every 1 cm increase in tumor size increased the risk of relapse by 25% (RR=1.25, 95% CI: 1.11‑1.41, p<0.001). Male sex, nodule diameter, and tumor diameter were detected to be independent parameters for relapse or persistent disease (p=0.002; p<0.0001, p<0.001 respectively). Conclusion. We demonstrated that tumor diameter and male sex were the only parameters affecting re‑ lapse or persistent disease in our cohort. A possible reason for different reports from different studies may be non‑standardization of study protocols and surgical cure rates. Copyright © 2018 Balkan Medical Union

    A high-capacity RNA affinity column for the purification of human IRP1 and IRP2 overexpressed in Pichia pastoris

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    Regulated expression of proteins involved in mammalian iron metabolism is achieved in part through the interaction of the iron regulatory proteins IRP1 and IRP2 with highly conserved RNA stem-loop structures, known as iron-responsive elements (IREs), that are located within the 5′ or 3′ untranslated regions of regulated transcripts. As part of an effort to determine the structures of the IRP–IRE complexes using crystallographic methods, we have developed an efficient process for obtaining functionally pure IRP1 and IRP2 that relies upon the improved overexpression (>10 mg of soluble IRP per liter of culture) of each human IRP in the yeast Pichia pastoris and large-scale purification using RNA affinity chromatography. Despite the utility of RNA affinity chromatography in the isolation of RNA-binding proteins, current methods for preparing RNA affinity matrices produce columns of low capacity and limited stability. To address these limitations, we have devised a simple method for preparing stable, reusable, high-capacity RNA affinity columns. This method utilizes a bifunctional linker to covalently join a 5′-amino tethered RNA with a thiol-modified Sepharose, and can be used to load 150 nmole or more of RNA per milliliter of solid support. We demonstrate here the use of an IRE affinity column in the large-scale purification of IRP1 and IRP2, and suggest that the convenience of this approach will prove attractive in the analysis of other RNA-binding proteins
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