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Physicians who care for these children need to exercise therapeutic restraint; a large majority of these tumors will never require treatment, except, perhaps, for placement of a ventriculoperitoneal shunt for hydrocephalus. Neurofibromin is expressed at low levels in resting mature astrocytes both in vitro and in vivo [Nordlund et al. The time course of increased neurofibromin expression correlates with periods of astrocyte growth arrest in vivo and actually precedes astrocyte growth arrest in vitro [Gutmann et al. In this regard, neurofibromin might function as a negative growth regulator (tumor suppressor) by inactivating p21-ras and Figure 3. Moderate or severe hydrocephalus was found in 41% of the patients, all requiring ventriculoperitoneal shunting. Most important, radiographic tumor progression was seen in only six of the 17 patients, and only three of these patients had concomitant clinical progression requiring therapy. In other words, 14 of the 17 patients did not require adjuvant therapy over a mean followup of 63 months. Eleven (55%) of the patients had symptoms leading to discovery of the tumor; five patients had hydrocephalus. Although 10 patients experienced either clinical or radiologic symptoms of progressive disease, only four patients received specific therapy for their tumors over a median follow-up of 3. Only one asymptomatic patient, whose tumor was discovered by screening neuroimaging, required treatment. Emergence of optic pathway gliomas in children with neurofibromatosis type 1 after normal neuroimaging results. Natural history of optic pathway tumors in children with neurofibromatosis type 1: a longitudinal study. Brainstem tumors in patients with neurofibromatosis type 1: a distinct clinical entity. Ras-mediated cell cycle arrest is altered by nuclear oncogenes to induce Schwann cell transformation. Region-specific astrogliosis in brains of mice heterozygous for mutations in the neurofibromatosis type 1 (Nf1) tumor suppressor. First, increased expression of a wildtype or mutated epidermal growth factor receptor is found in sporadic astrocytomas, where it leads to increased activation of p21-ras and cell proliferation [Guha et al. Second, inhibition of p21-ras pathway activation in sporadic astrocytoma cell lines is associated with decreased cell proliferation in vitro and in vivo [Guha et al. This increase in the number of astrocytes reflects increased astrocyte proliferation, which is inhibited in part by blockade of the p21-ras signaling pathway [Gutmann et al. Collectively, these data support the hypothesis that neurofibromin is a critical growth regulator for astrocytes and likely functions as a tumor suppressor by modulating the p21-ras signaling pathway. In agreement with the two-hit hypothesis for inherited cancer syndromes, it is possible that loss of neurofibromin function leads to the development of the "benign," nonprogressive tumors. Carboplatin-induced regression of an optic pathway tumor in a child with neurofibromatosis. Radiation-induced cerebral vasculopathy in children with neurofibromatosis and optic pathway glioma. Von Recklinghausen neurofibromatosis: a clinical and population study in southeast Wales. This new review highlights advances in our understanding of the pathophysiology and clinical behavior of these tumors made over the last 10 years. In genetically engineered mice, Nf1 inactivation in astrocytes does not result in glioma formation despite an increase in astrocyte proliferation. Lastly, studies are ongoing using these mice and others to define the contribution of specific cell types in the tumor microenvironment to glioma formation, which could represent additional targets for antitumor drug design. Proptosis was most commonly seen in patients 6 years or younger, whereas precocious puberty was found exclusively in patients older than 6 years. Although eight of these children received chemotherapy, significant changes in the ophthalmological examination before treatment could be documented in only three patients. Notably, there were no documented cases of tumor "spread" from an isolated optic nerve glioma into the optic chiasm. Asymptomatic tumors found on "screening neuroimaging" may never grow or cause symptoms.

Although many cases of amyloidosis are hereditary, most are acquired as the result of an underlying monoclonal B-cell/plasma cell malignancy, as a phenomenon of aging, or as the result of long-standing chronic inflammation. Specific amyloid-related diseases are therefore associated with specific amyloid proteins. Because treatment of amyloidosis patients differs radically for the different amyloid subtypes, it is critically important to accurately identify the proteins that constitute the amyloid deposits. The basic diagnosis of amyloidosis is typically achieved by Congo red staining of paraffin-embedded tissue biopsy specimens obtained from diverse anatomic sites and demonstrating Congo red-positive, apple-green birefringent, amyloid deposits in the tissues. It relies on laser microdissection of Congo red-positive amyloid deposits followed by analysis by liquid chromatography-tandem mass spectrometry to accurately determine the identity of the proteins that constitute the amyloid. Useful For: Definitive identification of amyloid proteins Interpretation: An interpretation will be provided. Amyloid typing by mass spectrometry in clinical practice: a comprehensive review of 16,175 samples. Most individuals begin to exhibit clinical symptoms between the third and seventh decades of life. Affected individuals may present with a variety of symptoms including sensorimotor and autonomic neuropathy, vitreous opacities, cardiomyopathy, nephropathy, and gastrointestinal dysfunction. Orthotopic liver transplantation is a treatment option for some patients who are diagnosed in early stages of the disease. Only the transthyretin (also known as prealbumin) is analyzed for amino acid substitutions. Other proteins involved in other less common forms of familial amyloidosis are not examined. Shimizu A, Nakanishi T, Kishikawa M, et al: Detection and identification of protein variants and adducts in blood and tissues: an application of soft ionization mass spectrometry to clinical diagnosis. Sekjima Y, Yoshida K, Tokuda T, Ikeda S: Familial Transthyretin Amyloidosis In GeneReviews. Finsterer J, Iglseder S, Wanschitz J, et al: Hereditary transthyretin-related amyloidosis. However, almost all infected patients will mount an effective immune response and clear the infection within 2 years without any long-term health consequences. Interpretation: Cytology: Suspicious or atypical results need further confirmation: clinical observation, repeat cytology, or perhaps appropriate biopsy. Positive results should be confirmed by histologic examination of tissue before definitive therapy is instituted. Human papillomavirus and anal cancer: Prevalence, genotype distribution, and prognosis aspects from Midwestern region of Brazil. Clues to the diagnosis of anaplasmosis in a patient with an acute febrile illness after tick exposure include laboratory findings of leukopenia or thrombocytopenia and elevated liver enzymes. Useful For: Identification of anaplastic lymphoma kinase overexpression Diagnosis of lung adenocarcinoma and inflammatory myofibroblastic tumor Interpretation: this test does not include pathologist interpretation, only technical performance of the stain. Consultation cases may be sent by a referring pathologist and directed to one of the pathologists who is an expert in the given area or directed more broadly to the subspecialty group. Cases are frequently shared and sometimes transferred between the pathologists, as deemed appropriate for the type of case or diagnostic problem encountered. In some cases, electron microscopy and other special procedures are utilized as required. A variety of ancillary studies are available (eg, cytochemistry, immunohistochemistry, immunofluorescence, electron microscopy, mass spectrometry, cytogenetics, and molecular genetics) to aid in establishing a diagnosis. These ancillary studies are often expensive and labor intensive, and are most efficiently utilized and interpreted in the context of the morphologic features. The goal is to provide the highest possible level of diagnostic consultative service, while trying to balance optimal patient care with a cost-conscious approach to solving difficult diagnostic problems. Useful For: Establishing the diagnosis of an allergy to anchovy Defining the allergen responsible for eliciting signs and symptoms Identifying allergens: - Responsible for allergic disease and/or anaphylactic episode - To confirm sensitization prior to beginning immunotherapy - To investigate the specificity of allergic reactions to insect venom allergens, drugs, or chemical allergens Testing for IgE antibodies is not useful in patients previously treated with immunotherapy to determine if residual clinical sensitivity exists, or in patients in whom the medical management does not depend upon identification of allergen specificity. It is normally expressed in a wide variety of tissues, including the epithelium and stromal cells of the prostate, endometrium, ovary, and breast. Useful For: Identification of tumors that express androgen receptor Interpretation: this test does not include pathologist interpretation, only technical performance of the stain.

Use of continuous pulse oximetry has been previously associated with increased admission rates and increased length of stay. The collated comments along with the results of the evidence review were then presented to the members of the panel. Two rounds of Delphi voting took place via electronic submission of votes by the panel. Validity and feasibility of each item was assessed by the Delphi panel on a nine-point scale for each of the 11 items and the mean of each item was obtained. The aggregate score of the means of validity and feasibility decided the final five items. Sources American Academy of Pediatrics, Diagnosis and Management of Bronchiolitis, Subcommittee on Diagnosis and Management of Bronchiolitis, Pediatrics. Chest radiograph in the evaluation of first time wheezing episodes: review of current clinical efficacy. Dexamethasone in salbutamol-treated inpatients with acute bronchiolitis: A randomized, controlled trial. Respiratory syncytial virus bronchiolitis: a double-blind dexamethasone efficacy study. Diagnosis and Management of Bronchiolitis, Subcommittee on Diagnosis and Management of Bronchiolitis. Impact of pulse oximetry and oxygen therapy on length of stay in bronchiolitis hospitalizations. Longitudinal assessment of hemoglobin oxygen saturation in healthy infants during the first 6 months of age. Continuous versus intermittent pulse oximetry monitoring of children hospitalized for bronchiolitis. Clinical evaluation and imaging often provide additive information and should be assessed together to make a reliable diagnosis and to plan care. A task force made up of the Steering Committee and specialty council/center leadership convened, and its members also provided recommendations. Minamimoto R, Senda M, Terauchi T, Jinnouchi S, Inoue T, Iinuma T, Inoue T, Ito K, Iwata H, Uno K, Oku S, Oguchi K, Tsukamoto E, Nakashima R, Nishizawa S, Fukuda H, Murano T, Yoshida T. Revised American Thyroid Association Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer. The current and continuing role of ventilation-perfusion scintigraphy in evaluating patients with suspected pulmonary embolism. Diagnostic imaging and risk stratification of patients with acute pulmonary embolism. Basic pathologies of neurodegenerative dementias and their relevance for state-of-the-art molecular imaging studies. Towards a nosology for frontotemporal lobar degenerations-a meta-analysis involving 267 subjects. Amyloid-beta plaque growth in cognitively normal adults: longitudinal [11C]Pittsburgh compound B data. Hormonal therapy is standard for all patients with hormone receptor positive disease. The omission of sentinel lymph node biopsy in clinically node negative women 70 years of age treated with hormonal therapy does not result in increased rates of locoregional recurrence and does not impact breast cancer mortality. Patients 70 years of with early stage hormone receptor positive breast cancer and no palpable axillary lymph nodes can be safely treated without axillary staging. There is a low risk of metastases and also a risk of detecting findings unrelated to the melanoma. Imaging should be performed if there are concerning findings on history and physical exam, and such tests should be driven by symptoms. The Quality Committee received submissions from all six disease sites; however, because the list was limited to five measures, the Committee felt it was precluded from incorporating measures representing all disease sites. As a means of refining the list of Choosing Wisely measures, the Quality Committee elected to include the five measures impacting the largest number of patients.

However, the estimate from the female rats is based on a more robust and more informative data set, since liver tumors occurred only in the high dose group in males but occurred in all dosed groups in females. Cancer risk (unitless) is calculated from the cancer potency factor and dose as follows: Risk = Potency Factor (ng/kg/day)-1 x Dose (ng/kg/day) From above, the cancer potency factor for hepatocellular tumors in female rats is 9. There is uncertainty about chronic effects including carcinogenicity in other species. Uncertainties about the human relevance of effects seen in animals are inherent to all risk assessments based on animal data. Perfluorooctanoic acid induced developmental toxicity in the mouse is dependent on expression of peroxisome proliferator activated receptor-alpha. Mortality of employees of a perfluorooctanesulphonyl fluoride manufacturing facility. Pharmacokinetic modeling of saturable, renal resorption of Perfluoroalkyl acids in monkeys-Probing the determinants of long plasma half-lives. Perfluorooctane sulfonate influences feeding behavior and gut motility via the hypothalamus. Persistent organic pollutants and transthyretin-bound thyroxin in plasma of Inuit women of childbearing age. The role of hepatocyte nuclear factor 4-alpha in perfluorooctanoic acid- and perfluorooctanesulfonic acid-induced hepatocellular dysfunction. Estrogen-like activity of perfluoroalkyl acids in vivo and interaction with human and rainbow trout estrogen receptors in vitro. Tissue distribution of 35S-labelled perfluorooctane sulfonate in adult mice after oral exposure to a low environmentally relevant dose or a high experimental dose. Perfluorinated compounds are related to breast cancer risk in Greenlandic Inuit: A case control study. Gestational exposure to endocrine-disrupting chemicals and reciprocal social, repetitive, and stereotypic behaviors in 4- and 5-year-old children: the Home Study. Perfluoroalkyl and polyfluoroalkyl substances in the environment: terminology, classification, and origins. Chronic dietary toxicity and carcinogenicity study with potassium perfluorooctanesulfonate in Sprague Dawley rats. Levels and trends of poly- and perfluorinated compounds in the arctic environment. Rat and rabbit oral developmental toxicology studies with two perfluorinated compounds. The influence of endocrine disruptors in a selected population of infertile women. Correlation of endocrine disrupting chemicals serum levels and white blood cells gene expression of nuclear receptors in a population of infertile women. Fourth National Report on Human Exposure to Environmental Chemicals, Updated Tables, Volume 1. A critical review of perfluorooctanoate and perfluorooctanesulfonate exposure and immunological health conditions in humans. Effects of perfluorooctanesulfonate exposure on plasma lipid levels in the Inuit population of Nunavik (Northern Quebec). Fluorescence study on site-specific binding of perfluoroalkyl acids to human serum albumin. Exposure to polyfluoroalkyl chemicals during pregnancy is not associated with offspring age at menarche in a contemporary British cohort. A critical review and comparison with regulatory criteria and persistent lipophilic compounds. Further improvements in the plaque technique for detecting single antibody-forming cells. Thyroid function and plasma concentrations of polyhalogenated compounds in Inuit adults. Association between prenatal exposure to perfluorinated compounds and symptoms of infections at age 1-4years among 359 children in the Odense Child Cohort. Serum perfluorooctanoic acid and perfluorooctane sulfonate concentrations in relation to birth outcomes in the mid-Ohio Valley, 2005-2010. First year growth in relation to prenatal exposure to endocrine disruptors - a Dutch prospective cohort study.