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Sample records for primary hemochromatosis presented

  1. Hemochromatosis

    MedlinePlus

    Hemochromatosis is a disease in which too much iron builds up in your body. Your body needs iron but too much of it ... types of hemochromatosis. Primary hemochromatosis is an inherited disease. Secondary hemochromatosis is usually the result of something ...

  2. [Hereditary hemochromatosis: presenting manifestations and diagnostic delay].

    PubMed

    Gasser, B; Courtois, F; Hojjat-Assari, S; Sauleau, E A; Buffet, C; Brissot, P

    2014-03-01

    Hereditary hemochromatosis is characterized by an excessive absorption and progressive accumulation of iron in the liver, the pancreas, the heart, and the joints. Tiredness and joint manifestations occur usually before hepatopathy, diabetes or cardiopathy. Such common and unspecific symptoms seem to be largely unknown and important diagnostic delays have been reported. The aim of this study was to investigate the discovery circumstances and the diagnostic delay. A survey was carried out amongst French patients with C282Y homozygous hemochromatosis who were contacted through patients associations or blood centers. The questionnaire was answered by 374 patients. Mean age at diagnosis was 48.6±11.9years. In 53% of the cases, the serum level of ferritin was greater than 1000 μg/L. Diagnosis was based on family genetic survey (29%), or fortuitous analyses showing an abnormal serum ferritin (26%), or clinical manifestations (45%). Main complaints were joint pain, tiredness or liver disease. Only 2.1% consulted for diabetes, cardiopathy or changed complexion. Time to diagnosis was lower than 1 year for 98% of patients who presented with fatigue but from 1 to 15 years for 23.4% and 29% of patients who presented with arthropathy and hepatopathy, respectively. For 55% of patients, diagnosis was based on familial genetic survey or fortuitous abnormal results of blood samples. An initial serum level of ferritin greater than 1000 μg/L was a factor of severity for 50% of patient. These two elements must be taken into account to consider a population mass screening. Long time to diagnosis required a sensitization of the population to be aware of the clinical manifestations of hemochromatosis. Copyright © 2013 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  3. Hemochromatosis

    MedlinePlus

    ... Fax: 407–333–1284 Email: mail@ americanhs. org Internet: www. americanhs. org American Liver Foundation 39 Broadway, ... or 212–668–1000 Fax: 212–483–8179 Internet: www. liverfoundation. org 7 Hemochromatosis Iron Disorders Institute ...

  4. Hemochromatosis

    MedlinePlus

    ... in the body. It is also called iron overload. Causes Hemochromatosis may be a genetic disorder passed ... blood transfusions over time may lead to iron overload. Long-term alcohol use and other health conditions. ...

  5. The prevalence of primary hereditary hemochromatosis in central Anatolia.

    PubMed

    Karaca, Halit; Güven, Kadri; Önal, Müge; Gürsoy, Şebnem; Başkol, Mevlüt; Özkul, Yusuf

    2013-01-01

    Hereditary hemochromatosis is an autosomal recessive disorder associated with the HFE genes. Early identification and diagnosis is important as end stage organ damage may occur if treatment is delayed.. This study aimed to identify the prevalence of hereditary hemochromatosis in Kayseri and surroundings known as Central Anatolia. 2304 participants (1220 males, 1084 females) who were older then the age of 17 were included in the study conducted between December 2005 and December 2006 in Kayseri, Turkey. Transferin saturation was measured from overnight fasting blood samples. Serum iron, total iron binding capacity, and transferin saturation were measured. Serum ferritin levels and hereditary hemochromatosis genetic analysis were also performed after an overnight fasting blood samples from participants whose transferin saturation results were more than 50% in man and more than 45% in women. The homozygote C282Y mutation and heterozygote C282Y mutation prevalences were found as 0.08% (1/1220) and 0.08% (1/1220) in male participants, respectively. The heterozygote H63D mutation prevalence was found in 0.09% (1/1084) of female participants. Calculated prevalences in general population are as follows; The homozygote C282Y mutation prevalence is 0.043% (1/2304), the heterozygote C282Y mutation prevalence is 0.043% (1/2304) and the heterozygote H63D mutation prevalence is 0.043% (1/2304). The prevalence of hereditary hemochromatosis in Central Anatolia is 0.043% (1/2304). Because of the relatively low frequency, population screening studies are not cost-effective.

  6. Hereditary hemochromatosis.

    PubMed

    Walker, E M; Wolfe, M D; Norton, M L; Walker, S M; Jones, M M

    1998-01-01

    Genetic (hereditary) hemochromatosis is probably the most common autosomal recessive disorder found in white Americans, of whom about 5/1,000 (0.5 percent) are homozygous for the associated gene. The hemochromatosis gene is probably located close to the HLA-A locus on the short arm of chromosome 6. Homozygous individuals may develop severe and potentially lethal hemochromatosis, especially after age 39. Hereditary hemochromatosis involves an increased rate of iron absorption from the gut with subsequent progressive storage of iron in soft organs of the body. Excess iron storage eventually produces pituitary, pancreatic, cardiac, and liver dysfunction and death may result from cardiac arrhythmias, congestive heart failure, and/or hepatic failure or cancer. Early diagnosis can prevent these excess iron-induced problems. Iron overload owing to HLA-linked hereditary hemochromatosis can be distinguished from other causes of hemochromatosis by liver biopsies and interpretations. Patients at risk for genetic hemochromatosis should be screened, identified, and treated as early as age 20 to prevent or minimize the deadly complications of hemochromatosis. Population screening should include measurements of serum iron concentration, total iron binding capacity (TIBC), percent saturation of transferrin, and serum ferritin concentrations. Family members of hereditary hemochromatosis patients are at increased risk and should be tested. Screening, identification and early treatment (phlebotomies, sometimes in combination with the use of Desferal or other iron-chelating agents) may help prevent or reduce iron-related organ damage and premature deaths. Early diagnosis and treatment will reduce the population of aging individuals with severe, complicated hemochromatosis and dramatically reduce medical costs (billions of U.S. dollars per annum) associated with the management of this disease.

  7. Hemochromatosis and Iron Overload Screening (HEIRS) study design for an evaluation of 100,000 primary care-based adults.

    PubMed

    McLaren, Christine E; Barton, James C; Adams, Paul C; Harris, Emily L; Acton, Ronald T; Press, Nancy; Reboussin, David M; McLaren, Gordon D; Sholinsky, Phyliss; Walker, Ann P; Gordeuk, Victor R; Leiendecker-Foster, Catherine; Dawkins, Fitzroy W; Eckfeldt, John H; Mellen, Beverly G; Speechley, Mark; Thomson, Elizabeth

    2003-02-01

    The HEIRS Study will evaluate the prevalence, genetic and environmental determinants, and potential clinical, personal, and societal impact of hemochromatosis and iron overload in a multiethnic, primary care-based sample of 100,000 adults over a 5-year period. Participants are recruited from 5 Field Centers. Laboratory testing and data management and analysis are performed in a Central Laboratory and Coordinating Center, respectively. Participants undergo testing for serum iron measures and common mutations of the hemochromatosis gene ( ) on chromosome 6p and answer questions on demographics, health, and genetic testing attitudes. Participants with elevated values of transferrin saturation and serum ferritin and/or C282Y homozygosity are invited to undergo a comprehensive clinical examination (CCE), as are frequency-matched control subjects. These examinations provide data on personal and family medical history, lifestyle characteristics, physical examination, genetic counseling, and assessment of ethical, legal, and social implications. Primary and secondary causes of iron overload will be distinguished by clinical criteria. Iron overload will be confirmed by quantification of iron stores. Recruiting family members of cases will permit DNA analysis for additional genetic factors that affect iron overload. Of the first 50,520 screened, 51% are white, 24% are African American, 11% are Asian, 11% are Hispanic, and 3% are of other, mixed, or unidentified race; 63% are female and 37% are male. Information from the HEIRS Study will inform policy regarding the feasibility, optimal approach, and potential individual and public health benefits and risks of primary care-based screening for iron overload and hemochromatosis.

  8. The hemochromatosis protein HFE 20 years later: An emerging role in antigen presentation and in the immune system

    PubMed Central

    Chung, Jacqueline W.; Santos, Manuela M.

    2017-01-01

    Abstract Introduction Since its discovery, the hemochromatosis protein HFE has been primarily defined by its role in iron metabolism and homeostasis, and its involvement in the genetic disease termed hereditary hemochromatosis (HH). While HH patients are typically afflicted by dysregulated iron levels, many are also affected by several immune defects and increased incidence of autoimmune diseases that have thereby implicated HFE in the immune response. Growing evidence has supported an immunological role for HFE with recent studies describing HFE specifically as it relates to MHC I antigen presentation. Methods/Results Here, we present a comprehensive overview of the relationship between iron metabolism, HFE, and the immune system to better understand the origin and cause of immune defects in HH patients. We further describe the role of HFE in MHC I antigen presentation and its potential to impair autoimmune responses in homeostatic conditions, a mechanism which may be exploited by tumors to evade immune surveillance. Conclusion Overall, this increased understanding of the role of HFE in the immune response sets the stage for better treatment and management of HH and other iron‐related diseases, as well as of the immune defects related to this condition. PMID:28474781

  9. Acquired Hemochromatosis with Pronounced Pigment Deposition of the Upper Eyelids

    PubMed Central

    Morrison, Brian; Hu, Shasa

    2013-01-01

    Hemochromatosis may be classified into two groups: primary (hereditary) or secondary (acquired). The acquired type most commonly occurs after massive intake of iron supplements or blood transfusions and is also known as transfusional iron overload. In the past, hemochromatosis was usually recognized at an advanced stage by the classic triad of hyperpigmentation, diabetes mellitus (“bronze diabetes”), and hepatic cirrhosis. Cutaneous hyperpigmentation is present in 70 percent of patients due to two different mechanisms: (1) hemosiderin deposition resulting in diffuse, slate-gray darkening and (2) increased production of melanin in the epidermis. A 47-year-old woman who receives regular transfusions due to low iron and chronic, unresolving anemia and who subsequently developed pronounced hyperpigmentation of the upper eyelids is described. The presentation, diagnosis, pathogenesis, and treatment options of hyperpigmentation due to secondary hemochromatosis are discussed. PMID:24155994

  10. The myths and realities of hemochromatosis

    PubMed Central

    Beaton, Melanie D; Adams, Paul C

    2007-01-01

    Hemochromatosis is a common genetic condition and yet there are still a number of misperceptions surrounding the diagnosis and management of this condition. Hemochromatosis affects both men and women. Typical patients do not have alcoholism or viral hepatitis, and often have normal liver enzymes. Clinical expression is highly variable. Genetic testing is widely available and particularly useful in family studies. Hemochromatosis can be readily diagnosed and treated. The purpose of the present review is to address the medical myths and misconceptions of hemochromatosis. PMID:17299614

  11. Transferrin saturation phenotype and HFE genotype screening for hemochromatosis and primary iron overload: predictions from a model based on national, racial, and ethnic group composition in central Alabama.

    PubMed

    Barton, J C; Acton, R T

    2000-01-01

    There is interest in general population screening for hemochromatosis and other primary iron overload disorders, although not all persons are at equal risk. We developed a model to estimate the numbers of persons in national, racial, or ethnic population subgroups in Jefferson County, Alabama, who would be detected using transferrin saturation (phenotype) or HFE mutation analysis (genotype) screening. Approximately 62% are Caucasians, 37% are African Americans, and the remainder are Hispanics, Asians, or Native Americans. The predicted phenotype frequencies are greatest in a Caucasian subgroup, ethnicity unspecified, which consists predominantly of persons of Scotch and Irish descent (0.0065 men, 0.0046 women), and in African Americans (0.0089 men, 0.0085 women). Frequencies of the HFE genotype C282Y/C282Y > or = 0.0001 are predicted to occur only among Caucasians; the greatest frequency (0.0080) was predicted to occur in the ethnicity-unspecified Caucasian population. C282Y/C282Y frequency estimates were lower in Italian, Greek, and Jewish subgroups. There is excellent agreement in the numbers of the ethnicity-unspecified Caucasians who would be detected using phenotype and genotype criteria. Our model also indicates that phenotyping would identify more persons with primary iron overload than would genotyping in our Italian Caucasian, Hispanic, and African American subgroups. This is consistent with previous observations that indicate that primary iron overload disorders in persons of southern Italian descent and African Americans are largely attributable to non-HFE alleles. Because the proportions of population subgroups and their genetic constitution may differ significantly in other geographic regions, we suggest that models similar to the present one be constructed to predict optimal screening strategies for primary iron overload disorders.

  12. Diabetes in HFE Hemochromatosis

    PubMed Central

    Acton, Ronald T.

    2017-01-01

    Diabetes in whites of European descent with hemochromatosis was first attributed to pancreatic siderosis. Later observations revealed that the pathogenesis of diabetes in HFE hemochromatosis is multifactorial and its clinical manifestations are heterogeneous. Increased type 2 diabetes risk in HFE hemochromatosis is associated with one or more factors, including abnormal iron homeostasis and iron overload, decreased insulin secretion, cirrhosis, diabetes in first-degree relatives, increased body mass index, insulin resistance, and metabolic syndrome. In p.C282Y homozygotes, serum ferritin, usually elevated at hemochromatosis diagnosis, largely reflects body iron stores but not diabetes risk. In persons with diabetes type 2 without hemochromatosis diagnoses, serum ferritin levels are higher than those of persons without diabetes, but most values are within the reference range. Phlebotomy therapy to achieve iron depletion does not improve diabetes control in all persons with HFE hemochromatosis. The prevalence of type 2 diabetes diagnosed today in whites of European descent with and without HFE hemochromatosis is similar. Routine iron phenotyping or HFE genotyping of patients with type 2 diabetes is not recommended. Herein, we review diabetes in HFE hemochromatosis and the role of iron in diabetes pathogenesis in whites of European descent with and without HFE hemochromatosis. PMID:28331855

  13. Hemochromatosis and Vibrio vulnificus wound infections.

    PubMed

    Barton, James C; Acton, Ronald T

    2009-10-01

    There are several reports of persons with hemochromatosis and Vibrio vulnificus primary septicemia, but few accounts of persons with hemochromatosis and V. vulnificus wound infection. A 58-year-old white man developed infection of a forearm injury exposed to seawater in the Gulf of Mexico near the Alabama coast. At age 66, he was diagnosed to have hemochromatosis. Transferrin saturation was 89% and serum ferritin was 4761 pmol/L. HFE genotype was C282Y/C282Y. Serum levels of hepatic enzymes, glucose, IgG, IgA, and IgM, and blood levels of T, B, and natural killer cells were normal. We identified previous reports of only 2 similar cases: a woman from Alabama and a man from northern Australia. Mean age of the 3 subjects was 51 years at diagnosis of infection. Each had elevated serum iron measures or iron overload complications; both men were diagnosed to have hemochromatosis after they developed infection. Each of the 3 had recent exposure of a wound on an extremity to seawater, rapid development of a necrotizing soft tissue infection that required debridement and skin grafting, and positive wound or blood cultures. Each subject survived the infection. V. vulnificus wound infection occurs in some persons with hemochromatosis, but the risk of infection may be small. All patients with V. vulnificus infections should be evaluated for hemochromatosis, iron overload, and liver disorders.

  14. Acquired hemochromatosis with pronounced pigment deposition of the upper eyelids.

    PubMed

    Chacon, Anna H; Morrison, Brian; Hu, Shasa

    2013-10-01

    primary (hereditary) or secondary (acquired). The acquired type most commonly occurs after massive intake of iron supplements or blood transfusions and is also known as transfusional iron overload. In the past, hemochromatosis was usually recognized at an advanced stage by the classic triad of hyperpigmentation, diabetes mellitus ("bronze diabetes"), and hepatic cirrhosis. Cutaneous hyperpigmentation is present in 70 percent of patients due to two different mechanisms: (1) hemosiderin deposition resulting in diffuse, slate-gray darkening and (2) increased production of melanin in the epidermis. A 47-year-old woman who receives regular transfusions due to low iron and chronic, unresolving anemia and who subsequently developed pronounced hyperpigmentation of the upper eyelids is described. The presentation, diagnosis, pathogenesis, and treatment options of hyperpigmentation due to secondary hemochromatosis are discussed.

  15. Hereditary Hemochromatosis (For Parents)

    MedlinePlus

    ... buildup can be prevented. Doctors usually diagnose iron overload with these blood tests: serum ferritin : measures the ... has the disease. Treatment Doctors treat the iron overload from hereditary hemochromatosis by regularly drawing blood to ...

  16. Primary polycythaemia presenting with chorea.

    PubMed Central

    Borg-Costanzi, J. M.; Mohr, P. D.; Lewis, D.

    1981-01-01

    A case of primary polycythaemia presenting with severe chorea is reported and compared with previous cases. The aetiological factors of the chorea are discussed and the importance of early diagnosis stressed. PMID:7291101

  17. Hemochromatosis simulating rheumatoid arthritis: a case report.

    PubMed

    Barbosa, Fabíola Brasil; Callegari, Amanda; Sarinho, José Célso; Lucena, Juliana; Casagrande, Renielly; de Souza, Branca Dias Batista

    2014-01-01

    This is a report of a patient who had a previous diagnosis of rheumatoid arthritis, nonerosive, rheumatoid factor negative, that despite the therapeutic approach presented progressive worsening of the articular and general condition. After extensive research, she had a diagnosis of hemochromatosis. Joint symptoms are common manifestations in hemochromatosis. The arthropathy of hemochromatosis may resemble inflammatory arthropathy mimicking RA, particularly in the most common sites as 2nd and 3rd metacarpophalangeal. Radiologically are observed decreased joint space, subchondral sclerosis, cyst formation and chondrocalcinosis. Treatment with disease modifying drugs for rheumatoid arthritis tend to worsen the clinical picture, since the liver is the major site of deposition of iron in hemochromatosis and these medications are known to be hepatotoxic. Phlebotomy treatment for hemochromatosis is apparently ineffective in reversing the articular manifestations, which requires the association with iron chelating drugs. Due to the apparent difficulty in differentiating between the two diseases, a screening profile of iron in patients with rheumatoid arthritis with atypical progression is necessary.

  18. Hereditary hemochromatosis of tongue.

    PubMed

    Al Wayli, Hessa; Rastogi, Sanjay; Verma, Neha

    2011-01-01

    Hereditary hemochromatosis (HH) refers to several inherited disorders of iron metabolism leading to tissue iron overload. Classical HH is associated with mutations in HFE (C282Y homozygotes or C282Y/H63D compound heterozygotes) and is almost exclusively found in populations of northern European descent. Non-HFE-associated HH is caused by mutations in other recently identified genes involved in iron metabolism. Hepcidin is an iron regulatory hormone that inhibits ferroportin-mediated iron export from enterocytes and macrophages. Defective hepcidin gene expression or function may underlie most forms of HH. Target organs and tissues affected by HH include the liver, heart, pancreas, joints, and skin, with cirrhosis and diabetes mellitus representing late signs of disease in patients with markedly elevated liver iron concentration. Recently, we have encountered the rare representation of this disease of the oral cavity associated with generalized burning sensation of the tongue. The diagnosis was established accidently, from the lab investigations, otherwise the patient was healthy and free from classical signs and symptoms of the disease. The patient was adequately treated by phlebotomy. To conclude, all patients with a chief complaint of burning sensation of the oral cavity and tongue should be adequately screened for hereditary hemochromatosis to prevent the associated mortality and morbidity with the hemochromatosis. Copyright © 2011 Mosby, Inc. All rights reserved.

  19. Musculoskeletal disease burden of hereditary hemochromatosis.

    PubMed

    Sahinbegovic, Enijad; Dallos, Tomáš; Aigner, Elmar; Axmann, Roland; Manger, Bernhard; Englbrecht, Matthias; Schöniger-Hekele, Maximilian; Karonitsch, Thomas; Stamm, Tanja; Farkas, Martin; Karger, Thomas; Stölzel, Ulrich; Keysser, Gernot; Datz, Christian; Schett, Georg; Zwerina, Jochen

    2010-12-01

    To determine the prevalence, clinical picture, and disease burden of arthritis in patients with hereditary hemochromatosis. In this cross-sectional observational study of 199 patients with hemochromatosis and iron overload, demographic and disease-specific variables, genotype, and organ involvement were recorded. The prevalence, intensity, and localization of joint pain were assessed, and a complete rheumatologic investigation was performed. Radiographs of the hands, knees, and ankles were scored for joint space narrowing, erosions, osteophytes, and chondrocalcinosis. In addition, the number and type of joint replacement surgeries were recorded. Joint pain was reported by 72.4% of the patients. Their mean ± SD age at the time of the initial joint symptoms was 45.8 ± 13.2 years. If joint pain was present, it preceded the diagnosis of hemochromatosis by a mean ± SD of 9.0 ± 10.7 years. Bony enlargement was observed in 65.8% of the patients, whereas synovitis was less common (13.6%). Joint space narrowing and osteophytes as well as chondrocalcinosis of the wrist and knee joints were frequent radiographic features of hemochromatosis. Joint replacement surgery was common, with 32 patients (16.1%) undergoing total joint replacement surgery due to severe OA. The mean ± SD age of these patients was 58.3 ± 10.4 years at time of joint replacement surgery. Female sex, metacarpophalangeal joint involvement, and the presence of chondrocalcinosis were associated with a higher risk of early joint failure (i.e., the need for joint replacement surgery). Arthritis is a frequent, early, and severe symptom of hemochromatosis. Disease is not confined to involvement of the metacarpophalangeal joints and often leads to severe damage requiring the replacement of joints. Copyright © 2010 by the American College of Rheumatology.

  20. A diagnostic approach to hemochromatosis

    PubMed Central

    Tavill, Anthony S; Adams, Paul C

    2006-01-01

    In the present clinical review, a diagnostic approach to hemochromatosis is discussed from the perspective of two clinicians with extensive experience in this area. The introduction of genetic testing and large-scale population screening studies have broadened our understanding of the clinical expression of disease and the utility of biochemical iron tests for the detection of disease and for the assessment of disease severity. Liver biopsy has become more of a prognostic test than a diagnostic test. The authors offer a stepwise, diagnostic algorithm based on current evidence-based data, that they regard as most cost-effective. An early diagnosis can lead to phlebotomy therapy to prevent the development of cirrhosis. PMID:16955151

  1. Early presentation of primary glioblastoma.

    PubMed

    Faguer, R; Tanguy, J-Y; Rousseau, A; Clavreul, A; Menei, P

    2014-08-01

    Clinical and neuroimaging findings of glioblastomas (GBM) at an early stage have rarely been described and those tumors are most probably under-diagnosed. Furthermore, their genetic alterations, to our knowledge, have never been previously reported. We report the clinical as well as neuroimaging findings of four early cases of patients with GBM. In our series, early stage GBM occurred at a mean age of 57 years. All patients had seizures as their first symptom. In all early stages, MRI showed a hyperintense signal on T2-weighted sequences and an enhancement on GdE-T1WI sequences. A hyperintense signal on diffusion sequences with a low ADC value was also found. These early observed occurrences of GBM developed rapidly and presented the MRI characteristics of classic GBM within a few weeks. The GBM size was multiplied by 32 in one month. Immunohistochemical analysis indicated the de novo nature of these tumors, i.e. absence of mutant IDH1 R132H protein expression, which is a diagnostic marker of low-grade diffuse glioma and secondary GBM. A better knowledge of early GBM presentation would allow a more suitable management of the patients and may improve their prognosis. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  2. Neonatal hemochromatosis. Case series from Bahrain.

    PubMed

    Isa, Hasan M; Mohamed, Afaf M

    2013-12-01

    To review clinical presentations, diagnosis, response to treatment, and outcome of infants with neonatal hemochromatosis (NH). This is a retrospective review of all cases admitted to the Pediatric Department at Salmaniya Medical Center, Manama, Bahrain between March 2008 and May 2011. The diagnosis was based on serum iron and ferritin, alpha-fetoprotein levels (AFP), liver and buccal biopsies, and abdominal MRI scan. Ten patients (8 males and 2 females) were diagnosed with NH. Two patients were intrauterine growth restriction (IUGR) and 6 were preterm. The median birth weight was 1.700 grams. The median age at presentation was 16 days, and at diagnosis was 23 days. Two patients had positive consanguinity. Clinical presentations of the infants were hepatosplenomegaly (n=5), ascites (n=3), and hypoglycemia (n=6). All patients had raised ferritin levels, prolonged prothrombin time, and 9 patients had high serum iron and serum AFP. Abdominal MRI showed iron overload in the liver (n=8). Liver biopsies showed evidence of hemochromatosis (n=3). Buccal biopsies stained positive for iron (n=1). Eight patients received antioxidant therapy and survived. Two patients passed away. Neonatal hemochromatosis is a rare liver disease of newborns with a spectrum of clinical severity. Elevated serum ferritin and AFP support the diagnosis after excluding other causes of neonatal liver failure. The use of antioxidant therapy helps to improve the outcome.

  3. Pathophysiology of Hereditary Hemochromatosis

    PubMed Central

    Fleming, Robert E.; Britton, Robert S.; Waheed, Abdul; Sly, William S.; Bacon, Bruce R.

    2008-01-01

    Hereditary hemochromatosis (HH) encompasses several inherited disorders of iron homeostasis characterized by increased gastrointestinal iron absorption and tissue iron deposition. The most common form of this disorder is HFE-related HH, nearly always caused by homozygosity for the C282Y mutation. A substantial proportion of C282Y homozygotes do not develop clinically significant iron overload, suggesting roles for environmental factors and modifier genes in determining the phenotype. Recent studies have demonstrated that the pathogenesis of nearly all forms of HH involves inappropriately decreased expression of the iron-regulatory hormone hepcidin. Hepcidin serves to decrease the export of iron from reticuloendothelial cells and absorptive enterocytes. Thus, HH patients demonstrate increased iron release from these cell types, elevated circulating iron, and iron deposition in vulnerable tissues. The mechanism by which HFE influences hepcidin expression is an area of current investigation and may offer insights into the phenotypic variability observed in persons with mutations in HFE. PMID:16315135

  4. Hereditary hemochromatosis, iron, hepcidin, and coronary heart disease.

    PubMed

    Mascitelli, Luca; Goldstein, Mark R

    2014-03-01

    Mounting evidence suggests that a state of sustained iron depletion may exert a primary protective action against coronary heart disease. A persistent criticism of the iron hypothesis has been that atherosclerosis may not be a prominent feature of hereditary hemochromatosis. The essence of this criticism is that iron cannot be a significant factor in atherogenesis in those unaffected by inherited iron overload unless an increase in atherosclerosis is observed in hereditary hemochromatosis. However, the emerging details of the physiology of hepcidin, the key hormone in iron recycling, suggest a resolution of the apparent paradox of an important role for iron in atherogenesis in the possible absence of increased plaque burden in most types of hereditary hemochromatosis. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. [Association of hereditary hemochromatosis and pernicious anaemia].

    PubMed

    Attout, H; Guez, S; Sériès, C

    2004-10-01

    Hereditary hemochromatosis is inherited as an autosomal recessive trait. It is characterized by increased absorption of dietary iron. The association between pernicious anaemia and hereditary hemochromatosis has never been described. We report a case of paradoxical association of hereditary hemochromatosis and pernicious anaemia. It seems that pernicious anaemia may prevent manifestations of hemochromatosis. We suppose that this protective role is due to atrophic body gastritis with iron malabsorption.

  6. A national survey of hemochromatosis patients.

    PubMed

    Mainous, Arch G; Knoll, Michele E; Everett, Charles J; Hulihan, Mary M; Grant, Althea M; Garrison, Cheryl; Koenig, Gerald; Sayers, Cynthia; Allen, Kelsey W

    2012-01-01

    Hereditary hemochromatosis (HH) is a common genetic disease in the United States, but little is known about the diagnosis from the patient's perspective. The purpose of this study was to characterize the circumstances surrounding the diagnosis of HH and assess treatments and health information needs. We surveyed US adults aged 18 years and older who were diagnosed with HH after 1996. Response rate was 46%, with a total sample size of 979. Respondents were asked about the use of genetic and clinical markers in their diagnosis, current treatments, and health information needs. Results were stratified by age, education, and income status. Total of 90.0% of women and 75.5% of men were genetically tested for HH (P < .01). Approximately half (52.5%) were diagnosed by a gastroenterologist, hematologist, or other specialty physician and half were diagnosed by a primary care provider. Most of the respondents thought their HH had improved with the initial treatment and most patients were still receiving treatment for HH. Patient interest in learning more about specific hemochromatosis topics was generally high. Since the introduction of genetic identification of HH, these tests have been used in the diagnosis of the majority of patients. Primary care physicians may need to be more aware HH and strategies for diagnosis.

  7. Hemochromatosis caused by excessive vitamin iron intake.

    PubMed Central

    Hennigar, G. R.; Greene, W. B.; Walker, E. M.; de Saussure, C.

    1979-01-01

    Rare cases of hemochromatosis have been reported in patients who underwent prolonged oral iron therapy for hemolytic anemia or prolonged self-treatment with iron pills. A proportionately large segment of the South African Bantu tribe, who ingest large quantities of an alcoholic beverage brewed in iron pots, are found to have the disease. Reports of health fadists developing hemochromatosis due to excessive dietary iron intake, however, are extremely rare. This report presents clinical considerations and pathologic findings in a compulsive health fadist who consumed large numbers of vitamins containing iron. Clinical findings included the development and progression of cirrhosis of the liver, bronzing of the skin, and diabetes mellitus, all consistent with a diagnosis of hemochromatosis. Light microscopy of liver biopsies taken late in the course of the disease revealed a massive buildup of iron in the hepatocytes, less in the Kupffer cells, and sparse deposition in the epithelial cells of the bile duct. Minimal periportal fibrosis was noted. Electron microscopy showed numerous pleomorphic siderosomes with varying degrees of crystallization and ferritin attached at uniform intervals to the membranes of residual bodies. Abundant free ferritin was observed in most cells. The aggregated and membrane-associated ferritin was verified by non-dispersive x-ray analysis. An additional finding, noted only by electron microscopy, was the presence of many fat-storing cells of Ito, which are thought to be involved in the onset of fibrosis. Images Figure 11 Figure 12 Figure 5 Figure 6 Figure 1 Figure 2 Figure 3 Figure 4 Figure 7 Figure 8 Figure 9 Figure 10 PMID:474711

  8. Molecular Diagnostic and Pathogenesis of Hereditary Hemochromatosis

    PubMed Central

    Santos, Paulo C. J. L.; Krieger, Jose E.; Pereira, Alexandre C.

    2012-01-01

    Hereditary hemochromatosis (HH) is an autosomal recessive disorder characterized by enhanced intestinal absorption of dietary iron. Without therapeutic intervention, iron overload leads to multiple organ damage such as liver cirrhosis, cardiomyopathy, diabetes, arthritis, hypogonadism and skin pigmentation. Most HH patients carry HFE mutant genotypes: homozygosity for p.Cys282Tyr or p.Cys282Tyr/p.His63Asp compound heterozygosity. In addition to HFE gene, mutations in the genes that encode hemojuvelin (HJV), hepcidin (HAMP), transferrin receptor 2 (TFR2) and ferroportin (SLC40A1) have been associated with regulation of iron homeostasis and development of HH. The aim of this review was to identify the main gene mutations involved in the pathogenesis of type 1, 2, 3 and 4 HH and their genetic testing indication. HFE testing for the two main mutations (p.Cys282Tyr and p.His63Asp) should be performed in all patients with primary iron overload and unexplained increased transferrin saturation and/or serum ferritin values. The evaluation of the HJV p.Gly320Val mutation must be the molecular test of choice in suspected patients with juvenile hemochromatosis with less than 30 years and cardiac or endocrine manifestations. In conclusion, HH is an example that genetic testing can, in addition to performing the differential diagnostic with secondary iron overload, lead to more adequate and faster treatment. PMID:22408404

  9. Preliminary investigation of bottlenose dolphins (Tursiops truncatus) for hfe gene-related hemochromatosis.

    PubMed

    Phillips, Brianne E; Venn-Watson, Stephanie; Archer, Linda L; Nollens, Hendrik H; Wellehan, James F X

    2014-10-01

    Hemochromatosis (iron storage disease) has been reported in diverse mammals including bottlenose dolphins (Tursiops truncatus). The primary cause of excessive iron storage in humans is hereditary hemochromatosis. Most human hereditary hemochromatosis cases (up to 90%) are caused by a point mutation in the hfe gene, resulting in a C282Y substitution leading to iron accumulation. To evaluate the possibility of a hereditary hemochromatosis-like genetic predisposition in dolphins, we sequenced the bottlenose dolphin hfe gene, using reverse transcriptase-PCR and hfe primers designed from the dolphin genome, from liver of affected and healthy control dolphins. Sample size included two case animals and five control animals. Although isotype diversity was evident, no coding differences were identified in the hfe gene between any of the animals examined. Because our sample size was small, we cannot exclude the possibility that hemochromatosis in dolphins is due to a coding mutation in the hfe gene. Other potential causes of hemochromatosis, including mutations in different genes, diet, primary liver disease, and insulin resistance, should be evaluated.

  10. A case report of neonatal diabetes due to neonatal hemochromatosis.

    PubMed

    Cetinkaya, Semra; Kunak, Benal; Kara, Cengiz; Demirçeken, Fulya; Yarali, Neşe; Polat, Emine; Aycan, Zehra

    2010-05-01

    A 6-week-old girl, the first child of non-consanguineous parents, was admitted to the hospital for evaluation of vomiting. She was small for gestational age (1500 g). On admission, she weighed 1830 g, and appeared dehydrated. The blood glucose was 880 mg/dL. Insulin and C-peptide levels were <1 microIU/ml and 0.1 pmol/L, respectively. Antibodies of diabetes were negative. The serum triglyceride level was markedly elevated (5322 mg/dL). After a few days of insulin therapy, the triglyceride levels dramatically decreased, but cholestasis persisted. A liver biopsy revealed diffuse iron deposition and the diagnosis of neonatal hemochromatosis was established. In neonatal hemochromatosis, diabetes may occur as a result of iron deposition in the pancreas. The coexistence of neonatal diabetes secondary to neonatal hemochromatosis with a fatal course during the infancy period has not been previously reported. In this report, an infant with neonatal diabetes secondary to neonatal hemochromatosis is presented as the first case in the literature involving the coexistence of these two conditions.

  11. Systemic malignancies presenting as primary osteolytic lesion.

    PubMed

    Sirelkhatim, A; Kaiserova, E; Kolenova, A; Puskacova, J; Subova, Z; Petrzalkova, D; Banikova, K; Suvada, J; Sejnova, D

    2009-01-01

    The tumor formation may be the earliest manifestation preceeding other symptoms, signs and bone marrow evidence of systemic malignancy - leukemia/lymphoma. Here we present three cases of systemic malignancy in which bone lesions were the first manifested signs of the disease. All three cases were thought to be orthopedic cases and had been treated as so without genuing improvement. We would like to draw an attention to children who present with multifocal musculoskeletal pain and the importance of whole-body scaning. We describe interesting cases of diffuse large cell lymphoma and leukemia that initially presented as primary osteolytic bone lesion and discuss the differential diagnosis, literature review of non-Hodgkin's lymphoma arising in bone as the primary site (Tab. 1, Fig. 3, Ref. 18). Full Text (Free, PDF) www.bmj.sk.

  12. Rare HFE variants are the most frequent cause of hemochromatosis in non-c282y homozygous patients with hemochromatosis.

    PubMed

    Hamdi-Rozé, Houda; Beaumont-Epinette, Marie-Pascale; Ben Ali, Zeineb; Le Lan, Caroline; Loustaud-Ratti, Véronique; Causse, Xavier; Loreal, Olivier; Deugnier, Yves; Brissot, Pierre; Jouanolle, Anne-Marie; Bardou-Jacquet, Edouard

    2016-12-01

    p.Cys282Tyr (C282Y) homozygosity explains most cases of HFE-related hemochromatosis, but a significant number of patients presenting with typical type I hemochromatosis phenotype remain unexplained. We sought to describe the clinical relevance of rare HFE variants in non-C282Y homozygotes. Patients referred for hemochromatosis to the National Reference Centre for Rare Iron Overload Diseases from 2004 to 2010 were studied. Sequencing was performed for coding region and intronic flanking sequences of HFE, HAMP, HFE2, TFR2, and SLC40A1. Nine private HFE variants were identified in 13 of 206 unrelated patients. Among those, five have not been previously described: p.Leu270Argfs*4, p.Ala271Valfs*25, p.Tyr52*, p.Lys166Asn, and p.Asp141Tyr. Our results show that rare HFE variants are identified more frequently than variants in the other genes associated with iron overload. Rare HFE variants are therefore the most frequent cause of hemochromatosis in non-C282Y homozygote HFE patients. Am. J. Hematol. 91:1202-1205, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  13. Presentations of primary hypersomnia in Chinese children.

    PubMed

    Han, Fang; Lin, Ling; Li, Jing; Aran, Adi; Dong, Song X; An, Pei; Zhao, Long; Li, Ming; Li, Qian Y; Yan, Han; Wang, Jie S; Gao, Hui Y; Li, Mei; Gao, Zhan C; Strohl, Kingman P; Mignot, Emmanuel

    2011-05-01

    To retrospectively describe childhood presentations of primary hypersomnia with an emphasis on narcolepsy-cataplexy in a Chinese population. A total of 417 children (< 18 years old) successively presenting with complaints of hypersomnia without anatomic cause or sleep apnea risk were evaluated using the Stanford Sleep Inventory, human leukocyte antigen (HLA) DQB1*0602 typing, and MSLT recordings. CSF hypocretin-1 was measured in 47 cases to document hypocretin deficiency. A subgroup ("narcolepsy/hypocretin deficiency") with likely hypocretin deficiency (low hypocretin-1 or HLA positive with clear-cut cataplexy) was further examined for presentations prior to, around, or after puberty. Narcolepsy with (n = 361) or without (n = 17) cataplexy presented at an earlier age and with increased male predominance when compared to idiopathic hypersomnia (n = 39, P < 0.01). Nearly 70% of those with narcolepsy/hypocretin deficiency (n = 271) had disease onset before age 10 y, and 15% had onset before age 6, an unusually young age distribution. Onset was prior to puberty in 78% of cases. Clinical features were similar in presentations across puberty groups except for sleep paralysis, which increased in frequency with age/puberty. Mean sleep latency (MSL) decreased and the number of sleep onset REM periods (SOREMPs) increased with age/puberty, but MSLT diagnosis criteria (MSL ≤ 8 min, ≥ 2 SOREMPs) were similarly positive across groups. Familial clustering was present in only 1.7% of probands. In children presenting with a complaint of primary hypersomnia to a sleep clinic in China, 86% (361/417) meet criteria for narcolepsy with cataplexy. Puberty did not affect positivity on the MSLT as a diagnostic feature. Sleep paralysis was the only symptom that increased with increasing age. In addition, narcolepsy with cataplexy in our clinic population appeared to begin at a younger age than usually reported in other studies.

  14. Presentations of Primary Hypersomnia in Chinese Children

    PubMed Central

    Han, Fang; Lin, Ling; Li, Jing; Aran, Adi; Dong, Song X.; An, Pei; Zhao, Long; Li, Ming; Li, Qian Y.; Yan, Han; Wang, Jie S.; Gao, Hui Y.; Li, Mei; Gao, Zhan C.; Strohl, Kingman P.; Mignot, Emmanuel

    2011-01-01

    Objective: To retrospectively describe childhood presentations of primary hypersomnia with an emphasis on narcolepsy-cataplexy in a Chinese population. Methods: A total of 417 children (< 18 years old) successively presenting with complaints of hypersomnia without anatomic cause or sleep apnea risk were evaluated using the Stanford Sleep Inventory, human leukocyte antigen (HLA) DQB1*0602 typing, and MSLT recordings. CSF hypocretin-1 was measured in 47 cases to document hypocretin deficiency. A subgroup (“narcolepsy/hypocretin deficiency”) with likely hypocretin deficiency (low hypocretin-1 or HLA positive with clear-cut cataplexy) was further examined for presentations prior to, around, or after puberty. Results: Narcolepsy with (n = 361) or without (n = 17) cataplexy presented at an earlier age and with increased male predominance when compared to idiopathic hypersomnia (n = 39, P < 0.01). Nearly 70% of those with narcolepsy/hypocretin deficiency (n = 271) had disease onset before age 10 y, and 15% had onset before age 6, an unusually young age distribution. Onset was prior to puberty in 78% of cases. Clinical features were similar in presentations across puberty groups except for sleep paralysis, which increased in frequency with age/puberty. Mean sleep latency (MSL) decreased and the number of sleep onset REM periods (SOREMPs) increased with age/puberty, but MSLT diagnosis criteria (MSL ≤ 8 min, ≥ 2 SOREMPs) were similarly positive across groups. Familial clustering was present in only 1.7% of probands. Conclusion: In children presenting with a complaint of primary hypersomnia to a sleep clinic in China, 86% (361/417) meet criteria for narcolepsy with cataplexy. Puberty did not affect positivity on the MSLT as a diagnostic feature. Sleep paralysis was the only symptom that increased with increasing age. In addition, narcolepsy with cataplexy in our clinic population appeared to begin at a younger age than usually reported in other studies. Citation: Han

  15. Diagnosis of hepatic iron overload: a family study illustrating pitfalls in diagnosing hemochromatosis.

    PubMed

    Schranz, Melanie; Talasz, Heribert; Graziadei, Ivo; Winder, Thomas; Sergi, Consolato; Bogner, Klaus; Vogel, Wolfgang; Zoller, Heinz

    2009-03-01

    Recent identification of genetic variants in iron storage disease has changed the classification system and diagnostic algorithms for hemochromatosis. Clinical diagnosis of the disease requires phenotypic evidence of iron overload because the commonly disease-associated HFE genotypes have an incomplete penetrance. Furthermore, approximately 20% of patients with a clinical diagnosis of hemochromatosis have no disease-associated genotype, which underlines the importance of clear phenotypic criteria of hemochromatosis. A diagnosis of hemochromatosis cannot be made even in patients with liver cirrhosis simply on the basis of genetic testing that indicates that iron overload is the cause of the disease and not its consequence. Proper diagnosis requires integration of clinical presentation, family history, and the results of biochemical and histopathologic tests. Here we propose a rational diagnostic algorithm for hepatic iron overload syndromes and illustrate potential pitfalls by presenting a family study in a pedigree with rare HFE variants (H63D and E168Q), in cis on the same chromosome. Although the clinical suspicion of hemochromatosis was confirmed by histology, chemical analysis of liver tissue revealed a normal hepatic iron concentration, which is compatible with the genetic finding of 1 normal and 1 doubly mutated allele. In conclusion, clinical suspicion of hemochromatosis and elevated serum iron parameters should prompt HFE genotyping for C282Y and H63D. Should they be uninformative, further genetic tests should be recommended only if iron overload in liver tissue has been confirmed chemically.

  16. Bloodletting therapy in hemochromatosis: Does it affect trace element homeostasis?

    PubMed

    Bolann, Bjørn J; Distante, Sonia; Mørkrid, Lars; Ulvik, Rune J

    2015-01-01

    Hemochromatosis is the most common hereditary disorder in the Nordic population, if left untreated it can result in severe parenchymal iron accumulation. Bloodletting is mainstay treatment. Iron and trace elements partially share cellular uptake and transport mechanisms, and the aim of the present study was to see if bloodletting for hemochromatosis affects trace elements homeostasis. We recruited patients referred for diagnosis and treatment of hemochromatosis, four women and 22 men 23-68 years of age. Thirteen were C282Y homozygote, one was C282Y heterozygote, three were H63D homozygote, seven were compound heterozygote and two had none of the mutations above. Iron and liver function tests were performed; serum levels of trace elements were measured using inductively coupled plasma mass spectrometry. Results before the start of treatment and after normalization of iron parameters were compared. On completion of the bloodlettings the following average serum concentrations increased: Co from 5.6 to 11.5 nmol/L, serum Cu 16.2-17.6 μmol/L, Ni increased from 50.0 to 52.6 nmol/L and Sb from 13.2 to 16.3 nmol/L. Average serum Mn concentration declined from 30.2 to 28.3 nmol/L. All changes were statistically significant (by paired t-test). B, Ba, Cs, Mo, Se, Sr and Zn were not significantly changed. We conclude that bloodlettings in hemochromatosis lead to changes in trace element metabolism, including increased absorption of potentially toxic elements. Copyright © 2014 Elsevier GmbH. All rights reserved.

  17. Late presentation of primary pulmonary lymphangiectasis.

    PubMed Central

    Wagenaar, S S; Swierenga, J; Wagenvoort, C A

    1978-01-01

    Pulmonary lymphangiectasis can occur either as a primary change or secondary to chronic congestion. Primary lymphangiectasis is generally considered to occur exclusively in young children. This report describes three male patients, aged 13, 16, and 19 years, in whom the changes are limited to one lobe or to two lobes and the mediastinum. So far as could be ascertained these patients are the oldest reported. Lymphangiectasis should be considered in the clinical differential diagnosis of "pulmonary cysts" in children and young adults. Images PMID:746507

  18. Hereditary hemochromatosis: awareness and genetic testing acceptability in Western Romania.

    PubMed

    Neghina, Adriana Maria; Anghel, Andrei

    2010-12-01

    a public health strategy to promote early diagnosis of hemochromatosis gene (HFE)-related hemochromatosis (HFE-HH) largely depends on people's acceptance of available screening tests. The present study aimed at evaluating patient awareness of HFE-HH and their acceptance of DNA testing in western Romania. a total of 221 participants were randomly recruited from the ambulatory unit of the Emergency County Hospital in Timisoara, Romania. They received brief information on HFE-HH and were assessed for the signs and symptoms of hemochromatosis. HFE genotyping was offered to all of them. Only two cases (0.9%) had previous knowledge of HFE-HH. Twenty-one cases (9.5%) underwent genetic testing. Characteristics associated with test acceptance were age <45 years, male gender, and educational attainment. Acceptance was associated with a desire to know if they had HFE-HH (85.7%). The most prevalent refusal reason was a desire for more information (41%). larger educational programs are required to increase people's awareness about HFE-HH in western Romania. Nevertheless, within health care settings, the importance of disease detection and patient's educational background appear to be essential for achieving high rates of participation in the genetic test.

  19. Hemochromatosis

    MedlinePlus

    ... and S65C HFE gene mutations, diet, and life-style factors on iron status in the general Mediterranean ... Health Information Diabetes Digestive Diseases Kidney Disease Weight Management Liver Disease Urologic Diseases Endocrine Diseases Diet & Nutrition ...

  20. Hemochromatosis

    MedlinePlus

    ... Liver Function Tests Clinical Trials Liver Transplant FAQs Medical Terminology Diseases of the Liver Alagille Syndrome Alcohol-Related ... the Liver The Progression of Liver Disease FAQs Medical Terminology HOW YOU CAN HELP Sponsorship Ways to Give ...

  1. Hemochromatosis

    MedlinePlus

    ... Learn more about getting to NIH Get Email Alerts Receive automatic alerts about NHLBI related news and ... Connect With Us Contact Us Directly Get Email Alerts Receive automatic alerts about NHLBI related news and ...

  2. R2*-relaxometry of the pancreas in patients with human hemochromatosis protein associated hereditary hemochromatosis.

    PubMed

    Henninger, B; Rauch, S; Zoller, H; Plaikner, M; Jaschke, W; Kremser, C

    2017-04-01

    To evaluate pancreatic iron in patients with human hemochromatosis protein associated hereditary hemochromatosis (HHC) using R2* relaxometry. 81 patients (58 male, 23 female; median age 49.5, range 10-81 years) with HHC were retrospectively studied. All underwent 1.5T magnetic resonance imaging (MRI) of the abdomen. A fat-saturated multi-gradient echo sequence with 12 echoes (TR=200ms; TE-initial 0.99ms; Delta-TE 1.41ms; 12 echoes; flip-angle: 20°) was used for the R2* quantification of the liver and the pancreas. Parameter maps were analyzed using regions of interest (3 in the liver and 2 in the pancreas) and R2* values were correlated. 59/81 patients had a liver R2*≥70 1/s of which 10/59 patients had a pancreas R2*≥50 1/s. No patient presented with a liver R2*<70 1/s and pancreas R2*≥50 1/s. All patients with pancreas R2* values≥50 1/s had liver R2* values≥70 1/s. ROC analysis resulted in a threshold of 209.4 1/s for liver R2* values to identify HFE positive patients with pancreas R2* values≥50 1/s with a median specificity of 78.87% and a median sensitivity of 90%. In patients with HHC R2* relaxometry of the pancreas should be performed when liver iron overload is present and can be omitted in cases with no sign of hepatic iron. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Primary appendicular adenocarcinoma presenting as haematuria

    PubMed Central

    Amr, Bassem; Santana-Vaz, Natasha; Munir, Komal

    2014-01-01

    Adenocarcinoma of the vermiform appendix is a rare malignant neoplasm of the gastrointestinal tract encountered rarely within general surgical practice. We present the case of a 49-year-old man who, while undergoing investigations for haematuria, was diagnosed with an appendicular adenocarcinoma following bladder biopsy. Consequently he underwent right hemicolectomy and partial cystectomy followed by adjuvant chemotherapy. By discussing this case we hope to raise awareness within the medical profession of this rare presentation so that it may be considered within clinicians’ differential diagnoses. PMID:25358831

  4. Primary energy: Present status and future perspectives

    NASA Astrophysics Data System (ADS)

    Thielheim, K. O.

    A survey of the base-load energy sources available to humans is presented, starting from the point of view that all energy used is ultimately derived from nuclear processes within the sun. Specific note is made of European energy options, noting the large dependence on imported oil. Detailed exploration of available nuclear fuel resources is carried out, with attention given to fission, fusion, and breeder reactor plants and to the state-of-the-art and technology for each. The problems of nuclear waste disposal are discussed, and long term burial in salt domes is outlined as a satisfactory method of containing the materials for acceptable periods of time. The CO2-greenhouse effect hazards caused by increased usage of coal-derived fuels are considered and precautions to be taken on a global scale to ameliorate the warming effects are recommended. The limitations to hydropower are examined, as are those of tidal power. Solar cells are projected to be produced in GW quantities by the year 2000, while wind-derived electricity is predicted to provide a minimum of 5% of the world energy needs in the future.

  5. Evaluation of a workplace hemochromatosis screening program.

    PubMed

    Stave, G M; Mignogna, J J; Powell, G S; Hunt, C M

    1999-05-01

    Hemochromatosis is a common inherited disorder of iron metabolism with significant health consequences for the employed population. Although screening for hemochromatosis has been recommended, workplace screening programs remain uncommon. In the first year of a newly initiated corporate screening program, 1968 employees were tested. The screening algorithm included measurement of serum iron and transferrin and subsequent ferritin levels in those employees with elevated iron/transferrin ratios. Thirteen percent of men and 21% of women had elevated iron/transferrin ratios. Of these, 14 men and 2 women had elevated ferritin levels. Of these 16, three had liver biopsies and all three have hemochromatosis. The cost of the screening program was $27,850. The cost per diagnosis was $9283 and the cost per year of life saved was $928. These costs compare very favorably with other common workplace screening programs. Several barriers to obtaining definitive diagnoses on all patients with a positive screening result were identified; strategies to overcome these barriers would further enhance the cost effectiveness of the program. We conclude that workplace hemochromatosis screening is highly cost effective and should be incorporated into health promotion/disease prevention programs.

  6. Non-Coding Keratin Variants Associate with Liver Fibrosis Progression in Patients with Hemochromatosis

    PubMed Central

    Lunova, Mariia; Guldiken, Nurdan; Lienau, Tim C.; Stickel, Felix; Omary, M. Bishr

    2012-01-01

    Background Keratins 8 and 18 (K8/K18) are intermediate filament proteins that protect the liver from various forms of injury. Exonic K8/K18 variants associate with adverse outcome in acute liver failure and with liver fibrosis progression in patients with chronic hepatitis C infection or primary biliary cirrhosis. Given the association of K8/K18 variants with end-stage liver disease and progression in several chronic liver disorders, we studied the importance of keratin variants in patients with hemochromatosis. Methods The entire K8/K18 exonic regions were analyzed in 162 hemochromatosis patients carrying homozygous C282Y HFE (hemochromatosis gene) mutations. 234 liver-healthy subjects were used as controls. Exonic regions were PCR-amplified and analyzed using denaturing high-performance liquid chromatography and DNA sequencing. Previously-generated transgenic mice overexpressing K8 G62C were studied for their susceptibility to iron overload. Susceptibility to iron toxicity of primary hepatocytes that express K8 wild-type and G62C was also assessed. Results We identified amino-acid-altering keratin heterozygous variants in 10 of 162 hemochromatosis patients (6.2%) and non-coding heterozygous variants in 6 additional patients (3.7%). Two novel K8 variants (Q169E/R275W) were found. K8 R341H was the most common amino-acid altering variant (4 patients), and exclusively associated with an intronic KRT8 IVS7+10delC deletion. Intronic, but not amino-acid-altering variants associated with the development of liver fibrosis. In mice, or ex vivo, the K8 G62C variant did not affect iron-accumulation in response to iron-rich diet or the extent of iron-induced hepatocellular injury. Conclusion In patients with hemochromatosis, intronic but not exonic K8/K18 variants associate with liver fibrosis development. PMID:22412904

  7. Counselling in Primary Care: Past, Present, and Future.

    ERIC Educational Resources Information Center

    Eatock, John

    2000-01-01

    Presents a brief history of the growth of counseling in primary care. Discusses the challenges for primary care counselors and counseling, as well as the need for coordination, regulation and management. Also discusses the imperative for research support and the unique nature of counseling in primary care including challenges to its survival. (MKA)

  8. Hereditary hemochromatosis as a risk factor for joint replacement surgery.

    PubMed

    Sahinbegovic, Enijad; Dallos, Tomás; Aigner, Elmar; Axmann, Roland; Engelbrecht, Matthias; Schöniger-Hekele, Maximilian; Karonitsch, Thomas; Farkas, Martin; Karger, Thomas; Willeit, Johann; Stölzel, Ulrich; Keysser, Gernot; Datz, Christian; Kiechl, Stefan; Schett, Georg; Zwerina, Jochen

    2010-07-01

    Hemochromatosis is an inherited disease with iron overload and joint involvement resembling osteoarthritis. To determine the rate of joint replacement surgery in patients with hemochromatosis, we performed a cross-sectional cohort study. A total of 199 individuals with hereditary hemochromatosis were included. The prevalence of joint replacement surgery in hip, knee, and ankle joints because of secondary osteoarthritis was assessed. Data were compared with 917 healthy subjects from the population-based Bruneck study. A total of 32 of 199 individuals with hemochromatosis received joint replacement surgery with a total number of 52 joints replaced. Compared with expected rates in healthy individuals, patients with hemochromatosis had a significantly higher risk for joint replacement surgery (odds ratio 9.0; confidence interval, 4.6-17.4). Joint replacement occurred significantly earlier in life in patients with hemochromatosis; 21.9% of the patients with hemochromatosis and 1.7% of healthy individuals required joint replacement before the age of 50 years (P=.0027). Moreover, patients with hemochromatosis were more likely to require multiple joint replacements (8.5%) than the control group (expected rate 0.3%; P=.0001). Hemochromatosis is a risk factor for joint replacement surgery because of severe secondary osteoarthritis. Copyright 2010 Elsevier Inc. All rights reserved.

  9. [Molecular genetic diagnostics and screening of hereditary hemochromatosis].

    PubMed

    Zlocha, J; Kovács, L; Pozgayová, S; Kupcová, V; Durínová, S

    2006-06-01

    Hereditary hemochromatosis is considered one of the most common hereditary diseases in population of Caucasian origin. In recent years, a candidate gene for HLA-linked hemochromatosis, HFE, has been cloned, and a single G-to-A mutation resulting in a cysteine-to-tyrosine substitution (C282Y) has been identified in up to 80% of study patients with type 1 hereditary hemochromatosis. The purpose of the paper was to confirm the importance of genetic testing for HFE mutations in making the diagnosis of hemochromatosis and find out a suitable diagnostic algorithm for the indication of this form of diagnostics in patients suspected of hereditary hemochromatosis. The examination of C282Y mutation was conducted in 500 subjects. The most frequent indications for DNA analysis were hepatopathy of unknown ethiology, liver cirrhosis, diabetes mellitus, bronze skin pigmentation in connection with high serum iron concentration, elevated transferrin saturation and elevated serum ferritin levels. In our group of patients, 29 homozygotes and 75 heterozygotes for C282Y mutation were identified, 10 patients carried both C282Y and H63D mutations of HFE gene (compound heterozygotes), whereas in 386 subjects the mutation was not found. The genotype-phenotype correlation showed that 22 homozygotes had liver affection proved by imaging and/or histologic methods. Except the liver disorders, the most common symptoms of these patients were type 2 diabetes mellitus or glucose tolerance disorder (10 patients), arthritis or joint pain (9 patients) and cardiovascular disorders, such as cardiomyopathy (2 patients). Bronze skin pigmentation was present in 9 homozygotes. Transferin saturation values were significantly higher in homozygotes for C282Y mutation as compared to C282Y heterozygotes (p < 0.001), C282Y/H63D compound heterozygotes (p < 0.05) or wild type subjects (p < 0.001) respectively. Also serum ferritin levels were significantly higher in homozygotes for C282Y mutation as compared to C

  10. [Molecular genetic analysis and clinical aspects of patients with hereditary hemochromatosis].

    PubMed

    Lange, U; Teichmann, J; Dischereit, G

    2014-08-01

    The purpose of the study was to perform a molecular genetic analysis and to document clinical aspects in patients with hereditary hemochromatosis. The study included 33 outpatients (23 males average age 50.6 years and 10 females average age 60.6 years) with a disorder of iron metabolism (transferrin saturation > 75 %) as confirmation of hemochromatosis who were subjected to molecular genetic and clinical analyses. A homozygous mutation of the hemochromatosis (HFE) gene (C282YY) was detected in 63.6 %, a compound heterozygous mutation (C282Y/H63D) in 30.3% and no mutation of the HFE gene was detected in 6.1 %. The following organ manifestations could be objectified: arthralgia (78.8 %), liver disease (39.9 %), skin hyperpigmentation (30.3 %), osteoporosis (24.2 %), diabetes mellitus (24.2 %) and cardiomyopathy (12.1 %). Comparison between patients with heterozygous and homozygous hemochromatosis revealed the following differences: compound heterozygote patients presented less frequently with osteoarthritis of the metacarpophalangeal (MCP) joints and hands (85.7 %/71.4 % homozygotes vs. 60 %/60 % heterozygotes). Osteoarthritis of the shoulder joints and osteoporosis as well as hypothyroidism were more frequent in compound heterozygote patients, whereas osteoarthritis of the knee and hip joints as well as liver disease were more common in homozygote patients. No differences between both groups were seen with respect to the clinical manifestations of cardiomyopathy and diabetes mellitus. Prevalent causes of death in hereditary hemochromatosis are heart failure, liver disease (cirrhosis and hepatocellular carcinoma) and portal hypertension. Therefore, an early diagnosis, adequate therapy and genetic screening of family members are of great importance. Medicinal treatment will only effectively prevent deleterious organ involvement and subsequent complications if initiated at an early stage. Furthermore, an overview of the current data is given.

  11. Toll-like receptor 4 gene polymorphism modulates phenotypic expression in patients with hereditary hemochromatosis.

    PubMed

    Krayenbuehl, Pierre-Alexandre; Hersberger, Martin; Truninger, Kaspar; Müllhaupt, Beat; Maly, Friedrich E; Bargetzi, Mario; Schulthess, Georg

    2010-07-01

    Clinical penetrance of hereditary hemochromatosis is highly variable. We hypothesized that it might be modified by factors involved in the cellular immune response, such as toll-like receptors (TLRs) or nucleotide oligomerization domain proteins (NODs). Clinical expression of hemochromatosis was assessed as a function of TLR4, TLR9, and NOD2 polymorphisms in 99 homozygous carriers of the HFE C282Y mutation with mild-to-severe iron overload. Thirteen (13%) of the 99 hemochromatosis patients were heterozygous for a TLR4 Asp299Gly polymorphism and 86 (87%) were TLR4 wild-type-only carriers. Clinical expression of hemochromatosis was observed more frequently in carriers of the TLR4 polymorphism (100%) than in TLR4 wild-type carriers (56%, P = 0.002). This was based on higher prevalences of liver disease (92 vs. 45%, P = 0.002) and arthropathy of metacarpophalangeal joints (69 vs. 35%, P = 0.018) in TLR4 polymorphism carriers. The finding was strengthened by the strong association of TLR4 polymorphism with liver fibrosis in the subgroup of 52 patients who underwent a liver biopsy (P = 0.011). The TLR4 polymorphism did, however, not correlate with body iron overload. The study results remained significant in multiple regression analyses after excluding possible confounding effects, such as age, sex, alcohol, or meat intake, and in the subgroup of 84 patients presenting as the first members of their families. TLR4 Asp299Gly polymorphism modulates clinical expression in patients with hereditary hemochromatosis. The polymorphism does not correlate with iron overload suggesting that TLR4 plays a role in an inflammatory process arising from toxic effects of iron accumulation.

  12. Sporadic Jakob-Creutzfeldt Disease Presenting as Primary Progressive Aphasia

    PubMed Central

    Johnson, David Y.; Dunkelberger, Diana L.; Henry, Maya; Haman, Aissatou; Greicius, Michael D.; Wong, Katherine; DeArmond, Stephen J.; Miller, Bruce L.; Gorno-Tempini, Maria Luisa; Geschwind, Michael D.

    2015-01-01

    Objective To report the clinical, neuropsychological, linguistic, imaging, and neuropathological features of a unique case of sporadic Jakob-Creutzfeldt disease in which the patient presented with a logopenic variant of primary progressive aphasia. Design Case report. Setting Large referral center for atypical memory and aging disorders, particularly Jakob-Creutzfeldt disease. Patient Patient presenting with logopenic variant primary progressive aphasia initially thought to be due to Alzheimer disease. Results Despite the long, slow 3.5-year course, the patient was shown to have pathology-proven sporadic Jakob-Creutzfeldt disease. Conclusions These findings expand the differential of primary progressive aphasia to include prion disease. PMID:23400721

  13. African Primary Care Research: Quantitative analysis and presentation of results

    PubMed Central

    Ogunbanjo, Gboyega A.

    2014-01-01

    Abstract This article is part of a series on Primary Care Research Methods. The article describes types of continuous and categorical data, how to capture data in a spreadsheet, how to use descriptive and inferential statistics and, finally, gives advice on how to present the results in text, figures and tables. The article intends to help Master's level students with writing the data analysis section of their research proposal and presenting their results in their final research report. PMID:26245435

  14. Juvenile primary extranasopharyngeal angiofibroma, presenting as cheek swelling

    PubMed Central

    Nandhini, J; Ramasamy, S; Kaul, Ronak Nazir; Austin, Ravi David

    2018-01-01

    Angiofibroma is a locally advancing immensely vascular tumor that essentially arises from the nasopharynx. The clinical characteristics of extranasopharyngeal angiofibroma (ENA) do not accord to that of nasopharyngeal angiofibroma and can present a diagnostic confront. We describe a case of primary juvenile ENA in a 19-year-old patient who presented with a rapidly enlarging mass of the cheek region. The case is unusual because of its anatomic location. The diagnostic and management particulars are sketched. PMID:29491611

  15. Primary human immunodeficiency virus infection presenting as elevated aminotransferases.

    PubMed

    Chen, Yi-Jan; Tsai, Hung-Chin; Cheng, Ming-Fang; Lee, Susan Shin-Jung; Chen, Yao-Shen

    2010-06-01

    Primary human immunodeficiency virus type 1 (HIV-1) infection is often under-diagnosed because of its nonspecific presentations. Elevated aminotransferase levels is one of its clinical manifestations, but is infrequently reported in the literature. The objective of this study was to investigate cases of elevated aminotransferases as a manifestation of primary HIV-1 infection. A retrospective chart review from October 1990 to May 2009 of HIV-1 infected patients in a registered database at a tertiary hospital was conducted to identify patients diagnosed with primary HIV-1 infection. An elevated aminotransferase level was broadly defined as above-normal values of alanine or aspartate aminotransferases. Acute hepatitis markers were determined using stored serum samples. Twenty-three of the 827 (2.8%) patients were identified as having a primary HIV-1 infection. All were male, with a median age of 26 years (range, 19-77 years), and the majority were men who had sex with men (19/23, 82.6%). The most common clinical manifestations were fever (95.7%), elevated aminotransferases (65.2%), fatigue (47.8%), and pharyngitis (47.8%). The median CD4 lymphocyte count was 374/μL (range, 109-674/μL) and the median log HIV viral load was 5.0 (range, 4.3-5.9). For the 15 patients with abnormal liver function tests, the median aspartate aminotransferase level was 112 U/L (range, 62-969 U/L) and the median alanine aminotransferase level was 146 U/L (range, 42-1,110 U/L). Elevated aminotransferases may be an initial manifestation of primary HIV infection and is more common than expected. Primary HIV-1 infection should be one of the differential diagnoses considered in young men presenting with unexplained, new-onset liver function impairment. Copyright © 2010 Taiwan Society of Microbiology. Published by Elsevier B.V. All rights reserved.

  16. Harlequin color change after abdominal paracentesis in a newborn with neonatal hemochromatosis.

    PubMed

    Cizmeci, Mehmet N; Alagoz, Demet; Avsar, Mehmet I; Alis, Gulten; Tutanc, Murat

    2014-01-01

    Harlequin color change is a distinctive cutaneous phenomenon presenting as a well-demarcated color change, with half of the body displaying erythema and the other half pallor. Only a few cases have been reported, possibly because of under-recognition. Recognition of this benign, self-limited condition may enable physicians to avoid unnecessary interventions. Herein we describe a neonate with nonimmune hydrops fetalis due to neonatal hemochromatosis who developed Harlequin color change after abdominal paracentesis. © 2014 Wiley Periodicals, Inc.

  17. Primary peritoneal serous carcinoma presenting as inflammatory breast cancer.

    PubMed

    Khalifeh, Ibrahim; Deavers, Michael T; Cristofanilli, Massimo; Coleman, Robert L; Malpica, Anais; Gilcrease, Michael Z

    2009-01-01

    Metastasis to the breast from extramammary malignancies is rare. Nevertheless, its recognition is important because the prognosis and treatment differ from that of primary breast cancer. We report a unique case of primary peritoneal serous carcinoma that initially presented as inflammatory breast cancer. The patient received neoadjuvant chemotherapy for breast cancer and subsequently underwent bilateral total mastectomy and bilateral sentinel lymph node biopsy. She was found to have extensive intralymphatic carcinoma in both breasts, with only focal minimal breast parenchymal involvement, and residual metastatic carcinoma in bilateral sentinel lymph nodes. Further work-up revealed pelvic ascites and omental nodularities. The patient underwent laparoscopic bilateral salpingo-oophorectomy, which revealed high-grade serous carcinoma involving both ovaries and fallopian tubes. Molecular testing of tumor from the ovary and axillary lymph node showed an identical pattern of allelic loss, confirming a common origin for both tumors. To our knowledge, this is the first reported case of an extramammary primary malignancy that not only presented as inflammatory breast cancer but also was diagnosed and initially treated as such.

  18. Primary tuberculosis clinically presenting as gingival enlargement: a case report.

    PubMed

    Sharma, C G Dileep; Pradeep, A R; Karthikeyan, B V

    2006-11-01

    Tuberculosis is a chronic systemic granulomatous disease which rarely affects the oral cavity. Oral lesions can be either primary or secondary to systemic tuberculosis, the former being rare. This is a never-before reported case of primary tuberculosis presenting as a localized diffuse gingival enlargement in an 11-year-old Indian female patient. The diagnosis was reached through identification of positive histopathological features, Tuberculin test results, presence of anti-tubercular antibodies confirmed by a polymerase chain reaction. In view of the recent increase in the incidence of tuberculosis and the prevalence of the same, it is reasonable to include tuberculosis in the differential diagnosis of gingival enlargements. This is essential to avoid any serious complications for both the clinician and patient due to a delay in the diagnosis of such a rare but plausible oral condition.

  19. Recurrent pregnancy-induced diabetes insipidus in a woman with hemochromatosis.

    PubMed

    Krysiak, Robert; Kobielusz-Gembala, Iwona; Okopien, Boguslaw

    2010-01-01

    Diabetes insipidus is a rare disorder in pregnant women, predating pregnancy or appearing for the first time during gestation. In pregnancy it usually affects women with HELLP syndrome or acute fatty liver of pregnancy and results from the reduced hepatic degradation of placental vasopressinase leading to its increased activity. Although infiltrative diseases have been found to cause diabetes insipidus in non-pregnant population, very few studies showed that these disorders may manifest for the first time during gestation. We describe here the case of transient diabetes insipidus in two subsequent pregnancies of a female with hemochromatosis. The first symptoms of this disease appeared for the first time at the beginning of the third trimester of her second pregnancy, and diagnosis was established on the basis of typical clinical presentation, confirmed by a water deprivation test. Diabetes insipidus resulted from the increased activity of vasopressinase, caused by hemochromatosis-induced liver dysfunction, the presence of which was confirmed between the pregnancies by liver biopsy and identification of the HFE gene mutation. Subsequent desferrioxamine treatment resulted in a less severe clinical course of diabetes insipidus in the last patient's pregnancy. In both pregnancies, the patient was successfully treated with oral desmopressin, which is resistant to degradation by placental vasopressinase. Although unrecognized pituitary disorders may pose a serious health problem to the mother and fetus, hemochromatosis-induced diabetes insipidus, as the case of our patient demonstrates, if effectively diagnosed and treated, cannot be regarded as a contraindication for pregnancy.

  20. Clinical manifestations of hemochromatosis in HFE C282Y homozygotes identified by screening.

    PubMed

    McLaren, Gordon D; McLaren, Christine E; Adams, Paul C; Barton, James C; Reboussin, David M; Gordeuk, Victor R; Acton, Ronald T; Harris, Emily L; Speechley, Mark R; Sholinsky, Phyliss; Dawkins, Fitzroy W; Snively, Beverly M; Vogt, Thomas M; Eckfeldt, John H

    2008-11-01

    Patients with hemochromatosis may suffer organ damage from iron overload, often with serious clinical consequences. To assess prevalences of self-reported symptoms and clinical signs and conditions in persons homozygous for the hemochromatosis gene (HFE) mutation (C282Y) identified by screening. Participants were adults 25 years of age or older enrolled in the Hemochromatosis and Iron Overload Screening (HEIRS) Study. C282Y homozygotes (n=282) were compared with control participants without the HFE C282Y or H63D alleles (ie, wild type/wild type; n=364). Previously diagnosed C282Y homozygotes and newly diagnosed homozygotes with elevated serum ferritin levels had higher prevalences of certain symptoms such as chronic fatigue (OR 2.8; 95% CI 1.34 to 5.95, and OR 2.0; 95% CI 1.07 to 3.75, respectively), and had more hyperpigmentation on physical examination (OR 4.7; 95% CI 1.50 to 15.06, and OR 3.7; 95% CI 1.10 to 12.16, respectively) and swelling or tenderness of the second and third metacarpophalangeal joints (OR 4.2; 95% CI 1.37 to 13.03, and OR 3.3; 95% CI 1.17 to 9.49, respectively) than control subjects. Joint stiffness was also more common among newly diagnosed C282Y homozygotes with elevated serum ferritin than among control subjects (OR 2.7; 95% CI 1.38 to 5.30). However, the sex- and age-adjusted prevalences of self-reported symptoms and signs of liver disease, heart disease, diabetes and most other major clinical manifestations of hemochromatosis were similar in C282Y homozygotes and control subjects. Some symptoms and conditions associated with hemochromatosis were more prevalent among C282Y homozygotes identified by screening than among control subjects, but prevalences of most outcomes were similar in C282Y homozygotes and controls in this primary care-based study.

  1. Clinical manifestations of hemochromatosis in HFE C282Y homozygotes identified by screening

    PubMed Central

    McLaren, Gordon D; McLaren, Christine E; Adams, Paul C; Barton, James C; Reboussin, David M; Gordeuk, Victor R; Acton, Ronald T; Harris, Emily L; Speechley, Mark R; Sholinsky, Phyliss; Dawkins, Fitzroy W; Snively, Beverly M; Vogt, Thomas M; Eckfeldt, John H

    2008-01-01

    BACKGROUND: Patients with hemochromatosis may suffer organ damage from iron overload, often with serious clinical consequences. OBJECTIVE: To assess prevalences of self-reported symptoms and clinical signs and conditions in persons homozygous for the hemochromatosis gene (HFE) mutation (C282Y) identified by screening. METHODS: Participants were adults 25 years of age or older enrolled in the Hemochromatosis and Iron Overload Screening (HEIRS) Study. C282Y homozygotes (n=282) were compared with control participants without the HFE C282Y or H63D alleles (ie, wild type/wild type; n=364). RESULTS: Previously diagnosed C282Y homozygotes and newly diagnosed homozygotes with elevated serum ferritin levels had higher prevalences of certain symptoms such as chronic fatigue (OR 2.8; 95% CI 1.34 to 5.95, and OR 2.0; 95% CI 1.07 to 3.75, respectively), and had more hyperpigmentation on physical examination (OR 4.7; 95% CI 1.50 to 15.06, and OR 3.7; 95% CI 1.10 to 12.16, respectively) and swelling or tenderness of the second and third metacarpophalangeal joints (OR 4.2; 95% CI 1.37 to 13.03, and OR 3.3; 95% CI 1.17 to 9.49, respectively) than control subjects. Joint stiffness was also more common among newly diagnosed C282Y homozygotes with elevated serum ferritin than among control subjects (OR 2.7; 95% CI 1.38 to 5.30). However, the sex- and age-adjusted prevalences of self-reported symptoms and signs of liver disease, heart disease, diabetes and most other major clinical manifestations of hemochromatosis were similar in C282Y homozygotes and control subjects. CONCLUSIONS: Some symptoms and conditions associated with hemochromatosis were more prevalent among C282Y homozygotes identified by screening than among control subjects, but prevalences of most outcomes were similar in C282Y homozygotes and controls in this primary care-based study. PMID:19018338

  2. Molecular basis of HFE-hemochromatosis

    PubMed Central

    Vujić, Maja

    2014-01-01

    Iron-overload disorders owing to genetic misregulation of iron acquisition are referred to as hereditary hemochromatosis (HH). The most prevalent genetic iron overload disorder in Caucasians is caused by mutations in the HFE gene, an atypical MHC class I molecule. Recent studies classified HFE/Hfe-HH as a liver disease with the primarily failure in the production of the liver iron hormone hepcidin in hepatocytes. Inadequate hepcidin expression signals for excessive iron absorption from the diet and iron deposition in tissues causing multiple organ damage and failure. This review focuses on the molecular actions of the HFE/Hfe and hepcidin in maintaining systemic iron homeostasis and approaches undertaken so far to combat iron overload in HFE/Hfe-HH. In the light of the recent investigations, novel roles of extra-hepatocytic Hfe are discussed raising a question to the relevance of the multipurpose functions of Hfe for the understanding of HH-associated pathologies. PMID:24653703

  3. Molecular basis of HFE-hemochromatosis.

    PubMed

    Vujić, Maja

    2014-01-01

    Iron-overload disorders owing to genetic misregulation of iron acquisition are referred to as hereditary hemochromatosis (HH). The most prevalent genetic iron overload disorder in Caucasians is caused by mutations in the HFE gene, an atypical MHC class I molecule. Recent studies classified HFE/Hfe-HH as a liver disease with the primarily failure in the production of the liver iron hormone hepcidin in hepatocytes. Inadequate hepcidin expression signals for excessive iron absorption from the diet and iron deposition in tissues causing multiple organ damage and failure. This review focuses on the molecular actions of the HFE/Hfe and hepcidin in maintaining systemic iron homeostasis and approaches undertaken so far to combat iron overload in HFE/Hfe-HH. In the light of the recent investigations, novel roles of extra-hepatocytic Hfe are discussed raising a question to the relevance of the multipurpose functions of Hfe for the understanding of HH-associated pathologies.

  4. Primary Jejunal Adenocarcinoma Presenting as Bilateral Ovarian Metastasis

    PubMed Central

    Ofori, Emmanuel; Ramai, Daryl; Papafragkakis, Charilaos; Changela, Kinesh; Krishnaiah, Mahesh

    2017-01-01

    Small intestinal tumors are rare with adenocarcinoma of the small intestine accounting for less than 2% of all gastrointestinal cancers. Primary jejunal adenocarcinoma constitutes a minute portion of small intestine adenocarcinomas. Clinically, this cancer presents at latter stages of its progression, mainly due to vague and non-specific symptoms, and the difficulty encountered in accessing the jejunum on upper endoscopy. Diagnosis of jejunal adenocarcinoma is usually inconclusive with the use of computed tomography (CT) scan, small bowel series, or upper endoscopy. Laparoscopy followed by frozen section biopsy provides a definitive diagnosis. In the past decade, balloon-assisted enteroscopy (BAE) and capsule endoscopy have become popular as useful modalities for diagnosing small bowel diseases. Wide excisional jejunectomy is the only treatment option with an estimated 5-year survival of 40-65%. Physicians are advised to suspect jejunal adenocarcinoma as a differential diagnosis in patients who present with non-specific symptoms of abdominal pain, nausea, vomiting, weight loss, anemia, gastrointestinal bleeding or signs of small bowel obstruction. We present a rare case of a 37-year-old woman with suspected bilateral ovarian masses, which was immunohistochemically confirmed as primary jejunal adenocarcinoma with bilateral ovarian metastasis. PMID:29317945

  5. Primary Jejunal Adenocarcinoma Presenting as Bilateral Ovarian Metastasis.

    PubMed

    Ofori, Emmanuel; Ramai, Daryl; Papafragkakis, Charilaos; Changela, Kinesh; Krishnaiah, Mahesh

    2017-12-01

    Small intestinal tumors are rare with adenocarcinoma of the small intestine accounting for less than 2% of all gastrointestinal cancers. Primary jejunal adenocarcinoma constitutes a minute portion of small intestine adenocarcinomas. Clinically, this cancer presents at latter stages of its progression, mainly due to vague and non-specific symptoms, and the difficulty encountered in accessing the jejunum on upper endoscopy. Diagnosis of jejunal adenocarcinoma is usually inconclusive with the use of computed tomography (CT) scan, small bowel series, or upper endoscopy. Laparoscopy followed by frozen section biopsy provides a definitive diagnosis. In the past decade, balloon-assisted enteroscopy (BAE) and capsule endoscopy have become popular as useful modalities for diagnosing small bowel diseases. Wide excisional jejunectomy is the only treatment option with an estimated 5-year survival of 40-65%. Physicians are advised to suspect jejunal adenocarcinoma as a differential diagnosis in patients who present with non-specific symptoms of abdominal pain, nausea, vomiting, weight loss, anemia, gastrointestinal bleeding or signs of small bowel obstruction. We present a rare case of a 37-year-old woman with suspected bilateral ovarian masses, which was immunohistochemically confirmed as primary jejunal adenocarcinoma with bilateral ovarian metastasis.

  6. Increased duodenal DMT-1 expression and unchanged HFE mRNA levels in HFE-associated hereditary hemochromatosis and iron deficiency.

    PubMed

    Byrnes, V; Barrett, S; Ryan, E; Kelleher, T; O'Keane, C; Coughlan, B; Crowe, J

    2002-01-01

    HFE-associated hereditary hemochromatosis is characterized by imbalances of iron homeostasis and alterations in intestinal iron absorption. The identification of the HFE gene and the apical iron transporter divalent metal transporter-1, DMT-1, provide a direct method to address the mechanisms of iron overload in this disease. The aim of this study was to evaluate the regulation of duodenal HFE and DMT-1 gene expression in HFE-associated hereditary hemochromatosis. Small bowel biopsies and serum iron indices were obtained from a total of 33 patients. The study population comprised 13 patients with hereditary hemochromatosis (C282Y homozygous), 10 patients with iron deficiency anemia, and 10 apparently healthy controls, all of whom were genotyped for the two common mutations in the HFE gene (C282Y and H63D). Total RNA was isolated from tissue and amplified via RT-PCR for HFE, DMT-1, and the internal control GAPDH. DMT-1 protein expression was additionally assessed by immunohistochemistry. Levels of HFE mRNA did not differ significantly between patient groups (P = 0.09), specifically between C282Y homozygotes and iron deficiency anemic patients, when compared to controls (P = 0.09, P = 0.9, respectively). In contrast, DMT-1 mRNA levels were at least twofold greater in patients with hereditary hemochromatosis and iron deficiency anemia when compared to controls (P = 0.02, P = 0.01, respectively). Heightened DMT-1 protein expression correlated with mRNA levels in all patients. Loss of HFE function in hereditary hemochromatosis is not derived from inhibition of its gene expression. DMT-1 expression in C282Y homozygote subjects is consistent with the hypothesis of a "paradoxical" duodenal iron deficiency in hereditary hemochromatosis. The observed twofold upregulation of the DMT-1 is consistent with the slow but steady increase in body iron stores observed in those presenting with clinical features of hereditary hemochromatosis.

  7. Prevalence of H63D, S65C, and C282Y hereditary hemochromatosis gene variants in Madeira Island (Portugal).

    PubMed

    Spínola, Carla; Brehm, António; Spínola, Hélder

    2011-01-01

    Hereditary HFE Hemochromatosis is an inherited disorder of iron metabolism that results from mutations in the HFE gene. Almost all patients with hereditary hemochromatosis show a C282Y mutation in homozygosity or in compound heterozygosity with H63D. Also, the mutation S65C has been shown to be associated to a milder iron overload. Since allele and genotype frequencies of these three variants of the HFE gene vary between populations, the determination of their prevalence in Madeira Island will clarify the population susceptibility to hereditary hemochromatosis. One hundred and fifty-four samples from Madeira Island were genotyped for the three most common HFE gene mutations, H63D, C282Y, and S65C, by polymerase chain reaction followed by restriction fragment length polymorphism analysis. Results have shown a prevalence of 20.5%, 0.33%, and 1% for H63D, C282Y, and S65C, respectively. Accordingly to our estimates, both genotypes associated to hereditary hemochromatosis, C282Y homozygotes and C282/H63D compound heterozygotes, could be present in Madeira Island population in 1,648 individuals, which represents 0.65% of the total population.

  8. Primary Gastric Lymphoma Presenting as Acute Pancreatitis: A Case Report.

    PubMed

    Raj, Mithun; Ghoshal, Uday C; Choudhuri, Gourdas; Mohindra, Samir

    2013-07-10

    Diffuse large B-cell lymphoma is the commonest form of non-Hodgkin lymphoma. Gastro-intestinal tract and bone marrow are common extra-nodal sites of lymphomatous involvement. A 54-year-old woman presented with acute onset epigastric pain. On evaluation, raised serum amylase and radiological features of acute pancreatitis were detected. Gastroscopy revealed thickened folds in distal stomach, which on histopathology revealed large B-cell lymphoma. Subsequently, the patient developed extra-hepatic biliary obstruction due to peripancreatic lymph nodal mass that was relieved with plastic biliary stenting. Subsequent chemotherapy regime directed against lymphoma led to resolution of lymphoma. In this patient , pancreatitis was the initial presentation of primary gastric lymphoma, which has not been commonly reported and therefore should be considered in the etiological workup.

  9. Rare Presentation of Primary Extramedullary Plasmacytoma as Lip Lesion.

    PubMed

    Him, Mali; Meier, Maggie; Mehta, Vikas

    2017-01-01

    Malignant plasma cell proliferation can be presented as part of disseminated disease of multiple myeloma, as solitary plasmacytoma of bone, or in soft tissue as extramedullary plasmacytoma. Extramedullary plasmacytomas represented approximately 3% of all plasma cell proliferation. Approximately 80% of extramedullary plasmacytomas occur in the head and neck region while the other 4% occur in the skin and to a lesser extent in the lip. In this paper, we report a rare case of primary cutaneous plasmacytoma involving the lip in a 65-year-old male. The patient presented with a nonhealing lower lip sore for the past 3 years. Upon further workup, there was no evidence of multiple myeloma or light chain disease. The patient was treated with radiation therapy and his last follow-up revealed no evidence of multiple myeloma or light chain disease.

  10. Rare Presentation of Primary Extramedullary Plasmacytoma as Lip Lesion

    PubMed Central

    Meier, Maggie; Mehta, Vikas

    2017-01-01

    Malignant plasma cell proliferation can be presented as part of disseminated disease of multiple myeloma, as solitary plasmacytoma of bone, or in soft tissue as extramedullary plasmacytoma. Extramedullary plasmacytomas represented approximately 3% of all plasma cell proliferation. Approximately 80% of extramedullary plasmacytomas occur in the head and neck region while the other 4% occur in the skin and to a lesser extent in the lip. In this paper, we report a rare case of primary cutaneous plasmacytoma involving the lip in a 65-year-old male. The patient presented with a nonhealing lower lip sore for the past 3 years. Upon further workup, there was no evidence of multiple myeloma or light chain disease. The patient was treated with radiation therapy and his last follow-up revealed no evidence of multiple myeloma or light chain disease. PMID:28409043

  11. Molecular Subgroup of Primary Prostate Cancer Presenting with Metastatic Biology.

    PubMed

    Walker, Steven M; Knight, Laura A; McCavigan, Andrena M; Logan, Gemma E; Berge, Viktor; Sherif, Amir; Pandha, Hardev; Warren, Anne Y; Davidson, Catherine; Uprichard, Adam; Blayney, Jaine K; Price, Bethanie; Jellema, Gera L; Steele, Christopher J; Svindland, Aud; McDade, Simon S; Eden, Christopher G; Foster, Chris; Mills, Ian G; Neal, David E; Mason, Malcolm D; Kay, Elaine W; Waugh, David J; Harkin, D Paul; Watson, R William; Clarke, Noel W; Kennedy, Richard D

    2017-10-01

    Approximately 4-25% of patients with early prostate cancer develop disease recurrence following radical prostatectomy. To identify a molecular subgroup of prostate cancers with metastatic potential at presentation resulting in a high risk of recurrence following radical prostatectomy. Unsupervised hierarchical clustering was performed using gene expression data from 70 primary resections, 31 metastatic lymph nodes, and 25 normal prostate samples. Independent assay validation was performed using 322 radical prostatectomy samples from four sites with a mean follow-up of 50.3 months. Molecular subgroups were identified using unsupervised hierarchical clustering. A partial least squares approach was used to generate a gene expression assay. Relationships with outcome (time to biochemical and metastatic recurrence) were analysed using multivariable Cox regression and log-rank analysis. A molecular subgroup of primary prostate cancer with biology similar to metastatic disease was identified. A 70-transcript signature (metastatic assay) was developed and independently validated in the radical prostatectomy samples. Metastatic assay positive patients had increased risk of biochemical recurrence (multivariable hazard ratio [HR] 1.62 [1.13-2.33]; p=0.0092) and metastatic recurrence (multivariable HR=3.20 [1.76-5.80]; p=0.0001). A combined model with Cancer of the Prostate Risk Assessment post surgical (CAPRA-S) identified patients at an increased risk of biochemical and metastatic recurrence superior to either model alone (HR=2.67 [1.90-3.75]; p<0.0001 and HR=7.53 [4.13-13.73]; p<0.0001, respectively). The retrospective nature of the study is acknowledged as a potential limitation. The metastatic assay may identify a molecular subgroup of primary prostate cancers with metastatic potential. The metastatic assay may improve the ability to detect patients at risk of metastatic recurrence following radical prostatectomy. The impact of adjuvant therapies should be assessed in

  12. Unusual Origin and Rare Presentation of Primary Cardiac Lymphoma

    PubMed Central

    Mohamed, Amir; Cherian, Sanjay; El-Ashmawy, Ahmed; Abdelmoneim, Salah Eldin; Soliman, Maher; Abu-Rayan, Mohamed; Kalangos, Afksendyios

    2011-01-01

    Non-Hodgkin lymphoblastic lymphomas are very uncommon tumors that rarely involve the heart; however, when they do, they typically cause cardiac symptoms. Herein, we describe the case of a young woman who presented with respiratory symptoms. These were caused by a high-grade lymphoblastic lymphoma, which originated in the left inferior pulmonary vein and extended into the left atrium. The tumor was surgically debulked, but it recurred in 1 month, and the patient underwent chemotherapy. Six months later, she had recurrent respiratory symptoms, and echocardiography revealed a persistent mass in the left lower lobar vein. A modified chemotherapy regimen led to complete resolution of the tumor within 2 months. We are unaware of other reports of a primary cardiac non-Hodgkin lymphoblastic lymphoma with this unusual site of origin and rare manifestation of symptoms. PMID:21841872

  13. [Palliative care in Primary Care: presentation of a case].

    PubMed

    Álvarez-Cordovés, M M; Mirpuri-Mirpuri, P G; Gonzalez-Losada, J; Chávez-Díaz, B

    2013-10-01

    We present a case of a patient diagnosed with glioblastoma multiforme refractory to treatment. Glioblastoma multiforme is the most common primary brain tumour and unfortunately the most aggressive, with an estimated mortality of about 90% in the first year after diagnosis. In our case the patient had reached a stage of life where quality of life was importsnt, with palliative care being the only recourse. The family is the mainstay in the provision of care of terminally ill patients, and without their active participation it would be difficult to achieve the objectives in patient care. We must also consider the family of the terminally ill in our care aim, as its members will experience a series of changes that will affect multiple areas where we should take action. Copyright © 2012 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

  14. Primary Visual Cortex Represents the Difference Between Past and Present

    PubMed Central

    Nortmann, Nora; Rekauzke, Sascha; Onat, Selim; König, Peter; Jancke, Dirk

    2015-01-01

    The visual system is confronted with rapidly changing stimuli in everyday life. It is not well understood how information in such a stream of input is updated within the brain. We performed voltage-sensitive dye imaging across the primary visual cortex (V1) to capture responses to sequences of natural scene contours. We presented vertically and horizontally filtered natural images, and their superpositions, at 10 or 33 Hz. At low frequency, the encoding was found to represent not the currently presented images, but differences in orientation between consecutive images. This was in sharp contrast to more rapid sequences for which we found an ongoing representation of current input, consistent with earlier studies. Our finding that for slower image sequences, V1 does no longer report actual features but represents their relative difference in time counteracts the view that the first cortical processing stage must always transfer complete information. Instead, we show its capacities for change detection with a new emphasis on the role of automatic computation evolving in the 100-ms range, inevitably affecting information transmission further downstream. PMID:24343889

  15. Primary angioplasty: the past, the present and the future.

    PubMed

    Oomman, A; Ramachandran, P

    2001-09-01

    Primary angioplasty (PTCA) in acute myocardial infarction has many theoretical advantages including better antegrade flow and reduced intracranial haemorrhage. However the improvement in the mortality and morbidity of primary angioplasty in the randomized trials from sophisticated centres has not been translated to the community setting. Primary PTCA is a suitable alternative to thrombolytic therapy if performed in a timely fashion by persons skilled in the procedure in a suitable laboratory. It is also recommended in patients with cardiogenic shock and in those with contraindications to thrombolytic therapy. Combination of thrombolytics and glycoprotein IIb/IIIa inhibitors with primary angioplasty may form the reperfusion strategy of the future.

  16. Primary breast lymphoma presenting as non-healing axillary abscess

    PubMed Central

    Anele, Chukwuemeka; Phan, Yih Chyn; Wong, Suanne; Poddar, Anil

    2015-01-01

    A 67-year-old woman with non-insulin dependent diabetes mellitus with a history consistent with a right axillary abscess, presented to her general practitioner (GP). A diagnosis of folliculitis was made and the GP started a course of flucloxacillin. Despite antibiotics, the patient's symptoms worsened and the abscess increased in size. This prompted her GP to perform an incision and drainage procedure of the abscess. The practice nurse subsequently oversaw the follow-up care of the wound. Two months after the incision and drainage, and after regular wound dressing, the patient was referred to the acute surgical team with a complicated, non-healing right axillary abscess cavity and associated generalised right breast cellulitis. There was no history of breast symptoms prior to the onset of the axillary abscess. The patient underwent wound debridement, washout and application of negative pressure vacuum therapy. Biopsies revealed primary breast lymphoma (B-cell). She underwent radical chemotherapy and is currently in remission. PMID:26446318

  17. Primary breast lymphoma presenting as non-healing axillary abscess.

    PubMed

    Anele, Chukwuemeka; Phan, Yih Chyn; Wong, Suanne; Poddar, Anil

    2015-10-07

    A 67-year-old woman with non-insulin dependent diabetes mellitus with a history consistent with a right axillary abscess, presented to her general practitioner (GP). A diagnosis of folliculitis was made and the GP started a course of flucloxacillin. Despite antibiotics, the patient's symptoms worsened and the abscess increased in size. This prompted her GP to perform an incision and drainage procedure of the abscess. The practice nurse subsequently oversaw the follow-up care of the wound. Two months after the incision and drainage, and after regular wound dressing, the patient was referred to the acute surgical team with a complicated, non-healing right axillary abscess cavity and associated generalised right breast cellulitis. There was no history of breast symptoms prior to the onset of the axillary abscess. The patient underwent wound debridement, washout and application of negative pressure vacuum therapy. Biopsies revealed primary breast lymphoma (B-cell). She underwent radical chemotherapy and is currently in remission. 2015 BMJ Publishing Group Ltd.

  18. Spontaneous haemothorax: an unusual presentation of primary lung cancer.

    PubMed Central

    Chou, S. H.; Cheng, Y. J.; Kao, E. L.; Chai, C. Y.

    1993-01-01

    An unusual case of spontaneous haemothorax caused by a subpleural primary lung cancer is reported. Tumour invasion of the pulmonary vessels and visceral pleura was the possible cause. Images PMID:8296269

  19. Primary School Children's Collaboration: Task Presentation and Gender Issues.

    ERIC Educational Resources Information Center

    Fitzpatrick, Helen; Hardman, Margaret

    2000-01-01

    Explores the characteristics of social interaction during an English language based task in the primary classroom, and the role of the computer in structuring collaboration when compared to a non-computer mode. Explains that seven and nine year old boys and girls (n=120) completed a computer and non-computer task. (CMK)

  20. Epidemiology of paediatric presentations with musculoskeletal problems in primary care.

    PubMed

    Tan, Albert; Strauss, Victoria Y; Protheroe, Joanne; Dunn, Kate M

    2018-02-06

    Musculoskeletal disease is a common cause of morbidity, but there is a paucity of musculoskeletal research focusing on paediatric populations, particularly in primary care settings. In particular, there is limited information on population consultation frequency in paediatric populations, and frequency varies by age and sex. Few studies have examined paediatric musculoskeletal consultation frequency for different body regions. The objective was to determine the annual consultation prevalence of regional musculoskeletal problems in children in primary care. Musculoskeletal codes within the Read morbidity Code system were identified and grouped into body regions. Consultations for children aged three to seventeen in 2006 containing these codes were extracted from recorded consultations at twelve general practices contributing to a general practice consultation database (CiPCA). Annual consultation prevalence per 10,000 registered persons for the year 2006 was determined, stratified by age and sex, for problems in individual body regions. Over 8 % (8.27%, 95% CI 7.86 to 8.68%) of the 16,862 children consulted with a musculoskeletal problem during 2006. Annual consultation prevalence for any musculoskeletal problem was significantly higher in males than females (male: female prevalence ratio 1.18, 95% CI 1.06 to 1.31). Annual consultation prevalence increased with age and the most common body regions consulted for were the foot, knee and back all of which had over 100 consultations (109, 104 and 101 respectively) per 10,000 persons per year. This study provides new and detailed information on patterns of paediatric musculoskeletal consultations in primary care. Musculoskeletal problems in children are varied and form a significant part of the paediatric primary care workload. The findings of this study may be used as a resource for planning future studies.

  1. Malignant Melanoma Presenting as a Mediastinal Malignant Melanoma Presenting as a Mediastinal Unknown Primary Origin?

    PubMed

    Pujani, Mukta; Hassan, Mohd Jaseem; Jetley, Sujata; Raina, Prabhat Kumar; Kumar, Mukesh

    2017-01-01

    The most common site of primary malignant melanoma is the skin, however, virtually any organ system may be involved. Metastatic melanoma of unknown primary origin accounts for approximately 2-6% of all melanoma cases. The mediastinum as the site for malignant melanoma is extremely rare, both as a primary or metastatic lesion. Primary malignant melanoma of mediastinum is very rare with only a handful of reports in the literature. We hereby report a rare case of malignant melanoma of mediastinum in a 31 year old male who was initially misdiagnosed on fine needle aspiration cytology as adenocarcinoma for which he received chemotherapy with clinical deterioration. Even on extensive meticulous search, no primary was discovered.

  2. Two middle-age-onset hemochromatosis patients with heterozygous mutations in the hemojuvelin gene in a Chinese family.

    PubMed

    Li, Shufeng; Xue, Jun; Chen, Baojun; Wang, Qiwei; Shi, Minke; Xie, Xiaojing; Zhang, Liang

    2014-04-01

    Hereditary hemochromatosis is a disorder characterized by enhanced intestinal absorption of dietary iron. Here, we report a heterozygous genotype at two mutation sites in hemojuvelin (HJV) present in two brothers with middle-age-onset hemochromatosis in a Chinese family. To date, only homozygous or compound heterozygous states of HJV gene have been reported as associated with iron overload. However, the patients here were heterozygous for two mutations in one HJV allele in cis: a premature termination mutation (962G>A and 963C>A; C321X) and a mutation in the signal peptide (18G>C; Q6H). Previously unrecognized environmental or other genetic factors may have interacted with the heterozygous genotype in these patients.

  3. Diplopia as the primary presentation of foodborne botulism.

    PubMed

    Khakshoor, Hamid; Moghaddam, Ali Akbar Saber; Vejdani, Amir Hossein; Armstrong, Blair K; Moshirfar, Majid

    2012-05-01

    Foodborne botulism is a serious condition caused by Clostridium botulinum neurotoxin. Clinically, botulism presents as bilateral cranial nerve neuropathy and descending paralysis. We report a unique presentation of botulism to remind clinicians of this potentially fatal condition. In this observational case report initial evaluation showed only esodeviation. This progressed to unilateral cranial nerve six (CN VI) paresis along with systemic signs. Clinical diagnosis was made based on in-depth history and concurrent symptoms in three other patients. Foodborne botulism presenting as diplopia and unilateral motility deficits is rare and can represent a diagnostic and therapeutic challenge to the ophthalmologist.

  4. Diplopia as the primary presentation of foodborne botulism

    PubMed Central

    Khakshoor, Hamid; Moghaddam, Ali Akbar Saber; Vejdani, Amir Hossein; Armstrong, Blair K.; Moshirfar, Majid

    2012-01-01

    Foodborne botulism is a serious condition caused by Clostridium botulinum neurotoxin. Clinically, botulism presents as bilateral cranial nerve neuropathy and descending paralysis. We report a unique presentation of botulism to remind clinicians of this potentially fatal condition. In this observational case report initial evaluation showed only esodeviation. This progressed to unilateral cranial nerve six (CN VI) paresis along with systemic signs. Clinical diagnosis was made based on in-depth history and concurrent symptoms in three other patients. Foodborne botulism presenting as diplopia and unilateral motility deficits is rare and can represent a diagnostic and therapeutic challenge to the ophthalmologist. PMID:22993467

  5. HLA-A and -B alleles and haplotypes in hemochromatosis probands with HFE C282Y homozygosity in central Alabama.

    PubMed

    Barton, James C; Acton, Ronald T

    2002-10-07

    We wanted to quantify HLA-A and -B allele and haplotype frequencies in Alabama hemochromatosis probands with HFE C282Y homozygosity and controls, and to compare results to those in other populations. Alleles were detected using DNA-based typing (probands) and microlymphocytotoxicity (controls). Alleles were determined in 139 probands (1,321 controls) and haplotypes in 118 probands (605 controls). In probands, A*03 positivity was 0.7482 (0.2739 controls; p = or < 0.0001; odds ratio (OR) 7.9); positivity for B*07, B*14, and B*56 was also increased. In probands, haplotypes A*03-B*07 and A*03-B*14 were more frequent (p < 0.0001, respectively; OR = 12.3 and 11.1, respectively). The haplotypes A*01-B*60, A*02-B*39, A*02-B*62, A*03-B*13, A*03-B*15, A*03-B*27, A*03-B*35, A*03-B*44, A*03-B*47, and A*03-B*57 were also significantly more frequent in probands. 37.3% of probands were HLA-haploidentical with other proband(s). A*03 and A*03-B*07 frequencies are increased in Alabama probands, as in other hemochromatosis cohorts. Increased absolute frequencies of A*03-B*35 have been reported only in the present Alabama probands and in hemochromatosis patients in Italy. Increased absolute frequencies of A*01-B*60, A*02-B*39, A*02-B*62, A*03-B*13, A*03-B*15, A*03-B*27, A*03-B*44, A*03-B*47, and A*03-B*57 in hemochromatosis cohorts have not been reported previously.

  6. High prevalence of fibromyalgia in patients with HFE-related hereditary hemochromatosis.

    PubMed

    Mohammad, Ausaf; Carey, John J; Storan, Eoin; Scarry, Margaret; Coughlan, Robert J; Lee, John M

    2013-07-01

    Subjects with HFE-related hereditary hemochromatosis (HH) may present with arthralgias, fatigue, and stiffness, yet little is known on the presence of fibromyalgia syndrome (FMS) in these subjects. We determined the prevalence of FMS in a cohort of subjects with HH and evaluated its relationship to subject demographics, disease status, and quality of life. In a cross-sectional study we collected data on 395 consecutive subjects diagnosed with HH who were attending a tertiary referral Hepatology outpatient clinic at Galway University Hospital, Ireland (between October 2009 and June 2010). Subjects underwent a standard assessment including history, clinical examination, and functional assessments for pain and disability. Univariate logistic regression was applied to determine risk factors independently associated with prevalent FMS in these subjects. Three hundred ninety-five subjects met the inclusion criteria. Mean age was 43 years (range, 21 to 59 y) and 260 (66%) were males. One hundred seventy (43%) of the subjects were diagnosed with FMS. Among those with fibromyalgia fatigue and ≥ 11 tender points were present in all of the subjects, widespread pain in 150 (88%), depression in 70 (41%), and arthralgia/joint stiffness in 70 (41%). In subjects with FMS 33% reported some functional impairment (HAQ-DI>0), with 10% reporting moderate-severe functional impairment (HAQ-DI ≥ 1.5). This study reveals a high prevalence of FMS (43%) among subjects with HFE-related hemochromatosis. Prospective studies are needed to better understand the risk factors for FMS in such patients.

  7. Primary Intimal Sarcoma of Thoracic Aorta Presenting as Hypertensive Crisis.

    PubMed

    Lin, Shu-I; Su, Min-I; Tsai, Cheng-Ting

    2015-11-01

    We report a 45-year-old woman who presented to our facility in a hypertensive crisis. Computed tomography (CT) revealed a thoracic aortic tumor, and tissues obtained via endovascular biopsy revealed undifferentiated sarcoma. A final diagnosis of intimal sarcoma was made by intra-operative pathological examination. Despite undergoing surgical resection followed by adjuvant chemotherapy, the patient died from progressive multiple metastasis and severe sepsis. Although aortic sarcoma is rarely diagnosed, it should be considered a possible etiology of hypertensive crisis. Aortic tumor; Endovascular biopsy; Hypertension crisis; Intimal sarcoma.

  8. Primary Intimal Sarcoma of Thoracic Aorta Presenting as Hypertensive Crisis

    PubMed Central

    Lin, Shu-I; Su, Min-I; Tsai, Cheng-Ting

    2015-01-01

    We report a 45-year-old woman who presented to our facility in a hypertensive crisis. Computed tomography (CT) revealed a thoracic aortic tumor, and tissues obtained via endovascular biopsy revealed undifferentiated sarcoma. A final diagnosis of intimal sarcoma was made by intra-operative pathological examination. Despite undergoing surgical resection followed by adjuvant chemotherapy, the patient died from progressive multiple metastasis and severe sepsis. Although aortic sarcoma is rarely diagnosed, it should be considered a possible etiology of hypertensive crisis. PMID:27122923

  9. Tmprss6 is a genetic modifier of the Hfe-hemochromatosis phenotype in mice

    PubMed Central

    Whittlesey, Rebecca L.; Andrews, Nancy C.

    2011-01-01

    The hereditary hemochromatosis protein HFE promotes the expression of hepcidin, a circulating hormone produced by the liver that inhibits dietary iron absorption and macrophage iron release. HFE mutations are associated with impaired hepatic bone morphogenetic protein (BMP)/SMAD signaling for hepcidin production. TMPRSS6, a transmembrane serine protease mutated in iron-refractory iron deficiency anemia, inhibits hepcidin expression by dampening BMP/SMAD signaling. In the present study, we used genetic approaches in mice to examine the relationship between Hfe and Tmprss6 in the regulation of systemic iron homeostasis. Heterozygous loss of Tmprss6 in Hfe−/− mice reduced systemic iron overload, whereas homozygous loss caused systemic iron deficiency and elevated hepatic expression of hepcidin and other Bmp/Smad target genes. In contrast, neither genetic loss of Hfe nor hepatic Hfe overexpression modulated the hepcidin elevation and systemic iron deficiency of Tmprss6−/− mice. These results indicate that genetic loss of Tmprss6 increases Bmp/Smad signaling in an Hfe-independent manner that can restore Bmp/Smad signaling in Hfe−/− mice. Furthermore, these results suggest that natural genetic variation in the human ortholog TMPRSS6 might modify the clinical penetrance of HFE-associated hereditary hemochromatosis, raising the possibility that pharmacologic inhibition of TMPRSS6 could attenuate iron loading in this disorder. PMID:21355094

  10. Hereditary Hemochromatosis Restores the Virulence of Plague Vaccine Strains

    PubMed Central

    Quenee, Lauriane E.; Hermanas, Timothy M.; Ciletti, Nancy; Louvel, Helene; Miller, Nathan C.; Elli, Derek; Blaylock, Bill; Mitchell, Anthony; Schroeder, Jay; Krausz, Thomas; Kanabrocki, Joseph; Schneewind, Olaf

    2012-01-01

    Nonpigmented Yersinia pestis (pgm) strains are defective in scavenging host iron and have been used in live-attenuated vaccines to combat plague epidemics. Recently, a Y. pestis pgm strain was isolated from a researcher with hereditary hemochromatosis who died from laboratory-acquired plague. We used hemojuvelin-knockout (Hjv−/−) mice to examine whether iron-storage disease restores the virulence defects of nonpigmented Y. pestis. Unlike wild-type mice, Hjv−/− mice developed lethal plague when challenged with Y. pestis pgm strains. Immunization of Hjv−/− mice with a subunit vaccine that blocks Y. pestis type III secretion generated protection against plague. Thus, individuals with hereditary hemochromatosis may be protected with subunit vaccines but should not be exposed to live-attenuated plague vaccines. PMID:22896664

  11. Hemochromatosis detection in a health screening program at an Alabama forest products mill.

    PubMed

    Barton, James C; Cheatwood, Susan M; Key, Timothy J; Acton, Ronald T

    2002-08-01

    We analyzed hemochromatosis detection in a 11.5-year multiphasic health screening program at a forest products mill. There were 2199 participants: 2032 Whites (1506 men, 526 women) and 167 African Americans (124 men, 43 women); 85.0% of employees were screened. Iron and transferrin saturation were measured in a serum biochemistry profile on specimens obtained after overnight fasting; ferritin was measured in participants with elevated iron concentrations or transferrin saturation > 48%. Participants with elevated ferritin levels underwent further evaluation. Eight White men were diagnosed to have hemochromatosis (frequency 0.0039 in Whites, 0.0053 in White men). The estimated cost per case detected was $8826. Family members of two participants with hemochromatosis were also diagnosed to have hemochromatosis or iron overload. We conclude that detecting hemochromatosis in a workplace multiphasic health screening program is efficacious and economical.

  12. Squamous cell carcinoma presenting with trigeminal anesthesia: An uncommon presentation of head & neck cancer with unknown primary.

    PubMed

    Shah, Ameer T; Dagher, Walid I; O'Leary, Miriam A; Wein, Richard O

    The differential diagnosis of facial anesthesia is vast. This may be secondary to trauma, neoplasm, both intracranial and extracranial, infection, and neurologic disease. When evaluating a patient with isolated facial anesthesia, the head and neck surgeon often thinks of adenoid cystic carcinoma, which has a propensity for perineural invasion and spread. When one thinks of head and neck squamous cell carcinoma with or without unknown primary, the typical presentation involves dysphagia, odynophagia, weight loss, hoarseness, or more commonly, a neck mass. Squamous cell carcinoma presenting as facial anesthesia and perineural spread, with no primary site is quite rare. Case presentations and review of the literature. Trigeminal anesthesia is an uncommon presentation of head and neck squamous cell carcinoma with unknown primary. We present two interesting cases of invasive squamous cell carcinoma of the trigeminal nerve, with no primary site identified. We will also review the literature of head and neck malignancies with perineural spread and the management techniques for the two different cases presented. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Serum ferritin is a biomarker for liver mortality in the Hemochromatosis and Iron Overload Screening Study.

    PubMed

    Adams, Paul C; Barton, James C; Guo, Helen; Alter, David; Speechley, Mark

    2015-01-01

    We identified no reports of long-term follow-up of participants in hemochromatosis screening programs. We evaluated causes of death and survival in non-C282Y homozygous Canadian participants in the primary care-based hemochromatosis and iron overload screening (HEIRS) study. Initial screening (IS) included transferrin saturation (TS), serum ferritin (SF), HFE genotyping (C282Y, H63D), and health questionnaire responses. By definition, participants without C282Y or H63D had HFE wt/wt. We linked 20,306 Canadian participants to the Ontario Death Registry for dates and causes of death 9 y after IS. We computed Cox proportional hazards to identify factors with increased death risks and Kaplan-Meier curves to estimate survival of non-C282Y homozygous participants with SF ≤ 1,000 μg/L and > 1,000 μg/dL. There were 19,052 evaluable participants (IS mean age 49 y; 60% women; 93 C282Y homozygotes). There were 988 deaths. Significantly increased hazard ratios for all-cause mortality were positively associated with TS, SF, men, and C282Y homozygosity, and liver disease, diabetes, and heart failure reports. Non-C282Y homozygous participants with SF > 1,000 μg/L had lower survival than those with SF ≤ 1,000 μg/L (p < 0.0001). Nine years after initial screening, non-C282Y homozygous participants and SF > 1,000 μg/L was associated with decreased survival.

  14. Effect of Native American ancestry on iron-related phenotypes of Alabama hemochromatosis probands with HFE C282Y homozygosity

    PubMed Central

    Barton, James C; Barton, Ellen H; Acton, Ronald T

    2006-01-01

    Background In age-matched cohorts of screening study participants recruited from primary care clinics, mean serum transferrin saturation values were significantly lower and mean serum ferritin concentrations were significantly higher in Native Americans than in whites. Twenty-eight percent of 80 Alabama white hemochromatosis probands with HFE C282Y homozygosity previously reported having Native American ancestry, but the possible effect of this ancestry on hemochromatosis phenotypes was unknown. Methods We compiled observations in these 80 probands and used univariate and multivariate methods to analyze associations of age, sex, Native American ancestry (as a dichotomous variable), report of ethanol consumption (as a dichotomous variable), percentage transferrin saturation and loge serum ferritin concentration at diagnosis, quantities of iron removed by phlebotomy to achieve iron depletion, and quantities of excess iron removed by phlebotomy. Results In a univariate analysis in which probands were grouped by sex, there were no significant differences in reports of ethanol consumption, transferrin saturation, loge serum ferritin concentration, quantities of iron removed to achieve iron depletion, and quantities of excess iron removed by phlebotomy in probands who reported Native American ancestry than in those who did not. In multivariate analyses, transferrin saturation (as a dependent variable) was not significantly associated with any of the available variables, including reports of Native American ancestry and ethanol consumption. The independent variable quantities of excess iron removed by phlebotomy was significantly associated with loge serum ferritin used as a dependent variable (p < 0.0001), but not with reports of Native American ancestry or reports of ethanol consumption. Loge serum ferritin was the only independent variable significantly associated with quantities of excess iron removed by phlebotomy used as a dependent variable (p < 0.0001) (p < 0

  15. HLA haplotype map of river valley populations with hemochromatosis traced through five centuries in Central Sweden.

    PubMed

    Olsson, K Sigvard; Ritter, Bernd; Hansson, Norbeth; Chowdhury, Ruma R

    2008-07-01

    The hemochromatosis mutation, C282Y of the HFE gene, seems to have originated from a single event which once occurred in a person living in the north west of Europe carrying human leukocyte antigen (HLA)-A3-B7. In descendants of this ancestor also other haplotypes appear probably caused by local recombinations and founder effects. The background of these associations is unknown. Isolated river valley populations may be fruitful for the mapping of genetic disorders such as hemochromatosis. In this study, we try to test this hypothesis in a study from central Sweden where the haplotyope A1-B8 was common. HLA haplotypes and HFE mutations were studied in hemochromatosis patients with present or past parental origin in a sparsely populated (1/km(2)) rural district (n = 8366 in the year of 2005), in central Sweden. Pedigrees were constructed from the Swedish church book registry. Extended haplotypes were studied to evaluate origin of recombinations. There were 87 original probands, 36 females and 51 males identified during 30 yr, of whom 86% carried C282Y/C282Y and 14% C282Y/H63D. Of 32 different HLA haplotypes A1-B8 was the most common (34%), followed by A3-B7 (16%), both in strong linkage disequilibrium with controls, (P < 0.001). Twenty-nine different families with A1-B8 had a common founder origin 15 generations ago in small bottleneck populations of the late 16th century. A second A1-B8 founder born 1655 was of Norwegian origin. Most of the A3 carriers (n = 26) had a common founder origin 16 generations ago in an even smaller nearby river valley. A fourth founder family carrying HLA-A2 seems to have originated from a recombination along the descendant lines from the A3 ancestor supported by extended haplotype studies. A1-haplotypes with alleles at the B locus different from B8 had a similar recombination origin as HLA-A2 alleles and a common founder origin 11 generations ago. The intergenerational time interval averaged 35.5 +/- 7.9 yr in men and 31.9 +/- 5.9 in

  16. Successful management of neonatal hemochromatosis by exchange transfusion and immunoglobulin: a case report.

    PubMed

    Babor, F; Hadzik, B; Stannigel, H; Mayatepek, E; Hoehn, T

    2013-01-01

    Neonatal hemochromatosis (NH) is a rare and severe liver disease of mainly intra-uterine onset, characterized by neonatal liver failure, hepatic and extrahepatic iron accumulation. This leads to an altered iron metabolism with resulting siderosis. The disease represents the most common cause of liver failure in neonates and is also the most common indication for neonatal liver transplantation. We present a case of a newborn diagnosed with NH and life threatening liver failure. Initial treatment consisted of chelation therapy and antioxidants, but lack of laboratory and clinical improvement led to an exchange transfusion followed by the singular substitution of intravenous immunoglobulin (IVIG). Both, exchange transfusion and IVIG were tolerated well and led to an improvement of the general condition of the patient and recovery of liver synthetic function. The subsequent favorable course of the disease is described in this case report.

  17. Phenotypic analysis of hemochromatosis subtypes reveals variations in severity of iron overload and clinical disease.

    PubMed

    Sandhu, Kam; Flintoff, Kaledas; Chatfield, Mark D; Dixon, Jeannette L; Ramm, Louise E; Ramm, Grant A; Powell, Lawrie W; Subramaniam, V Nathan; Wallace, Daniel F

    2018-05-09

    The clinical progression of HFE-related hereditary hemochromatosis (HH) and its phenotypic variability has been well studied. Less is known about the natural history of non-HFE HH caused by mutations in the HJV , HAMP or TFR2 genes. The purpose of this study was to compare the phenotypic and clinical presentations of hepcidin-deficient forms of HH. A literature review of all published cases of genetically confirmed HJV, HAMP and TFR2 HH was performed. Phenotypic and clinical data from a total of 156 subjects with non-HFE HH was extracted from 53 publications and compared with data from 984 subjects with HFE -p.C282Y homozygous HH from the QIMR Berghofer Hemochromatosis Database. Analyses confirmed that non-HFE forms of HH have an earlier age of onset and a more severe clinical course than HFE HH. HJV and HAMP HH are phenotypically and clinically very similar and have the most severe presentation, with cardiomyopathy and hypogonadism being particularly prevalent findings. TFR2 HH is more intermediate in its age of onset and severity. All clinical outcomes analyzed were more prevalent in the juvenile forms of HH, with the exception of arthritis and arthropathy which were more commonly seen in HFE HH. This is the first comprehensive analysis comparing the different phenotypic and clinical aspects of the genetic forms of HH and the results will be valuable for the differential diagnosis and management of these conditions. Importantly, our analyses indicate that factors other than iron overload may be contributing to joint pathology in subjects with HFE HH. Copyright © 2018 American Society of Hematology.

  18. A Mouse Model of Cardiomyopathy Induced by Mutations in the Hemochromatosis HFE Gene.

    PubMed

    Djemai, Haidar; Thomasson, Rémi; Trzaskus, Yvan; Mougenot, Nathalie; Meziani, Amira; Toussaint, Jean-François; Noirez, Philippe; Vitiello, Damien

    2017-07-01

    The heart is 1 of the organs most affected by hereditary hemochromatosis (HH). The clinical impact of cardiomyopathy in patients with HH requires a particular diagnosis and less invasive treatments. We developed a model of cardiomyopathy in knockout (KO) mice for the high-Fe (HFE) gene and assessed left ventricular (LV) function and structure from 7-20 months. Male wild-type (WT) heterozygous and KO SV129 mice for the HFE gene were used in this study. Twenty-four mice were used to assess LV function and structure by echocardiography at 7, 14, 18, and 20 months. Evaluations of LV function and structure and myocardial fibrosis were performed at 7 and 20 months. The percent decrease of LV thickness-to-radius ratio between 7 and 20 months was higher in KO mice compared with WT mice (-30.2% ± 5.3% vs -10.5% ± 4.9%; P < 0.01). The LV diameters were higher in old mice compared with young mice (+13% at end-diastole; +33% at end-systole; P < 0.001). The LV ejection fraction values were lower in KO mice compared with WT mice between 7 and 20 months. The highest difference was found at 14 months (60.0% ± 7.6% vs 78.1% ± 3.5%; P < 0.001). Myocardial fibrosis was higher in old KO mice compared with old WT mice (+55%; P < 0.001), and myocardial iron deposition was slightly increased in old KO mice compared with old WT mice (1.31% ± 0.33% vs 0.84% ± 0.22%; P = 0.056). The present mouse model has the potential to allow the determination of underlying mechanisms involved in the cardiomyopathy induced by HFE-related hemochromatosis. Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  19. Incidence of cardiac arrhythmias in asymptomatic hereditary hemochromatosis subjects with C282Y homozygosity.

    PubMed

    Shizukuda, Yukitaka; Tripodi, Dorothy J; Zalos, Gloria; Bolan, Charles D; Yau, Yu-Ying; Leitman, Susan F; Waclawiw, Myron A; Rosing, Douglas R

    2012-03-15

    It is not well known whether systemic iron overload per se in hereditary hemochromatosis (HH) is associated with cardiac arrhythmias before other signs and symptoms of cardiovascular disease occur. In the present study, we examined the incidence of cardiac arrhythmia in cardiac asymptomatic subjects with HH (New York Heart Association functional class I) and compared it to that in age- and gender-matched normal volunteers. The 42 subjects with HH and the 19 normal control subjects were recruited through the National Heart, Lung, and Blood Institute-sponsored "Heart Study of Hemochromatosis." They completed 48-hour Holter electrocardiography ambulatory monitoring at the baseline evaluation. The subjects with HH were classified as newly diagnosed (group A) and chronically treated (group B) subjects. All subjects with HH had C282Y homozygosity, and the normal volunteers lacked any HFE gene mutations known to cause HH. Although statistically insignificant, the incidence of ventricular and supraventricular ectopy tended to be greater in the combined HH groups than in the controls. Supraventricular ectopy was more frequently noted in group B compared to in the controls (ectopy rate per hour 11.1 ± 29.9 vs 1.5 ± 3.5, p < 0.05, using the Kruskal-Wallis test). No examples of heart block, other than first-degree atrioventricular node block, were seen in any of the subjects. The incidence of cardiac arrhythmias was not significantly reduced after 6 months of intensive iron removal therapy in the group A subjects. No life-threatening arrhythmias were observed in our subjects with HH. In conclusion, our data suggest that the incidence of cardiac arrhythmias is, at most, marginally increased in asymptomatic subjects with HH. A larger clinical study is warranted to further clarify our observation. Published by Elsevier Inc.

  20. Paraoxonase-1 status in patients with hereditary hemochromatosis.

    PubMed

    Martinelli, Nicola; García-Heredia, Anabel; Roca, Helena; Aranda, Núria; Arija, Victoria; Mackness, Bharti; Mackness, Michael; Busti, Fabiana; Aragonès, Gerard; Pedro-Botet, Juan; Pedica, Federica; Cataldo, Ivana; Marsillach, Judit; Joven, Jorge; Girelli, Domenico; Camps, Jordi

    2013-05-01

    Hereditary hemochromatosis (HH) is characterized by accumulation of iron, oxidative stress, inflammation, and fibrogenesis in liver tissue. In this setting, research on the protection afforded by intracellular antioxidants is of clinical relevance. Paraoxonase-1 (PON1) is an enzyme that degrades lipid peroxides. This study investigates the alterations in serum PON1 status, PON1 gene polymorphisms, and PON1 hepatic expression in patients with HH. We performed a case-control study in 77 patients with HH (80.5% men, 22-70 years of age) and 408 healthy individuals (43.1% men, 26-74 years of age). Serum PON1 activities against different substrates and PON1192 and PON155 polymorphisms were analyzed. PON1 protein expression was investigated in 20 liver biopsies. HH patients had significantly lower serum PON1 activity, which was inversely correlated with ferritin (marker of iron stores) and serum 8-isoprostane concentrations (index of oxidative stress). PON1 protein expression in liver tissue was higher in patients and showed stronger staining in hepatocytes surrounding the areas of inflammation. Our study provides preliminary evidence that PON1 may play a role in protecting against iron-induced oxidative stress in hereditary hemochromatosis.

  1. Paraoxonase-1 status in patients with hereditary hemochromatosis

    PubMed Central

    Martinelli, Nicola; García-Heredia, Anabel; Roca, Helena; Aranda, Núria; Arija, Victoria; Mackness, Bharti; Mackness, Michael; Busti, Fabiana; Aragonès, Gerard; Pedro-Botet, Juan; Pedica, Federica; Cataldo, Ivana; Marsillach, Judit; Joven, Jorge; Girelli, Domenico; Camps, Jordi

    2013-01-01

    Hereditary hemochromatosis (HH) is characterized by accumulation of iron, oxidative stress, inflammation, and fibrogenesis in liver tissue. In this setting, research on the protection afforded by intracellular antioxidants is of clinical relevance. Paraoxonase-1 (PON1) is an enzyme that degrades lipid peroxides. This study investigates the alterations in serum PON1 status, PON1 gene polymorphisms, and PON1 hepatic expression in patients with HH. We performed a case-control study in 77 patients with HH (80.5% men, 22–70 years of age) and 408 healthy individuals (43.1% men, 26–74 years of age). Serum PON1 activities against different substrates and PON1192 and PON155 polymorphisms were analyzed. PON1 protein expression was investigated in 20 liver biopsies. HH patients had significantly lower serum PON1 activity, which was inversely correlated with ferritin (marker of iron stores) and serum 8-isoprostane concentrations (index of oxidative stress). PON1 protein expression in liver tissue was higher in patients and showed stronger staining in hepatocytes surrounding the areas of inflammation. Our study provides preliminary evidence that PON1 may play a role in protecting against iron-induced oxidative stress in hereditary hemochromatosis. PMID:23471031

  2. Age-related variation in primary care-type presentations to emergency departments.

    PubMed

    Freed, Gary; Gafforini, Sarah; Carson, Norman

    2015-08-01

    A significant amount of attention has been paid to the increase in emergency department (ED) presentations in Australia. Questions have arisen regarding whether all of those presenting to the ED are actually in need of true emergency services. Under-standing the characteristics of those patients who may be cared for in non-emergency settings is important for future health system strategies. The aim of this study was to identify age-related variation in primary care type emergency department (ED) presentations over time. A secondary analysis of data from the Victorian emergency minimum dataset (VEMD) between 2002-13 was conducted. The main outcomes were patterns of primary care type ED presentations for different ages groups over time, age-specific patterns of specific primary care type exclusion criteria and primary care type ED presentations by residents from aged care facilities. The proportion of triage category 4 or 5 ED presentations that met the criteria for a primary care type visit was greatest in the 0-4-year age group and tended to decrease as the age of the patient increased. Triage category 4 or 5 presentation by ambulance was uncommon in the younger age groups, surpassed 10% in the 50-54-year age group, and was >70% for those aged >90 years. The greater proportion of residential aged care facility patients who arrived by ambulance resulted in a much smaller proportion of primary care type visits. There are marked differences by age in the proportion of triage category 4 or 5 ED presentations that met the criteria for primary care type visits. These results indicate it was primarily younger patients who presented to the ED with non-urgent conditions. Most might be able to safely receive care in a primary care setting.

  3. Synchrotron X-ray microscopy and spectroscopy analysis of iron in hemochromatosis liver and intestines

    SciTech Connect

    Ko, J .Y. Peter; Sham, Tsun-Kong; Chakrabarti, Subrata

    2009-12-01

    Hemochromatosis is a genetic disorder that causes body to store excess iron in organs such as heart or liver. Distribution of iron, as well as copper, zinc and calcium, and chemical identity of iron in hemochromatosis liver and intestine were investigated by X-ray microprobe experiments, which consist of X-ray microscopy and micro-X-ray absorption fine structure. Our results show that iron concentration in hemochromatosis liver tissue is high, while much less Fe is found in intestinal tissue. Moreover, chemical identity of Fe in hemochromatosis liver can be identified. X-ray microprobe experiments allows for examining elemental distribution at an excellent spatial resolution.more » Moreover, chemical identity of element of interest can be obtained.« less

  4. Rare Presentations of Primary Melanoma and Special Populations: A Systematic Review

    PubMed Central

    Kottschade, Lisa A.; Grotz, Travis E.; Dronca, Roxana S.; Salomao, Diva R.; Pulido, Jose S.; Wasif, Nabil; Jakub, James W.; Bagaria, Sanjay P.; Kumar, Riten; Kaur, Judith S.; Morita, Shane Y.; Moran, Steven L.; Nguyen, Jesse T.; Nguyen, Emily C.; Hand, Jennifer L.; Erickson, Lori A.; Brewer, Jerry D.; Baum, Christian L.; Miller, Robert C.; Swanson, David L.; Lowe, Val; Markovic, Svetomir N.

    2013-01-01

    A subset of patients with melanoma present in rare and unique clinical circumstances requiring specific considerations with respect to diagnostic and therapeutic interventions. Herein we present our review of patients with: (1) primary mucosal melanoma of the head and neck, gastrointestinal and genitourinary tracts; (2) primary melanoma of the eye; (3) desmoplastic melanoma; (4) subungual melanoma; (5) melanoma in special populations: children, non-Caucasians, as well as a discussion of familial melanoma. PMID:23563206

  5. Primary pulmonary mucinous cystadenocarcinoma presenting as a complex bronchocele: a case report

    PubMed Central

    2009-01-01

    Introduction Primary pulmonary mucinous cystadenocarcinoma is a rare variety of lung cancer. It is characterized pathologically by copious mucin production predominantly in the extracellular space. This tumour has a remarkably favorable prognosis. Case presentation We present imaging and histopathological findings of primary pulmonary mucinous cystadenocarcinoma presenting as a complex bronchocele in a 67-year-old Caucasian woman. Conclusion Diagnosis of pulmonary mucinous cystadenocarcinoma should be considered in patients presenting with bronchocele that has suspicious imaging features, because the results of fine needle aspiration cytology and bronchoscopy are frequently inconclusive in these tumours. Positive emission tomography has an important role in helping to identify these tumours. PMID:19830231

  6. Frequency of the S65C mutation in the hemochromatosis gene in Brazil.

    PubMed

    Oliveira, V C; Caxito, F A; Gomes, K B; Castro, A M; Pardini, V C; Ferreira, A C S

    2009-07-14

    Development of hereditary hemochromatosis is associated with the C282Y, H63D or S65C mutations in the hemochromatosis gene. Though there is extensive knowledge about the former two, there is little information on the mechanism of action and the allelic frequency of the S65C mutation. We examined the prevalence of the S65C mutation of the hemochromatosis gene in Brazilians with clinical suspicion of hereditary hemochromatosis. Genotyping for this mutation was carried out in 633 individuals with clinical suspicion of hereditary hemochromatosis, using the polymerase chain reaction, followed by enzymatic digestion. The sample comprised 77.1% men and 22.9% women, giving a ratio of approximately 3:1; the mean age was 48.8 +/- 13.8 years. More than half (57.3%) of the individuals in the sample were 41 to 60 years old. The frequency of heterozygotes for this mutation was 0.016; no homozygous mutant patients were found. This is the first analysis of the S65C mutation in individuals suspected of having hereditary hemochromatosis in Brazil.

  7. Addison disease presenting with acute neurologic deterioration: a rare presentation yields new lessons from old observations in primary adrenal failure.

    PubMed

    Myers, Kenneth A; Kline, Gregory A

    2010-01-01

    To report a rare case of Addison disease presenting with acute neurologic deterioration, and to discuss previous reports and illustrative clinical lessons drawn from the case. We detail the clinical presentation and sequence of events leading to diagnosis of Addison disease in a 20-year-old man whose initial symptoms were those of acute neurologic deterioration. A 20-year-old man presented with acute, rapid neurologic deterioration. The patient required intubation, but his condition responded very well to mannitol and dexamethasone. Head computed tomography showed a fourth ventricle reduced in size and basal cistern effacement, changes consistent with mild cerebral edema. Primary adrenal insufficiency was diagnosed after a low morning cortisol concentration prompted a corticotropin-stimulation test and serum aldosterone measurement (undetectable). The diagnosis was almost missed because of suspected confounders of dexamethasone and etomidate use. Subsequently, the patient tested positive for anti-21- hydroxylase antibodies. Cerebral edema rarely occurs with Addison disease and is most likely secondary to hyponatremia. Diagnosis in such cases may be complicated by resuscitative therapies; however, low cortisol levels should always be thoroughly investigated. This patient's presentation was also unique in that he maintained a normal electrolyte profile despite hypoaldosteronism, a phenomenon that may be explained by enhanced mineralocorticoid activity of exogenous cortisol. The diagnosis of primary adrenal insufficiency may not be suspected in the absence of classic hyperpigmentation and hyperkalemia, but should remain in the differential diagnosis of acute confusion. While the use of dexamethasone and etomidate in initial resuscitation can transiently suppress adrenal function, any unusually low cortisol level merits thorough investigation.

  8. An immunohistochemical study of placental syncytiotrophoblasts in neonatal hemochromatosis.

    PubMed

    Shimono, Aiko; Imoto, Yuko; Sakamoto, Haruhiko; Chiba, Yoichi; Matsumoto, Koichi; Kawauchi, Machi; Kusaka, Takashi; Tanaka, Hirokazu; Hata, Toshiyuki; Kushida, Yoshio; Ueno, Masaki

    2016-12-01

    Neonatal hemochromatosis (NH) is a rare neonatal disorder that results in liver cirrhosis with hemosiderin deposition in the liver and other organs, similarly to hereditary hemochromatosis. Excess iron is transferred from the mother to fetus through the placenta in NH. We examined the expression of iron metabolism-related substances in placental syncytiotrophoblasts (STB) by immunostaining to clarify how the transfer of iron through STB increases in NH. Immunostaining was performed using formalin-fixed, paraffin-embedded sections of placentae from three NH cases, four gestational age-matched controls, and, depending on the antibody examined, five to seven full-term controls. The reactivity of immunostaining was assessed by averages of scores assigned by 3 researchers. On the microvillar surface of STB, the reactions of the antibodies against transferrin receptor 1 (TFR1), transferrin, ferritin, hepcidin, ferroportin, divalent metal transporter-1 (DMT1), hephaestin, and HFE were stronger in NH than in controls. In the cytoplasm, the reactions of antibodies against TFR1, transferrin, ferritin, hepcidin, DMT1, hephaestin, HFE, and ZIP 14 were stronger in NH than in gestational age-matched controls. Among these reactions, those of anti-TFR1 antibody on the surface of STB in NH was especially marked. In the placenta of NH, increases in expressions of TFR1, transferrin, and ferritin of which those of TFR1 were especially marked, reflect increased iron influx from the mother to fetus. The hepcidin observed on the surface and in the cytoplasm of STB of NH is suggested to be from the mother, possibly to compensate for the decreased fetal liver-derived hepcidin. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Primary diffuse large B-cell lymphoma of the corpora cavernosa presented as a perineal mass

    PubMed Central

    Carlos, González-Satué; Ivanna, Valverde Vilamala; Gustavo, Tapia Melendo; Joan, Areal Calama; Javier, Sanchez Macias; Luis, Ibarz Servio

    2012-01-01

    Primary male genital lymphomas may appear rarely in testis, and exceptionally in the penis and prostate, but there is not previous evidence of a lymphoma arising from the corpora cavernosa. We report the first case in the literature of a primary diffuse cell B lymphoma of the corpora cavernosa presented with low urinary tract symptoms, perineal pain and palpable mass. Diagnosis was based on trucut biopsy, histopathological studies and computed tomographic images. PMID:22919138

  10. Primary Intestinal Lymphangiectasia (Waldmann's Disease) Presenting with Chylous Effusions in a 15-Year-Old.

    PubMed

    Surampalli, Vijay; Ramaswamy, Srinath; Surendran, Deepanjali; Bammigatti, Chanaveerappa; Swaminathan, Rathinam Palamalai

    2017-08-01

    Primary Intestinal Lymphangiectasia (PIL) is a rare disease of unknown aetiology which presents in the paediatric age group with anasarca, diarrhoea, hypoproteinaemia, lymphoedema and chylous effusions. Tuberculosis, filariasis, chest trauma, malignancies and haematological disorders usually contribute to most cases of secondary lymphangiectasia and chylous effusions. We hereby describe a case of PIL presenting with chylous effusions which remained undiagnosed for eight years.

  11. An unusual presentation of primary malignant B-cell-type dural lymphoma

    PubMed Central

    Low, Yin Yee Sharon; Lai, Siang Hui; Ng, Wai Hoe

    2014-01-01

    Primary malignant B-cell-type dural lymphoma is a rare subtype of primary central nervous system lymphoma (PCNSL). We herein report an unusual case of diffuse B-cell lymphoma that presents as a chronic subdural haematoma without extracranial involvement. The notable aspects of this case include the patient’s immunocompetence, a short clinical history of symptom onset, rapid neurological deterioration and a final diagnosis of high-grade PCNSL. This case highlights the challenges neurosurgeons face, especially in the emergency setting, when the disease manifests in varied presentations. PMID:25631982

  12. Distortion product otoacoustic emissions: comparison of sequential vs. simultaneous presentation of primary tones.

    PubMed

    Kumar, U Ajith; Maruthy, Sandeep; Chandrakant, Vishwakarma

    2009-03-01

    Distortion product otoacoustic emissions are one form of evoked otoacoustic emissions. DPOAEs provide the frequency specific information about the hearing status in mid and high frequency regions. But in most screening protocols TEOAEs are preferred as it requires less time compared to DPOAE. This is because, in DPOAE each stimulus is presented one after the other and responses are analyzed. Grason and Stadler Incorporation 60 (GSI-60) offer simultaneous presentation of four sets of primary tones at a time and checks for the DPOAE. In this mode of presentation, all the pairs are presented at a time and following that response is extracted separately whereas, in sequential mode primaries are presented in orderly fashion one after the other. In this article simultaneous and sequential protocols were used to compare the Distortion product otoacoustic emission amplitude, noise floor and administration time in individuals with normal hearing and mild sensori-neural (SN) hearing loss. In simultaneous protocols four sets of primary tones (i.e. 8 tones) were presented together whereas, in sequential presentation mode one set of primary tones was presented each time. Simultaneous protocol was completed in less than half the time required for the completion of sequential protocol. Two techniques yielded similar results at frequencies above 1000 Hz only in normal hearing group. In SN hearing loss group simultaneous presentation yielded signifi cantly higher noise floors and distortion product amplitudes. This result challenges the use of simultaneous presentation technique in neonatal hearing screening programmes and on other pathologies. This discrepancy between two protocols may be due to some changes in biomechanical process in the cochlear and/or due to higher distortion/noise produced by the system during the simultaneous presentation mode.

  13. Multiple Primary Merkel Cell Carcinomas Presenting as Pruritic, Painful Lower Leg Tumors

    PubMed Central

    Blumenthal, Laura; VandenBoom, Timothy; Melian, Edward; Peterson, Anthony; Hutchens, Kelli A.

    2015-01-01

    Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine tumor of the skin which almost exclusively presents as a solitary tumor. It is most often seen on sun-exposed regions, historically almost exclusively on the head and neck, with only rare case reports on the extremities. Although recent studies have shown increased incidence with up to 20% on the extremities, here we present one of these rare emerging presentations, with the addition of a unique treatment option. Our patient is an 80-year-old male with a 3-month history of multiple raised, rapidly enlarging tumors on the right ankle. Two separate biopsies were performed and demonstrated sheets and clusters of small blue cells filling the dermis with scant cytoplasm, dusty chromatin, and nuclear molding. Subsequent immunohistochemical stains confirmed the diagnosis of multiple primary MCC. Despite the characteristic immunohistochemical profile of primary MCC, the possibility of a metastatic neuroendocrine carcinoma from an alternate primary site was entertained, given his unusual clinical presentation. A complete clinical workup including CT scans of the chest, abdomen, and pelvis showed no evidence of disease elsewhere. Instead of amputation, the patient opted for nonsurgical treatment with radiation therapy alone, resulting in a rapid and complete response. This case represents an unusual presentation of primary MCC and demonstrates further evidence that radiation as monotherapy is an effective local treatment option for inoperable MCC. PMID:26594171

  14. Primary lymphoma of appendix presenting as acute appendicitis: A case report.

    PubMed

    Caristo, Giuseppe; Griseri, Guido; Fornaro, Rosario; Langone, Antonio; Franceschi, Angelo; Errigo, Veronica; Ferrari, Cecilia; Casaccia, Marco; Frascio, Marco; Schirru, Angelo

    2018-05-07

    Primary lymphomas of appendix are extremely rare tumors. The incidence is 0.015% of all gastrointestinal lymphomas. We present a case of a 75 year-old male patient who presented with acute abdominal pain in the lower right quadrant and fever. The patient received laparotomic appendectomy. The definitive histopathological examination revealed the presence of diffuse large cell B-lymphoma of the appendix. The neoplasms of appendix usually manifest clinically with sign and symptoms of acute appendicitis from luminal obstruction (30-50%). Preoperative diagnosis is difficult and often occurs through histopathological examination. Primary appendiceal lymphoma is rare and there are no clear guidelines for therapy. Primary surgical resection followed by post-operative chemotherapy showed high efficacy. The histopathological examination of all appendectomy is essential. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Primary Traits of Oral Business Presentation: Translatable Use for Assessment in a Virtual Learning Environment

    ERIC Educational Resources Information Center

    Leeds, Elke M.; Raven, Arjan; Brawley, Dorothy

    2007-01-01

    As more and more classes are taught on-line, new challenges for assessment of student learning have come about. In this paper on the use of digital video (DV) as an acceptable means to assess student oral business presentation skills, content analysis was used to test for the presence of primary traits inherent in effective formal business…

  16. Primary pleuropulmonary synovial sarcoma with brain metastases in a paediatric patient: an unusual presentation.

    PubMed

    Chirmade, Pushpak Chandrakant; Parikh, Sonia; Anand, Asha; Panchal, Harsha; Patel, Apurva; Shah, Sandip

    2017-01-01

    Primary lung neoplasms are rare in children. The most common primary lung malignancies in children are pleuropulmonary blastoma and carcinoid tumour. Synovial sarcoma (SS) accounts for approximately 1% of all childhood malignancies. In absolute terms, the SS of the lungs and pleura are extremely rare and pose a diagnostic difficulty. Soft tissue sarcomas usually have a high potential for metastases, however, metastasis to the brain is rare, even in widely disseminated disease, and it has been described only in 3 case reports previously. Primary pleuropulmonary SS with brain metastases is even rarer. Here we present a case of an 11-year-old boy who presented with respiratory complaints, viz. fever and cough for 20 days. Initial impression was lung abscess, however, on histopathological, immunohistochemical and molecular study, the disorder was diagnosed as synovial sarcoma. After a week from the first consult, the child developed neurological symptoms, viz., an episode of convulsion and gradually worsening power of the lower limb. Computed tomography scan and Magnetic Resonance Spectroscopy was suggestive of brain metastases. Given the rarity of primary lung neoplasms in children, clinical detection remains a challenge. Delayed diagnoses are common as respiratory symptoms may be attributed to inflammatory or infective processes. Primary pleuropulmonary synovial sarcoma is a rare tumour and it is not known to commonly metastasise to the brain. Though rare, primary pleuropulmonary SS should be considered an important differential among peadiatric primary lung neoplasms due to its potential for curability if detected early, and more aggressive metastatic pattern, e.g. brain metastases making early detection imperative.

  17. Primary aortoduodenal fistula associated with abdominal aortic aneurysm with presentation of gastrointestinal bleeding: a case report.

    PubMed

    Lin, Tzu-Chieh; Tsai, Chung-Lin; Chang, Yao-Tien; Hu, Sung-Yuan

    2018-06-07

    Primary aortoduodenal fistula (ADF) is a rare cause of gastrointestinal (GI) bleeding and is difficult to diagnose as the clinical presentation is subtle. Clinicians should keep a high level of suspicion for an unknown etiology of GI bleeding, especially in older patients with or without abdominal aortic aneurysm (AAA). Computed tomographic angiography (CTA) can be used to detect primary ADF. Open surgery or endovascular aortic repair (EVAR) for ADF with bleeding will improve the survival rate. We report a rare case of AAA complicating ADF with massive GI bleeding in a 73-year-old Taiwanese man. He presented with abdominal pain and tarry stool for 5 days and an initial upper GI endoscopy at a rural hospital showed gastric ulcer only, but hypotension with tachycardia and a drop in hemoglobin of 9 g/dl from 12 g/dl occurred the next day. He was referred to our hospital for EVAR and primary closure of fistula defect due to massive GI bleeding with shock from ADF caused by AAA. Diagnosis was made by CTA of aorta. A timely and accurate diagnosis of primary ADF may be challenging due to insidious episodes of GI bleeding, which are frequently under-diagnosed until the occurrence of massive hemorrhage. Clinical physicians should keep a high index of awareness for primary ADF, especially in elderly patients with unknown etiology of upper GI bleeding with or without a known AAA.

  18. Clinical presentation, diagnosis, and pharmacotherapy of patients with primary brain tumors.

    PubMed

    Newton, H B; Turowski, R C; Stroup, T J; McCoy, L K

    1999-01-01

    To briefly review the clinical presentation and diagnosis of patients with primary brain tumors, followed by an in-depth survey of the pertinent pharmacotherapy. A detailed search of the neurologic, neurosurgical, and oncologic literature for basic science research, clinical studies, and review articles related to chemotherapy and pharmacotherapy of primary brain tumors. Relevant studies on tissue culture systems, animals, and humans examining the mechanisms of action, pharmacokinetics, clinical pharmacology, and treatment results of chemotherapeutic agents for primary brain tumors. In addition, studies of pharmacologic agents administered for supportive care and symptom control are reviewed. Primary brain tumors derive from cells within the intracranial cavity and generally present with headache, seizure activity, cognitive changes, and weakness. They are diagnosed most efficiently with magnetic resonance imaging. After diagnosis, the most common supportive medications include corticosteroids, gastric acid inhibitors, and anticonvulsants. Chemotherapy is adjunctive treatment for patients with malignant tumors and selected recurrent or progressive benign neoplasms. In general, the most effective chemotherapeutic drugs are alkylating agents such as the nitrosoureas, procarbazine, cisplatin, and carboplatin. Other agents used include cyclophosphamide, methotrexate, vincristine, and etoposide. Angiogenesis inhibitors and gene therapy comprise some of the novel therapeutic strategies under investigation. The efficacy of chemotherapy for primary brain tumors remains modest. Novel agents must be discovered that are more specific and attack tumor cells at the molecular level of tumorigenesis. Furthermore, strategies must be developed to counteract the pervasive problem of brain tumor chemoresistance.

  19. Clinical and Laboratory Associations with Persistent Hyperferritinemia in 373 Black Hemochromatosis and Iron Overload Screening Study Participants.

    PubMed

    Barton, James C; Barton, J Clayborn; Adams, Paul C

    2017-01-01

    373 black participants had elevated screening and post-screening serum ferritin (SF) (> 300 μg/L men; > 200 μg/L women). We retrospectively studied SF and post-screening age; sex; body mass index; transferrin saturation (TS); ALT; AST; GGT; elevated C-reactive protein; ß-thalassemia; neutrophils; lymphocytes; monocytes; platelets; metacarpophalangeal joint hypertrophy; hepatomegaly; splenomegaly; diabetes; HFE H63D positivity; iron/alcohol intakes; and blood/erythrocyte transfusion units. Liver disease was defined as elevated ALT or AST. We computed correlations of SF and TS with: age; body mass index; ALT; AST; GGT; C-reactive protein; blood cell counts; and iron/alcohol. We compared participants with SF > 1,000 and ≤ 1,000 μg/L and performed regressions on SF. There were 237 men (63.5%). Mean age was 55 ± 13 (SD) y. 143 participants had liver disease (62 hepatitis B or C). There were significant correlations of SF: TS, ALT, AST, GGT, and monocytes (positive); and SF and TS with platelets (negative). 22 participants with SF > 1,000 μg/L had significantly higher median TS, ALT, and AST, and prevalences of anemia and transfusion > 10 units; and lower median platelets. Regression on SF revealed significant associations: TS; male sex; age; GGT; transfusion units (positive); and splenomegaly (negative) (p < 0.0001, 0.0016, 0.0281, 0.0025, 0.0001, and 0.0096, respectively). Five men with SF > 1,000 μg/L and elevated TS had presumed primary iron overload (hemochromatosis). Four participants had transfusion iron overload. Persistent hyperferritinemia in 373 black adults was associated with male sex, age, TS, GGT, and transfusion. 2.4% had primary iron overload (hemochromatosis) or transfusion iron overload.

  20. Primary Conjunctival Tuberculosis Presenting as Dry Eye: A Rare Case Report and Review of the Literature.

    PubMed

    Brar, Rupinder Kaur; Singh, Ashok; Deshpande, Archana Hemant; Gargade, Chitrawati Bal; Das, Sujit

    2017-11-01

    Primary conjunctival tuberculosis is very rare in the developed countries. In an endemic country like India, it should be considered in the differential diagnosis of any unusual conjunctival lesion with unilaterality, chronicity, and nonresolution of symptoms after steroid use. We present the case of a 52-year-old female who presented with unilateral itching and blurring of vision for 20 days. There were irregular nodular elevated areas with shrinkage of the lower palpebral conjunctiva. A biopsy of the lesion revealed necrotizing epithelioid cell granulomas along with Langhans type of giant cells. However, no acid-fast bacilli were seen on Ziehl-Neelsen stain. Systemic examination of the patient was normal, and there was no evidence of pulmonary tuberculosis. Polymerase chain reaction of conjunctival scrapings was positive for Mycobacterium tuberculosis . The patient was started on antitubercular drugs. We present this very rare case of primary tuberculosis of the conjunctiva presenting with dryness of the eye.

  1. TUBULOINTERSTITIAL NEPHRITIS AND UVEITIS SYNDROME WITH A PRIMARY PRESENTATION OF ACUTE POSTERIOR MULTIFOCAL PLACOID PIGMENT EPITHELIOPATHY.

    PubMed

    Lee, Andrew R; Sharma, Sumit; Mahmoud, Tamer H

    2017-01-01

    To report a case of tubulointerstitial nephritis and uveitis syndrome with a primary presentation of acute posterior multifocal placoid pigment epitheliopathy after use of lamotrigine. Retrospective case report with ultra-widefield fundus imaging, optical coherence tomography, and fluorescein angiography. A 19-year-old woman presented with decreased visual acuity and acute renal failure after starting lamotrigine. Her examination demonstrated 1+ anterior chamber cell and numerous white deep retinal plaque-like lesions predominantly in the macula in both eyes. After extensive ophthalmic and systemic evaluation, the patient was diagnosed with tubulointerstitial nephritis and uveitis syndrome with a primary presentation of acute posterior multifocal placoid pigment epitheliopathy. She had excellent visual recovery with topical and systemic steroids. Acute posterior multifocal placoid pigment epitheliopathy is a rare but important clinical presentation of tubulointerstitial nephritis and uveitis syndrome. Oral corticosteroid treatment can be considered for tubulointerstitial nephritis but is generally not necessary for acute posterior multifocal placoid pigment epitheliopathy.

  2. Juvenile hemochromatosis: HAMP mutation and severe iron overload treated with phlebotomies and deferasirox.

    PubMed

    Lescano, Manuel A; Tavares, Letícia C; Santos, Paulo C J L

    2017-10-16

    Juvenile hemochromatosis (JH) is a rare condition classified as an autosomal recessive disorder that leads to severe iron absorption. JH usually affects people under the age of 30 and presents symptoms such as chronic liver damage, hypogonadotropic hypogonadism, cardiac diseases and endocrine dysfunctions. The present case reports a 29-year-old Brazilian woman with JH condition due to HAMP mutation (g.47G>A), treated with phlebotomies and deferasirox. She presented symptoms such as weakness, skin hyperpigmentation, joint pain in the shoulders and hands and amenorrhea. First laboratory tests showed altered biochemical parameters [serum ferritin (SF): 5696 ng/mL, transferrin saturation (TS): 85%]. After sessions of phlebotomies (450 mL every 15 d), the patient presented partial symptomatic improvements and biochemical parameters (SF: 1000 ng/mL, Hb: 11 g/dL). One year later, deferasirox (15 mg/kg per day) was introduced to the treatment, and the patient showed total symptomatic improvement, with significant clearing of the skin, SF: 169 ng/mL, and TS: 50%. Furthermore, after the combined deferasirox-phlebotomy therapy, magnetic resonance imaging measurements revealed normalized level for liver iron (30 μmol/g; reference value < 36 μmol/g). In conclusion, combined deferasirox-phlebotomy treatment was able to normalize iron levels and improve symptoms.

  3. Juvenile hemochromatosis: HAMP mutation and severe iron overload treated with phlebotomies and deferasirox

    PubMed Central

    Lescano, Manuel A; Tavares, Letícia C; Santos, Paulo C J L

    2017-01-01

    Juvenile hemochromatosis (JH) is a rare condition classified as an autosomal recessive disorder that leads to severe iron absorption. JH usually affects people under the age of 30 and presents symptoms such as chronic liver damage, hypogonadotropic hypogonadism, cardiac diseases and endocrine dysfunctions. The present case reports a 29-year-old Brazilian woman with JH condition due to HAMP mutation (g.47G>A), treated with phlebotomies and deferasirox. She presented symptoms such as weakness, skin hyperpigmentation, joint pain in the shoulders and hands and amenorrhea. First laboratory tests showed altered biochemical parameters [serum ferritin (SF): 5696 ng/mL, transferrin saturation (TS): 85%]. After sessions of phlebotomies (450 mL every 15 d), the patient presented partial symptomatic improvements and biochemical parameters (SF: 1000 ng/mL, Hb: 11 g/dL). One year later, deferasirox (15 mg/kg per day) was introduced to the treatment, and the patient showed total symptomatic improvement, with significant clearing of the skin, SF: 169 ng/mL, and TS: 50%. Furthermore, after the combined deferasirox-phlebotomy therapy, magnetic resonance imaging measurements revealed normalized level for liver iron (30 μmol/g; reference value < 36 μmol/g). In conclusion, combined deferasirox-phlebotomy treatment was able to normalize iron levels and improve symptoms. PMID:29085829

  4. Primary Sjögren syndrome that initially presented with repeated hypergammaglobulinemic purpura after prolonged sitting

    PubMed Central

    Zhou, Zhihua; Jiang, Weiqiang; Wang, Ming; Liu, Yongyuan; Zhang, Wei; Huang, Manping; Liang, Donghui

    2017-01-01

    Abstract Rationale: Purpura is a common dermatologic manifestation in Sjögren syndrome (SS). When a patient presents with sicca symptoms, the diagnosis of SS is not difficult. Patient concerns: Here, we reported a case of a 52-year-old Chinese woman who initially presented with nonpalpable purpura on both lower extremities, and these lesions had developed soon after prolonged sitting. In the past 2 years, she had repeated cutaneous nonpalpable purpura 4 times. She had no sicca symptoms, dry eyes, or dry mouth. Diagnoses: Combining the laboratory findings, Schirmer test, and labial gland biopsy, primary SS was confirmed. Interventions: The patient was placed on a trial of hydroxychloroquine (200 mg once daily). Outcomes: The purpura on both lower extremities had faded at the sixth day after onset and at the third day after hydroxychloroquine treatment. Lessons: These case was not easy to diagnosis primary SS because she had no sicca symptoms. A patient with primary SS who initially presented with recurrent purpura associated with prolonged sitting. Prolonged sitting had been a possible aggravating factor for the cutaneous purpura of this patient with primary SS. PMID:29390329

  5. Primary neurolymphomatosis of the lower cranial nerves presenting as Dysphagia and hoarseness: a case report.

    PubMed

    Sakai, Naoto; Ito-Yamashita, Tae; Takahashi, Goro; Baba, Satoshi; Koizumi, Shinichiro; Yamasaki, Tomohiro; Tokuyama, Tsutomu; Namba, Hiroki

    2014-08-01

    Primary neurolymphomatosis is an extremely rare tumor. We report the case of a 74-year-old patient presenting with dysphagia and hoarseness. Initial contrast-enhanced computed tomography of the head, neck, and chest did not reveal any lesions. His symptoms improved with short-term administration of prednisone but recurred and deteriorated. Magnetic resonance (MR) imaging revealed a tumor along the ninth and tenth cranial nerves across the jugular foramen. Fluorine-18 fluorodeoxyglucose positron emission tomography indicated this was a primary tumor. Repeated MR imaging after 2 months revealed considerable tumor enlargement. A left suboccipital craniotomy was performed to remove the tumor that infiltrated the ninth and tenth cranial nerves. The histopathologic diagnosis was diffuse large B-cell lymphoma. Although focal radiation therapy was administered to ensure complete eradication of the tumor, the patient died of aspiration pneumonia with systemic metastasis. To our knowledge, this is the first reported case of primary neurolymphomatosis in the lower cranial nerves.

  6. Screening for hemochromatosis by measuring ferritin levels: a more effective approach

    PubMed Central

    Waalen, Jill; Felitti, Vincent J.; Gelbart, Terri

    2008-01-01

    Because the penetrance of HFE hemochromatosis is low, traditional population screening measuring the transferrin saturation is unlikely to be cost-effective because the majority of subjects detected neither have clinical disease nor are likely to develop it. Three independent studies show that only patients with serum ferritin concentrations more than 1000 μg/L are at risk for cirrhosis, one of the main morbidities of hemochromatosis. Among 29 699 white subjects participating in the Scripps/Kaiser hemochromatosis study, only 59 had serum ferritin levels more than 1000 μg/L; 24 had homozygous mutant or compound heterozygous mutant HFE genotypes. In all but 5 of the other subjects, the causes of elevated ferritin were excessive alcohol intake, cancer, or liver disease. Screening for hemochromatosis with serum ferritin levels will detect the majority of patients who will be clinically affected and may detect other clinically significant disease in patients who do not have hemochromatosis genotypes. Because the ferritin level of the majority of adult homozygotes for HFE mutations does not rise over long periods of time, excluding subjects with serum ferritin levels less than or equal to 1000 μg/L should not result in missed opportunities for early treatment of patients who could benefit. PMID:18025154

  7. Unusual Presentation of a Primary Ewing's Sarcoma of the Spine with Paraplegia: A Case Report.

    PubMed

    Kannan, Karthik Kailash; Sundarapandian, Rajkumar Jayachandran; Surulivel, Vignesh Jayabalan

    2015-03-01

    Ewing's sarcoma is a primary malignancy of the bone affecting individuals in the second decade of life. Primary sarcomas of the spine are rare and the occurrence of Primary Ewing's sarcoma in the spine is very rare. Ewing's sarcoma occurring in the spine is divided into two types, Ewing's sarcoma of sacral spine which are very aggressive with poor prognosis and Ewing's sarcoma of the non sacral spine which is an extremely rare occurrence. Patient may present with neurological deficit when the tumour extends into the spinal canal causing spinal cord compression. Magnetic resonance imaging (MRI) is very sensitive in diagnosing the tumour and defining the extent of the tumour. Here we report an 18-year-old boy who presented with back pain and complete paraplegia of two months duration. The MRI gave a differential diagnosis of infective pathology due to the fluid collection in the paraspinal region, followed by primary malignancy as the second diagnosis. Patient underwent posterior spinal decompression and stabilization, and intaoperatively there was significant collection of pus whose culture showed no growth. The histopathology and immunohistochemistry studies confirmed the diagnosis of Ewing's sarcoma and patient was started on combination chemotherapy and radiotherapy.

  8. Physicists in Primary Schools (PIPS) Project: Fun Presentations for Physicists to Take into Schools Worldwide (abstract)

    NASA Astrophysics Data System (ADS)

    Marks, Ann

    2009-04-01

    The Physicists in Primary Schools (PIPS) project is a joint venture initiated by the UK Women in Physics Group. A team from the University of Sheffield, with Engineering and Physical Sciences Research Council funding, has developed fun presentations and novel class activities using everyday articles for physicists to take into primary schools. The objectives are to instill enthusiasm in young children-including girls-through the enjoyment and excitement of physics, and support primary school teachers with a curriculum which includes many abstract concepts. All PIPS material is free to download from the Institute of Physics website (www.iop.org/pips), providing PowerPoint presentations and detailed explanations, as well as videos of the activities in classrooms. The topics are suitable for children age 4 to 11 years. There is interest in translating the presentations into other languages as there are few words on the slides and the material is likely valuable for older age groups. The presentations therefore have the potential to be useful worldwide.

  9. A Rare, Unusual Presentation of Primary Tuberculosis in the Temporomandibular Joint.

    PubMed

    Towdur, Geetha N; Upasi, Amarnath P; Veerabhadrappa, Umashankara Kagathur; Rai, Kirthikumar

    2018-04-01

    Tuberculosis (TB) is a very common health problem in developing nations such as India. It can present as its primary form or as secondary forms (extrapulmonary TB). Maxillofacial manifestations of TB compose nearly 10% of all extrapulmonary manifestations of the disease. Extrapulmonary TB involving the maxillofacial region is very rare and can present in any tissues in this region. These infections generally involve the head and neck through hematogenous or lymphatic routes. Very few cases of primary TB of the temporomandibular joint (TMJ) have been reported in the literature. The presentation of TB infection of the TMJ can resemble arthritis, osteomyelitis, or any other kind of chronic joint disease. It is very important to diagnose this disease at an early stage. If left untreated, it can prove fatal within 5 years in more than half the cases. Therefore, early diagnosis and management of these cases is critical. This article describes a case of primary TB of the TMJ that presented as a preauricular swelling. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  10. The WT hemochromatosis protein HFE inhibits CD8⁺ T-lymphocyte activation.

    PubMed

    Reuben, Alexandre; Phénix, Mikaël; Santos, Manuela M; Lapointe, Réjean

    2014-06-01

    MHC class I (MHC I) antigen presentation is a ubiquitous process by which cells present endogenous proteins to CD8(+) T lymphocytes during immune surveillance and response. Hereditary hemochromatosis protein, HFE, is involved in cellular iron uptake but, while structurally homologous to MHC I, is unable to bind peptides. However, increasing evidence suggests a role for HFE in the immune system. Here, we investigated the impact of HFE on CD8(+) T-lymphocyte activation. Using transient HFE transfection assays in a model of APCs, we show that WT HFE (HFEWT ), but not C282Y-mutated HFE, inhibits secretion of MIP-1β from antigen-specific CD8(+) T lymphocytes. HFEWT expression also resulted in major decreases in CD8(+) T-lymphocyte activation as measured by 4-1BB expression. We further demonstrate that inhibition of CD8(+) T-lymphocyte activation was independent of MHC I surface levels, β2-m competition, HFE interaction with transferrin receptor, antigen origin, or epitope affinity. Finally, we identified the α1-2 domains of HFEWT as being responsible for inhibiting CD8(+) T-lymphocyte activation. Our data imply a new role for HFEWT in altering CD8(+) T-lymphocyte reactivity, which could modulate antigen immunogenicity. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Review of epidemiology, clinical presentation, diagnosis, and treatment of common primary psychiatric causes of cutaneous disease.

    PubMed

    Krooks, J A; Weatherall, A G; Holland, P J

    2018-06-01

    Approximately half of all patients presenting to dermatologists exhibit signs and symptoms of psychiatric conditions that are either primary or secondary to cutaneous disease. Because patients typically resist psychiatric consult, dermatologists often are on the front line in evaluating and treating these patients. Accordingly, distinguishing the specific underlying or resulting psychiatric condition is essential for effective treatment. The etiology, epidemiology, clinical presentation, diagnosis, and first-line treatment of specific primary psychiatric causes of dermatologic conditions, including delusional infestation, Morgellons syndrome, olfactory reference syndrome, body dysmorphic disorder, excoriation disorder, trichotillomania, and dermatitis artefacta are discussed here, followed by a discussion of the recommended treatment approach with an overview of the different first-line therapies discussed in this review, specifically cognitive behavioral therapy, atypical antipsychotics, selective serotonin reuptake inhibitors, and tricyclic antidepressants. Included is a guide for dermatologists to use while prescribing these medications.

  12. Pericardial Effusion with Cardiac Tamponade as a form of presentation of Primary Hypothyroidism.

    PubMed

    Agarwal, Arun; Chowdhury, Nikhil; Mathur, Ankit; Sharma, Samiksha; Agarwal, Aakanksha

    2016-12-01

    Hypothyroidism is a rare cause of pericardial effusion (PE). Pericardial effusion secondary to hypothyroidism remains a diagnostic challenge for clinicians because of its inconsistency between symptoms and amount of pericardial effusion. We report an atypical case that presented with ascites and was diagnosed to have cardiac tamponade secondary to primary hypothyroidism. Besides repeated pericardiocentesis she eventually required surgical management and optimization of medical therapy to manage the massive pericardial effusion. © Journal of the Association of Physicians of India 2011.

  13. [Primary carcinoma of the thyroid growing in thyroglossal duct cyst: presentation of two cases].

    PubMed

    Godlewska, Paulina; Bruszewska, Elzbieta; Kozłowicz-Gudzińska, Izabella; Prokurat, Andrzej I; Chrupek, Małgorzata; Zegadło-Mylik, Maria A; Kluge, Przemysław

    2007-01-01

    Thyroglossal duct remnants (TGDR), most often cysts, are the most common type of developmental abnormalities of the thyroid gland. In about 1 to 2% of TGDR neoplastic transformation occurs. Papillary carcinoma of the thyroid may be encountered in over 90% of such cases. Two cases of primary papillary carcinoma of the thyroid in TGDR in young girls are presented. The diagnostic and therapeutic problems are shared, and up-to-date management guidelines in similar cases are discussed.

  14. Lung cancer in symptomatic patients presenting in primary care: a systematic review of risk prediction tools

    PubMed Central

    Schmidt-Hansen, Mia; Berendse, Sabine; Hamilton, Willie; Baldwin, David R

    2017-01-01

    Background Lung cancer is the leading cause of cancer deaths. Around 70% of patients first presenting to specialist care have advanced disease, at which point current treatments have little effect on survival. The issue for primary care is how to recognise patients earlier and investigate appropriately. This requires an assessment of the risk of lung cancer. Aim The aim of this study was to systematically review the existing risk prediction tools for patients presenting in primary care with symptoms that may indicate lung cancer Design and setting Systematic review of primary care data. Method Medline, PreMedline, Embase, the Cochrane Library, Web of Science, and ISI Proceedings (1980 to March 2016) were searched. The final list of included studies was agreed between two of the authors, who also appraised and summarised them. Results Seven studies with between 1482 and 2 406 127 patients were included. The tools were all based on UK primary care data, but differed in complexity of development, number/type of variables examined/included, and outcome time frame. There were four multivariable tools with internal validation area under the curves between 0.88 and 0.92. The tools all had a number of limitations, and none have been externally validated, or had their clinical and cost impact examined. Conclusion There is insufficient evidence for the recommendation of any one of the available risk prediction tools. However, some multivariable tools showed promising discrimination. What is needed to guide clinical practice is both external validation of the existing tools and a comparative study, so that the best tools can be incorporated into clinical decision tools used in primary care. PMID:28483820

  15. Anti-obesity and pro-diabetic effects of hemochromatosis.

    PubMed

    Abbas, Mousa Al; Abraham, Deveraprabu; Kushner, James P; McClain, Donald A

    2014-10-01

    Levels of tissue iron contribute to determining diabetes risk, but little is known about the effects of higher iron levels on weight, and on the interaction of weight and iron overload on diabetes risk. Therefore, the effect of iron on body mass index and diabetes in individuals with iron overload from hereditary hemochromatosis (HH), compared to non-HH siblings and historical controls was examined. Chart reviews were performed on a cohort of adults (age ≥40, N = 101) with the common C282Y/C282Y HFE genotype, compared to wild type siblings (N = 32) and comparable NHANES cohorts, with respect to body mass index and diabetes status. Males with HH have lower body mass index (BMI) than control siblings. Females had a trend toward decreased BMI that was not significant, possibly related to decreased degrees of iron overload. In both males and females, increased rates of diabetes were seen, especially in the overweight or obese. High tissue iron levels may be both pro- and anti-diabetic. The prevalence of obesity and diabetes in HH is likely dependent upon the degree of iron overload, caloric intake, and other genetic and environmental factors, contributing to the observed heterogeneity in the frequency of disease-related morbidities in HH. Copyright © 2014 The Obesity Society.

  16. Anti-Obesity and Pro-Diabetic Effects of Hemochromatosis

    PubMed Central

    Abbas, Mousa Al; Abraham, Deveraprabu; Kushner, James P.; McClain, Donald A.

    2014-01-01

    Objective Levels of tissue iron contribute to determining diabetes risk, but little is known about the effects of higher iron levels on weight, nor on the interaction of weight and iron overload on diabetes risk. We therefore examined the effect of iron on body mass index and diabetes in individuals with iron overload from hereditary hemochromatosis (HH), compared to non-HH siblings and historical controls. Methods Chart reviews were performed on a cohort of adults (age ≥40, N=101) with the common C282Y/C282Y HFE genotype, compared to wild type siblings (N=32) and comparable NHANES cohorts, with respect to body mass index and diabetes status. Results Males with HH have lower body mass index (BMI) than control siblings. Females had a trend toward decreased BMI that was not significant, possibly related to decreased degrees of iron overload. In both males and females, increased rates of diabetes were seen, especially in the overweight or obese. Conclusions High tissue iron levels may be both pro- and anti-diabetic. The prevalence of obesity and diabetes in HH is likely dependent upon the degree of iron overload, caloric intake, and other genetic and environmental factors, contributing to the observed heterogeneity in the frequency of disease-related morbidities in HH. PMID:25044717

  17. The infectious disease blood safety risk of Australian hemochromatosis donations.

    PubMed

    Hoad, Veronica; Bentley, Peter; Bell, Barbara; Pathak, Praveen; Chan, Hiu Tat; Keller, Anthony

    2016-12-01

    It has been suggested that blood donors with hereditary hemochromatosis may pose an increased infectious disease risk and adversely affect recipient outcomes. This study compares the infectious disease risk of whole blood (WB) donors enrolled as therapeutic (T) donors to voluntary WB donors to evaluate the safety of blood products provided by the T donors. This was a retrospective cohort study of all WB donations at the Australian Red Cross Blood Service who donated between January 1, 2011, and December 31, 2013, comparing a yearly mean of 11,789 T donors with 107,773 total donations and a yearly mean of 468,889 voluntary WB donors with 2,584,705 total donations. We compared postdonation notification of infectious illnesses, bacterial contamination screening results, and positive tests for blood borne viruses in T and WB donors. Rates of transfusion-transmissible infections in donations destined for component manufacture were significantly lower in therapeutic donations compared to voluntary donations (8.4 vs. 21.6 per 100,000 donations). Bacterial contamination (43.0 vs. 45.9 per 100,000 donations) and postdonation illness reporting (136.2 vs. 110.8 per 100,000 donations) were similar in both cohorts. The Australian therapeutic venisection program enables T donors to provide a safe and acceptable source of donated WB that has a low infectious disease risk profile. © 2016 AABB.

  18. Non-healing gastro-duodenal ulcer: A rare presentation of primary abdominal tuberculosis

    PubMed Central

    Merali, Nabeel; Chandak, Pankaj; Doddi, Sudeendra; Sinha, Prakash

    2014-01-01

    INTRODUCTION We present a case of primary gastrointestinal tuberculosis that has culminated in ulcer formation, in the absence of pulmonary involvement in an immunocompetent patient. PRESENTATION OF CASE A 28-year-old Asian male presented to casualty with a 1-week history of epigastric cramping abdominal pain and several episodes of non-bilious vomiting. The patient deteriorated clinically, becoming more cachectic and given his unexplained weight loss, an oesophageal-gastro-duodenal endoscopic imaging confirmed a duodenal ulcer. The biopsy of the non-healing ulcer was the hallmark of the disease, revealing evidence of granulomatous inflammation consistent with tuberculosis bacilli. DISCUSSION Gastrointestinal tuberculosis with ulceration is rare with respect to the oesophagus, stomach and duodenum. This case proves to be unique, as our patient had experienced primary isolated gastric tuberculosis in the absence of pulmonary tuberculosis in a healthy individual. Immunohistochemical staining, histopathology and radiological investigations have demonstrated their importance in confirming abdominal tuberculosis and the extent of bowel involvement. CONCLUSION This case has illustrated the difficulties associated with a prompt diagnosis of an unusual case of primary duodenal tuberculosis from chronic peptic ulcer disease in an immunocompetent patient. PMID:25506841

  19. Extracavitary/solid variant of primary effusion lymphoma presenting as a gastric mass.

    PubMed

    Liao, Guanghong; Cai, Junchao; Yue, Changjun; Qing, Xin

    2015-12-01

    Primary effusion lymphoma (PEL) is a rare subtype of large B-cell lymphoma associated with human herpesvirus 8 (HHV8). It has the highest incidence in HIV-positive individuals. It often presents as a malignant pleural, peritoneal and/or pericardial effusion without a detectable solid mass. Most cases are co-infected with Epstein-Barr virus (EBV). Rare cases of HHV8-positive lymphoma with features similar to PEL can present as tumor masses and are considered to represent an extracavitary or solid variant of PEL. We report a case of EBV negative, extracavitary/solid variant of primary effusion lymphoma presenting as a gastric mass. A 48-year-old man was admitted to an outside hospital with abdominal pain and weight loss. At the outside hospital, he was found to be HIV positive and have a 3 × 2 cm gastric mass. He was subsequently diagnosed with ALK negative anaplastic large cell lymphoma by gastric biopsy. The patient was referred to Harbor-UCLA Medical Center for further management. Review of the outside slides and additional stains performed at our hospital revealed sheets of large anaplastic lymphoma cells that were positive for CD30, CD138, MUM1 and HHV8, focally weakly positive for CD3, and negative for other T- and B-cell markers and EBER, consistent with extracavitary/solid variant of primary effusion lymphoma. Interestingly, for the first time, cyclin D1 positivity was also demonstrated in PEL. Primary effusion lymphoma, particularly the extracavitary/solid variant, is very rare, and the diagnosis can be challenging. In some cases, when CD30 is uniformly positive, this lymphoma can be misdiagnosed as ALK negative anaplastic large cell lymphoma. This lymphoma can also aberrantly express T-cell markers as seen in this case, making diagnosis even more difficult. Awareness of the existence and the features of solid variant PEL and assessment for HHV8 infection are essential for correct diagnosis. Published by Elsevier Inc.

  20. Potential nonresponse bias in a clinical examination after initial screening using iron phenotyping and HFE genotyping in the hemochromatosis and iron overload screening study.

    PubMed

    Speechley, Mark; Barton, James C; Passmore, Leah; Harrison, Helen; Reboussin, David M; Harris, Emily L; Rivers, Charles A; Fadojutimi-Akinsiku, Margaret; Wenzel, Lari; Diaz, Sharmin

    2009-12-01

    Little is known about the factors affecting participation in clinical assessments after HEmochromatosis and IRon Overload Screening. Initial screening of 101,168 primary care patients in the HEmochromatosis and IRon Overload Screening study was performed using serum iron measures and hemochromatosis gene (HFE) genotyping. Using iron phenotypes and HFE genotypes, we identified 2256 cases and 1232 controls eligible to participate in a clinical examination. To assess the potential for nonresponse bias, we compared the sociodemographic, health status, and attitudinal characteristics of participants and nonparticipants using adjusted odds ratios (ORs) and 95% confidence interval (CI). Overall participation was 74% in cases and 52% in controls; in both groups, participation was highest at a health maintenance organization and lowest among those under 45 years of age (cases: OR = 0.68; 95% CI 0.53, 0.87; controls: OR = 0.59; 95% CI 0.44, 0.78). In controls only, participation was also lower among those over 65 years of age than the reference group aged 46-64 (OR = 0.64; 95% CI 0.47, 0.88). Among cases, participation was higher in HFE C282Y homozygotes (OR = 3.98; 95% CI 2.60, 6.09), H63D homozygotes (OR = 2.79; 95% CI 1.23, 6.32), and C282Y/H63D compound heterozygotes (OR = 1.82; 95% CI 1.03, 3.22) than in other genotypes, and lower among non-Caucasians and those who preferred a non-English language than in Caucasians and those who preferred English (p < 0.0001). Subjects with greatest risk to have iron overload (C282Y homozygotes; cases > or =45 years; Caucasians) were more likely to participate in a postscreening clinical examination than other subjects. We detected no evidence of strong selection bias.

  1. Therapeutic management of neonatal hemochromatosis: report of four cases and literature review.

    PubMed

    Annagür, Ali; Altunhan, Hüseyin; Yüksekkaya, Hasan Ali; Örs, Rahmi

    2011-10-01

    Neonatal hemochromatosis (NH) is a rare disease of iron metabolism that starts at intrauterine period causing liver failure and extrahepatic siderozis. The etiology of NH has not been understood exactly, yet it is accepted that a maternofetal alloimmune disorder that leads to liver failure in fetus causes the illness. The prognosis of NH is generally bad and death is inevitable if left untreated. The efficiency of chelation-antioxidant coctail used in medical treatment is between 10% and 20% and these patients frequently need liver transplantation. In our study, we presented four newborn cases diagnosed as NH and treated medically. Of the four patients, one died of pulmonary hemorrhage and another died of multiorgan failure in the first week of hospitalization. The other two patients' clinical status and laboratory parameters recovered with medical treatment. However, since liver transplantation was not carried out, one of these patients died at the age of two and a half months and the other at eighth month due to sepsis. In this study, we would like to emphasize the importance of early liver transplantation in patients recovered with medical treatment.

  2. EMQN best practice guidelines for the molecular genetic diagnosis of hereditary hemochromatosis (HH).

    PubMed

    Porto, Graça; Brissot, Pierre; Swinkels, Dorine W; Zoller, Heinz; Kamarainen, Outi; Patton, Simon; Alonso, Isabel; Morris, Michael; Keeney, Steve

    2016-04-01

    Molecular genetic testing for hereditary hemochromatosis (HH) is recognized as a reference test to confirm the diagnosis of suspected HH or to predict its risk. The vast majority (typically >90%) of patients with clinically characterized HH are homozygous for the p.C282Y variant in the HFE gene, referred to as HFE-related HH. Since 1996, HFE genotyping was implemented in diagnostic algorithms for suspected HH, allowing its early diagnosis and prevention. However, the penetrance of disease in p.C282Y homozygotes is incomplete. Hence, homozygosity for p.C282Y is not sufficient to diagnose HH. Neither is p.C282Y homozygosity required for diagnosis as other rare forms of HH exist, generally referred to as non-HFE-related HH. These pose significant challenges when defining criteria for referral, testing protocols, interpretation of test results and reporting practices. We present best practice guidelines for the molecular genetic diagnosis of HH where recommendations are classified, as far as possible, according to the level and strength of evidence. For clarification, the guidelines' recommendations are preceded by a detailed description of the methodology and results obtained with a series of actions taken in order to achieve a wide expert consensus, namely: (i) a survey on the current practices followed by laboratories offering molecular diagnosis of HH; (ii) a systematic literature search focused on some identified controversial topics; (iii) an expert Best Practice Workshop convened to achieve consensus on the practical recommendations included in the guidelines.

  3. EMQN best practice guidelines for the molecular genetic diagnosis of hereditary hemochromatosis (HH)

    PubMed Central

    Porto, Graça; Brissot, Pierre; Swinkels, Dorine W; Zoller, Heinz; Kamarainen, Outi; Patton, Simon; Alonso, Isabel; Morris, Michael; Keeney, Steve

    2016-01-01

    Molecular genetic testing for hereditary hemochromatosis (HH) is recognized as a reference test to confirm the diagnosis of suspected HH or to predict its risk. The vast majority (typically >90%) of patients with clinically characterized HH are homozygous for the p.C282Y variant in the HFE gene, referred to as HFE-related HH. Since 1996, HFE genotyping was implemented in diagnostic algorithms for suspected HH, allowing its early diagnosis and prevention. However, the penetrance of disease in p.C282Y homozygotes is incomplete. Hence, homozygosity for p.C282Y is not sufficient to diagnose HH. Neither is p.C282Y homozygosity required for diagnosis as other rare forms of HH exist, generally referred to as non-HFE-related HH. These pose significant challenges when defining criteria for referral, testing protocols, interpretation of test results and reporting practices. We present best practice guidelines for the molecular genetic diagnosis of HH where recommendations are classified, as far as possible, according to the level and strength of evidence. For clarification, the guidelines' recommendations are preceded by a detailed description of the methodology and results obtained with a series of actions taken in order to achieve a wide expert consensus, namely: (i) a survey on the current practices followed by laboratories offering molecular diagnosis of HH; (ii) a systematic literature search focused on some identified controversial topics; (iii) an expert Best Practice Workshop convened to achieve consensus on the practical recommendations included in the guidelines. PMID:26153218

  4. Tumor-Like Presentation of Primary Angiitis of the Central Nervous System.

    PubMed

    de Boysson, Hubert; Boulouis, Grégoire; Dequatre, Nelly; Godard, Sophie; Néel, Antoine; Arquizan, Caroline; Detante, Olivier; Bloch-Queyrat, Coralie; Zuber, Mathieu; Touzé, Emmanuel; Bienvenu, Boris; Aouba, Achille; Guillevin, Loïc; Naggara, Olivier; Pagnoux, Christian

    2016-09-01

    We aimed to describe the clinical and imaging features of patients with tumor-like presentation of primary angiitis of the central nervous system. We retrospectively analyzed 10 patients enrolled in the French primary angiitis of the central nervous system cohort, who initially presented tumor-like brain lesions and compared them with other patients within the cohort. The 10 patients with tumor-like presentation in the cohort were younger and had more seizures at diagnosis than the other 75 patients (median of 37 [30-48] years versus 46 [18-79] years; P=0.008; 9 [90%] with seizures versus 22 [29%], P<0.001; respectively). All 10 patients had a biopsy (stereotactic procedure in 7 and open-wedge surgery in 3). Histological findings suggestive of vasculitis were observed in 9 patients in whom conventional cerebral angiography and magnetic resonance angiography were negative. In the remaining patient, vascular imaging demonstrated diffuse bilateral large- and medium-sized vessel involvement (biopsy did not reveal vasculitis). All patients with tumor-like presentation received glucocorticoids, combined with cyclophosphamide in 9 cases. With a median follow-up of 27 (12-130) months, 5 (50%) patients relapsed, but achieved remission again after treatment intensification. Patients with tumor-like presentation of primary angiitis of the central nervous system represent a subgroup characterized with mainly small-sized vessel disease that requires histological confirmation because vascular imaging is often normal. Although relapses are not uncommon, global outcomes are good under treatment with glucocorticoids and cyclophosphamide. © 2016 American Heart Association, Inc.

  5. Non-healing gastro-duodenal ulcer: A rare presentation of primary abdominal tuberculosis.

    PubMed

    Merali, Nabeel; Chandak, Pankaj; Doddi, Sudeendra; Sinha, Prakash

    2015-01-01

    We present a case of primary gastrointestinal tuberculosis that has culminated in ulcer formation, in the absence of pulmonary involvement in an immunocompetent patient. A 28-year-old Asian male presented to casualty with a 1-week history of epigastric cramping abdominal pain and several episodes of non-bilious vomiting. The patient deteriorated clinically, becoming more cachectic and given his unexplained weight loss, an oesophageal-gastro-duodenal endoscopic imaging confirmed a duodenal ulcer. The biopsy of the non-healing ulcer was the hallmark of the disease, revealing evidence of granulomatous inflammation consistent with tuberculosis bacilli. Gastrointestinal tuberculosis with ulceration is rare with respect to the oesophagus, stomach and duodenum. This case proves to be unique, as our patient had experienced primary isolated gastric tuberculosis in the absence of pulmonary tuberculosis in a healthy individual. Immunohistochemical staining, histopathology and radiological investigations have demonstrated their importance in confirming abdominal tuberculosis and the extent of bowel involvement. This case has illustrated the difficulties associated with a prompt diagnosis of an unusual case of primary duodenal tuberculosis from chronic peptic ulcer disease in an immunocompetent patient. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Primary Intracranial Sarcoma Presenting as Chronic Subdural Fluid Collections in a Child.

    PubMed

    Glenn, Chad A; Fung, Kar-Ming; Tullos, Hurtis J; McNall-Knapp, Rene Y; Gunda, Divya; Mapstone, Timothy B

    2016-02-01

    Chronic subdural hematoma in the pediatric population often results from trauma. Asymptomatic and benign-appearing subdural collections are generally managed conservatively without operative intervention. Primary intracranial sarcomas are uncommon entities. Diagnosis of sarcoma can be difficult because these lesions often manifest as apparent hematoma. Presented is the case of a primary intracranial mucoid spindle cell sarcoma that arose in a child with a history of benign-appearing bilateral subdural fluid collections in the setting of nonaccidental trauma. The patient was initially managed conservatively because her neurological examination result was normal and her subdural collections decreased in size on repeated imaging. The collections did not resolve completely. Years later, she exhibited weakness, seizure, and an increase in the size of her subdural fluid collection. Subdural drainage was attempted without significant effect. Cytologic assessment of fluid was negative for malignant cells. Magnetic resonance imaging revealed multiple enhancing masses along the subdural collection. The patient eventually underwent craniotomy in which a diagnosis of sarcoma was obtained. Pathological and radiographic findings as well as oncological management are reviewed. The authors also review the natural history and treatment of primary intracranial sarcoma in the pediatric population. Early contrasted magnetic resonance imaging should be obtained in patients with subdural fluid collections that appear asymmetric or do not resolve in the expected time course, despite having a normal neurologic examination result. Negative cytologic assessment does not exclude sarcoma diagnosis. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Thyroid-stimulating hormone and free thyroxine levels in persons with HFE C282Y homozygosity, a common hemochromatosis genotype: the HEIRS study.

    PubMed

    Barton, James C; Leiendecker-Foster, Catherine; Reboussin, David M; Adams, Paul C; Acton, Ronald T; Eckfeldt, John H

    2008-08-01

    Relationships of thyroid and iron measures in large cohorts are unreported. We evaluated thyroid-stimulating hormone (TSH) and free thyroxine (T4) in white participants of the primary care-based Hemochromatosis and Iron Overload Screening (HEIRS) Study. We measured serum TSH and free T4 in 176 HFE C282Y homozygotes without previous hemochromatosis diagnoses and in 312 controls without HFE C282Y or H63D who had normal serum iron measures and were matched to C282Y homozygotes for Field Center, age group, and initial screening date. We defined hypothyroidism as having TSH >5.00 mIU/L and free T4 <0.70 ng/dL, and hyperthyroidism as having TSH <0.400 mIU/L and free T4 >1.85 ng/dL. Multivariate analyses were performed using age, sex, Field Center, log(10) serum ferritin (SF), HFE genotype, log(10) TSH, and log(10) free T4. Prevalences of hypothyroidism in C282Y homozygotes and controls were 1.7% and 1.3%, respectively, and of hyperthyroidism 0% and 1.0%, respectively. Corresponding prevalences did not differ significantly. Correlations of log(10) SF with log(10) free T4 were positive (p = 0.2368, C282Y homozygotes; p = 0.0492, controls). Independent predictors of log(10) free T4 were log(10) TSH (negative association) and age (positive association); positive predictors of log(10) SF were age, male sex, and C282Y homozygosity. Proportions of C282Y homozygotes and controls who took medications to supplement or suppress thyroid function did not differ significantly. Prevalences of hypothyroidism and hyperthyroidism are similar in C282Y homozygotes without previous hemochromatosis diagnoses and controls. In controls, there is a significant positive association of SF with free T4. We conclude that there is no rationale for routine measurement of TSH or free T4 levels in hemochromatosis or iron overload screening programs.

  8. Diagnoses during follow-up of patients presenting with fatigue in primary care.

    PubMed

    Nijrolder, Iris; van der Windt, Daniëlle; de Vries, Henk; van der Horst, Henriëtte

    2009-11-10

    Little is known about the distribution of diagnoses that account for fatigue in patients in primary care. We evaluated the diagnoses established within 1 year after presentation with fatigue in primary care that were possibly associated with the fatigue. We conducted a prospective observational cohort study with 1-year follow-up. We included adult patients who presented with a new episode of fatigue between June 2004 and January 2006. We extracted data on diagnoses during the follow-up period from the patients' medical records as well as data on pre-existing chronic diseases. Of the 571 patients for whom diagnostic data were available, 268 (46.9%) had received one or more diagnoses that could be associated with fatigue. The diagnoses were diverse and mostly included symptom diagnoses, with main categories being musculoskeletal (19.4%) and psychological problems (16.5%). Clear somatic pathology was diagnosed in 47 (8.2%) of the patients. Most diagnoses were not made during the consultation when fatigue was presented. Only a minority of patients were diagnosed with serious pathology. Half of the patients did not receive any diagnosis that could explain their fatigue. Nevertheless, because of the wide range of conditions and symptoms that may explain or co-occur with the fatigue, fatigue is a complex problem that deserves attention not only as a symptom of underlying specific disease.

  9. [Thinking about the present primary open angle glaucoma early diagnosis concepts and methods].

    PubMed

    Ren, Zeqin

    2014-05-01

    Early diagnosis of primary open-angle glaucoma has not been clear and consistent in concepts and methods. At present, according to the pathophysiology process of optic nerve damage and its detection technology, early diagnosis on the concept still belongs to the early clinical diagnosis instead of preclinical diagnosis, and on the method depends on the fundus as morphological index combined with the visual field as functional index. The direction of early clinical diagnosis mainly lies in exploring more effective diagnosis index, rather than blindly adopt new diagnostic technology.

  10. Precipitating factors of porphyria cutanea tarda in Brazil with emphasis on hemochromatosis gene (HFE) mutations. Study of 60 patients.

    PubMed

    Vieira, Fatima Mendonça Jorge; Nakhle, Maria Cristina; Abrantes-Lemos, Clarice Pires; Cançado, Eduardo Luiz Rachid; Reis, Vitor Manoel Silva dos

    2013-01-01

    Porphyria cutanea tarda is the most common form of porphyria, characterized by the decreased activity of the uroporphyrinogen decarboxylase enzyme. Several reports associated HFE gene mutations of hereditary hemochromatosis with porphyria cutanea tarda worldwide, although up to date only one study has been conducted in Brazil. Investigation of porphyria cutanea tarda association with C282Y and H63D mutations in the HFE gene. Identification of precipitating factors (hepatitis C, HIV, alcoholism and estrogen) and their link with HFE mutations. An ambispective study of 60 patients with PCT was conducted during the period from 2003 to 2012. Serological tests for hepatitis C and HIV were performed and histories of alcohol abuse and estrogen intake were investigated. HFE mutations were identified with real-time PCR. Porphyria cutanea tarda predominated in males and alcohol abuse was the main precipitating factor. Estrogen intake was the sole precipitating factor present in 25% of female patients. Hepatitis C was present in 41.7%. All HIV-positive patients (15.3%) had a history of alcohol abuse. Allele frequency for HFE mutations, i.e., C282Y (p = 0.0001) and H63D (p = 0.0004), were significantly higher in porphyria cutanea tarda patients, compared to control group. HFE mutations had no association with the other precipitating factors. Alcohol abuse, hepatitis C and estrogen intake are prevalent precipitating factors in our porphyria cutanea tarda population; however, hemochromatosis in itself can also contribute to the outbreak of porphyria cutanea tarda, which makes the research for HFE mutations necessary in these patients.

  11. Precipitating factors of porphyria cutanea tarda in Brazil with emphasis on hemochromatosis gene (HFE) mutations. Study of 60 patients*

    PubMed Central

    Vieira, Fatima Mendonça Jorge; Nakhle, Maria Cristina; Abrantes-Lemos, Clarice Pires; Cançado, Eduardo Luiz Rachid; dos Reis, Vitor Manoel Silva

    2013-01-01

    BACKGROUND Porphyria cutanea tarda is the most common form of porphyria, characterized by the decreased activity of the uroporphyrinogen decarboxylase enzyme. Several reports associated HFE gene mutations of hereditary hemochromatosis with porphyria cutanea tarda worldwide, although up to date only one study has been conducted in Brazil. OBJECTIVES Investigation of porphyria cutanea tarda association with C282Y and H63D mutations in the HFE gene. Identification of precipitating factors (hepatitis C, HIV, alcoholism and estrogen) and their link with HFE mutations. METHODS An ambispective study of 60 patients with PCT was conducted during the period from 2003 to 2012. Serological tests for hepatitis C and HIV were performed and histories of alcohol abuse and estrogen intake were investigated. HFE mutations were identified with real-time PCR. RESULTS Porphyria cutanea tarda predominated in males and alcohol abuse was the main precipitating factor. Estrogen intake was the sole precipitating factor present in 25% of female patients. Hepatitis C was present in 41.7%. All HIV-positive patients (15.3%) had a history of alcohol abuse. Allele frequency for HFE mutations, i.e., C282Y (p = 0.0001) and H63D (p = 0.0004), were significantly higher in porphyria cutanea tarda patients, compared to control group. HFE mutations had no association with the other precipitating factors. CONCLUSIONS Alcohol abuse, hepatitis C and estrogen intake are prevalent precipitating factors in our porphyria cutanea tarda population; however, hemochromatosis in itself can also contribute to the outbreak of porphyria cutanea tarda, which makes the research for HFE mutations necessary in these patients PMID:24068123

  12. Bone morphogenetic protein signaling is impaired in an Hfe knockout mouse model of hemochromatosis

    PubMed Central

    Corradini, Elena; Garuti, Cinzia; Montosi, Giuliana; Ventura, Paolo; Andriopoulos, Billy; Lin, Herbert Y.; Pietrangelo, Antonello; Babitt, Jodie L.

    2009-01-01

    Background and Aims Mutations in HFE are the most common cause of the iron-overload disorder hereditary hemochromatosis (HH). Levels of the main iron regulatory hormone, hepcidin, are inappropriately low in HH mouse models and patients with HFE mutations, indicating that HFE regulates hepcidin. The bone morphogenetic protein 6 (BMP6)-SMAD signaling pathway is an important endogenous regulator of hepcidin expression. We investigated whether HFE is involved in BMP6-SMAD regulation of hepcidin expression. Methods The BMP6-SMAD pathway was examined in Hfe knockout (KO) mice and in wild-type (WT) mice as controls. Mice were placed on diets of varying iron content. Hepcidin induction by BMP6 was examined in primary hepatocytes from Hfe KO mice; data were compared with those of WT mice. Results Liver levels of Bmp6 mRNA were higher in Hfe KO mice; these were appropriate for the increased hepatic levels of iron in these mice, compared with WT mice. However, levels of hepatic phosphorylated Smad 1/5/8 protein (an intracellular mediator of Bmp6 signaling) and Id1 mRNA (a target gene of Bmp6) were inappropriately low for the body iron burden and Bmp6 mRNA levels in Hfe KO, compared with WT mice. BMP6 induction of hepcidin expression was reduced in Hfe KO hepatocytes compared with WT hepatocytes. Conclusions HFE is not involved in regulation of BMP6 by iron, but does regulate the downstream signals of BMP6 that are triggered by iron. PMID:19591830

  13. Recurrent parotitis as a presentation of primary pediatric Sjögren syndrome.

    PubMed

    Baszis, Kevin; Toib, Dana; Cooper, Megan; French, Anthony; White, Andrew

    2012-01-01

    Parotitis is a common condition seen in the pediatric population, usually as an isolated occurrence associated with viral or bacterial infection. The differential diagnosis expands when recurrent parotitis is encountered. One etiology is primary pediatric Sjögren syndrome (SS), an autoimmune condition typically associated with dryness of the eyes and mouth in adults. Pediatric patients often present with isolated recurrent bilateral parotitis, however, and we describe 4 such cases in children aged 9 to 17 years at presentation. Despite lack of ocular complaints, 3 of these patients had ocular findings on ophthalmologic exam. Our patients also exhibited classic laboratory abnormalities, including positive antinuclear antibody, SS A, and SS B antibodies; presence of rheumatoid factor; and hypergammaglobulinemia. Consideration of SS in the child with recurrent parotitis is important for timely and appropriate referral and treatment. We review the differential diagnosis of parotitis in children as well as the salient features of pediatric SS.

  14. Diagnosis of systemic lupus erythematosus in an unusual presentation: what a primary care physician should know.

    PubMed

    Pramanik, Bimalendu

    2014-01-01

    Systemic Lupus Erythematosus (SLE) is a multisystem autoimmune disease affecting millions of people worldwide. It can affect any organ systems of the body. However, all systems may not be involved initially rather than they may be affected gradually, sometimes over years. Diagnosis depends on characteristic clinical features and laboratory test results. Some features such as skin rash, joint symptoms and oral ulcers are common in SLE. But initial presentation of many patients is unusual because either they do not have these common features of the disease or the presentation mimics other illnesses. As a result, delayed diagnosis and misdiagnosis are common. Therefore, high index of initial suspicion of SLE is critical. In clinical practice, SLE should be suspected in any patient presenting with an unexplained disease process involving two or more organ systems. To make a diagnosis in an unusual presentation, thorough clinical evaluation with details history of both present and past illnesses as well as laboratory tests for SLE should be performed. Usually primary-care physicians first evaluate SLE patients; but there is no single article, where all the information on when to suspect SLE in an unusual presentation, is available in an integrated form. In this article, a list of conditions, when SLE should be suspected in an unusual presentation, has been given and some relatively common areas with diagnostic challenges of SLE have been briefly described. To prepare this manuscript, most articles have been identified through 'Pubmed' search using keywords-atypical/ unusual presentation of SLE, case reports on SLE, gastrointestinal manifestations of SLE, neuropsychiatric SLE, diagnostic challenges with SLE, etc. Selected most articles are from currently medline-indexed journals.

  15. Patient characteristics associated with self-presentation, treatment delay and survival following primary percutaneous coronary intervention.

    PubMed

    Austin, David; Yan, Andrew T; Spratt, James C; Kunadian, Vijay; Edwards, Richard J; Egred, Mohaned; Bagnall, Alan J

    2014-09-01

    Delayed arrival to a primary percutaneous coronary intervention (PPCI)-capable hospital following ST-elevation myocardial infarction (STEMI) is associated with poorer outcome. The influence of patient characteristics on delayed presentation during STEMI is unknown. This was a retrospective observational study. Patients presenting for PPCI from March 2008 to November 2011 in the north of England (Northumbria, Tyne and Wear) were included. The outcomes were self-presentation to a non-PPCI-capable hospital, symptom to first medical contact (STFMC) time, total ischaemic time and mortality during follow-up. STEMI patients included numbered 2297; 619 (26.9%) patients self-presented to a non-PPCI-capable hospital. STFMC of >30 min and total ischaemic time of >180 min was present in 1521 (70.7%) and 999 (44.9%) cases, respectively. Self-presentation was the strongest predictor of prolonged total ischaemic time (odds ratio, OR (95% confidence interval, CI): 5.05 (3.99-6.39)). Married patients (OR 1.38 (1.10-1.74)) and patients living closest to an Emergency Room self-presented more commonly (driving time (vs. ≤10 min) 11-20 min OR 0.66 (0.52-0.83), >20 minutes OR 0.46 (0.33-0.64). Unmarried females waited longest to call for help (OR vs. married males 1.89 (1.29-2.78) and experienced longer total ischaemic times (OR 1.51 (1.10-2.07)). Married patients had a borderline association with lower mortality (hazard ratio 0.75 (0.53-1.05), p=0.09). Unmarried female patients had the longest treatment delays. Married patients and those living closer to an Emergency Room self-present more frequently. Early and exclusive use of the ambulance service may reduce treatment delay and improve STEMI outcome. © The European Society of Cardiology 2014.

  16. Contrast enema findings in patients presenting with poor functional outcome after primary repair for Hirschsprung disease.

    PubMed

    Garrett, Kevin M; Levitt, Marc A; Peña, Alberto; Kraus, Steven J

    2012-09-01

    The radiologic evaluation of Hirschsprung disease is well described in the literature. However, there is a paucity of literature describing the appearance of the neo-rectum and colon after repair, specifically describing findings in patients with poor functional outcome, which would suggest the need for reoperation. We describe findings on contrast enema and correlate them with surgical findings at reoperation in children with poor functional outcome after primary repair for Hirschsprung disease who suffer from bowel dysfunction that can manifest with either soiling or obstructive symptoms such as enterocolitis. Children were identified from our colorectal surgery database. At the time of abstract submission, 35 children had contrast enemas prior to reoperation. Additional children continue to present for evaluation. The majority of children included in the study had their primary repair performed elsewhere. The initial procedures included: Duhamel (n = 11), Soave (n = 20) or Swenson (n = 3). One child had undergone a primary Soave repair and subsequently had a Swenson-type reoperation but continued to have a poor outcome. One child's initial surgical repair could not be determined. Images were reviewed by a staff pediatric radiologist and a pediatric radiology fellow. Findings encountered on contrast enema in these children include a distal narrowed segment due to stricture or aganglionic/transitional zone segment (8), dilated/hypomotile distal segment (7), thickened presacral space due to compressing Soave cuff (11), dilated Duhamel pouch (8), active enterocolitis (3) and partially obstructing twist of the pull-through segment (1). Multiple anatomical and pathological complications exist that can lead to bowel dysfunction in children after repair of Hirschsprung disease. Little recent literature exists regarding the radiographic findings in children. We had the opportunity to review a substantial series of these children, describe the contrast enema

  17. Delayed breast cancer presentation: hospital data should inform proactive primary care

    PubMed Central

    Lunda, Samy; Fernandez, Leticia

    2013-01-01

    Abstract Background Breast (and cervical) cancer affects a growing proportion of women in South Africa. Although treatable, where health literacy is low, women typically seek medical attention only when their condition is at an advanced stage and difficult to contain. Objectives To understand the sociodemographic characteristics of women who present with advanced breast cancer in order to intervene proactively in primary care. Method A retrospective analysis of women with advanced breast cancer (Stage IIb and higher) at a Level 2 regional hospital in South Africa (2007–2010). Results The average age amongst the 103 women enrolled in this study was 59. One-third of the women had secondary education, 35% were unemployed and two-thirds were not married. Nearly 11% (n = 11) of the women had previously had cancer. Lumps (n = 87) were the most common reason for seeking healthcare and were, together with axillary lymph node abnormalities (84.5% and 19.4% respectively), the most common clinical symptoms. Symptoms were noticed by 52% (n = 54) of the women more than six months prior to their first consultation. A personal history of cancer increased threefold the odds of presenting within three months. Middle-aged women were twice as likely as those < 45 and > 65 to report within three to six months. Secondary education increased the odds of presenting within three to six months by 56%. Employment and marital status were not significant. Conclusion The women most at risk for delayed detection and treatment were those without a history of breast cancer, aged < 45 and > 65, with low education. They can best be reached through low-cost community-orientated primary care that proactively provides health education and promotes self- and clinical examination at the individual, family, clinic and general practitioner level.

  18. RCGP Research and Surveillance Centre Annual Report 2014–2015: disparities in presentations to primary care

    PubMed Central

    de Lusignan, Simon; Correa, Ana; Pathirannehelage, Sameera; Byford, Rachel; Yonova, Ivelina; Elliot, Alex J; Lamagni, Theresa; Amirthalingam, Gayatri; Pebody, Richard; Smith, Gillian; Jones, Simon; Rafi, Imran

    2017-01-01

    Background The Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) comprises over 100 general practices in England, with a population of around 1 million, providing a public health surveillance system for England and data for research. Aim To demonstrate the scope of data with the RCGP Annual Report 2014–2015 (May 2014 to April 2015) by describing disparities in the presentation of six common conditions included in the report. Design and setting This is a report of respiratory and communicable disease incidence from a primary care sentinel network in England. Method Incidence rates and demographic profiles are described for common cold, acute otitis media, pneumonia, influenza-like illness, herpes zoster, and scarlet fever. The impact of age, sex, ethnicity, and deprivation on the diagnosis of each condition is explored using a multivariate logistic regression. Results With the exception of herpes zoster, all conditions followed a seasonal pattern. Apart from pneumonia and scarlet fever, the odds of presenting with any of the selected conditions were greater for females (P<0.001). Older people had a greater probability of a pneumonia diagnosis (≥75 years, odds ratio [OR] 6.37; P<0.001). Common cold and influenza-like illness were more likely in people from ethnic minorities than white people, while the converse was true for acute otitis media and herpes zoster. There were higher odds of acute otitis media and herpes zoster diagnosis among the less deprived (least deprived quintile, OR 1.32 and 1.48, respectively; P<0.001). Conclusion The RCGP RSC database provides insight into the content and range of GP workload and provides insight into current public health concerns. Further research is needed to explore these disparities in presentation to primary care. PMID:27993900

  19. Genetic disruption of NRF2 promotes the development of necroinflammation and liver fibrosis in a mouse model of HFE-hereditary hemochromatosis.

    PubMed

    Duarte, Tiago L; Caldas, Carolina; Santos, Ana G; Silva-Gomes, Sandro; Santos-Gonçalves, Andreia; Martins, Maria João; Porto, Graça; Lopes, José Manuel

    2017-04-01

    In hereditary hemochromatosis, iron deposition in the liver parenchyma may lead to fibrosis, cirrhosis and hepatocellular carcinoma. Most cases are ascribed to a common mutation in the HFE gene, but the extent of clinical expression is greatly influenced by the combined action of yet unidentified genetic and/or environmental modifying factors. In mice, transcription factor NRF2 is a critical determinant of hepatocyte viability during exposure to acute dietary iron overload. We evaluated if the genetic disruption of Nrf2 would prompt the development of liver damage in Hfe -/- mice (an established model of human HFE-hemochromatosis). Wild-type, Nrf2 -/- , Hfe -/- and double knockout (Hfe/Nrf2 -/- ) female mice on C57BL/6 genetic background were sacrificed at the age of 6 (young), 12-18 (middle-aged) or 24 months (old) for evaluation of liver pathology. Despite the parenchymal iron accumulation, Hfe -/- mice presented no liver injury. The combination of iron overload (Hfe -/- ) and defective antioxidant defences (Nrf2 -/- ) increased the number of iron-related necroinflammatory lesions (sideronecrosis), possibly due to the accumulation of toxic oxidation products such as 4-hydroxy-2-nonenal-protein adducts. The engulfment of dead hepatocytes led to a gradual accumulation of iron within macrophages, featuring large aggregates. Myofibroblasts recruited towards the injury areas produced substantial amounts of collagen fibers involving the liver parenchyma of double-knockout animals with increased hepatic fibrosis in an age-dependent manner. The genetic disruption of Nrf2 promotes the transition from iron accumulation (siderosis) to liver injury in Hfe -/- mice, representing the first demonstration of spontaneous hepatic fibrosis in the long term in a mouse model of hereditary hemochromatosis displaying mildly elevated liver iron. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  20. Three forms of somatization presenting in primary care settings in Spain.

    PubMed

    García-Campayo, J; Lobo, A; Pérez-Echeverría, M J; Campos, R

    1998-09-01

    The objective of this paper is to study the prevalence and clinical characteristics of functional, hypochondriacal, and presenting somatization (FSTS, HSTS, and PSTS, respectively) defined by standardized criteria, as well as the validity of their distinction in primary care in Spain. A two-stage epidemiological study of a representative sample (N = 1559) of primary care patients was carried out. In the first phase, the validated Spanish versions of General Health Questionnaire, Mini-Mental State Examination, and CAGE were used. In the second phase, the Standardized Polyvalent Psychiatric Interview, an interview for the multiaxial assessment of medical patients, was employed. The prevalence of any form of somatization in Spain was 21.3% (FSTS: 16.2%, PSTS: 9.4%, HSTS: 6.7%). Overlap of any of the three clinical forms was very frequent (42.7%). FSTS patients tended to be more chronic and showed higher scores in fatigue but lower scores in both depression and anxiety. Chronicity was frequent among somatizers, particularly in those who fulfilled more than one kind of somatization. Differences in diagnostic distribution among the three groups were also observed. In conclusion, this is the first study giving support to the validity of the distinction among three types of somatization in Spain, but overlap was more frequent than reported in North American studies.

  1. Incidence of fatigue symptoms and diagnoses presenting in UK primary care from 1990 to 2001.

    PubMed

    Gallagher, Arlene M; Thomas, Janice M; Hamilton, William T; White, Peter D

    2004-12-01

    Little is known about whether the incidence of symptoms of fatigue presented in primary care, and the consequent diagnoses made, change over time. The UK General Practice Research Database was used to investigate the annual incidence of both fatigue symptoms and diagnoses recorded in UK primary care from 1990 to 2001. The overall incidence of all fatigue diagnoses decreased from 87 per 100 000 patients in 1990 to 49 in 2001, a reduction of 44%, while postviral fatigue syndromes decreased from 81% of all fatigue diagnoses in 1990 to 60% in 2001. Chronic fatigue syndrome (CFS) and myalgic encephalomyelitis (ME) together increased from 9% to 26% of all fatigue diagnoses. The incidence of fibromyalgia increased from less than 1 per 100 000 to 35 per 100 000. In contrast, there was no consistent change in the incidence of all recorded symptoms of fatigue, with an average of 1503 per 100 000, equivalent to 1.5% per year. CFS/ME and fibromyalgia were rarely diagnosed in children and were uncommon in the elderly. All symptoms and diagnoses were more common in females than in males. The overall incidence of fatigue diagnoses in general has fallen, but the incidence rates of the specific diagnoses of CFS/ME and fibromyalgia have risen, against a background of little change in symptom reporting. This is likely to reflect fashions in diagnostic labelling rather than true changes in incidence.

  2. Genetic Alzheimer Disease and Sporadic Dementia With Lewy Bodies: A Comorbidity Presenting as Primary Progressive Aphasia.

    PubMed

    Picková, Tereza; Matěj, Radoslav; Bezdicek, Ondrej; Keller, Jiří; van der Zee, Julie; Van Broeckhoven, Christine; Cséfalvay, Zsolt; Rusina, Robert

    2017-03-01

    We report a 44-year-old woman, with a family history of early-onset dementia, presenting with primary progressive aphasia. This clinically variable syndrome has multiple underlying pathologies, and correlations between clinical manifestations and postmortem neuropathologic findings are controversial. Our patient suffered worsening language impairment with major word-finding difficulties but preserved comprehension. She also developed episodic memory impairment. Her condition progressed to dementia with behavioral changes. Magnetic resonance imaging showed early left perisylvian and bitemporal atrophy. The patient died shortly afterward from colon cancer. Neuropathologic examination revealed advanced early-onset Alzheimer and Lewy body disease, plus a clinically nonrelevant metastasis of her colon cancer in her left parietal lobe. Genetic examination revealed a p.Glu184Asp mutation in the presenilin1 gene. Our findings confirm the importance of a thorough appreciation for the clinical and neuropathologic correlations in patients with atypical neurodegenerative dementias.

  3. Atypical presentation of Leigh syndrome associated with a Leber hereditary optic neuropathy primary mitochondrial DNA mutation.

    PubMed

    Fruhman, Gary; Landsverk, Megan L; Lotze, Timothy E; Hunter, Jill V; Wangler, Michael F; Adesina, Adekunle M; Wong, Lee-Jun C; Scaglia, Fernando

    2011-06-01

    Leber hereditary optic neuropathy (LHON) is caused by point mutations in mitochondrial DNA (mtDNA), and is characterized by bilateral, painless sub-acute visual loss that develops during the second decade of life. Here we report the case of a five year old girl who presented with clinical and neuroradiological findings reminiscent of Leigh syndrome but carried a mtDNA mutation m.11778G>A (p.R340H) in the MTND4 gene usually observed in patients with LHON. This case is unusual for age of onset, gender, associated neurological findings and evolution, further expanding the clinical spectrum associated with primary LHON mtDNA mutations. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Putative lung adenocarcinoma with epidermal growth factor receptor mutation presenting as carcinoma of unknown primary site

    PubMed Central

    Yamasaki, Masahiro; Funaishi, Kunihiko; Saito, Naomi; Sakano, Ayaka; Fujihara, Megumu; Daido, Wakako; Ishiyama, Sayaka; Deguchi, Naoko; Taniwaki, Masaya; Ohashi, Nobuyuki; Hattori, Noboru

    2018-01-01

    Abstract Rationale: Only a few cases of putative lung adenocarcinoma presenting as carcinoma of unknown primary site (CUP) with epidermal growth factor receptor (EGFR) mutation have been reported, and the efficacy of EGFR-tyrosine kinase inhibitors (TKIs) for these cases is unclear. Patient concerns and diagnoses: A 67-year-old man complained of paresis of the right lower extremity, dysarthria, and memory disturbance. Computed tomography and magnetic resonance imaging showed multiple brain tumors with brain edema and swelling of the left supraclavicular, mediastinal, and upper abdominal lymph nodes. Moreover, a metastatic duodenal tumor was detected via upper gastrointestinal endoscopy examination. The biopsy specimen of the lesion was examined and was diagnosed as adenocarcinoma with CK7 and TTF-1 positivity. Finally, the case was diagnosed as EGFR mutation-positive putative lung adenocarcinoma presenting as CUP. Interventions and outcomes: Oral erlotinib, an EGFR-TKI, was administered at 150 mg daily. Five weeks later, the brain lesions and several swollen lymph nodes showed marked improvement, and the symptoms of the patient also improved. Three months later, the duodenal lesion was undetected on upper gastrointestinal endoscopy. After an 8-month follow-up, the patient was well with no disease progression. Lessons: Putative lung adenocarcinoma presenting as CUP may have EGFR mutation, and EGFR-TKI therapy may be effective for such malignancy. PMID:29443782

  5. Tethered capsule OCT endomicroscopy: from bench to bedside at the primary care office (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Gora, Michalina J.; Simmons, Leigh H.; Tiernan, Aubrey R.; Grant, Catriona N.; Soomro, Amna R.; Walker Corkery, Elizabeth S.; Rosenberg, Mireille; Metlay, Joshua P.; Tearney, Guillermo J.

    2016-03-01

    We have developed a swallowable tethered capsule OCT endomicroscopy (TCE) device that acquires microscopic images of the entire esophagus in unsedated subjects in a quick and comfortable procedure. To test its capabilities of TCE to become a population-based screening device, we conducted a clinical feasibility study in the primary care office. The swept-source OCT imaging system (1310nm central wavelength, 40kHz A-line rate, 10um axial resolution) together with the tethered capsule catheter (11x25mm capsule attached to a flexible tether) were transferred to the PCP office where unsedated patients scheduled for non-urgent PCP visits swallowed the capsule and microscopic OCT images of the entire esophagus were collected. After the whole length of the esophagus was imaged, the catheter was disinfected for reuse. Twenty subjects were enrolled in the study, including nine female and eleven male. All TCE procedures were performed by a nurse and lasted in average 5:42 ± 1:54 min. High-resolution images of the esophagus were obtained in all seventeen subjects that swallowed the capsule. Our clinical experience in this cohort, subject feedback, image quality, and technological adaptations for efficient utilization in this setting will be presented. The ease and simplicity of the procedure combined with high quality of the images demonstrate the potential for this technology to become a population-based screening device. Technology limitations and future development guided by findings from this initial experience will be discussed with the goal of effectively translating TCE to the outpatient primary care setting.

  6. Acute myeloid leukemia mimicking primary testicular neoplasm. Presentation of a case with review of literature.

    PubMed

    McIlwain, Laura; Sokol, Lubomir; Moscinski, Lynn C; Saba, Hussain I

    2003-04-01

    We describe a new unique case of acute myeloid leukemia (AML) in a 21-yr-old male presenting with abdominal pain, bilateral testicular masses and gynecomastia. Further work-up with computed tomography of the chest, abdomen and pelvis revealed massive retroperitoneal, peripancreatic and mediastinal lymphadenopathy, suggesting primary testicular neoplasm. The patient was subjected to right orchiectomy that showed infiltration of testicular tissue with malignant cells, originally misinterpreted as undifferentiated carcinoma. Immunohistochemistry studies, however, showed these cells to be strongly positive for myeloperoxidase and CD45, indicating a myeloid cell origin. Bone marrow (BM) aspirate and biopsy demonstrated replacement of marrow with immature myeloid cells. Both the morphology and immunophenotype of the blast cells were consistent with AML type M4 (acute myelo-monocytic leukemia), using French-American-British (FAB) classification. The patient received standard induction chemotherapy with cytosine arabinoside (ARA-C) and daunorubicin followed with two cycles of consolidation therapy with high dose ARA-C, which resulted in remission of BM disease and resolution of lymphadenopathy and left testicular masses. After the second cycle of consolidation therapy, the patient developed sepsis that was complicated by refractory disseminated intravascular coagulopathy. He expired with a clinical picture of multiple organ failure. The unique features of this case are presented and the related literature is reviewed.

  7. Sex Difference in the Clinical Presentation of Primary Hyperparathyroidism: Influence of Menopausal Status.

    PubMed

    Castellano, Elena; Attanasio, Roberto; Boriano, Alberto; Pellegrino, Micaela; Garino, Francesca; Gianotti, Laura; Borretta, Giorgio

    2017-11-01

    Female-to-male ratio in primary hyperparathyroidism (PHPT) is 3:1, but data on sex impact on the clinical presentation are limited. We evaluated, retrospectively, sex difference in biochemistry and clinical presentation at diagnosis in a monocentric series of 417 patients with PHPT: 93 men (58.6 ± 14.5 years), and 324 women (61.7 ± 12.8 years), of whom 54 were premenopausal (pre-F) and 270 postmenopausal (post-F). Men were significantly younger (P = 0.046) and more frequently symptomatic than women (62.3% vs 47%, P = 0.016). No sex difference was found in serum parathyroid hormone, calcium, creatinine, 25-hydroxy-vitamin D, and urinary calcium levels, whereas serum phosphate was higher in women. Nephrolithiasis (detected by imaging or history of passing stones) was more frequent in men (50.5% vs 33% in women, P = 0.003) and osteoporosis (T-score <-2.5 at any site) was more frequent in women (52.2% vs 35.5% in men, P = 0.0066). Symptomatic patients were 43.3%, 64.8%, and 62.3% in post-F women, pre-F women, and men, respectively. Kidney stones were less frequent and osteoporosis more frequent in post-F women than in pre-F women (28.1% vs 59.2% and 58.9% vs 18.5%, respectively). After combining symptomatic and asymptomatic patients meeting surgical criteria recommended by current guidelines, no sex difference was observed in the proportion of patients to be referred for surgery (84.6% in men vs 84.9% in women). Biochemical activity of PHPT seems to be independent of sex, but clinical presentation is different, mostly due to menopausal state. However, surgical referral was indicated equally in men and women. Copyright © 2017 Endocrine Society

  8. Iranian hereditary hemochromatosis patients: baseline characteristics, laboratory data and gene mutations.

    PubMed

    Zamani, Farhad; Bagheri, Zohreh; Bayat, Maryam; Fereshtehnejad, Seyed-Mohammad; Basi, Ali; Najmabadi, Hossein; Ajdarkosh, Hossein

    2012-10-01

    Hereditary hemochromatosis (HH) is the most common autosomal recessive disorder in white people, characterized by highly abnormal uptake of iron from the gastrointestinal tracts. Recently, mutation studies have focused to detect the genes responsible for HH. In this cross-sectional study, 12 HH patients were recruited, who were referred to Firoozgar Hospital, Tehran, Iran. In addition to the clinical assessments, a complete laboratory evaluation, imaging modalities, histopathologic assessment, atomic absorption spectrophotometry and gene mutation study were performed. The genetic study for HFE gene mutation was examined for all of the patients since 2006, while non-HFE mutation was conducted since December 2010 (only for 1 of them). Twelve patients were evaluated consisting of 11 men and 1 woman, with the mean age of 39.58±12.68 yr. The average of atomic iron loads was 13.25±4.83-fold higher than normal standards. Four patients had heterozygotic mutation of H63D (33.3%). There was no significant difference in either the iron load of liver (P=0.927) and heart (P=0.164) or serum concentration of ferritin (P=0.907) and TIBC (P=0.937) between the HFE-mutant and without HFE mutation HH cases. In contrast to other studies, C282Y mutation was not detected in any of our Iranian HH patients. Heterozygotic mutations of H63D (HFE) and TFR2 (non-HFE) genes were found to be more common in these patients. Similar to previous reports, these mutations were not found to be significantly associated with severity of presentation in HH patients.

  9. Invariant Natural Killer T Cells are Reduced in Hereditary Hemochromatosis Patients.

    PubMed

    Maia, M L; Pereira, C S; Melo, G; Pinheiro, I; Exley, M A; Porto, G; Macedo, M F

    2015-01-01

    Invariant natural killer T (iNKT) cells are CD1d restricted-T cells that react to lipid antigens. iNKT cells were shown to be important in infection, autoimmunity and tumor surveillance. Alterations in the number and function of these cells were described in several pathological conditions including autoimmune and/or liver diseases. CD1d is critical for antigen presentation to iNKT cells, and its expression is increased in liver diseases. The liver is the major organ affected in Hereditary Hemochromatosis (HH), an autosomal recessive disorder caused by excessive iron absorption. Herein, we describe the study of iNKT cells of HH patients. Twenty-eight HH patients and 24 control subjects from Santo António Hospital, Porto, were included in this study. Patient's iron biochemical parameters (serum transferrin saturation and ferritin levels) and the liver function marker alanine transaminase (ALT) were determined at the time of study. Peripheral blood iNKT cells were analyzed by flow cytometry using an anti-CD3 antibody and the CD1d tetramer loaded with PBS57. We found a decrease in the percentage and number of circulating iNKT cells from HH patients when compared with control population independently of age. iNKT cell defects were more pronounced in untreated patients, relating with serum ferritin and transferrin saturation levels. No correlation was found with ALT, a marker of active liver dysfunction. Altogether, our results demonstrate that HH patients have reduced numbers of iNKT cells and that these are influenced by iron overload.

  10. Progressive Primary Pulmonary Tuberculosis Presenting as the Sudden Unexpected Death in Infancy: A Case Report

    PubMed Central

    Dempers, Johan; Sens, Mary Ann; Wadee, Shabbir Ahmed; Kinney, Hannah C.; Odendaal, Hein J.; Wright, Colleen A.

    2010-01-01

    The classification of an unexpected infant death as the sudden infant death syndrome (SIDS) depends upon a complete autopsy and death scene investigation to exclude known causes of death. Here we report the death of a four-month-old infant in a tuberculosis endemic area that presented as a sudden unexpected death in infancy (SUDI) with no apparent explanation based on the death scene characteristics. The autopsy, however, revealed progressive primary pulmonary tuberculosis with intrathoracic adenopathy, compression of the tracheobronchial tree and miliary lesions in the liver. This case underscores the clinical difficulties in the diagnosis of infantile tuberculosis, as well as the possibility of sudden death as part of its protean manifestations. The pathology and clinical progression of tuberculosis in infants differs from older children and adults due to the immature immune response in infants. This case dramatically highlights the need for complete autopsies in all sudden and unexpected infant deaths, as well as the public health issues in a sentinel infant tuberculosis diagnosis. PMID:20705406

  11. Understanding pathogenetic aspects and clinical presentation of primary effusion lymphoma (PEL) through its derived cell lines

    PubMed Central

    Carbone, Antonino; Cesarman, Ethel; Gloghini, Annunziata; Drexler, Hans G.

    2013-01-01

    Primary effusion lymphoma (PEL) is a very rare subgroup of B-cell lymphomas presenting as pleural, peritoneal and pericardial neoplastic effusions in the absence of a solid tumor mass or recognizable nodal involvement. There is strong evidence that Kaposi’s sarcoma associated herpesvirus (KSHV) is a causal agent of PEL. PEL tumor cells are latently infected by KSHV with consistent expression of several viral proteins and microRNAs that can affect cellular proliferation, differentiation and survival. The most relevant data on pathogenesis and biology of KSHV have been provided by studies on PEL derived cell lines. Fourteen continuous cell lines have been established from the malignant effusions of patients with AIDS-and non-AIDS-associated PEL. These KSHV+ EBV+/− cell lines are wellcharacterized, authenticated and mostly available from public biological ressource centers. The PEL cell lines display unique features and are clearly distinct from other lymphoma cell lines. PEL cell lines represent an indispensable tool for the understanding of KSHV biology and its impact on the clinical manifestation of PEL. Studies on PEL cell lines have shown that a number of viral genes, expressed during latency or lytic life cycle, have effects on cell binding, proliferation, angiogenesis and inflammation. Also PEL cell lines are important model systems for the study of the pathology of PEL including the lack of invasive or destructive growth patterns and the peculiar propensity of PEL to involve body cavity surfaces. PMID:20051807

  12. Primary Lung Signet Ring Cell Carcinoma Presenting as a Cavitary Pancoast Tumor in a 32-Year-Old Man.

    PubMed

    Corvini, Michael; Koorji, Alysha; Sgroe, Erica; Nguyen, Uyen

    2018-06-01

    Signet ring cell carcinoma, a subtype of adenocarcinoma, is a rare cause of primary lung cancer. The authors report a case of primary lung signet ring cell carcinoma presenting as a cavitary Pancoast tumor in a 32-year-old male smoker. Beyond the rarity of primary lung signet ring cell carcinoma itself, the youth of the patient, his smoking status, the presence of cavitation, and the location of the tumor in the superior sulcus make it especially atypical.

  13. Ductular reaction in hereditary hemochromatosis: the link between hepatocyte senescence and fibrosis progression.

    PubMed

    Wood, Marnie J; Gadd, Victoria L; Powell, Lawrie W; Ramm, Grant A; Clouston, Andrew D

    2014-03-01

    The development of portal fibrosis following the iron loading of hepatocytes is the first stage of fibrogenesis in hereditary hemochromatosis. In other chronic liver diseases it has been shown that a ductular reaction (DR) appears early, correlates with fibrosis progression, and is a consequence of activation of an alternative pathway of hepatocyte replication. This study was designed to investigate the presence of the DR in hemochromatosis and describe its associations. Liver biopsies from 63 C282Y homozygous patients were assessed for hepatic iron concentration (HIC) and graded for iron loading, fibrosis stage, steatosis, and inflammation. Immunostaining allowed quantification of the DR, hepatocyte senescence and proliferation, and analysis incorporated clinical data. Hepatocyte senescence was positively correlated with HIC, serum ferritin, and oxidative stress. A DR was demonstrated and occurred prior to histological fibrosis. HIC, age, hepatocyte senescence and proliferation, portal inflammation, and excessive alcohol consumption all had significant associations with the extent of the DR. In multivariate analysis, iron loading, hepatocyte replicative arrest, and portal inflammation remained independently and significantly associated with the DR. Of factors associated with fibrosis progression, the DR (odds ratio [OR] 10.86 P<0.0001) and the presence of portal inflammation (OR 4.31, P=0.028) remained significant after adjustment for cofactors. The extent of the DR regressed following therapeutic venesection. Iron loading of hepatocytes leads to impaired replication, stimulating the development of the DR in hemochromatosis and this correlates strongly with hepatic fibrosis. Portal inflammation occurs in hemochromatosis and is independently associated with the DR and fibrosis, and thus its role in this disease should be evaluated further. © 2014 by the American Association for the Study of Liver Diseases.

  14. Model of reticuloendothelial iron metabolism in humans: Abnormal behavior in idiopathic hemochromatosis and in inflammation

    SciTech Connect

    Fillet, G.; Beguin, Y.; Baldelli, L.

    1989-08-01

    Iron transport in the reticuloendothelial (RE) system plays a central role in iron metabolism, but its regulation has not been characterized physiologically in vivo in humans. In particular, why serum iron is elevated and RE cells are much less iron-loaded than parenchymal cells in idiopathic hemochromatosis is not known. The processing of erythrocyte iron by the RE system was studied after intravenous (IV) injection of 59Fe heat-damaged RBCs (HDRBCs) and 55Fe transferrin in normal subjects and in patients with iron deficiency, idiopathic hemochromatosis, inflammation, marrow aplasia, or hyperplastic erythropoiesis. Early release of 59Fe by the RE system was calculated frommore » the plasma iron turnover and the 59Fe plasma reappearance curve. Late release was calculated from the ratio of 59Fe/55Fe RBC utilization in 2 weeks. The partitioning of iron between the early (release from heme catabolism) and late (release from RE stores) phases depended on the size of RE iron stores, as illustrated by the inverse relationship observed between early release and plasma ferritin (P less than .001). There was a strong correlation between early release and the rate of change of serum iron levels during the first three hours in normal subjects (r = .85, P less than .001). Inflammation produced a blockade of the early release phase, whereas in idiopathic hemochromatosis early release was considerably increased as compared with subjects with similar iron stores. Based on these results, we describe a model of RE iron metabolism in humans. We conclude that the RE system appears to determine the diurnal fluctuations in serum iron levels through variations in the immediate output of heme iron. In idiopathic hemochromatosis, a defect of the RE cell in withholding iron freed from hemoglobin could be responsible for the high serum iron levels and low RE iron stores.« less

  15. Cardiac iron deposition in idiopathic hemochromatosis: histologic and analytic assessment of 14 hearts from autopsy.

    PubMed

    Olson, L J; Edwards, W D; McCall, J T; Ilstrup, D M; Gersh, B J

    1987-12-01

    In each heart taken from autopsies of 14 men with idiopathic hemochromatosis, the conduction system, atria and 10 sites in the ventricles were histologically graded for stainable iron. Stainable iron was exclusively sarcoplasmic; none was observed in the interstitium. The histologic grade for the same anatomic site varied among hearts and among different anatomic sites in the same heart. Ten hearts had stainable iron in all ventricular sites; one of the three hearts from patients who had undergone therapeutic phlebotomy had no iron at any site. Seven hearts had iron in the atria but at a lesser grade than that found in the ventricles; six hearts had mild focal iron deposition in the atrioventricular conduction system. None of the 14 hearts had stainable iron in the sinus node. Elemental iron was quantitated by atomic absorption spectroscopy in ventricular specimens contiguous to those studied histologically and also in age-matched control hearts. Elemental iron content was markedly increased in hearts with idiopathic hemochromatosis compared with control hearts (p less than 0.01). The quantity of elemental iron varied greatly, similar to stainable iron, but was highest subepicardially. Among the hearts from the 11 patients without prior phlebotomy, three had no stainable iron in the right ventricular septal subendocardium, suggesting that sampling error may be a problem in the evaluation of hemochromatosis by endomyocardial biopsy. The sarcoplasmic location of the iron indicates that cardiac involvement in idiopathic hemochromatosis represents a storage disease and not an infiltrative process; this finding is consistent with the normal ventricular wall thicknesses observed.

  16. Patients with primary insomnia in the sleep laboratory: do they present with typical nights of sleep?

    PubMed

    Hirscher, Verena; Unbehaun, Thomas; Feige, Bernd; Nissen, Christoph; Riemann, Dieter; Spiegelhalder, Kai

    2015-08-01

    The validity of sleep laboratory investigations in patients with insomnia is important for researchers and clinicians. The objective of this study was to examine the first-night effect and the reverse first-night effect in patients with chronic primary insomnia compared with good sleeper controls. A retrospective comparison of a well-characterised sample of 50 patients with primary insomnia and 50 good sleeper controls was conducted with respect to 2 nights of polysomnography, and subjective sleep parameters in the sleep laboratory and the home setting. When comparing the first and second sleep laboratory night, a significant first-night effect was observed across both groups in the great majority of the investigated polysomnographic and subjective variables. However, patients with primary insomnia and good sleeper controls did not differ with respect to this effect. Regarding the comparison between the sleep laboratory nights and the home setting, unlike good sleeper controls, patients with primary insomnia reported an increased subjective sleep efficiency on both nights (in part due to a reduced bed time) and an increased subjective total sleep time on the second night. These results suggest that even the second sleep laboratory night does not necessarily provide clinicians and researchers with a representative insight into the sleep perception of patients with primary insomnia. Future studies should investigate whether these findings also hold for other patient populations. © 2015 European Sleep Research Society.

  17. [The present status of aspirin use for primary prevention among hypertensive outpatients in China].

    PubMed

    Liu, J; Zhao, D; Liu, J; Qi, Y; Sun, J Y; Wang, W

    2016-04-01

    To evaluate the current status of aspirin for primary prevention in hypertensive outpatients in China, and the gap between aspirin use and guidelines. This was a multi-center cross-sectional study and carried out in hypertensive patients from 46 hospitals of twenty two cities in China from June to December in 2009. At least 100 essential hypertensive outpatients were consecutively recruited from each participant hospitals according to the consistent inclusion criteria. The patients underwent physical examinations and biochemical analyses, and answered questionnaires. Based on the relevant guidelines, the risk assessment of cardiovascular disease (CVD) is a prerequisite for the proper use of aspirin in primary prevention. A total of 5 206 hypertensive outpatients were included. Among them, 1 324 (25.4%) were with a history of CVD. Among those with no history of CVD, 2 705 patients (69.7%) were at high risk of CVD, and the aspirin utilization rate for primary prevention was 29.2%, with 32.2% patients at high risk and 22.4% patients at low-medium risk of CVD, respectively. In the application of aspirin for CVD primary prevention, the inappropriate aspirin use rate in patients at low-medium risk was 23.3%. The proportion of subjects at high risk for CVD is high in hypertensive outpatients suggesting a wide range of application space for aspirin.There exists underutilization for high risk and overutilization for low-medium risk patients in current aspirin primary prevention application.

  18. [Primary glucocorticoid resistance syndrome presenting as pseudo-precocious puberty and galactorrhea].

    PubMed

    Xiang, Shu-lin; He, Li-ping; Ran, Xing-wu; Tian, Hao-ming; Li, Xiu-jun; Liang, Jin-zhong

    2008-09-01

    Primary glucocorticoid resistance syndrome (PGRS) is a rare condition characterized by hypercortisolism without Cushing's syndrome. This report describes a 7-year-old boy of PGRS with pseudo-precocious puberty and galactorrhea as the main manifestation. His height was 135 cm and body weight was 31 kg. Pigmentation could be seen in the skin, mammary areola and penis. He had hirsutism, low hair line, coarse voice, Tanner stage 3 pubic hair, penis in adult form, accelerated linear growth, and advanced bone age (13 yr.), but normal (for age) testes. Furthermore, he had mammoplasia and galactorrhea. There were no features of glucocorticoid (GC) excess. Hepatic function was impaired (ALT 1426 IU/L, AST 611 IU/L) with no definite causes. Serum cortisol concentration was 1294 nmol/L, 777 nmol/L, 199.3 nmol/L at 8:00, 16:00 and 24:00 respectively. Plasma adrenocorticotropic hormone (ACTH) was normal or a little higher (43.9-80 ng/L). Urinary-free cortisol (UFC) was normal (55.5-62.4 microg/24 h). Serum estradiol (E2), progesterone (P), testosterone (T), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were normal. Serum dehydroepiandrosterone sulfate (DHEAS, 60 microg/dL) and serum prolactin (PRL, 58.7-183.9 ng/mL) level were high, urinary dehydroepiandrosterone (DHEA) level was also elevated (0.96-3.2 mg/mL). Gonadotrophin hormone-releasing hormone (GnRH) stimulation test was negative. Serum cortisol responded normally to insulin-induced hypoglycemia. However, serum cortisol and plasma ACTH concentration was suppressed to more than 50% by 0.5 mg dexamethasone (DEX). The diagnosis of PGRS was made. TREATMENT AND FOLLOW-UP: The patient received a treatment of 0.75-1.0 mg/d DEX. Because of galactorrhea, bromocriptine was given by 1.25-3.75 mg/d. After 24 months follow-up, the pigmentation was relieved and galactorrhea disappeared. No advanced development of the external genitalia and breast was found. The acceleration of the bone age was also slowed down. But

  19. Severity of iron overload of proband determines serum ferritin levels in families with HFE-related hemochromatosis: the HEmochromatosis FAmily Study.

    PubMed

    Jacobs, Esther M G; Hendriks, Jan C M; van Deursen, Cees Th B M; Kreeftenberg, Herman G; de Vries, Richard A; Marx, Joannes J M; Stalenhoef, Anton F H; Verbeek, André L M; Swinkels, Dorine W

    2009-01-01

    In families of patients with clinically detected hereditary hemochromatosis (HH) early screening has been suggested to prevent morbidity and mortality. Here, we aim to identify determinants for iron overload in first-degree family members of C282Y homozygous probands with clinically detected HH. Data on HFE-genotype, iron parameters, demographics, lifestyle factors and health, were collected from 224 Dutch C282Y homozygous patients with clinically diagnosed HH and 735 of their first-degree family members (FDFM), all participating in the HEmochromatosis FAmily Study (HEFAS). The best predictive multivariable model forecasted 45% of variation of the serum ferritin levels. In this model severity of iron overload in the proband significantly predicted serum ferritin levels in FDFM. Other significant determinants in this model consisted of C282Y homozygosity, compound heterozygosity, age at testing for serum ferritin and supplemental iron intake, whereas a low body mass index showed a protective effect. This study provides a model to assess the risk of development of iron overload for relatives of probands with HH. These results might be instrumental in the development of an optimal strategy for future family screening programs.

  20. Primary Amoebic Meningoencephalitis Caused by Naegleria fowleri: An Old Enemy Presenting New Challenges

    PubMed Central

    Siddiqui, Ruqaiyyah; Khan, Naveed Ahmed

    2014-01-01

    First discovered in 1899, Naegleria fowleri is a protist pathogen, known to infect the central nervous system and produce primary amoebic meningoencephalitis. The most distressing aspect is that the fatality rate has remained more than 95%, despite our advances in antimicrobial chemotherapy and supportive care. Although rare worldwide, most cases have been reported in the United States, Australia, and Europe (France). A large number of cases in developing countries go unnoticed. In particular, religious, recreational, and cultural practices such as ritual ablution and/or purifications, Ayurveda, and the use of neti pots for nasal irrigation can contribute to this devastating infection. With increasing water scarcity and public reliance on water storage, here we debate the need for increased awareness of primary amoebic meningoencephalitis and the associated risk factors, particularly in developing countries. PMID:25121759

  1. Primary Eosinophilic Granuloma of Adult Cervical Spine Presenting as a Radiculomyelopathy

    PubMed Central

    Bang, Woo-Seok; Cho, Dae-Chul; Sung, Joo-Kyung

    2013-01-01

    We report a case of 29-year-old man diagnosed as a primary eosinophilic granuloma (EG) lesion of the seventh cervical vertebra. He had paresthesia on both arms, and grasping weakness for 10 days. Cervical magnetic resonance image (MRI) showed an enhancing mass with ventral epidural bulging and cord compression on the seventh cervical vertebra. Additionally, we performed spine series MRI, bone scan and positive emission tomography for confirmation of other bone lesions. These studies showed no other pathological lesions. He underwent anterior cervical corpectomy of the seventh cervical vertebra and plate fixation with iliac bone graft. After surgical management, neurological symptoms were much improved. Histopathologic evaluation confirmed the diagnosis of EG. There was no evidence of tumor recurrence at 12 months postoperative cervical MRI follow-up. We reported symptomatic primary EG of cervical spine successfully treated with surgical resection. PMID:24044083

  2. Primary intraosseous Kaposi's sarcoma presenting as an asymptomatic periapical radiolucency: a case report.

    PubMed

    Noel, Kenson E; Mardirossian, George; Schneider, Lawrence

    2007-05-01

    Kaposi's sarcoma (KS) is a common mucocutaneous manifestation of acquired immunodeficiency syndrome (AIDS). Primary bone lesions have been reported but are rare. A 38-year-old African-American male who was human immunodeficiency virus (HIV)-positive appeared for the evaluation of an asymptomatic well-defined radiolucency of the mandibular midline discovered on routine radiographic examination. The adjacent central incisors were asymptomatic, nonmobile, and vital. The overlying mucosa and cortical plate were intact. Excision of the lesion revealed a fleshy, pink-red soft tissue mass with a uniform consistency. Histological examination showed a malignant spindle cell neoplasm containing numerous extravasated erythrocytes. The tumor cells exhibited positive immunohistochemical staining for CD31, CD34, and human herpesvirus 8. One year after surgical procedure, the surgical defect showed radiographic evidence of repair and there was no sign of recurrent tumor. This case represents the fourth reported instance of primary intraosseous involvement of the jaws with KS.

  3. Presenting hydrothorax predicts failure of needle aspiration in primary spontaneous pneumothorax.

    PubMed

    Wu, Kwok Kei; Lui, Chun Tat; Ho, Chik Leung; Tsui, Kwok Leung; Fung, Hin Tat

    2016-06-01

    The objective was to evaluate if existence of hydrothorax in initial chest radiograph predicts treatment outcome in patients with primary spontaneous pneumothorax who received needle thoracostomy. This is a retrospective cohort study carried out from January 2011 to August 2014 in 1 public hospital in Hong Kong. All consecutive adult patients aged 18years or above who attended the emergency department with the diagnosis of primary spontaneous pneumothorax with needle aspiration performed as primary treatment were included. Age, smoking status, size of pneumothorax, previous history of pneumothorax, aspirated gas volume and presence of hydropneumothorax in initial radiograph were included in the analysis. The outcome was success or failure of the needle aspiration. Logistic regression was used to identify the predicting factors of failure of needle aspiration. There were a total of 127 patients included. Seventy-three patients (57.5%) were successfully treated with no recurrence upon discharge. Among 54 failure cases, 13 patients (10.2%) failed immediately after procedure as evident by chest radiograph and required second treatment. Forty-one patients (32.3%) failed upon subsequent chest radiographs. Multivariate logistic regression showed factors independently associated with the failure of needle aspiration, which included hydropneumothorax in the initial radiograph (odds ratio [OR]=4.47 [1.56i12.83], P=.005), previous history of pneumothorax (OR=3.92 [1.57-9.79], P=.003), and large size of pneumothorax defined as apex-to-cupola distance ≥5cm (OR=2.75 [1.21-6.26], P=.016). Hydropneumothorax, previous history of pneumothorax, and large size were independent predictors of failure of needle aspiration in treatment of primary spontaneous pneumothorax. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Increased risk of death from iron overload among 422 treated probands with HFE hemochromatosis and serum levels of ferritin greater than 1000 μg/L at diagnosis.

    PubMed

    Barton, James C; Barton, J Clayborn; Acton, Ronald T; So, Jeffrey; Chan, Susanne; Adams, Paul C

    2012-04-01

    We investigated the risk of death from iron overload among treated hemochromatosis probands who were homozygous for HFE C282Y and had serum levels of ferritin greater than 1000 μg/L at diagnosis. We compared serum levels of ferritin at diagnosis and other conditions with the rate of iron overload-associated death using data from 2 cohorts of probands with hemochromatosis who were homozygous for HFE C282Y (an Alabama cohort, n = 294, 63.9% men and an Ontario cohort, n = 128, 68.8% men). We defined iron overload-associated causes of death as cirrhosis (including hepatic failure and primary liver cancer) caused by iron deposition and cardiomyopathy caused by myocardial siderosis. All probands received phlebotomy and other appropriate therapy. The mean survival times after diagnosis were 13.2 ± 7.3 y and 12.5 ± 8.3 y in Alabama and Ontario probands, respectively. Serum levels of ferritin greater than 1000 μg/L at diagnosis were observed in 30.1% and 47.7% of Alabama and Ontario probands, respectively. In logistic regressions of serum ferritin greater than 1000 μg/L, there were significant positive associations with male sex and cirrhosis in Alabama probands and with age, male sex, increased levels of alanine and aspartate aminotransferases, and cirrhosis in Ontario probands. Of probands with serum levels of ferritin greater than 1000 μg/L at diagnosis, 17.9% of those from Alabama and 14.8% of those from Ontario died of iron overload. Among probands with serum levels of ferritin greater than 1000 μg/L, the relative risk of iron overload-associated death was 5.4 for the Alabama group (95% confidence interval [CI], 2.2-13.1; P = .0002) and 4.9 for the Ontario group (95% CI, 1.1-22.0; P = .0359). In hemochromatosis probands homozygous for HFE C282Y, serum levels of ferritin greater than 1000 μg/L at diagnosis were positively associated with male sex and cirrhosis. Even with treatment, the relative risk of death from iron overload was 5-fold greater in probands with

  5. Primary intraosseous atypical inflammatory meningioma presenting as a lytic skull lesion: Case report with review of literature.

    PubMed

    Bohara, Sangita; Agarwal, Swapnil; Khurana, Nita; Pandey, P N

    2016-01-01

    Primary extradural meningiomas of the skull comprise 1% of all meningiomas, and lytic skull meningiomas are still rarer and are said to be more aggressive. We present a case of 38-year-old male with an extradural tumor which on histopathological examination showed features of inflammatory atypical meningioma (WHO Grade II). The intense inflammatory nature of osteolytic primary intraosseous meningioma has not been reported before. This entity deserves special mention because of the need for adjuvant therapy and proper follow-up.

  6. Primary soft tissue Ewing's sarcoma of the maxillary sinus in elderly patients: presentation, management and prognosis.

    PubMed

    Dutta, M; Ghatak, S; Biswas, G; Sen, A

    2014-06-01

    Nonosseous or soft tissue Ewing's sarcoma is a rare form of Ewing's sarcoma/primitive neuroectodermal tumour that seldom affects the head and neck region. Involvement of the nose and paranasal sinuses is extremely uncommon, with only eight of such patients being reported to date, mostly affecting adolescents and young adults. To our knowledge, this study is the first comprehensive report of primary soft tissue Ewing's sarcoma involving the paranasal sinuses in an elderly patient who successfully completed treatment. We herein discuss the pathogenesis, management and factors affecting the prognosis of this rare group of tumours involving the nose and paranasal sinuses, in relation to the available literature.

  7. [Clinical diagnosis of primary unknown cancer-the present situation and problems].

    PubMed

    Mukai, Hirofumi

    2009-06-01

    The first step of diagnosis of primary unknown cancer(PUC)the detailed history intake and physical examination including breast, genitourinary system and rectum. Laboratory test, chest X-p and systemic computed tomography are allowed to be performed for all patients with PUC. Other tests should be performed according to the results of clinical and pathological evaluation. Utility of the tumor marker is limited, and this test is not recommended as a routine usage. There is not enough evidence on the utility of FDG-PTT or FDG-PET/CT for patients with PUC. Diagnosis of PUC should be made within one month from a patient's first visit to a hospital.

  8. Does emergency presentation of cancer represent poor performance in primary care? Insights from a novel analysis of linked primary and secondary care data.

    PubMed

    Murchie, Peter; Smith, Sarah M; Yule, Michael S; Adam, Rosalind; Turner, Melanie E; Lee, Amanda J; Fielding, Shona

    2017-04-25

    People diagnosed with cancer following emergency presentation have poorer short-term survival. To what extent this signifies a missed opportunity for earlier diagnosis in primary care remains unclear as little detailed data exist on the patient/general practitioner interaction beforehand. Analysis of primary care and regional data for 1802 cancer patients from Northeast Scotland. Adjusted odds ratios (OR) and 95% confidence intervals (CIs) for patient and GP practice predictors of emergency presentation. Qualitative context coding of primary care interaction before emergency presentation. Emergency presentations equalled 20% (n=365). Twenty-eight per cent had no relevant prior GP contact. Of those with prior GP contact 30% were admitted while waiting to be seen in secondary care, and 19% were missed opportunities for earlier diagnosis. Associated predictors: no prior GP contact (OR=3.89; CI 95% 2.14-7.09); having lung (OR=23.24; 95% CI 7.92-68.21), colorectal (OR=18.49; CI 95% 6.60-51.82) and upper GI cancer (OR=18.97; CI 95% 6.08-59.23); ethnicity (OR=2.78; CI 95% 1.27-6.06). Our novel approach has revealed that emergency cancer presentation is more complex than previously thought. Patient delay, prolonged referral pathways and missed opportunities by GPs all contribute, but emergency presentation can also represent effective care. Resources should be used proportionately to raise public and GP awareness and improve post-referral pathways.

  9. Intracranial meningioma as primary presentation for an undiagnosed collision metastatic breast cancer: Case report and literature review

    PubMed Central

    Farrag, Ashraf; Ansari, Jawaher; Ali, Muhammad; Sunbuli, Ghanem; Kassem, Hassan; Al Hamad, Abdul-Aziz

    2018-01-01

    Intracranial metastasis from breast cancer is a relatively common finding, however, the appearance of breast cancer metastasis in a meningioma is very rare. Several cases of tumor-to-tumor metastasis and collision tumors have been reported previously, with meningioma being implicated as the most common benign intracranial neoplasm to harbour the metastasis. Occasionally, the discovery of a tumor-to-meningioma metastasis may herald the diagnosis of an occult primary malignancy. Careful histopathological assessment of the resected meningioma specimen is pivotal to the management of these patients, as this will alter the treatment plan and prognosis considerably. Intracranial meningioma with collision breast cancer as primary presentation of an undiagnosed metastatic breast cancer is extremely rare. The current study presents a case of intracranial meningioma with collision breast cancer as a primary presentation, and reviews the available evidence for this unusual disease entity. PMID:29725531

  10. Intracranial meningioma as primary presentation for an undiagnosed collision metastatic breast cancer: Case report and literature review.

    PubMed

    Farrag, Ashraf; Ansari, Jawaher; Ali, Muhammad; Sunbuli, Ghanem; Kassem, Hassan; Al Hamad, Abdul-Aziz

    2018-05-01

    Intracranial metastasis from breast cancer is a relatively common finding, however, the appearance of breast cancer metastasis in a meningioma is very rare. Several cases of tumor-to-tumor metastasis and collision tumors have been reported previously, with meningioma being implicated as the most common benign intracranial neoplasm to harbour the metastasis. Occasionally, the discovery of a tumor-to-meningioma metastasis may herald the diagnosis of an occult primary malignancy. Careful histopathological assessment of the resected meningioma specimen is pivotal to the management of these patients, as this will alter the treatment plan and prognosis considerably. Intracranial meningioma with collision breast cancer as primary presentation of an undiagnosed metastatic breast cancer is extremely rare. The current study presents a case of intracranial meningioma with collision breast cancer as a primary presentation, and reviews the available evidence for this unusual disease entity.

  11. Back pain caused by a pseudo-tumorous vertebral collapse: atypical presentation of primary vertebral hydatidosis.

    PubMed

    Mrabet, D; Rekik, S; Khiari, H; Mizouni, H; Meddeb, N; Cheour, I; Elleuch, M; Mnif, E; Mrabet, A; Sahli, H; Sellami, S

    2011-03-24

    Hydatidosis, also known as echinococcosis, is a rare but serious parasitic disease in endemic areas. Primary spinal location is extremely rare. This case report describes a rare instance of hydatid cyst that caused severe and progressive low-back pain and neurologic dysfunction. Spine MRI showed a unique vertebral collapse of Th12 body with multicystic lesions filling the spinal canal. In addition, hydatidosis serodiagnostic test was positive at 1/725. Treatment depended on the actual surgical removal of the cysts. Surgery consisted in excision and extirpation of the cysts, associated with decompressive laminectomy. The diagnosis was confirmed on the basis of histological results. No coincidental hydatid visceral involvement was found. Antihelminthic drugs (Albendazole) were promptly given before surgery for a long period. The outcome was satisfactorily marked by total regression of the motor deficit and sphincter disorders.

  12. MicroRNA Expression Analysis in Serum of Patients with Congenital Hemochromatosis and Age-Related Macular Degeneration (AMD)

    PubMed Central

    Szemraj, Maciej; Oszajca, Katarzyna; Szemraj, Janusz; Jurowski, Piotr

    2017-01-01

    Background Congenital hemochromatosis is a disorder caused by mutations of genes involved in iron metabolism, leading to increased levels of iron concentration in tissues and serum. High concentrations of iron can lead to the development of AMD. The aim of this study was to analyze circulating miRNAs in the serum of congenital hemochromatosis patients with AMD and their correlation with the expression of genes involved in iron metabolism. Material/Methods Peripheral blood monolayer cells and serum were obtained from patients with congenital hemochromatosis, congenital hemochromatosis and AMD, AMD patients without congenital hemochromatosis, and healthy controls. Serum miRNAs expressions were analyzed by RT-PCR (qRT-PCR) using TaqMan MicroRNA probes, and proteins levels were measured by ELSA kits. Gene polymorphisms in TF and TFRC genes were determined using the TaqMan discrimination assay. Results Statistical analysis of the miRNAs expressions selected for further study the miR-31, miR-133a, miR-141, miR-145, miR-149, and miR-182, which are involved in the posttranscriptional expression of iron-related genes: TF, TFRI, DMT1, FTL, and FPN1. It was discovered that the observed changes in the expressions of the miRNAs was correlated with the level of protein in the serum of the analyzed genes. There were no statistically significant differences in the distribution of genotype and allele frequencies in TF and TFRC genes between analyzed groups of patients. Conclusions The differences studied in the miRNA serum profile, in conjunction with the changes in the analyzed protein levels, may be useful in the early detection of congenital hemochromatosis in patients who may develop AMD disease. PMID:28827515

  13. Sister Mary Joseph's nodule as the first presenting sign of primary fallopian tube adenocarcinoma.

    PubMed

    Kirshtein, Boris; Meirovitz, Mihai; Okon, Elimelech; Piura, Benjamin

    2006-01-01

    Umbilical metastasis (Sister Mary Joseph's nodule) is often the first sign of intraabdominal and/or pelvic carcinoma. We describe the fourth case reported in the literature of Sister Mary Joseph's nodule originating from fallopian tube carcinoma. In a 54-year-old woman, Sister Mary Joseph's nodule was unexpectedly detected during umbilical hernia repair. Subsequent laparoscopy revealed a 2-cm friable tumor located at the fimbriated end of right fallopian tube and 1-cm peritoneal implant in the pouch of Douglas. Laparoscopic bilateral adnexectomy and resection of the peritoneal implant were performed. Because frozen section examination revealed fallopian tube carcinoma, the procedure was continued with laparotomy including total abdominal hysterectomy, omentectomy, and pelvic lymph node sampling. Final diagnosis was stage IIIB fallopian tube carcinoma. The patient received postoperative adjuvant chemotherapy with single-agent carboplatin and has remained alive and with no evidence of disease. It is concluded that in cases of Sister Mary Joseph's nodule, laparoscopy can be a useful tool in the search of the primary tumor in the abdomen and/or pelvis. Laparoscopy can provide crucial information with respect to the location, size, and feasibility of optimal surgical resection of the intraabdominal and/or pelvic tumors.

  14. [Using value of information analysis in decision making about applied research. The case of genetic screening for hemochromatosis in Germany].

    PubMed

    Rogowski, W H; Grosse, S D; Meyer, E; John, J; Palmer, S

    2012-05-01

    Public decision makers face demands to invest in applied research in order to accelerate the adoption of new genetic tests. However, such an investment is profitable only if the results gained from further investigations have a significant impact on health care practice. An upper limit for the value of additional information aimed at improving the basis for reimbursement decisions is given by the expected value of perfect information (EVPI). This study illustrates the significance of the concept of EVPI on the basis of a probabilistic cost-effectiveness model of screening for hereditary hemochromatosis among German men. In the present example, population-based screening can barely be recommended at threshold values of 50,000 or 100,000 Euro per life year gained and also the value of additional research which might cause this decision to be overturned is small: At the mentioned threshold values, the EVPI in the German public health care system was ca. 500,000 and 2,200,000 Euro, respectively. An analysis of EVPI by individual parameters or groups of parameters shows that additional research about adherence to preventive phlebotomy could potentially provide the highest benefit. The potential value of further research also depends on methodological assumptions regarding the decision maker's time horizon as well as on scenarios with an impact on the number of affected patients and the cost-effectiveness of screening.

  15. Primary epidermoid carcinoma of the breast presenting as a breast abscess and sepsis.

    PubMed

    Damin, Andrea Pires; Nascimento, Fernanda Costa; Andreola, João Batista; Cerutti, Talita Haubert; Roehe, Adriana; Damin, Daniel Carvalho

    2011-12-01

    Squamous cell carcinoma (SCC) of the breast is an extremely rare form of cancer, accounting for approximately 0.04% of all malignant breast tumors. To date, only a limited number of cases of SCC of the breast have been reported, and most of them presented like the usual breast carcinomas. A 39-year-old woman presented with a large breast abscess and signs of sepsis. After surgical debridement of the lesion, histopathological examination of the abscess capsule revealed the presence of SCC of the breast. The definitive treatment for the tumor consisted of modified radical mastectomy with resection of the residual lesion in the right breast. This unusual case illustrates how an apparently benign disorder such as a breast abscess might be related to a clinically occult malignancy. A review of the literature on SCC of the breast is presented.

  16. Usefulness of Magnetic Resonance Imaging for the Diagnosis of Hemochromatosis with Severe Hepatic Steatosis in Nonalcoholic Fatty Liver Disease.

    PubMed

    Nozaki, Yuichi; Sato, Noriko; Tajima, Tsuyoshi; Hasuo, Kanehiro; Kojima, Yasushi; Umemoto, Kumiko; Mishima, Saori; Mikami, Shintaro; Nakayama, Tomohiro; Igari, Toru; Akiyama, Junichi; Imamura, Masatoshi; Masaki, Naohiko; Yanase, Mikio

    2016-01-01

    The ratio of the number of patients with non-alcoholic steatohepatitis (NASH) to the total number of patients with liver dysfunction has increased in many countries around the world. Liver dysfunction is also caused by multiple blood transfusions in patients with leukemia and other hematological diseases, with liver dysfunction often accompanied by secondary hemochromatosis. This study describes a 25-year-old man with secondary hemochromatosis combined with NASH. Magnetic resonance imaging was useful for visualizing the distributions of both iron and fat in the liver of this patient in order to make a differential diagnosis and to evaluate the effect of treatment.

  17. A case of acute confusion: Cushing's syndrome presenting with primary hyperparathyroidism.

    PubMed

    Irvine, Esmee; Yap, Yew Wen; Purewal, Tej; Irvine, Esmee

    2017-06-30

    Cushing's syndrome is a rare disease. Cushing's syndrome presenting as acute psychosis is an exceptional occurrence. We present the case of a 37-year-old woman who was admitted with acute confusion associated with mild hypercalcaemia and was subsequently diagnosed with parathyroid and adrenal adenomas. Our hospital sees approximately 6000 endocrine patients per year, with an incidence of around four Cushing's cases annually. This is the first such case to occur in our hospital and one of few described in the literature. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  18. Creating an optical spectroscopy system for use in a primary care clinical setting (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Eshein, Adam; Nguyen, The-Quyen; Radosevich, Andrew J.; Gould, Bradley; Wu, Wenli; Konda, Vani; Yang, Leslie W.; Koons, Ann; Feder, Seth; Valuckaite, Vesta; Roy, Hemant K.; Backman, Vadim

    2016-03-01

    While there are a plethora of in-vivo spectroscopic techniques that have demonstrated the ability to detect a number of diseases in research trials, very few techniques have successfully become a fully realized clinical technology. This is primarily due to the stringent demands on a clinical device for widespread implementation. Some of these demands include: simple operation requiring minimal or no training, safe for in-vivo patient use, no disruption to normal clinic workflow, tracking of system performance, warning for measurement abnormality, and meeting all FDA guidelines for medical use. Previously, our group developed a fiber optic probe-based optical sensing technique known as low-coherence enhanced backscattering spectroscopy (LEBS) to quantify tissue ultrastructure in-vivo. Now we have developed this technique for the application of prescreening patients for colonoscopy in a primary care (PC) clinical setting. To meet the stringent requirements for a viable medical device used in a PC clinical setting, we developed several novel components including an automated calibration tool, optical contact sensor for signal acquisition, and a contamination sensor to identify measurements which have been affected by debris. The end result is a state-of-the-art medical device that can be realistically used by a PC physician to assess a person's risk for harboring colorectal precancerous lesions. The pilot study of this system shows great promise with excellent stability and accuracy in identifying high-risk patients. While this system has been designed and optimized for our specific application, the system and design concepts are universal to most in-vivo fiber optic based spectroscopic techniques.

  19. Assessment of the Effectiveness of the Educational Environment Supported by Computer Aided Presentations at Primary School Level

    ERIC Educational Resources Information Center

    Kose, Erdogan

    2009-01-01

    The objective of this study is to assess the effectiveness of the educational environment supported by computer aided presentations at primary school. The effectiveness of the environment has been evaluated in terms of students' learning and remembering what they have learnt. In the study, we have compared experimental group and control group in…

  20. Childhood Emotional Abuse and Neglect as Predictors of Psychological and Physical Symptoms in Women Presenting to a Primary Care Practice

    ERIC Educational Resources Information Center

    Spertus, Ilyse L.; Yehuda, Rachel; Wong, Cheryl M.; Halligan, Sarah; Seremetis, Stephanie V.

    2003-01-01

    Objective: There were two aims to this study: first to examine whether emotional abuse and neglect are significant predictors of psychological and somatic symptoms, and lifetime trauma exposure in women presenting to a primary care practice, and second to examine the strength of these relationships after controlling for the effects of other types…

  1. The Use of Interactive Computer Animations Based on POE as a Presentation Tool in Primary Science Teaching

    ERIC Educational Resources Information Center

    Akpinar, Ercan

    2014-01-01

    This study investigates the effects of using interactive computer animations based on predict-observe-explain (POE) as a presentation tool on primary school students' understanding of the static electricity concepts. A quasi-experimental pre-test/post-test control group design was utilized in this study. The experiment group consisted of 30…

  2. A Systematic Review of Interventions for Children Presenting with Dyscalculia in Primary Schools

    ERIC Educational Resources Information Center

    Monei, Thato; Pedro, Athena

    2017-01-01

    The acquisition of numerical competency is regarded as imperative for quality of life and economic well-being. Many children have significant mathematical learning difficulties known as dyscalculia. The aim of this research was to systematically review the available literature for interventions with children presenting with dyscalculia in primary…

  3. A Novel Rat Model of Hereditary Hemochromatosis Due to a Mutation in Transferrin Receptor 2

    PubMed Central

    Bartnikas, Thomas B; Wildt, Sheryl J; Wineinger, Amy E; Schmitz-Abe, Klaus; Markianos, Kyriacos; Cooper, Dale M; Fleming, Mark D

    2013-01-01

    Sporadic iron overload in rats has been reported, but whether it is due to genetic or environmental causes is unknown. In the current study, phenotypic analysis of Hsd:HHCL Wistar rats revealed a low incidence of histologically detected liver iron overload. Here we characterized the pathophysiology of the iron overload and showed that the phenotype is heritable and due to a mutation in a single gene. We identified a single male rat among the 132 screened animals that exhibited predominantly periportal, hepatocellular iron accumulation. This rat expressed low RNA levels of the iron regulatory hormone hepcidin and low protein levels of transferrin receptor 2 (Tfr2), a membrane protein essential for hepcidin expression in humans and mice and mutated in forms of hereditary hemochromatosis. Sequencing of Tfr2 in the iron-overloaded rat revealed a novel Ala679Gly polymorphism in a highly conserved residue. Quantitative trait locus mapping indicated that this polymorphism correlated strongly with serum iron and transferrin saturations in male rats. Expression of the Gly679 variant in tissue culture cell lines revealed decreased steady-state levels of Tfr2. Characterization of iron metabolism in the progeny of polymorphic rats suggested that homozygosity for the Ala679Gly allele leads to a hemochromatosis phenotype. However, we currently cannot exclude the possibility that a polymorphism or mutation in the noncoding region of Tfr2 contributes to the iron-overload phenotype. Hsd:HHCL rats are the first genetic rat model of hereditary hemochromatosis and may prove useful for understanding the molecular mechanisms underlying the regulation of iron metabolism. PMID:23582421

  4. [Early child morbidity and late development following primary abdominal cesarean section in breech presentation near term].

    PubMed

    Kouam, L; Werner-Spangenberg, I; Saling, E

    1986-09-01

    This study concerns the results obtained in respect of early morbidity and late development of 115 and 57 children, respectively, born between 1978 and 1983, who had been delivered by primary low cervical Caesarean section shortly before term. Early morbidity of the 115 children was analysed taking into consideration the risk factors, such as premature rupture, gestation diabetes, EPH gestosis, condition following Caesarean section, abnormal amnioscopic and antepartal cardiotocographic findings, as well as the methods of anaesthesia employed. In the study on late development 57 children between 1 1/4 and 6 years of age were followed up and examined with regard to several faculties (social contact, fine motoricity and adaptation, speech and gross motoricity) according to the Denver Developmental Screening Test. Children with abnormal findings were subjected to special examination. Children with abnormal findings were also subjected to a positional test according to Vojta and to the Munich functional developmental diagnosis after Hellbrüge et al. While employing physiotherapy after Bobath and early rehabilitation training by the parents, these children were followed up at regular intervals. There was no clinically relevant acidosis in the group of 115 newborn. A total of 44 newborn (38%) displayed slight to medium enhanced acidity (pH value, umbilical artery: 7.20 to 7.29) according to the stage classification after Saling and Wulf. Slight to medium acidosis (umbilical artery pH 7.10 to 7.19) was seen in 3 cases only (2.6%). In 112 newborn we found a correlation between the good Apgar score values (7-10) and normal acidity in the umbilical artery blood (act. umbilical artery pH greater than or equal to 7.30). In the remaining 3 newborn with lower Apgar scores (3-6) there was no acidosis in the umbilical artery blood. In the follow-up group (57 cases) we found one child with psychomotor retardation of speech (disturbed articulation and reduced vocabulary) and 6

  5. Primary intimal sarcoma of the left atrium presenting with constitutional symptoms

    PubMed Central

    Ferreira, António; Felgueiras, Paula; Silva, Augusta; Ribeiro, Carlos; Guerra, Diana; de Melo, Daniel Pereira; Manuel Lopes, José

    2017-01-01

    Abstract Intimal (spindle-cell) sarcomas are exceptionally rare and are highly aggressive cardiac tumors. The authors describe a case of a 43-year-old female, presenting with a 3-month history of constitutional symptoms with fever, night sweats, anorexia and weight loss, associated with productive cough and pleural effusion that was admitted with clinical suspicion of pulmonary tuberculosis. The patient developed sudden acute heart failure symptoms during hospitalization, leading to mechanical ventilation. Computed tomography scan with contrast showed a cardiac tumor filling the left atrium causing compression of pulmonary veins. Surgical resection was performed and histologic examination revealed an intimal sarcoma. Although commenced on adjuvant chemotherapy, local tumor recurrence occurred with pericardium invasion. The patient died within 4 months of initial diagnosis. This report aims to describe an unusual presentation of this rare disease entity, and to discuss its highly aggressive clinical course. PMID:28694971

  6. Primary obturator externus pyomyositis in a child presenting as hip pain: a case report.

    PubMed

    Kumar, Abhishek; Anderson, David

    2008-02-01

    Hip pain in children often poses a diagnostic dilemma. Septic arthritis, Perthes disease, and slipped capital femoral epiphysis are among the most important causes. Pyomyositis involving muscles around the hip can present with similar features as septic arthritis and are difficult to diagnose because of their rarity and indolent presentation. Obturator internus and iliopsoas muscle abscess have been most commonly reported, with only 1 such report on isolated obturator externus muscle abscess. Routine laboratory investigations are nonspecific, and the diagnosis rests on imaging modalities. Magnetic resonance scan is the most useful investigation in the diagnosis and can pick up early changes in the muscle. Treatment involves appropriate antibiotic therapy with or without drainage. Most cases resolve completely. We report here a case of isolated obturator externus muscle abscess in an 11-year-old child illustrating the similarities with septic arthritis of hip and problems encountered during diagnosis and management.

  7. Gastric Metastasis as the First Presentation One Year Before Diagnosis of Primary Breast Cancer.

    PubMed

    Woo, Joohyun; Lee, Joo-Ho; Lee, Kyoung Eun; Sung, Sun Hee; Lim, Woosung

    2018-03-26

    BACKGROUND Metastasis to the stomach can be found as the first presentation of breast cancer, although it is very rare. The authors report an unusual case of metastasis to the stomach as the first presentation of breast cancer, which had a good prognosis. CASE REPORT A 51-year-old female underwent radical subtotal gastrectomy and chemotherapy because of gastric cancer with distant metastasis. At the time of diagnosis of gastric cancer, she had a negative result from routine mammography. One year later, a newly detected lesion on routine mammography was confirmed as breast cancer. Initial diagnosis of gastric cancer was changed to metastatic carcinoma from breast cancer through immunohistochemistry after bilateral mastectomy. After the completion of chemotherapy, she is currently receiving treatment with letrozole, without recurrence for 66 months. CONCLUSIONS Considering metastasis from breast cancer might be needed when unusual presentation of gastric cancer is observed even though gastric cancer is still one of the most common malignancies in Korea. Immunohistochemical analysis is helpful for diagnosis. Surgery for metastatic carcinoma of the stomach could be another option for treatment.

  8. Does emergency presentation of cancer represent poor performance in primary care? Insights from a novel analysis of linked primary and secondary care data

    PubMed Central

    Murchie, Peter; Smith, Sarah M; Yule, Michael S; Adam, Rosalind; Turner, Melanie E; Lee, Amanda J; Fielding, Shona

    2017-01-01

    Background: People diagnosed with cancer following emergency presentation have poorer short-term survival. To what extent this signifies a missed opportunity for earlier diagnosis in primary care remains unclear as little detailed data exist on the patient/general practitioner interaction beforehand. Methods: Analysis of primary care and regional data for 1802 cancer patients from Northeast Scotland. Adjusted odds ratios (OR) and 95% confidence intervals (CIs) for patient and GP practice predictors of emergency presentation. Qualitative context coding of primary care interaction before emergency presentation. Results: Emergency presentations equalled 20% (n=365). Twenty-eight per cent had no relevant prior GP contact. Of those with prior GP contact 30% were admitted while waiting to be seen in secondary care, and 19% were missed opportunities for earlier diagnosis. Associated predictors: no prior GP contact (OR=3.89; CI 95% 2.14–7.09); having lung (OR=23.24; 95% CI 7.92–68.21), colorectal (OR=18.49; CI 95% 6.60–51.82) and upper GI cancer (OR=18.97; CI 95% 6.08–59.23); ethnicity (OR=2.78; CI 95% 1.27–6.06). Conclusions: Our novel approach has revealed that emergency cancer presentation is more complex than previously thought. Patient delay, prolonged referral pathways and missed opportunities by GPs all contribute, but emergency presentation can also represent effective care. Resources should be used proportionately to raise public and GP awareness and improve post-referral pathways. PMID:28334728

  9. Coinheritance of hereditary spherocytosis and reversibility of cirrhosis in a young female patient with hereditary hemochromatosis.

    PubMed

    Höblinger, A; Erdmann, C; Strassburg, C P; Sauerbruch, T; Lammert, F

    2009-04-16

    Here we report a 33-years-old woman with hereditary spherocytosis and hemochromatosis due to homozygosity for the C282Y mutation of the HFE gene. The coinheritance of both conditions led to severe iron overload and liver cirrhosis at young age. The patient was treated by repeated phlebotomy, and reversibility of cirrhosis was documented by transient elastography. This report discusses the pathophysiology of iron accumulation in patients with hemolytic anemia combined with HFE C282Y homozygosity. The case indicates that patients with hematological disorders characterized by increased erythropoetic activity should be screened for HFE mutations.

  10. Primary Sjögren syndrome that initially presented with repeated hypergammaglobulinemic purpura after prolonged sitting: A case report.

    PubMed

    Zhou, Zhihua; Jiang, Weiqiang; Wang, Ming; Liu, Yongyuan; Zhang, Wei; Huang, Manping; Liang, Donghui

    2017-12-01

    Purpura is a common dermatologic manifestation in Sjögren syndrome (SS). When a patient presents with sicca symptoms, the diagnosis of SS is not difficult. Here, we reported a case of a 52-year-old Chinese woman who initially presented with nonpalpable purpura on both lower extremities, and these lesions had developed soon after prolonged sitting. In the past 2 years, she had repeated cutaneous nonpalpable purpura 4 times. She had no sicca symptoms, dry eyes, or dry mouth. Combining the laboratory findings, Schirmer test, and labial gland biopsy, primary SS was confirmed. The patient was placed on a trial of hydroxychloroquine (200 mg once daily). The purpura on both lower extremities had faded at the sixth day after onset and at the third day after hydroxychloroquine treatment. These case was not easy to diagnosis primary SS because she had no sicca symptoms. A patient with primary SS who initially presented with recurrent purpura associated with prolonged sitting. Prolonged sitting had been a possible aggravating factor for the cutaneous purpura of this patient with primary SS. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  11. Breast abscess as the initial manifestation of primary pure squamous cell carcinoma: a rare presentation and literature review.

    PubMed

    Salemis, Nikolaos S

    2011-01-01

    Primary squamous cell carcinoma of the breast is a very rare tumor accounting for less than 0.4% of all breast cancers. Fewer than 100 cases have been reported in the literature so far. The diagnosis requires strict pathologic criteria to be fulfilled. Due to the rarity of this tumor the optimal treatment and prognosis are both unclear. Breast abscess as the initial presentation of a primary squamous cell breast carcinoma is an extremely rare clinical entity. In this study, we describe a case of a 61-year-old postmenopausal woman who presented with typical manifestations of a breast abscess and was diagnosed with a pure primary squamous cell breast carcinoma. Diagnostic evaluation and management of the patient are discussed along with a review of the literature. Despite its rarity, the possibility of a primary pure squamous cell breast carcinoma should always be considered in the differential diagnosis in postmenopausal patients presenting with manifestations of a breast abscess, especially in those who respond poorly to the initial treatment. Physicians should be aware of this rare malignancy in order to avoid delays in diagnosis and treatment.

  12. Nutritional status of older persons presenting in a primary care clinic in Nigeria.

    PubMed

    Adebusoye, L A; Ajayi, I O; Dairo, M D; Ogunniyi, A O

    2012-01-01

    The study objective was to determine the nutritional status and its association with sociodemographic characteristics and health complaints of older persons presenting at the General Outpatients Department (GOPD) Clinic of University College Hospital (UCH), Ibadan, Nigeria. A cross-sectional descriptive design was used to select 500 consecutively presenting participants aged 60 years and older between September and December, 2009. The Mini-Nutritional Assessment (MNA) tool and body mass index were used to assess undernutrition and overweight, respectively. The prevalence of nutritional problems was 61.9% (undernutrition = 7.8% and overweight = 54.1%). Being unmarried (P < 0.001), engagement in a job after the age of 60 years (P < 0.001), constipation (P = 0.009), rectal bleeding (P = 0.008), and oral problems (mouth, teeth, and tongue) were significantly (P < 0.001) associated with undernutrition. Younger age (P = 0.050) and female gender (P = 0.011) were significantly associated with being overweight. Logistic regression analysis showed being unmarried OR = 1.355 (95%CI 1.075-1.708) to be the most important factor for the development of undernutrition. The high prevalence of nutritional problems in this study underscores the need for intervention in this population. Correlation analysis (Pearson's) showed a positive association between BMI and MNA scores (r = 0.152, P = 0.001).

  13. Unconvincing diagnosis of a rare subtype of primary gastric lymphoma with incongruent endoscopic presentation: a case of gastric schwannoma.

    PubMed

    Lee, Seung Soo; Kim, In Ho

    2013-12-01

    Primary gastric lymphoma is a rare gastric malignancy. Its diagnostic process is complex. Clinician may find initial diagnosis of primary gastric lymphoma unreliable, especially when it indicates the rarest subtype of gastric lymphoma, while its initial endoscopic presentation fails to raise the slightest suspicion of primary gastric lymphoma. A 53-year-old Korean man was diagnosed, by endoscopic examination, with a round submucosal tumor of the stomach. Deep endoscopic biopsy, however, confirmed CD5 positive gastric lymphoma. Surgical treatment was performed for diagnosis and treatment. Postoperative histo-logical examination confirmed gastric schwannoma. Gastric schwannoma is a spindle cell tumor, characterized by a peripheral cuff-like lymphocytic infiltration. Deep endoscopic biopsy may have been misdirected to the peripheral lymphoid cuff, failing to acquire spindle cells. The literature has been reviewed, and options for diagnostic accuracy have been suggested.

  14. Profiling for primary-care presentation, investigation and referral for liver cancers: evidence from a national audit.

    PubMed

    Hughes, Daniel L; Neal, Richard D; Lyratzopoulos, Georgios; Rubin, Greg

    2016-04-01

    The incidence of liver cancer across Europe is increasing. There is a lack of evidence within the current literature on the identification and investigation of liver cancer within primary care. We aimed to profile liver cancer recognition and assessment as well as the timeliness of liver cancer diagnosis from within the primary-care setting in the UK. Data were obtained from the National Audit of Cancer Diagnosis in Primary Care 2009-2010 and analysed. We calculated the patient interval, the primary-care interval and the number of prereferral consultations for liver cancer. We then compared these data with prior data on the respective indicators for other common cancers. The median patient interval was 9 days (interquartile range 0-31 days), and the median primary-care interval for liver cancer was 11 days (interquartile range 0-40 days). Of the 90 patients, 21 (23.3%) had three or more consultations with their general practitioner before specialist referral. For the three metrics (patient interval, primary-care interval and number of prereferral consultations), liver cancer has average or longer intervals when compared with other cancers. The most common symptomatic presentation of liver cancer within the primary-care setting was right upper quadrant pain (11%), followed by decompensated liver failure (9%). Of the patients, 12% were diagnosed with liver cancer on the basis of an incidental finding of an abnormal liver function test. This study provides a detailed and thorough overview of the recognition of liver cancer and the promptness of liver cancer identification in an English context, and should inform strategies for improving the timeliness of diagnosis.

  15. [Primary presentation of non-hodgkin lymphoma. Report of a case].

    PubMed

    Mirpuri-Mirpuri, P G; Alvarez-Cordovés, M M; Pérez-Monje, A

    2013-09-01

    Lymphomas are the most common non-epithelial tumors of the head and neck and its incidence has increased in recent decades. Around 10% are extranodal lymphomas, and in more than half of the cases are located in Waldeyer's lymphatic ring. The most common presenting symptoms are odynophagia and dysphagia (68%), and symptoms suggestive of oropharyngeal cancer such as cough, hoarseness, earache, feeling of occupation in the back of the mouth, throat or neck. In non-Hodgkin lymphomas in this location, B symptoms (weight loss, fever and sweating) are rare (5%). The histological subtype of each individual lymphoma affects the evaluation, therapy and prognosis. Copyright © 2012 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

  16. Adult-onset nemaline myopathy in a dog presenting with persistent atrial standstill and primary hypothyroidism.

    PubMed

    Nakamura, R K; Russell, N J; Shelton, G D

    2012-06-01

    A nine-year-old neutered female mixed breed dog presented for evaluation following a five-day history of lethargy, inappetence, weakness, abdominal distension and generalised muscle atrophy. Persistent vatrial standstill with a junctional rhythm was identified on electrocardiogram. Echocardiogram identified moderate dilation of all cardiac chambers and mild thickening of the mitral and tricuspid valves. Serology was negative for Neospora caninum and Toxoplasma gondii. Permanent pacemaker implantation was performed in addition to endomyocardial and skeletal muscle biopsies. Cryosections from the biceps femoris muscle showed numerous nemaline rod bodies while endomyocardial biopsies were possibly consistent with end-stage myocarditis. Rod bodies have rarely been reported in the veterinary literature. To the authors' knowledge, this is the first report of adult-onset nemaline rod myopathy and hypothyroidism with concurrent cardiac disease in a dog. © 2012 British Small Animal Veterinary Association.

  17. Initial presentations and final outcomes of primary pyogenic liver abscess: a cross-sectional study

    PubMed Central

    2014-01-01

    Background Although pyogenic liver abscess (PPLA) fatalities are decreasing owing to early diagnosis and effective treatments, PPLA-associated complications still exist. The purpose of this study was to analyze the characteristic features of initial presentations and final outcomes of PPLA caused by different pathogens. Methods This retrospective study collected and analyzed information regarding initial presentations and final outcomes in patients diagnosed with PPLA at admitted at Changhua Christian Hospital from January 1 to December 31, 2010. Results During the study period, we analyzed the records of a total of 134 patients with documented PPLA. There were no significant causative pathogen-related differences in symptoms at initial presentation. Compared with the survivor group, patients in the mortality group were characterized by male gender (p < 0.001), malignancy (p < 0.001), respiratory distress (p =0.007), low blood pressure (p = 0.024), jaundice (p = < 0.001), rupture of liver abscess (p < 0.001), endophthalmitis (p = 0.003), and multiple organ failure (p < 0.001). No patients received liver transplantation or were diagnosed with HIV during the study period. According to univariate logistic regression analysis, gender (OR = 1.185, 95% CI: 0.284–11.130, p = 0.006), malignancy (OR = 2.067, 95% CI: 1.174–13.130, p = 0.004), respiratory distress (OR = 1.667, 95% CI: 1.164–14.210, p = 0.006), low blood pressure (OR = 2.167, 95% CI: 2.104–13.150, p = 0.003), jaundice (OR = 1.9, 95% CI: 1.246–3.297, p = 0.008), rupture of liver abscess (OR = 5.167, 95% CI: 2.194–23.150, p = 0.003), endophthalmitis (OR = 2.167, 95% CI: 1.234–13.140, p = 0.005), and multiple organ failure (OR = 3.067, 95% CI: 1.184–15.150, p = 0.001) differed significantly between the mortality and survivor groups. Conclusion Although the initial presentations of PPLA caused by different

  18. 'Cardiogenic vertigo'--true vertigo as the presenting manifestation of primary cardiac disease.

    PubMed

    Newman-Toker, David E; Camargo, Carlos A

    2006-03-01

    A 90-year-old woman presented to a hospital emergency department with a brief loss of consciousness that was heralded by spinning vertigo lasting approximately 2 min. She had a long history of intermittent brief episodes of rotatory vertigo, presyncope, and non-vertiginous dizziness, occurring either with or without loss of consciousness. Although initially attributed to symptomatic carotid artery stenosis, these episodes persisted, despite surgical restoration of carotid artery blood flow 1 year after her first syncope. Her medical history was otherwise notable for hypertension, mild depression and a gradual decline in gait and balance function attributed to left hip arthritis and older age. Bedside history and examination, non-contrast head CT scan, electrocardiogram, transthoracic echocardiogram, and bedside cardiac telemetry. Sick sinus syndrome or severe reflex bradycardia with asystole causing recurrent, episodic vertigo, presyncope, non-vertiginous dizziness and syncope (Stokes-Adams attacks). Placement of a temporary pacing wire, followed by surgical implantation of a single-chamber ventricular (VVI) pacemaker.

  19. Paraneoplastic cerebellar degeneration with bilateral facial palsy: a rare primary presentation of breast cancer.

    PubMed

    Jain, Arihant; Vats, Manu; Neogi, Sushanto; Khwaja, Geeta Anjum

    2018-06-21

    Paraneoplastic cerebellar degeneration is a rare dysfunction of the cerebellum associated with malignancy. Nevertheless, it is the most common paraneoplastic syndrome affecting the brain. A 50-year-old woman presented to the neurology outpatient department (OPD) with symptoms of cerebellar dysfunction since 4 months and complaints of a painless lump in the right breast and drooling from mouth since 1 month. Examination revealed classical signs of cerebellar dysfunction and a 5×5 cm lump in the right breast with a single right axillary lymph node. Serum anti-Yo antibody titre was strongly positive. The patient was referred to General Surgery OPD for opinion. After establishing the diagnosis of right breast carcinoma; she underwent a right modified radical mastectomy. She was referred to the oncologist for chemo/radiotherapy but because of poor performance status, only symptomatic treatment was pursued. Follow-up till now shows no improvement in the neurological dysfunction. © BMJ Publishing Group Limited [2018]. No commercial re-use. See rights and permissions. Published by BMJ.

  20. Primary omental gastrointestinal stromal tumour (GIST) presenting with a large abdominal mass and spontaneous haemoperitoneum.

    PubMed

    Seow-En, Isaac; Seow-Choen, Francis; Lim, Tony Kiat Hon; Leow, Wei Qiang

    2014-11-03

    A 60-year-old Indonesian woman presented with a 9-day history of increasing abdominal distension, pain and tiredness. Physical examination revealed significant pallor with a palpable mass in the abdomen. CT of the abdomen reported a 22 cm complex mass in the peritoneal cavity with free intra-abdominal fluid. Laboratory results showed anaemia with a raised serum CA 125 level. At laparotomy a large haemorrhagic tumour with blood filled cystic cavities was found attached to both greater omentum and the transverse mesocolon with 2.2 L of blood in the peritoneal cavity. There was no invasion of any part of the stomach or intestines and there were no metastases seen. Histopathology of the resected specimen was consistent with that of a gastrointestinal stromal tumour arising from the omentum. Immunohistochemical studies revealed the tumour to be strongly positive for discovered on GIST-1 (DOG1) but negative for both CD117 and CD34. Platelet-derived growth factor receptor α (PDGFRA) exon 18 mutation D842V was detected. 2014 BMJ Publishing Group Ltd.

  1. Cortical Inhibition Reduces Information Redundancy at Presentation of Communication Sounds in the Primary Auditory Cortex

    PubMed Central

    Gaucher, Quentin; Huetz, Chloé; Gourévitch, Boris

    2013-01-01

    In all sensory modalities, intracortical inhibition shapes the functional properties of cortical neurons but also influences the responses to natural stimuli. Studies performed in various species have revealed that auditory cortex neurons respond to conspecific vocalizations by temporal spike patterns displaying a high trial-to-trial reliability, which might result from precise timing between excitation and inhibition. Studying the guinea pig auditory cortex, we show that partial blockage of GABAA receptors by gabazine (GBZ) application (10 μm, a concentration that promotes expansion of cortical receptive fields) increased the evoked firing rate and the spike-timing reliability during presentation of communication sounds (conspecific and heterospecific vocalizations), whereas GABAB receptor antagonists [10 μm saclofen; 10–50 μm CGP55845 (p-3-aminopropyl-p-diethoxymethyl phosphoric acid)] had nonsignificant effects. Computing mutual information (MI) from the responses to vocalizations using either the evoked firing rate or the temporal spike patterns revealed that GBZ application increased the MI derived from the activity of single cortical site but did not change the MI derived from population activity. In addition, quantification of information redundancy showed that GBZ significantly increased redundancy at the population level. This result suggests that a potential role of intracortical inhibition is to reduce information redundancy during the processing of natural stimuli. PMID:23804094

  2. Primary Gastric ALK-negative EBV-negative Anaplastic Large Cell Lymphoma Presenting with Iron Deficiency Anemia.

    PubMed

    Zhang, Wei; Burton, Samuel; Wu, Shaobin; Qian, Xia; Rajeh, Mhd Nabeel; Schroeder, Katie; Shuldberg, Mark; Merando, Adam; Lai, Jin-Ping

    2017-01-01

    Anaplastic large cell lymphoma (ALCL) is a rare subtype of non-Hodgkin lymphoma (NHL). Primary gastric anaplastic lymphoma kinase (ALK) negative ALCL is extremely rare. Diagnosis of primary gastric ALK-negative ALCL is difficult to establish and prognosis is worse than ALK-positive ALCL. Here, we report a case of an 82-year-old man with a history of cerebrovascular disease presented with weakness and iron deficiency anemia. He denied any abdominal discomforts. The esophagogastroduodenoscopy revealed a large ulcerated, friable mass in the gastric body which encompassed about 80% of entire stomach. Biopsy showed a high grade malignant tumor composed of undifferentiated epithelioid atypical cells, making it difficult to determine the cell of origin. Immunostains for lymphoma, carcinoma, and sarcoma were performed. The tumor cells were positive for CD30, CD4, and CD43, negative for CD20, CD3, ALK-1 and Epstein-Barr virus (EBV)-encoded small RNAs (EBERs) in situ hybridization, establishing the diagnosis of primary gastric ALK-negative ALCL. The patient is currently undergoing chemotherapy with clinical improvement. To the best of our knowledge, this is the first reported case of primary gastric ALK-negative and EBV-negative anaplastic large T-cell lymphoma that presented without gastroenterological symptoms. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  3. Intratumoral hemorrhage because of primary spinal mixed germ cell tumor presenting with atypical radiological features in an adult.

    PubMed

    Yamamoto, Junkoh; Takahashi, Mayu; Nakano, Yoshiteru; Saito, Takeshi; Kitagawa, Takehiro; Ueta, Kunihiro; Miyaoka, Ryo; Nakamura, Eiichiro; Nishizawa, Shigeru

    2013-10-01

    Germ cell tumors are known to arise in the central nervous system, usually in the intracranial regions. However, primary spinal mixed germ cell tumors are extremely rare. This is the first reported case of intratumoral hemorrhage because of a primary spinal mixed germ cell tumor consisting of germinoma and immature teratoma in the conus medullaris of an adult patient that presented with rapid changes on magnetic resonance image (MRI). We report this rare case and discuss the clinical manifestations of an intramedullary spinal mixed germ cell tumor in adult. A case report. A 42-year-old woman experienced buttock numbness, and a spinal cord tumor was observed on the conus medullaris on MRI. The patient was scheduled for an operation in 1 month, but she developed sudden-onset neurologic deterioration. Rapid progression of the tumor was observed on follow-up MRI. The tumor was removed by emergency surgery and was identified as a primary mixed germinoma and immature teratoma. The patient received adjuvant chemotherapy and radiotherapy after gross total resection. The neurologic deficit of the patient was relieved, and recurrence of the tumor was not observed 26 months after the surgery. We present this rare case and emphasize the necessity of precise diagnosis and early treatment of primary spinal germ cell tumor. Close observation on MRI is required after surgery, and adjuvant chemotherapy and radiotherapy should be considered according to the pathologic features. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Unusual Presentation of a Primary Ewing’s Sarcoma of the Spine with Paraplegia: A Case Report

    PubMed Central

    Sundarapandian, Rajkumar Jayachandran; Surulivel, Vignesh Jayabalan

    2015-01-01

    Ewing’s sarcoma is a primary malignancy of the bone affecting individuals in the second decade of life. Primary sarcomas of the spine are rare and the occurrence of Primary Ewing’s sarcoma in the spine is very rare. Ewing’s sarcoma occurring in the spine is divided into two types, Ewing’s sarcoma of sacral spine which are very aggressive with poor prognosis and Ewing’s sarcoma of the non sacral spine which is an extremely rare occurrence. Patient may present with neurological deficit when the tumour extends into the spinal canal causing spinal cord compression. Magnetic resonance imaging (MRI) is very sensitive in diagnosing the tumour and defining the extent of the tumour. Here we report an 18-year-old boy who presented with back pain and complete paraplegia of two months duration. The MRI gave a differential diagnosis of infective pathology due to the fluid collection in the paraspinal region, followed by primary malignancy as the second diagnosis. Patient underwent posterior spinal decompression and stabilization, and intaoperatively there was significant collection of pus whose culture showed no growth. The histopathology and immunohistochemistry studies confirmed the diagnosis of Ewing’s sarcoma and patient was started on combination chemotherapy and radiotherapy. PMID:25954672

  5. Pediatric primary Sjögren syndrome presenting with bilateral ranulas: A case report and systematic review of the literature.

    PubMed

    Means, Casey; Aldape, Mark A; King, Ericka

    2017-10-01

    Primary Sjögren syndrome is uncommon in children, and the standard clinical criteria used in diagnosis of adult Sjögren syndrome will miss many children with the disease. Floor of mouth ranulas have not been described in Sjögren syndrome. This study aims to describe a novel presentation of juvenile primary Sjögren syndrome, and to present a comprehensive systematic review of the literature regarding the presentation and diagnosis of Sjögren syndrome in children. Ovid MEDLINE. A MEDLINE literature search was performed using the following search terms: primary, Sjögren, disease, and children. Results were limited to human subjects and articles written in English between 1981 and 2014. Applicable articles were reviewed and qualitatively summarized. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRIMA). Initial MEDLINE search yielded 146 articles, 80 of which were excluded as not clinically pertaining to Sjögren syndrome. An additional 25 were excluded due to lack of pediatric-specific data. Systematic review of the literature revealed no reports of ranula in association with Sjögren syndrome. 6 papers were manually included from review of reference lists of included articles. Our review indicated that recurrent parotitis is the most commonly reported presenting symptom in children, followed by ocular and oral symptoms, musculoskeletal, and renal symptoms. Compared to adults, children are less likely to present with dry eyes and mouth. All studies were retrospective chart reviews, case series or case reports. This is the first report of a child presenting with floor of mouth ranulas in association with Sjögren syndrome. While recurrent parotitis is the most common presentation in children, other salivary gland and extra-salivary manifestations may be seen, and the clinician must maintain a high index of suspicion for underlying Sjögren syndrome. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Clinical cofactors and hepatic fibrosis in hereditary hemochromatosis: the role of diabetes mellitus.

    PubMed

    Wood, Marnie J; Powell, Lawrie W; Dixon, Jeannette L; Ramm, Grant A

    2012-09-01

    The risk of hepatic fibrosis and cirrhosis in hereditary hemochromatosis relates to the degree of iron loading, but iron alone does not explain the variability in disease penetrance. This study sought to identify clinical cofactors that increase the risk of progressive liver disease. We identified 291 patients from our database who were homozygous for the C282Y mutation in HFE and had undergone a liver biopsy with quantification of hepatic iron concentration (HIC) and fibrosis staging. Data were collected from a retrospective chart review, including age, gender, alcohol consumption, medical therapy, smoking history, metabolic risk factors, mobilizable iron, and laboratory results. Male gender, excess alcohol consumption, HIC, and the presence of diabetes were independently associated with increasing fibrosis stage in multivariate analysis. Of these, the presence of diabetes showed the strongest association (odds ratio, 7.32; P = 0.03). The presence of steatosis was associated with higher fibrosis scores, but this was of borderline statistical significance. Risk factors for hepatic steatosis were male gender, impaired glucose tolerance, and increased body mass index. The presence of diabetes was associated with more severe hepatic fibrosis independent of iron loading, male gender, and alcohol consumption. The mechanism for this association is unknown and deserves further evaluation; however, it is possible that diabetes produces an additional hepatic oxidative injury from hyperglycemia. Thus, management of such cofactors in patients with hemochromatosis is important to reduce the risk of liver injury and fibrosis. Copyright © 2012 American Association for the Study of Liver Diseases.

  7. Small bowel intussusception due to a primary non-Hodgkin's lymphoma. An unusual presentation and clinical course.

    PubMed

    Salemis, Nikolaos S; Tsiambas, Evangelos; Liatsos, Christos; Karameris, Andreas; Tsohataridis, Efstathios

    2010-12-01

    Adult intussusception is a rare clinical entity accounting for 5% of all intussusceptions. Symptoms and signs are often vague and non-specific making a preoperative diagnosis difficult. The purpose of this study is to present a rare case of a jejuno-jejunal intussusception due to primary intestinal non-Hodgkin's lymphoma in a patient with an unusual clinical course. A 78-year-old man presented with a 1-month history of abdominal pain, nausea, epigastric fullness, and weight loss. Computed tomography scan and ultrasonography findings were suggestive of small bowel intussusception. Laparotomy revealed a jejuno-jejunal intussusception caused by a primary B cell non-Hodgkin's lymphoma 20 cm distal to the ligament of Treitz. Resection without prior reduction was performed. The patient refused postoperative adjuvant chemotherapy. Seven months later, he presented with upper gastrointestinal bleeding, and the diagnostic evaluation revealed gastric infiltration of large B cell non-Hodgkin's lymphoma. Despite chemotherapy, he died of disseminated progressive disease 7 months later. Adult jejuno-jejunal intussusception due to primary non-Hodgkin's lymphoma is a rare clinical entity. A high index of suspicion is needed as symptoms and signs are not pathognomonic. Appropriate investigations can lead to a prompt preoperative diagnosis. Resection without prior reduction is the treatment of choice. Our patient's refusal of postoperative adjuvant chemotherapy likely resulted in relapse of the disease in another part of the gastrointestinal tract.

  8. Primary Sjögren's syndrome: fatigue is an ever-present, fluctuating, and uncontrollable lack of energy.

    PubMed

    Mengshoel, Anne Marit; Norheim, Katrine B; Omdal, Roald

    2014-08-01

    To examine how fatigue may differ from ordinary tiredness in patients with primary Sjögren's syndrome (SS). A purposive, heterogeneous sample of individuals with primary SS who had participated in a study that examined the effects of medication on fatigue was asked to participate in individual interviews. Patients were asked about their fatigue before and after the onset of illness, changes due to medications, and how fatigue was experienced in daily life. An inductive thematic analysis founded on a social constructionist perspective was performed. Five women and 4 men ages 27-76 years participated. Two themes were identified. "A heavy, resistant body and ever-present lack of vitality" represented a profound, ever-present lack of energy along with an unfamiliar bodily heaviness quite different from the experience after alleviation by the drug and being healthy. The patients had scaled down their everyday life in different ways to manage this lack of energy. "Unpredictable and uncontrollable fluctuations in fatigue" expressed how the level of fatigue fluctuated from day to day and even within a particular day. The informants tried to portion out their energy without knowing exactly how much energy they would have at any time. On bad days, patients felt that their "batteries were flat," and they had to put their life on hold. Fatigue in primary SS clearly differs from ordinary tiredness. Patients describe it as an ever-present, fluctuating, and nonrelievable lack of vitality being beyond one's own control. Copyright © 2014 by the American College of Rheumatology.

  9. Prevalence of urinary tract infection (UTI) in sequential acutely unwell children presenting in primary care: exploratory study.

    PubMed

    O'Brien, Kathryn; Stanton, Naomi; Edwards, Adrian; Hood, Kerenza; Butler, Christopher C

    2011-03-01

    Due to the non-specific nature of symptoms of UTI in children and low levels of urine sampling, the prevalence of UTI amongst acutely ill children in primary care is unknown. To undertake an exploratory study of acutely ill children consulting in primary care, determine the feasibility of obtaining urine samples, and describe presenting symptoms and signs, and the proportion with UTI. Exploratory, observational study. Four general practices in South Wales. A total of 99 sequential attendees with acute illness aged less than five years. UTI defined by >10(5) organisms/ml on laboratory culture of urine. Urine samples were obtained in 75 (76%) children. Three (4%) met microbiological criteria for UTI. GPs indicated they would not normally have obtained urine samples in any of these three children. However, all had received antibiotics for suspected alternative infections. Urine sample collection is feasible from the majority of acutely ill children in primary care, including infants. Some cases of UTI may be missed if children thought to have an alternative site of infection are excluded from urine sampling. A larger study is needed to more accurately determine the prevalence of UTI in children consulting with acute illness in primary care, and to explore which symptoms and signs might help clinicians effectively target urine sampling.

  10. Differences in hepatic phenotype between hemochromatosis patients with HFE C282Y homozygosity and other HFE genotypes.

    PubMed

    Cheng, Raymond; Barton, James C; Morrison, Elizabeth D; Phatak, Pradyumna D; Krawitt, Edward L; Gordon, Stuart C; Kowdley, Kris V

    2009-07-01

    There are limited data comparing hepatic phenotype among hemochromatosis patients with different HFE genotypes. The goal of this study was to compare hepatic histopathologic features and hepatic iron concentration (HIC) among patients with phenotypic hemochromatosis and different HFE genotypes. We studied 182 US patients with phenotypic hemochromatosis. Degree of hepatic fibrosis, pattern of iron deposition, presence of steatosis or necroinflammation, and HIC were compared among different HFE genotypes. C282Y/H63D compound heterozygotes and patients with HFE genotypes other than C282Y/C282Y were more likely to have stainable Kupffer cell iron (31.1% vs. 9.5%; P=0.02), portal or lobular inflammation (28.9% vs. 15.6%; P=0.03), and steatosis (33.3% vs. 10.2%; P<0.01) on liver biopsy than C282Y homozygotes. Mean log10 HIC (P<0.05) and log10 ferritin (P<0.05) were higher among C282Y homozygotes than in patients with other HFE genotypes. In a logistic regression analysis using age, sex, HFE genotype, log10 ferritin, and log10 HIC as independent variables, log10 serum ferritin (P=0.0008), male sex (P=0.0086), and log10 HIC (P=0.047), but not HFE genotype (P=0.0554) were independently associated with presence or absence of advanced hepatic fibrosis. C282Y/H63D compound heterozygotes and other non-C282Y homozygotes which express the hepatic hemochromatosis phenotype frequently have evidence of steatosis or chronic hepatitis and lower body iron stores than C282Y homozygotes. These data suggest that presence of concomitant liver disease may explain expression of the hemochromatosis phenotype among non-C282Y homozygotes. Increased age, HIC, and ferritin are associated with advanced hepatic fibrosis, regardless of HFE genotype.

  11. Primary Malignant Lymphoma in a Spinal Cord Presenting as an Epidural Mass with Myelopathy: A Case Report

    PubMed Central

    Cho, Jae-Hoon; Cho, Dae-Chul; Sung, Joo-Kyung

    2012-01-01

    We report the case of a 47-year-old man who presented with progressive paraparesis and sphincter changes over 2 weeks. Magnetic resonance imaging revealed a spinal epidural mass from T9 to L2. We performed a decompressive laminectomy and mass removal. The histopathology was consistent with a small lymphocytic lymphoma. No metastatic lesion was noted in the chest and abdomen-pelvic computerized tomography (CT) and positron emission tomography computerized tomography (PET-CT) scan. The final diagnosis was primary spinal lymphoma, so we performed chemotherapy combined with radiotherapy. At one year follow-up, he had no neurological deficit and no recurrence on neurologic and radiologic exams. Primary spinal cord lymphomas should be considered in the differential diagnosis of spinal cord tumors. Early surgical management is mandatory to achieve a recovery of neurologic function, especially if the patient has a neurological deficit. PMID:25983828

  12. Calcified Suprasellar Xanthogranuloma Presenting with Primary Amenorrhea in a 17-Year-Old Girl: Case Report and Literature Review.

    PubMed

    Ben Nsir, Atef; Thai, Quoc-Anh; Chaieb, Larbi; Jemel, Hafedh

    2015-09-01

    Xanthogranuloma, also known as cholesterol granuloma, is an extremely rare intracranial neoplasm most commonly located in the middle ear, petrous apex, or choroid plexus. Exclusively suprasellar xanthogranulomas are exceptional and this report presents a very rare case in the pediatric population, particularly unique due to the presence of calcification. A 17-year-old girl presented with primary amenorrhea with computed tomography and magnetic resonance imaging showing a large calcified enhancing suprasellar mass, which was presumptively diagnosed as a craniopharyngioma on the basis of its clinical and radiologic appearance. Gross total resection of a well-encapsulated, exclusively suprasellar tumor was achieved, without postoperative neurologic deficits. Histologic examination found fibrous tissue with abundant cholesterol clefts, multinucleated giant cells, and hemosiderin deposits but no epithelial cells. The final histologic diagnosis was a xanthogranuloma. Xanthogranuloma, although extremely rare in the pediatric population, may present as a calcified suprasellar mass and manifest with primary amenorrhea. The prognosis after gross total resection is likely favorable; however, long-term follow-up is indicated for these rare neoplasms. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Loss of Proliferation and Antigen Presentation Activity following Internalization of Polydispersed Carbon Nanotubes by Primary Lung Epithelial Cells

    PubMed Central

    Kumari, Mandavi; Sachar, Sumedha; Saxena, Rajiv K.

    2012-01-01

    Interactions between poly-dispersed acid functionalized single walled carbon nanotubes (AF-SWCNTs) and primary lung epithelial (PLE) cells were studied. Peritoneal macrophages (PMs, known phagocytic cells) were used as positive controls in this study. Recovery of live cells from cultures of PLE cells and PMs was significantly reduced in the presence of AF-SWCNTs, in a time and dose dependent manner. Both PLE cells as well as PMs could take up fluorescence tagged AF-SWCNTs in a time dependent manner and this uptake was significantly blocked by cytochalasin D, an agent that blocks the activity of acto-myosin fibers and therefore the phagocytic activity of cells. Confocal microscopic studies confirmed that AF-SWCNTs were internalized by both PLE cells and PMs. Intra-trachially instilled AF-SWCNTs could also be taken up by lung epithelial cells as well as alveolar macrophages. Freshly isolated PLE cells had significant cell division activity and cell cycling studies indicated that treatment with AF-SWCNTs resulted in a marked reduction in S-phase of the cell cycle. In a previously standardized system to study BCG antigen presentation by PLE cells and PMs to sensitized T helper cells, AF-SWCNTs could significantly lower the antigen presentation ability of both cell types. These results show that mouse primary lung epithelial cells can efficiently internalize AF-SWCNTs and the uptake of nanotubes interfered with biological functions of PLE cells including their ability to present BCG antigens to sensitized T helper cells. PMID:22384094

  14. Primary appendiceal lymphoma presenting as suspected perforated acute appendicitis: clinical, sonography and CT findings with pathologic correlation.

    PubMed

    Guo, Jingjing; Wu, Gang; Chen, Xiaojun; Li, Xiaodong

    2014-01-01

    The gastrointestinal tract is the most common site for extranodal involvement by non-Hodgkin's lymphoma. However, primary appendiceal lymphomas presenting as perforated acute appendicitis are very rare: they occur in only 0.015% of all gastrointestinal lymphoma cases. The management of this condition is still controversial, and a multimodality approach (e.g., surgery, radiation therapy, and chemotherapy) is the optimal treatment. In these cases, appendiceal non-Hodgkin's lymphomas typically manifest with acute symptoms in patients with no prior lymphoma history. Additionally, we treated our patient with a right hemicolectomy and postoperative multiagent chemotherapy.

  15. Primary hyperoxaluria in an adult presenting with end-stage renal failure together with hypercalcemia and hypothyroidism.

    PubMed

    Karadag, Serhat; Gursu, Meltem; Aydin, Zeki; Uzun, Sami; Dogan, Oner; Ozturk, Savas; Kazancioglu, Rumeyza

    2011-10-01

    Primary hyperoxaluria (PH) is a rare genetic disorder characterized by overproduction of oxalate due to specific enzyme deficiencies in glyoxylate metabolism. The primary clinical presentation is in the form of recurrent urolithiasis, progressive nephrocalcinosis, end-stage renal disease, and systemic oxalosis. Herein, we present a case of PH who was diagnosed at 47 years of age after 6 years on hemodialysis. He presented with fatigue, anorexia, weight loss, and was found to have cachexia, diffuse edema, hepatomegaly, ascites, hypercalcemia, hyperphosphatemia, hypoalbuminemia, low parathyroid hormone levels, lytic and resorptive areas in the vertebrae, diffusely increased echogenity of the liver, multiple renal stones, and bilateral nephrocalcinosis. Bone marrow biopsy showed calcium oxalate crystals and crystal granulomas. The liver biopsy could not be performed. The absence of an identifiable reason for secondary forms, the severity of the clinical presentation, and pathological findings led to the diagnosis of PH2. He died while waiting for a potential liver and kidney donor. The presented case is consistent with the literature as he had renal stone disease in the third decade and end-stage renal disease in the fifth decade. Hypercalcemia was thought to be due to osteoclast-stimulating activity of macrophages constituting the granuloma. Erythropoietin-resistant anemia and hypothyroidism were thought to be due to accumulation of oxalate in the bone marrow and thyroid gland, respectively. It is very important to keep in mind the possibility of PH when faced with a patient with nephrocalcinosis and oxalate stone disease. © 2011 The Authors; Hemodialysis International © 2011 International Society for Hemodialysis.

  16. Impact of gender, work, and clinical presentation on diagnostic delay in Italian patients with primary ankylosing spondylitis.

    PubMed

    Bandinelli, F; Salvadorini, G; Delle Sedie, A; Riente, L; Bombardieri, S; Matucci-Cerinic, M

    2016-02-01

    The variability of demographic, social, genetic, and clinical factors might influence the time between the onset of symptoms and the diagnosis [diagnostic delay (DD)] of ankylosing spondylitis (AS) in different geographic areas. Different clinical manifestations in men and women affected by AS might indicate a possible role of gender in DD. The aim of the present study was to investigate the influence of demographic, social, genetic, and clinical factors on DD and the differences of DD between men and women related to the presence of different demographic, social, clinical, and genetic parameters in an Italian cohort of primary AS patients. A total of 135 Italian primary AS patients (45 female and 90 male, 27.9 ± 0.89 years old at onset) were studied. The DD, gender, education and work (manual or non-manual) levels, and type of first clinical presentation (inflammatory back pain, arthritis, enthesitis) at onset, family history of AS, and HLA B27 presence were analyzed. The DD (8.744 mean ±0.6869) was significantly higher in men (p = 0.0023), in axial presentation (p = 0.0021), and in manual work (even if with low significance, p = 0.047). The lower DD in women in comparison to that in men was likely related to higher education (p = 0.0045) and work (p = 0.0186) levels, peripheral involvement (p = 0.0009), and HLA B27 positivity (p = 0.0231). DD was higher in AS patients: male, employed in manual jobs, and with axial symptoms at onset. In men, DD seemed to be negatively influenced by lower level of education and work, axial clinical presentation, and HLA B27.

  17. Misdiagnosis of cerebellar hemorrhage - features of 'pseudo-gastroenteritis' clinical presentations to the ED and primary care.

    PubMed

    Lee, Seung-Han; Stanton, Victoria; Rothman, Richard E; Crain, Barbara; Wityk, Robert; Wang, Zheyu; Newman-Toker, David E

    2017-03-01

    Early-stage cerebellar hemorrhage can present with nausea or vomiting absent other neurological symptoms or signs, potentially leading to an incorrect diagnosis of gastroenteritis. We sought to determine the frequency of gastroenteritis-like presentations and delayed or missed diagnoses among patients with spontaneous cerebellar hemorrhage. This is a retrospective, case-control analysis of atraumatic, primary cerebellar hemorrhages derived from a systematic search of surgical pathology and autopsy databases at two large urban, academic medical centers from 1984 to 2006. Hospital visit and clinical symptom data were abstracted from electronic and paper medical records for included patients. Delayed or missed diagnoses were defined as those at least one previous visit for relevant clinical symptoms in the 7 days prior to the correct diagnosis being confirmed. Among 254 records captured by our search filter, we identified 35 cases of pathologically proven primary cerebellar hemorrhage. Four patients (11%) were misdiagnosed initially - three with "gastroenteritis" and one with "hypertension". In this small sample, misdiagnosed patients presented more often with normal mental state (100% vs. 35%, p=0.07) and nausea/vomiting (100% vs. 58%, p=0.22). Although patients deteriorated clinically after the initial misdiagnosis, and potentially dangerous diagnostic tests and treatment strategies were instituted as a result of misdiagnosis, none of the misdiagnosed patients died or suffered major permanent harms due to diagnostic delay. Our study is limited by the small number of identified cases. Nevertheless, it appears that patients with cerebellar hemorrhages can present with relatively unimpressive clinical findings without obvious neurological manifestations. Such individuals are sometimes misdiagnosed with gastroenteritis or other benign disorders initially, possibly when neurologic examination, particularly gait testing, is omitted or abridged. A careful search for subtle

  18. Parents' level of support for adults' purchase and consumption of alcohol at primary school events when children are present.

    PubMed

    Ward, Bernadette; Kippen, Rebecca; Buykx, Penny; Gilligan, Conor; Chapman, Kathy

    2015-03-01

    Environmental and societal factors are significant determinants of children's initiation to and use of alcohol. Schools are important settings for promoting well-being and substantial resources have been devoted to curriculum-based alcohol programs, but the effects of these in reducing the misuse of alcohol have been modest. Adults can and do consume alcohol at school events when students are present, but there is a dearth of evidence about parents' level of support for the practice. The aim of this study was to examine parents' level of support for the purchase and consumption of alcohol at primary school fundraising events when children are present. Four hundred seventy-nine Australian parents of children aged 0-12 years participated in an online survey. Logistic regression was used to assess the impact of parent characteristics on the level of agreement with parental purchase and consumption of alcohol at school fundraising events when children are present. The majority of parents (60%) disagreed/strongly disagreed with the practice of adults being able to purchase and consume alcohol at school fundraising events when children were present. The 21% of parents who supported the practice were more likely to be daily smokers and/or have higher (>6) Alcohol Use Disorders Identification Test-alcohol consumption scores. Despite the fact that the majority of parents disagree with this practice, published reports suggest that adults' use of alcohol at primary school events is an emerging issue. It is important that school decision-makers are mindful of the financial and educational value of fundraising activities. © 2014 Australasian Professional Society on Alcohol and other Drugs.

  19. Absorption of Manganese and Iron in a Mouse Model of Hemochromatosis

    PubMed Central

    Kim, Jonghan; Buckett, Peter D.; Wessling-Resnick, Marianne

    2013-01-01

    Hereditary hemochromatosis, an iron overload disease associated with excessive intestinal iron absorption, is commonly caused by loss of HFE gene function. Both iron and manganese absorption are regulated by iron status, but the relationships between the transport pathways of these metals and how they are affected by HFE-associated hemochromatosis remain poorly understood. Loss of HFE function is known to alter the intestinal expression of DMT1 (divalent metal transporter-1) and Fpn (ferroportin), transporters that have been implicated in absorption of both iron and manganese. Although the influence of HFE deficiency on dietary iron absorption has been characterized, potential effects on manganese metabolism have yet to be explored. To investigate the role of HFE in manganese absorption, we characterized the uptake and distribution of the metal in Hfe −/− knockout mice after intravenous, intragastric, and intranasal administration of 54Mn. These values were compared to intravenous and intragastric administration of 59Fe. Intestinal absorption of 59Fe was increased and clearance of injected 59Fe was also increased in Hfe−/− mice compared to controls. Hfe −/− mice displayed greater intestinal absorption of 54Mn compared to wild-type Hfe+/+ control mice. After intravenous injection, the distribution of 59Fe to heart and liver was greater in Hfe −/− mice but no remarkable differences were observed for 54Mn. Although olfactory absorption of 54Mn into blood was unchanged in Hfe −/− mice, higher levels of intranasally-instilled 54Mn were associated with Hfe−/− brain compared to controls. These results show that manganese transport and metabolism can be modified by HFE deficiency. PMID:23705020

  20. Mutations in the HFE, TFR2, and SLC40A1 genes in patients with hemochromatosis.

    PubMed

    Del-Castillo-Rueda, Alejandro; Moreno-Carralero, María-Isabel; Cuadrado-Grande, Nuria; Alvarez-Sala-Walther, Luis-Antonio; Enríquez-de-Salamanca, Rafael; Méndez, Manuel; Morán-Jiménez, María-Josefa

    2012-10-15

    Hereditary hemochromatosis causes iron overload and is associated with a variety of genetic and phenotypic conditions. Early diagnosis is important so that effective treatment can be administered and the risk of tissue damage avoided. Most patients are homozygous for the c.845G>A (p.C282Y) mutation in the HFE gene; however, rare forms of genetic iron overload must be diagnosed using a specific genetic analysis. We studied the genotype of 5 patients who had hyperferritinemia and an iron overload phenotype, but not classic mutations in the HFE gene. Two patients were undergoing phlebotomy and had no iron overload, 1 with metabolic syndrome and no phlebotomy had mild iron overload, and 2 patients had severe iron overload despite phlebotomy. The patients' first-degree relatives also underwent the analysis. We found 5 not previously published mutations: c.-408_-406delCAA in HFE, c.1118G>A (p.G373D), c.1473G>A (p.E491E) and c.2085G>C (p.S695S) in TFR2; and c.-428_-427GG>TT in SLC40A1. Moreover, we found 3 previously published mutations: c.221C>T (p.R71X) in HFE; c.1127C>A (p.A376D) in TFR2; and c.539T>C (p.I180T) in SLC40A1. Four patients were double heterozygous or compound heterozygous for the mutations mentioned above, and the patient with metabolic syndrome was heterozygous for a mutation in the TFR2 gene. Our findings show that hereditary hemochromatosis is clinically and genetically heterogeneous and that acquired factors may modify or determine the phenotype. Copyright © 2012. Published by Elsevier B.V.

  1. Characteristics of participants with self-reported hemochromatosis or iron overload at HEIRS Study initial screening

    PubMed Central

    Barton, James C.; Acton, Ronald T.; Leiendecker-Foster, Catherine; Lovato, Laura; Adams, Paul C.; Eckfeldt, John H.; McLaren, Christine E.; Reiss, Jacob A.; McLaren, Gordon D.; Reboussin, David M.; Gordeuk, Victor R.; Speechley, Mark R.; Press, Richard D.; Dawkins, Fitzroy W.

    2013-01-01

    There are few descriptions of young adults with self-reported hemochromatosis or iron overload (H/IO). We analyzed initial screening data in 7,343 HEmochromatosis and IRon Overload Screening (HEIRS) Study participants ages 25–29 years, including race/ethnicity and health information; transferrin saturation (TS) and ferritin (SF) measurements; and HFE C282Y and H63D genotypes. We used denaturing high-pressure liquid chromatography and sequencing to detect mutations in HJV, TFR2, HAMP, SLC40A1, and FTL. Fifty-one participants reported previous H/IO; 23 (45%) reported medical conditions associated with H/IO. Prevalences of reports of arthritis, diabetes, liver disease or liver cancer, heart failure, fertility problems or impotence, and blood relatives with H/IO were significantly greater in participants with previous H/IO reports than in those without. Only 7.8% of the 51 participants with previous H/IO reports had elevated TS; 13.7% had elevated SF. Only one participant had C282Y homozygosity. Three participants aged 25–29 years were heterozygous for potentially deleterious mutations in HFE2, TFR2, and HAMP promoter, respectively. Prevalences of self-reported conditions, screening iron phenotypes, and C282Y homozygosity were similar in 1,165 participants aged 30 years or greater who reported previous H/IO. We conclude that persons who report previous H/IO diagnoses in screening programs are unlikely to have H/IO phenotypes or genotypes. Previous H/IO reports in some participants could be explained by treatment that induced iron depletion before initial screening, misdiagnosis, or participant misunderstanding of their physician or the initial screening questionnaire. PMID:17726683

  2. Decreased cardiovascular and extrahepatic cancer-related mortality in treated patients with mild HFE hemochromatosis.

    PubMed

    Bardou-Jacquet, Edouard; Morcet, Jeff; Manet, Ghislain; Lainé, Fabrice; Perrin, Michèle; Jouanolle, Anne-Marie; Guyader, Dominique; Moirand, Romain; Viel, Jean-François; Deugnier, Yves

    2015-03-01

    Mortality studies in patients with hemochromatosis give conflicting results especially with respect to extrahepatic causes of death. Our objective was to assess mortality and causes of death in a cohort of patients homozygous for the C282Y mutation in the HFE gene, diagnosed since the availability of HFE testing. We studied 1085 C282Y homozygotes, consecutively diagnosed from 1996 to 2009, and treated according to current recommendations. Mortality and causes of death were obtained from death certificates and compared to those of the general population. Standardized mortality ratios (SMRs) were used to assess specific causes of death and the Cox model was used to identify prognostic factors for death. Patients were followed for 8.3±3.9 years. Overall the SMR was the same as in the general population (0.94 CI: 0.71-1.22). Patients with serum ferritin⩾2000 μg/L had increased liver-related deaths (SMR: 23.9 CI: 13.9-38.2), especially due to hepatic cancer (SMR: 49.1 CI: 24.5-87.9). Patients with serum ferritin between normal and 1000 μg/L had a lower mortality than the general population (SMR: 0.27 CI: 0.1-0.5), due to a decreased mortality, related to reduced cardiovascular events and extrahepatic cancers in the absence of increased liver-related mortality. Age, diabetes, alcohol consumption, and hepatic fibrosis were independent prognostic factors of death. In treated HFE hemochromatosis, only patients with serum ferritin higher than 2000 μg/L have an increased mortality, mainly related to liver diseases. Those with mild iron burden have a decreased overall mortality in relation to reduced cardiovascular and extrahepatic cancer-related events. These results support a beneficial effect of early and sustained management of patients with iron excess, even when mild. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  3. Erythrocytic Pyruvate Kinase Mutations Causing Hemolytic Anemia, Osteosclerosis, and Secondary Hemochromatosis in Dogs

    PubMed Central

    Gultekin, G. Inal; Raj, K.; Foureman, P.; Lehman, S.; Manhart, K.; Abdulmalik, O.; Giger, U.

    2013-01-01

    Background Erythrocytic pyruvate kinase (PK) deficiency, first documented in Basenjis, is the most common inherited erythroenzymopathy in dogs. Objectives To report 3 new breed-specific PK-LR gene mutations and a retrospective survey of PK mutations in a small and selected group of Beagles and West Highland White Terriers (WHWT). Animals Labrador Retrievers (2 siblings, 5 unrelated), Pugs (2 siblings, 1 unrelated), Beagles (39 anemic, 29 other), WHWTs (22 anemic, 226 nonanemic), Cairn Terrier (n = 1). Methods Exons of the PK-LR gene were sequenced from genomic DNA of young dogs (<2 years) with persistent highly regenerative hemolytic anemia. Results A nonsense mutation (c.799C>T) resulting in a premature stop codon was identified in anemic Labrador Retriever siblings that had osteosclerosis, high serum ferritin concentrations, and severe hepatic secondary hemochromatosis. Anemic Pug and Beagle revealed 2 different missense mutations (c.848T>C, c.994G>A, respectively) resulting in intolerable amino acid changes to protein structure and enzyme function. Breed-specific mutation tests were developed. Among the biased group of 248 WHWTs, 9% and 35% were homozygous (affected) and heterozygous, respectively, for the previously described mutation (mutant allele frequency 0.26). A PK-deficient Cairn Terrier had the same insertion mutation as the affected WHWTs. Of the selected group of 68 Beagles, 35% were PK-deficient and 3% were carriers (0.37). Conclusions and Clinical Importance Erythrocytic PK deficiency is caused by different mutations in different dog breeds and causes chronic severe hemolytic anemia, hemosiderosis, and secondary hemochromatosis because of chronic hemolysis and, an as yet unexplained osteosclerosis. The newly developed breed-specific mutation assays simplify the diagnosis of PK deficiency. PMID:22805166

  4. How the probability of presentation to a primary care clinician correlates with cancer survival rates: a European survey using vignettes.

    PubMed

    Harris, Michael; Frey, Peter; Esteva, Magdalena; Gašparović Babić, Svjetlana; Marzo-Castillejo, Mercè; Petek, Davorina; Petek Ster, Marija; Thulesius, Hans

    2017-03-01

    European cancer survival rates vary widely. System factors, including whether or not primary care physicians (PCPs) are gatekeepers, may account for some of these differences. This study explores where patients who may have cancer are likely to present for medical care in different European countries, and how probability of presentation to a primary care clinician correlates with cancer survival rates. Seventy-eight PCPs in a range of European countries assessed four vignettes representing patients who might have cancer, and consensus groups agreed how likely those patients were to present to different clinicians in their own countries. These data were compared with national cancer survival rates. A total of 14 countries. Consensus groups of PCPs. Probability of initial presentation to a PCP for four clinical vignettes. There was no significant correlation between overall national 1-year relative cancer survival rates and the probability of initial presentation to a PCP (r  = -0.16, 95% CI -0.39 to 0.08). Within that there was large variation depending on the type of cancer, with a significantly poorer lung cancer survival in countries where patients were more likely to initially consult a PCP (lung r = -0.57, 95% CI -0.83 to -0.12; ovary: r = -0.13, 95% CI -0.57 to 0.38; breast r = 0.14, 95% CI -0.36 to 0.58; bowel: r = 0.20, 95% CI -0.31 to 0.62). There were wide variations in the degree of gatekeeping between countries, with no simple binary model as to whether or not a country has a "PCP-as-gatekeeper" system. While there was case-by-case variation, there was no overall evidence of a link between a higher probability of initial consultation with a PCP and poorer cancer survival. KEY POINTS European cancer survival rates vary widely, and health system factors may account for some of these differences. The data from 14 European countries show a wide variation in the probability of initial presentation to a PCP. The degree to

  5. How the probability of presentation to a primary care clinician correlates with cancer survival rates: a European survey using vignettes

    PubMed Central

    Harris, Michael; Frey, Peter; Esteva, Magdalena; Gašparović Babić, Svjetlana; Marzo-Castillejo, Mercè; Petek, Davorina; Petek Ster, Marija; Thulesius, Hans

    2017-01-01

    Objective European cancer survival rates vary widely. System factors, including whether or not primary care physicians (PCPs) are gatekeepers, may account for some of these differences. This study explores where patients who may have cancer are likely to present for medical care in different European countries, and how probability of presentation to a primary care clinician correlates with cancer survival rates. Design Seventy-eight PCPs in a range of European countries assessed four vignettes representing patients who might have cancer, and consensus groups agreed how likely those patients were to present to different clinicians in their own countries. These data were compared with national cancer survival rates. Setting A total of 14 countries. Subjects Consensus groups of PCPs. Main outcome measures Probability of initial presentation to a PCP for four clinical vignettes. Results There was no significant correlation between overall national 1-year relative cancer survival rates and the probability of initial presentation to a PCP (r  = −0.16, 95% CI −0.39 to 0.08). Within that there was large variation depending on the type of cancer, with a significantly poorer lung cancer survival in countries where patients were more likely to initially consult a PCP (lung r = −0.57, 95% CI −0.83 to −0.12; ovary: r = −0.13, 95% CI −0.57 to 0.38; breast r = 0.14, 95% CI −0.36 to 0.58; bowel: r = 0.20, 95% CI −0.31 to 0.62). Conclusions There were wide variations in the degree of gatekeeping between countries, with no simple binary model as to whether or not a country has a “PCP-as-gatekeeper” system. While there was case-by-case variation, there was no overall evidence of a link between a higher probability of initial consultation with a PCP and poorer cancer survival. Key points European cancer survival rates vary widely, and health system factors may account for some of these differences. The data from 14 European

  6. [Study of migratory grief in immigrant patients seen in primary care clinics. Presentation of a migratory grief evaluation questionnaire].

    PubMed

    de la Revilla, Luis; de los Ríos Álvarez, Ana M; Luna del Castillo, Juan de Dios; Gómez García, Mercedes; Valverde Morillas, Carmen; López Torres, Ginesa

    2011-09-01

    To validate a questionnaire designed to show the existence of migratory grief (MG) and its dimensions in the immigrant population, and to study its relationship with certain sociodemographic variables. A descriptive, cross-sectional, multicentre study. Consultations in Primary Health Care. The study included 290 Primary Health Care immigrant patients over 18-years old. There were 12 rejections due to, lack of time, absence of a translator, and lack of understanding. An MG questionnaire with 17 questions was employed, carrying out a factor analysis with final extraction of 4 factors explaining 52.1% of overall variance. Sociodemographic variables were collected: gender, age, marital status, nationality, social network, time in Spain, legal and work situation and communication difficulties. Multivariate analysis was performed using the sociodemographic variables. Four factors were found (fear, homesickness, concern and loss of identity), showing that non-communality was < 0.30 and considering that the 4 factors represent the group of variables from the questionnaire. After analysing the correlations between the different factors, it was observed that concern is related to fear and homesickness, this latter being independent from fear. The loss of identity had a low correlation with other factors. Cronbach's alpha showed good consistency in factors 1, 2 and 3. Some sociodemographic variables are associated with the presence of each factor. We present a validated instrument to study and characterise MG, adapted to study the different dimensions of the grief in immigrant population. Copyright © 2010 Elsevier España, S.L. All rights reserved.

  7. Comparison of the clinical presentations of Naegleria fowleri primary amoebic meningoencephalitis with pneumococcal meningitis: a case-control study.

    PubMed

    Zahid, Mohammad Faizan; Saad Shaukat, Muhammad Hamza; Ahmed, Bilal; Beg, Mohammad Asim; Kadir, Muhammad Masood; Mahmood, Syed Faisal

    2016-08-01

    Primary amoebic meningoencephalitis (PAM) is a rare but fatal infection caused by Naegleria fowleri. The infection is acquired by deep nasal irrigation with infected water. Patients present with signs and symptoms similar to pneumococcal meningitis, leading to delayed diagnosis and treatment and hence high mortality. We conducted a case-control study comparing culture proven cases of PAM with pneumococcal meningitis presenting to our center between April 2008 and September 2014. Only patients with blood and/or cerebrospinal fluid cultures positive for Streptococcus pneumoniae during the same time period were included for comparison. There were 19 cases of PAM and pneumococcal meningitis, each. When comparing PAM with pneumococcal meningitis, patients with PAM were more likely to be male (89.5 vs. 36.8 %), younger (mean age: 30 vs. 59 years), present with seizures (42.1 vs. 5.3 %). Both groups of patients presented with similar vital signs and there were no remarkable differences on physical examinations, Glasgow Coma Scale scores, laboratory and radiological investigations and cerebrospinal fluid parameters. PAM was also more likely to present if the city's average maximum temperature was higher in the previous week (mean: 34.6 vs. 30 °C). There was history of fresh water contact in only one patient. On multivariate analysis, PAM was more likely if patients presented when the city's average maximum temperature was high, being young males. PAM and pneumococcal meningitis remain virtually indistinguishable; however, these predictive features should be validated in a prospective study and may lead to a viable algorithm for early management of these patients.

  8. The Use of Interactive Computer Animations Based on POE as a Presentation Tool in Primary Science Teaching

    NASA Astrophysics Data System (ADS)

    Akpınar, Ercan

    2014-08-01

    This study investigates the effects of using interactive computer animations based on predict-observe-explain (POE) as a presentation tool on primary school students' understanding of the static electricity concepts. A quasi-experimental pre-test/post-test control group design was utilized in this study. The experiment group consisted of 30 students, and the control group of 27 students. The control group received normal instruction in which the teacher provided instruction by means of lecture, discussion and homework. Whereas in the experiment group, dynamic and interactive animations based on POE were used as a presentation tool. Data collection tools used in the study were static electricity concept test and open-ended questions. The static electricity concept test was used as pre-test before the implementation, as post-test at the end of the implementation and as delay test approximately 6 weeks after the implementation. Open-ended questions were used at the end of the implementation and approximately 6 weeks after the implementation. Results indicated that the interactive animations used as presentation tools were more effective on the students' understanding of static electricity concepts compared to normal instruction.

  9. Stereo 3-D and non-stereo presentations of a computer-generated pictorial primary flight display with pathway augmentation

    NASA Technical Reports Server (NTRS)

    Nataupsky, Mark; Crittenden, Lucille

    1988-01-01

    Stereo 3-D was researched as a means to present cockpit displays which enhance a pilot's situational awareness while maintaining a desirable level of mental workload. The initial study at the NASA Langley Research Center used two different pathways-in-the-sky to augment a computer-generated pictorial primary flight display. One pathway resembled the outline of signposts, while the other pathway resembled a monorail. That display was configured for a curved approach to a landing such as could be used in a Microwave Landing System (MLS) approach. It could also be used for military transports which would have to fly a precision curved pathway. Each trial was initialized with the pilot on the desired flight path. After 2 seconds, he suddenly was shifted to one of eight flight path offsets. The pilot was then required to make the initial pitch and/or roll input to correct back to the nominal flight path. As soon as the input was made, the trial was over. No input was required for control trials with no flight path offset. Pilots responded statistically significantly faster when the display was presented in the stereo version than when it was presented in the nonstereo version.

  10. Hereditary Hemochromatosis

    MedlinePlus

    ... or in people who have to get many blood transfusions. People who have certain kinds of anemia or ... Aid and Injury Prevention Crisis Situations Pets and Animals myhealthfinder Food and Nutrition Healthy Food Choices Weight ...

  11. Eighty percent of French sport winners in Olympic, World and Europeans competitions have mutations in the hemochromatosis HFE gene.

    PubMed

    Hermine, Olivier; Dine, Gérard; Genty, Vincent; Marquet, Laurie-Anne; Fumagalli, Gabriela; Tafflet, Muriel; Guillem, Flavia; Van Lierde, Françoise; Rousseaux-Blanchi, Marie-Philippe; Palierne, Christian; Lapostolle, Jean-Claude; Cervetti, Jean-Pierre; Frey, Alain; Jouven, Xavier; Noirez, Philippe; Toussaint, Jean-François

    2015-12-01

    The HFE gene encodes a protein involved in iron homeostasis; individuals with mutations in both alleles develop hemochromatosis. 27% of the French population is heterozygous for mutations in this gene. We found that 80% of the French athletes who won international competitions in rowing, Nordic skiing and judo display mutations in one allele of HFE, thus demonstrating the existence of a favourable phenotype linked to this heterozygosity. Copyright © 2015. Published by Elsevier B.V.

  12. Clinical penetrance in hereditary hemochromatosis: estimates of the cumulative incidence of severe liver disease among HFE C282Y homozygotes.

    PubMed

    Grosse, Scott D; Gurrin, Lyle C; Bertalli, Nadine A; Allen, Katrina J

    2018-04-01

    Iron overload (hemochromatosis) can cause serious, symptomatic disease that is preventable if detected early and managed appropriately. The leading cause of hemochromatosis in populations of predominantly European ancestry is homozygosity of the C282Y variant in the HFE gene. Screening of adults for iron overload or associated genotypes is controversial, largely because of a belief that severe phenotypes are uncommon, although cascade testing of first-degree relatives of patients is widely endorsed. We contend that severe liver disease (cirrhosis or hepatocellular cancer) is not at all uncommon among older males with hereditary hemochromatosis. Our review of the published data from a variety of empirical sources indicates that roughly 1 in 10 male HFE C282Y homozygotes is likely to develop severe liver disease during his lifetime unless iron overload is detected early and treated. New evidence from a randomized controlled trial of treatment allows for evidence-based management of presymptomatic patients. Although population screening for HFE C282Y homozygosity faces multiple barriers, a potentially effective strategy for increasing the early detection and prevention of clinical iron overload and severe disease is to include HFE C282Y homozygosity in lists of medically actionable gene variants when reporting the results of genome or exome sequencing.

  13. Investigation of the primary plasticisers present in polyvinyl chloride (PVC) products currently authorised as food contact materials.

    PubMed

    Carlos, Katherine S; de Jager, Lowri S; Begley, Timothy H

    2018-03-15

    PVC is a common food contact material that is usually plasticised to increase its flexibility. Phthalates are one class of chemical compounds that are often used as plasticisers in PVC in a wide range of industries. They may be used in packaging materials for foods and can also be found in components of certain food processing equipment such as conveyor belts and tubing. Transfer of plasticisers from packaging to foods can occur. In recent years, there has been increased interest in understanding the health effects of phthalates, as well as the possible human exposure levels. However, there is limited information available about the routes of exposure to phthalates. In July 2014, the Chronic Hazard Advisory Panel (CHAP) produced a report for the U.S. Consumer Product Safety Commission detailing the potential health hazards of phthalates and phthalate alternatives. This report listed diet as one factor contributing greater than or equal to 10% of total phthalate exposure. As a result of this report, the U.S. Food and Drug Administration (FDA) is interested in determining the types of the primary plasticiser present in food packaging and processing materials as well as their concentrations. An investigation was conducted of 56 different samples of PVC food packaging and food processing materials available in the US market using a solvent extraction and GC-MS analysis. Nine different plasticisers including three phthalates, di(2-ethylhexyl) phthalate, diisononyl phthalate and diisodecyl phthalate, were identified in the products tested. The plasticiser concentrations ranged from 1 to 53% depending on the types of food contact materials and the type of plasticiser. Overall, it appears that manufacturers are switching away from phthalates as their primary plasticiser to alternate compounds such as ESBO, ATBC, DEHT, DINCH, DEHA and DINA.

  14. Explanatory models and distress in primary caregivers of patients with acute psychotic presentations: A study from South India.

    PubMed

    Joy, Deepa S; Manoranjitham, S D; Samuel, P; Jacob, K S

    2017-11-01

    Emotional distress among caregivers of people with mental illness is common, changes overtime and requires appropriate coping strategies to prevent long-term disability. Explanatory models, which underpin understanding of disease and illness, are crucial to coping. To study the association of explanatory models and distress among caregivers of people with acute psychotic illness. A total of 60 consecutive patients and their primary caregivers who presented to the Department of Psychiatry, Christian Medical College, Vellore, were recruited for the study. Positive and Negative Syndrome Scale (PANSS), Short Explanatory Model Interview (SEMI) and the General Health Questionnaire-12 (GHQ-12) were used to assess severity of psychosis, explanatory models of illness and emotional distress. Standard bivariate and multivariable statistics were employed. Majority of the caregivers simultaneously held multiple models of illness, which included medical and non-medical perspectives. The GHQ-12 score were significantly lower in people who held multiple explanatory models of illness when compared to the caregivers who believed single explanations. Explanatory models affect coping in caregivers of patients with acute psychotic presentations. There is a need to have a broad-based approach to recovery and care.

  15. Immediate chest X-ray for patients at risk of lung cancer presenting in primary care: randomised controlled feasibility trial

    PubMed Central

    Neal, Richard D; Barham, Allan; Bongard, Emily; Edwards, Rhiannon Tudor; Fitzgibbon, Jim; Griffiths, Gareth; Hamilton, Willie; Hood, Kerenza; Nelson, Annmarie; Parker, David; Porter, Cath; Prout, Hayley; Roberts, Kirsty; Rogers, Trevor; Thomas-Jones, Emma; Tod, Angela; Yeo, Seow Tien; Hurt, Chris N

    2017-01-01

    Background: Achieving earlier stage diagnosis is one option for improving lung cancer outcomes in the United Kingdom. Patients with lung cancer typically present with symptoms to general practitioners several times before referral or investigation. Methods: We undertook a mixed methods feasibility individually randomised controlled trial (the ELCID trial) to assess the feasibility and inform the design of a definitive, fully powered, UK-wide, Phase III trial of lowering the threshold for urgent investigation of suspected lung cancer. Patients over 60, with a smoking history, presenting with new chest symptoms to primary care, were eligible to be randomised to intervention (urgent chest X-ray) or usual care. Results: The trial design and materials were acceptable to GPs and patients. We randomised 255 patients from 22 practices, although the proportion of eligible patients who participated was lower than expected. Survey responses (89%), and the fidelity of the intervention (82% patients X-rayed within 3 weeks) were good. There was slightly higher anxiety and depression in the control arm in participants aged >75. Three patients (1.2%) were diagnosed with lung cancer. Conclusions: We have demonstrated the feasibility of individually randomising patients at higher risk of lung cancer, to a trial offering urgent investigation or usual care. PMID:28072761

  16. Determining early referral criteria for patients with suspected inflammatory arthritis presenting to primary care physicians: a cross-sectional study.

    PubMed

    Almoallim, Hani; Janoudi, Nahid; Attar, Suzan M; Garout, Mohammed; Algohary, Shereen; Siddiqui, Muhammad Irfanullah; Alosaimi, Hanan; Ibrahim, Ashraf; Badokhon, Amira; Algasemi, Zaki

    2017-01-01

    Early diagnosis and initiation of treatment for inflammatory arthritis can greatly improve patient outcome. We aimed to provide standardized and validated criteria for use by primary care physicians (PCPs) in the identification of individuals requiring referral to a rheumatologist. We analyzed the predictive value of a wide variety of demographic variables, patient-reported complaints, physical examination results, and biomarkers in order to identify the most useful factors for indicating a requirement for referral. Patients for this cross-sectional study were enrolled from various centers of the city of Jeddah, Saudi Arabia, if they were ≥18 years of age and presented to a PCP with small joint pain that had been present for more than 6 weeks. A total of 203 patients were enrolled, as indicated by the sample size calculation. Each patient underwent a standardized physical examination, which was subsequently compared to ultrasound findings. Biomarker analysis and a patient interview were also carried out. Results were then correlated with the final diagnosis made by a rheumatologist. A total of 9 variables were identified as having high specificity and good predictive value: loss of appetite, swelling of metacarpophalangeal joint 2 or 5, swelling of proximal inter-phalangeal joint 2 or 3, wrist swelling, wrist tenderness, a positive test for rheumatoid factor, and a positive test for anti-citrullinated protein antibodies. Nine variables should be the basis of early referral criteria. It should aid PCPs in making appropriate early referrals of patients with suspected inflammatory arthritis, accelerating diagnosis and initiation of treatment.

  17. Autoanti-C in a patient with primary sclerosing cholangitis and autoimmune hemolytic anemia: a rare presentation.

    PubMed

    Bajpai, Meenu; Maheshwari, Ashish; Gupta, Shruti; Bihari, Chhagan

    2016-09-01

    Primary sclerosing cholangitis (PSC) is rarely associated with autoimmune hemolytic anemia (AIHA), and the presence of specific autoantibodies has not been reported previously. We present a unique case report of PSC associated with AIHA implicating autoanti-C. A 17-year-old girl was admitted to our hospital with PSC along with AIHA. Her blood sample demonstrated a positive direct antiglobulin test and a positive autocontrol in the antihuman globulin phase, confirming the patient had warm-reactive AIHA. Further testing showed the possibility of anti-C. The patient’s Rh phenotype was C+D+E–c–e+. Further testing with select cells, serial alloadsorption, and an elution confirmed anti-C specificity. The patient was transfused with two C–, crossmatch-compatible packed red blood cell units. The patient’s hemoglobin level and general condition showed improvement. This unique case report shows PSC associated with AIHA caused by autoanti-C. Usually, warm AIHA presents with a panreactive pattern, and it is difficult to find compatible blood. In this rare case, we could determine the specific antibody; efforts should always be made in cases of AIHA to identify the specificity of autoantibody.

  18. Anonymous marker loci within 400 kb of HLA-A generate haplotypes in linkage disequilibrium with the hemochromatosis gene (HFE)

    SciTech Connect

    Yaouanq, J.; Perichon, M.; Treut, A.L.

    1994-02-01

    The hemochromatosis gene (HFE) maps to 6p21.3 and is less than 1 cM from the HLA class I gene; however, the precise physical location of the gene has remained elusive and controversial. The unambiguous identification of a crossover event within hemochromatosis families is very difficult; it is particularly hampered by the variability of the phenotypic expression as well as by the sex- and age-related penetrance of the disease. For these considerations, traditional linkage analysis could prove of limited value in further refining the extrapolated physical position of HFE. The authors therefore embarked upon a linkage-disequilibrium analysis of HFE and normalmore » chromosomes for the Brittany population. In this report, 66 hemochromatosis families yielding 151 hemochromatosis chromosomes and 182 normal chromosomes were RFLP-typed with a battery of probes, including two newly derived polymorphic markers from the 6.7 and HLA-F loci located 150 and 250 kb telomeric to HLA-A, respectively. The results suggest a strong peak of existing linkage disequilibrium focused within the i82-to-6.7 interval (approximately 250 kb). The zone of linkage disequilibrium is flanked by the i97 locus, positioned 30 kb proximal to i82, and the HLA-F gene, found 250 kb distal to HLA-A, markers of which display no significant association with HFE. These data support the possibility that HFE resides within the 400-kb expanse of DNA between i97 and HLA-F. Alternatively, the very tight association of HLA-A3 and allele 1 of the 6.7 locus, both of which are comprised by the major ancestral or founder HFE haplotype in Brittany, supports the possibility that the disease gene may reside immediately telomeric to the 6.7 locus within the linkage-disequilibrium zone. Additionally, hemochromatosis haplotypes possessing HLA-A11 and the low-frequency HLA-F polymorphism (allele 2) are supportive of a separate founder chromosome containing a second, independently arising mutant allele. 69 refs., 1 fig., 5

  19. An Intraoral Appliance to Retract the Protrusive Premaxilla in Bilateral Cleft Lip Patients Presenting Late for Primary Lip Repair.

    PubMed

    Vura, Nandagopal; Gaddipati, Rajasekhar; Palla, Yudhistar; Kumar, Pranay

    2018-04-01

    The protruding and deviated premaxilla in bilateral complete cleft lip and palate (BCL/P) patients causes a perplexing problem in achieving a tension-free primary lip closure. An innovative noninvasive active intraoral Fixed Pre-Surgical Cleft Orthopedic (FPSCO) appliance is presented that has enabled to successfully reposition the premaxillary segment to a more favorable position prior to the surgical repair in 4 BCL/P patients, who reported late for treatment with a mean age of 18 ± 3 months. All the patients had at least 1 deciduous tooth erupted in 3 cleft segments, 1 premaxilla (PM), and 2 lateral maxillary (LM) segments. This innovative approach is a noninvasive method of getting the cleft segments closer prior to chelioplasty, where conventional presurgical nasoalveolar molding (PNAM) is not possible, which needs to be done early in life as it requires circulating maternal estrogen levels to achieve results preferably possible in patients younger than 3 to 6 months. Bonding to erupted teeth with glass ionomer cement was implemented to secure the appliance. Nickel-titanium (Ni-Ti) closed-coil springs were used that delivered continuous forces of 150 g/5 oz per side to retract the premaxillary segment. The mean active period of treatment time was 3.5 ± 1.6 months and the retention period was 1.2 ± 0.6 months, following which cheiloplasty was performed.

  20. Myxedema coma of both primary and secondary origin, with non-classic presentation and extremely elevated creatine kinase.

    PubMed

    Benvenga, S; Squadrito, S; Saporito, F; Cimino, A; Arrigo, F; Trimarchi, F

    2000-09-01

    Myxedema coma is a rare, often fatal endocrine emergency that concerns elderly patients with long-standing primary hypothyroidism; myxedema coma of central origin is exceedingly rare. Here, we report a 37-year-old woman in whom classical symptoms of hypothyroidism had been absent. Six years earlier, she had severe obstetric hemorrhage and, shortly after, two subsequent episodes of pericardial effusion. On the day of admission, pericardiocentesis was performed for the third episode of pericardial effusion. Because of the subsequent grave arrhythmias and unconsciousness, she was transferred to our ICU. Prior to the endocrine consultation, a silent myocardial infarction had been suspected, based on the extremely high serum levels of creatine kinase (CK) and isoenzyme CK-MB. However, based on thyroid sonography, pituitary computed tomography, elevated titers of antithyroid antibodies and pituitary stimulation tests, the final diagnosis was myxedema coma of dual origin: an atrophic variant of Hashimoto's thyroiditis and post-necrotic pituitary atrophy (Sheehan syndrome). Substitutive therapy caused a prompt clinical amelioration and normalization of CK levels. Our patient is the first case of myxedema coma of double etiology, and illustrates how its presentation deviates markedly from the one endocrinologists and physicians at ICU are prepared to encounter. In addition, cardiac problems as those of our patient should not discourage from substitutive treatment (using L-thyroxine and the gastrointestinal route of absorption), if the age is relatively low.

  1. Primary School Puberty/Sexuality Education: Student-Teachers' Past Learning, Present Professional Education, and Intention to Teach These Subjects

    ERIC Educational Resources Information Center

    Goldman, Juliette D. G.; Coleman, Stephanie J.

    2013-01-01

    Primary school teachers are often tasked with puberty/sexuality education for students who are undergoing sexual maturation at ever-earlier ages. This study explores the changing trajectories of the pre-service learning and teaching of primary school puberty/sexuality education at an urban university, including student-teachers' childhood…

  2. Effect of C282Y genotype on self-reported musculoskeletal complications in hereditary hemochromatosis.

    PubMed

    Camacho, António; Funck-Brentano, Thomas; Simão, Márcio; Cancela, Leonor; Ottaviani, Sébastien; Cohen-Solal, Martine; Richette, Pascal

    2015-01-01

    Arthropathy that mimics osteoarthritis (OA) and osteoporosis (OP) is considered a complication of hereditary hemochromatosis (HH). We have limited data comparing OA and OP prevalence among HH patients with different hemochromatosis type 1 (HFE) genotypes. We investigated the prevalence of OA and OP in patients with HH by C282Y homozygosity and compound heterozygosity (C282Y/H63D) genotype. A total of 306 patients with HH completed a questionnaire. Clinical and demographic characteristics and presence of OA, OP and related complications were compared by genotype, adjusting for age, sex, body mass index (BMI), current smoking and menopausal status. In total, 266 of the 306 patients (87%) were homozygous for C282Y, and 40 (13%) were compound heterozygous. The 2 groups did not differ by median age [60 (interquartile range [IQR] 53 to 68) vs. 61 (55 to 67) years, P=0.8], sex (female: 48.8% vs. 37.5%, P=0.18) or current smoking habits (12.4% vs. 10%, P=0.3). As compared with compound heterozygous patients, C282Y homozygous patients had higher median serum ferritin concentration at diagnosis [1090 (IQR 610 to 2210) vs. 603 (362 to 950) µg/L, P<0.001], higher median transferrin saturation [80% (IQR 66 to 91%) vs. 63% (55 to 72%), P<0.001]) and lower median BMI [24.8 (22.1 to 26.9) vs. 26.2 (23.5 to 30.3) kg/m2, P<0.003]. The overall prevalence of self-reported OA was significantly higher with C282Y homozygosity than compound heterozygosity (53.4% vs. 32.5%; adjusted odds ratio [aOR] 2.4 [95% confidence interval 1.2-5.0]), as was self-reported OP (25.6% vs. 7.5%; aOR 3.5 [1.1-12.1]). Patients with C282Y homozygosity may be at increased risk of musculoskeletal complications of HH.

  3. Effect of C282Y Genotype on Self-Reported Musculoskeletal Complications in Hereditary Hemochromatosis

    PubMed Central

    Simão, Márcio; Cancela, Leonor; Ottaviani, Sébastien; Cohen-Solal, Martine; Richette, Pascal

    2015-01-01

    Objective Arthropathy that mimics osteoarthritis (OA) and osteoporosis (OP) is considered a complication of hereditary hemochromatosis (HH). We have limited data comparing OA and OP prevalence among HH patients with different hemochromatosis type 1 (HFE) genotypes. We investigated the prevalence of OA and OP in patients with HH by C282Y homozygosity and compound heterozygosity (C282Y/H63D) genotype. Methods A total of 306 patients with HH completed a questionnaire. Clinical and demographic characteristics and presence of OA, OP and related complications were compared by genotype, adjusting for age, sex, body mass index (BMI), current smoking and menopausal status. Results In total, 266 of the 306 patients (87%) were homozygous for C282Y, and 40 (13%) were compound heterozygous. The 2 groups did not differ by median age [60 (interquartile range [IQR] 53 to 68) vs. 61 (55 to 67) years, P=0.8], sex (female: 48.8% vs. 37.5%, P=0.18) or current smoking habits (12.4% vs. 10%, P=0.3). As compared with compound heterozygous patients, C282Y homozygous patients had higher median serum ferritin concentration at diagnosis [1090 (IQR 610 to 2210) vs. 603 (362 to 950) µg/L, P<0.001], higher median transferrin saturation [80% (IQR 66 to 91%) vs. 63% (55 to 72%), P<0.001]) and lower median BMI [24.8 (22.1 to 26.9) vs. 26.2 (23.5 to 30.3) kg/m2, P<0.003]. The overall prevalence of self-reported OA was significantly higher with C282Y homozygosity than compound heterozygosity (53.4% vs. 32.5%; adjusted odds ratio [aOR] 2.4 [95% confidence interval 1.2–5.0]), as was self-reported OP (25.6% vs. 7.5%; aOR 3.5 [1.1–12.1]). Conclusion Patients with C282Y homozygosity may be at increased risk of musculoskeletal complications of HH. PMID:25822977

  4. Unusual presentations of melanoma: melanoma of unknown primary site, melanoma arising in childhood, and melanoma arising in the eye and on mucosal surfaces.

    PubMed

    Sondak, Vernon K; Messina, Jane L

    2014-10-01

    Most melanomas present as primary tumors on the skin surface in adults; however, melanomas also arise in the eye and on the mucosal surfaces or present as apparently metastatic disease without any known history of a cutaneous primary. Melanoma is also being diagnosed during childhood more frequently than ever. Surgeons need to be aware of and understand these unusual presentations of melanoma to optimally manage their patients. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Emerging Implications of Balancing Disinfection and Primary Treatment as an Element in CSO Control: Model Requirements. A presentation.

    EPA Science Inventory

    This paper describes early results and directions arising from ongoing research into factors that affect the preferred balance between primary treatment and disinfection in a conventional wastewater treatment plant during periods of wet weather overflow. Despite the fact that na...

  6. Excitability of the Primary Motor Cortex Increases More Strongly with Slow- than with Normal-Speed Presentation of Actions

    PubMed Central

    Moriuchi, Takefumi; Iso, Naoki; Sagari, Akira; Ogahara, Kakuya; Kitajima, Eiji; Tanaka, Koji; Tabira, Takayuki; Higashi, Toshio

    2014-01-01

    Introduction The aim of the present study was to investigate how the speed of observed action affects the excitability of the primary motor cortex (M1), as assessed by the size of motor evoked potentials (MEPs) induced by transcranial magnetic stimulation (TMS). Methods Eighteen healthy subjects watched a video clip of a person catching a ball, played at three different speeds (normal-, half-, and quarter-speed). MEPs were induced by TMS when the model's hand had opened to the widest extent just before catching the ball (“open”) and when the model had just caught the ball (“catch”). These two events were locked to specific frames of the video clip (“phases”), rather than occurring at specific absolute times, so that they could easily be compared across different speeds. MEPs were recorded from the thenar (TH) and abductor digiti minimi (ADM) muscles of the right hand. Results The MEP amplitudes were higher when the subjects watched the video clip at low speed than when they watched the clip at normal speed. A repeated-measures ANOVA, with the factor VIDEO-SPEED, showed significant main effects. Bonferroni's post hoc test showed that the following MEP amplitude differences were significant: TH, normal vs. quarter; ADM, normal vs. half; and ADM, normal vs. quarter. Paired t-tests showed that the significant MEP amplitude differences between TMS phases under each speed condition were TH, “catch” higher than “open” at quarter speed; ADM, “catch” higher than “open” at half speed. Conclusions These results indicate that the excitability of M1 was higher when the observed action was played at low speed. Our findings suggest that the action observation system became more active when the subjects observed the video clip at low speed, because the subjects could then recognize the elements of action and intention in others. PMID:25479161

  7. Clinicopathological and Prognostic Analysis of Primary Gastrointestinal Stromal Tumor Presenting with Gastrointestinal Bleeding: a 10-Year Retrospective Study.

    PubMed

    Yin, Zhijie; Gao, Jinbo; Liu, Weizhen; Huang, Cheng; Shuai, Xiaoming; Wang, Guobin; Tao, Kaixiong; Zhang, Peng

    2017-05-01

    The objectives of this paper were to investigate the clinicopathological characteristics and prognostic factors of GI-bleeding GIST patients and explore whether GI bleeding is a risk factor for GIST relapse. Primary GIST patients with initial symptoms of GI bleeding or no GI bleeding were retrospectively studied. Up to 178 GI-bleeding GIST patients including 108 (60.7%) males and 70 (39.3%) females were evaluated for the clinicopathological characteristics. The stomach, small bowel, and colorectum were the tumor sites in 82 (46.1%), 85 (47.8%), and 11 (6.2%) patients. Of the 178 patients, 163 GI-bleeding patients had follow-up while another 363 patients from the total population presented without GI bleeding were followed up. Up to 526 patients who received postoperative follow-up were included in the survival analysis. Compared with the 363 non-GI-bleeding patients, GI-bleeding patients developed smaller tumors (P = 0.015) and had a longer relapse-free survival (RFS; P = 0.014). For the 163 GI-bleeding patients, a Cox regression analysis showed that the mitotic count and the platelet-lymphocyte ratio before surgery were independent prognostic predictors for poor outcome regarding RFS. For all 526 patients, a Cox regression analysis indicated that tumor location, mitotic index, platelet-lymphocyte ratio, and GI bleeding were independent prognosis predictors. Compared to non-GI-bleeding GIST patients, patients with GI bleeding were more likely to be male and to have more small intestine GISTs, smaller tumors, and a longer RFS. For GI-bleeding patients, mitotic count and platelet-lymphocyte ratio were independent prognostic indicators. GI bleeding served as a surrogate for smaller GIST and was a protective factor for GIST recurrence.

  8. Genome-wide association study identifies TF as a significant modifier gene of iron metabolism in HFE hemochromatosis.

    PubMed

    de Tayrac, Marie; Roth, Marie-Paule; Jouanolle, Anne-Marie; Coppin, Hélène; le Gac, Gérald; Piperno, Alberto; Férec, Claude; Pelucchi, Sara; Scotet, Virginie; Bardou-Jacquet, Edouard; Ropert, Martine; Bouvet, Régis; Génin, Emmanuelle; Mosser, Jean; Deugnier, Yves

    2015-03-01

    Hereditary hemochromatosis (HH) is the most common form of genetic iron loading disease. It is mainly related to the homozygous C282Y/C282Y mutation in the HFE gene that is, however, a necessary but not a sufficient condition to develop clinical and even biochemical HH. This suggests that modifier genes are likely involved in the expressivity of the disease. Our aim was to identify such modifier genes. We performed a genome-wide association study (GWAS) using DNA collected from 474 unrelated C282Y homozygotes. Associations were examined for both quantitative iron burden indices and clinical outcomes with 534,213 single nucleotide polymorphisms (SNP) genotypes, with replication analyses in an independent sample of 748 C282Y homozygotes from four different European centres. One SNP met genome-wide statistical significance for association with transferrin concentration (rs3811647, GWAS p value of 7×10(-9) and replication p value of 5×10(-13)). This SNP, located within intron 11 of the TF gene, had a pleiotropic effect on serum iron (GWAS p value of 4.9×10(-6) and replication p value of 3.2×10(-6)). Both serum transferrin and iron levels were associated with serum ferritin levels, amount of iron removed and global clinical stage (p<0.01). Serum iron levels were also associated with fibrosis stage (p<0.0001). This GWAS, the largest one performed so far in unselected HFE-associated HH (HFE-HH) patients, identified the rs3811647 polymorphism in the TF gene as the only SNP significantly associated with iron metabolism through serum transferrin and iron levels. Because these two outcomes were clearly associated with the biochemical and clinical expression of the disease, an indirect link between the rs3811647 polymorphism and the phenotypic presentation of HFE-HH is likely. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  9. Does oxidative stress modulate left ventricular diastolic function in asymptomatic subjects with hereditary hemochromatosis?

    PubMed

    Shizukuda, Yukitaka; Bolan, Charles D; Tripodi, Dorothy J; Sachdev, Vandana; Nguyen, Tammy T; Botello, Gilberto; Yau, Yu-Ying; Sidenko, Stanislav; Inez, Ernst; Ali, Mir I; Waclawiw, Myron A; Leitman, Susan F; Rosing, Douglas R

    2009-11-01

    Little is known about the early mechanisms mediating left ventricular (LV) diastolic dysfunction in patients with hereditary hemochromatosis (HH). However, the increased oxidative stress related to iron overload may be involved in this process, and strain rate (SR), a sensitive echocardiography-derived measure of diastolic function, may detect such changes. we evaluated the relationship between left ventricular diastolic function measured with tissue Doppler SR and oxidative stress in asymptomatic HH subjects and control normal subjects. Ninety-four consecutive visits of 43 HH subjects, age 30-74 (50 +/- 10, mean +/- SD), and 37 consecutive visits of 21 normal volunteers, age 30-63 (48 +/- 8), were evaluated over a 3-year period. SR was obtained from the basal septum in apical four-chamber views. All patients had confirmed C282Y homozygosity, a documented history of iron overload, and were New York Heart Association functional class I. Normal volunteers lacked HFE gene mutations causing HH. In the HH subjects, the SR demonstrated moderate but significant correlations with biomarkers of oxidative stress; however, no correlations were noted in normal subjects. The biomarkers of iron overload per se did not show significant correlations with the SR. Although our study was limited by the relatively small subject number, these results suggest that a possible role of oxidative stress to affect LV diastolic function in asymptomatic HH subjects and SR imaging may be a sensitive measure to detect that effect.

  10. Minihepcidins prevent iron overload in a hepcidin-deficient mouse model of severe hemochromatosis

    PubMed Central

    Ramos, Emilio; Ruchala, Piotr; Goodnough, Julia B.; Kautz, Léon; Preza, Gloria C.; Nemeth, Elizabeta

    2012-01-01

    The deficiency of hepcidin, the hormone that controls iron absorption and its tissue distribution, is the cause of iron overload in nearly all forms of hereditary hemochromatosis and in untransfused iron-loading anemias. In a recent study, we reported the development of minihepcidins, small drug-like hepcidin agonists. Here we explore the feasibility of using minihepcidins for the prevention and treatment of iron overload in hepcidin-deficient mice. An optimized minihepcidin (PR65) was developed that had superior potency and duration of action compared with natural hepcidin or other minihepcidins, and favorable cost of synthesis. PR65 was administered by subcutaneous injection daily for 2 weeks to iron-depleted or iron-loaded hepcidin knockout mice. PR65 administration to iron-depleted mice prevented liver iron loading, decreased heart iron levels, and caused the expected iron retention in the spleen and duodenum. At high doses, PR65 treatment also caused anemia because of profound iron restriction. PR65 administration to hepcidin knockout mice with pre-existing iron overload had a more moderate effect and caused partial redistribution of iron from the liver to the spleen. Our study demonstrates that minihepcidins could be beneficial in iron overload disorders either used alone for prevention or possibly as adjunctive therapy with phlebotomy or chelation. PMID:22990014

  11. Structural basis of urea-induced unfolding: Unraveling the folding pathway of hemochromatosis factor E.

    PubMed

    Khan, Parvez; Prakash, Amresh; Haque, Md Anzarul; Islam, Asimul; Hassan, Md Imtaiyaz; Ahmad, Faizan

    2016-10-01

    Hereditary hemochromatosis factor E (HFE) is a type 1 transmembrane protein, and acts as a negative regulator of iron-uptake. The equilibrium unfolding and conformational stability of the HFE protein was examined in the presence of urea. The folding and unfolding transitions were monitored with the help of circular dichroism (CD), intrinsic fluorescence and absorption spectroscopy. Analysis of transition curves revealed that the folding of HFE is not a two-state process. However, it involved stable intermediates. Transition curves (plot of fluorescence (F346) and CD signal at 222nm (θ222) versus [Urea], the molar urea concentration) revealed a biphasic transition with midpoint (Cm) values at 2.88M and 4.95M urea. Whereas, absorption analysis shows one two-state transition centered at 2.96M. To estimate the protein stability, denaturation curves were analyzed for Gibbs free energy change in the absence of urea (ΔGD(0)) associated with the equilibrium of denaturation exist between native state↔denatured state. The intermediate state was further characterized by hydrophobic probe, 1-anilinonaphthalene-8-sulfonic acid (ANS-binding). For seeing the effect of urea on the structure and dynamics of HFE, molecular dynamics simulation for 60ns was also performed. A clear correspondence was established between the in vitro and in silico studies. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Identification of novel mutations in HFE, HFE2, TfR2, and SLC40A1 genes in Chinese patients affected by hereditary hemochromatosis.

    PubMed

    Wang, Yongwei; Du, Yali; Liu, Gang; Guo, Shanshan; Hou, Bo; Jiang, Xianyong; Han, Bing; Chang, Yanzhong; Nie, Guangjun

    2017-04-01

    Hereditary hemochromatosis (HH) is a group of inherited iron-overload disorders associated with pathogenic defects in the genes encoding hemochromatosis (HFE), hemojuvelin (HJV/HFE2), hepcidin (HAMP), transferrin receptor 2 (TfR2), and ferroportin (FPN1/SLC40A1) proteins, and the clinical features are well described. However, there have been only a few detailed reports of HH in Chinese populations. Thus, there is insufficient patient information for population-based analyses in Chinese populations or comparative studies among different ethical groups. In the current work, we describe eight Chinese cases of hereditary hemochromatosis. Gene sequencing results revealed eight mutations (five novel mutations) in HFE, HFE2, TfR2, and SLC40A1 genes in these Chinese HH patients. In addition, we used Polymorphism Phenotyping v2 (Polyphen), Sorting Intolerant From Tolerant (SIFT), and a sequence alignment program to predict the molecular consequences of missense mutations.

  13. Iron storage disease (hemochromatosis) and hepcidin response to iron load in two species of pteropodid fruit bats relative to the common vampire bat.

    PubMed

    Stasiak, Iga M; Smith, Dale A; Ganz, Tomas; Crawshaw, Graham J; Hammermueller, Jutta D; Bienzle, Dorothee; Lillie, Brandon N

    2018-07-01

    Hepcidin is the key regulator of iron homeostasis in the body. Iron storage disease (hemochromatosis) is a frequent cause of liver disease and mortality in captive Egyptian fruit bats (Rousettus aegyptiacus), but reasons underlying this condition are unknown. Hereditary hemochromatosis in humans is due to deficiency of hepcidin or resistance to the action of hepcidin. Here, we investigated the role of hepcidin in iron metabolism in one species of pteropodid bat that is prone to iron storage disease [Egyptian fruit bat (with and without hemochromatosis)], one species of pteropodid bat where iron storage disease is rare [straw-colored fruit bat (Eidolon helvum)], and one species of bat with a natural diet very high in iron, in which iron storage disease is not reported [common vampire bat (Desmodus rotundus)]. Iron challenge via intramuscular injection of iron dextran resulted in significantly increased liver iron content and histologic iron scores in all three species, and increased plasma iron in Egyptian fruit bats and straw-colored fruit bats. Hepcidin mRNA expression increased in response to iron administration in healthy Egyptian fruit bats and common vampire bats, but not in straw-colored fruit bats or Egyptian fruit bats with hemochromatosis. Hepcidin gene expression significantly correlated with liver iron content in Egyptian fruit bats and common vampire bats, and with transferrin saturation and plasma ferritin concentration in Egyptian fruit bats. Induction of hepcidin gene expression in response to iron challenge is absent in straw-colored fruit bats and in Egyptian fruit bats with hemochromatosis and, relative to common vampire bats and healthy humans, is low in Egyptain fruit bats without hemochromatosis. Limited hepcidin response to iron challenge may contribute to the increased susceptibility of Egyptian fruit bats to iron storage disease.

  14. Cost-effectiveness of different strategies for diagnosis of uncomplicated urinary tract infections in women presenting in primary care

    PubMed Central

    Coupé, Veerle M. H.; Knottnerus, Bart J.; Geerlings, Suzanne E.; Moll van Charante, Eric P.; ter Riet, Gerben

    2017-01-01

    Background Uncomplicated Urinary Tract Infections (UTIs) are common in primary care resulting in substantial costs. Since antimicrobial resistance against antibiotics for UTIs is rising, accurate diagnosis is needed in settings with low rates of multidrug-resistant bacteria. Objective To compare the cost-effectiveness of different strategies to diagnose UTIs in women who contacted their general practitioner (GP) with painful and/or frequent micturition between 2006 and 2008 in and around Amsterdam, The Netherlands. Methods This is a model-based cost-effectiveness analysis using data from 196 women who underwent four tests: history, urine stick, sediment, dipslide, and the gold standard, a urine culture. Decision trees were constructed reflecting 15 diagnostic strategies comprising different parallel and sequential combinations of the four tests. Using the decision trees, for each strategy the costs and the proportion of women with a correct positive or negative diagnosis were estimated. Probabilistic sensitivity analysis was used to estimate uncertainty surrounding costs and effects. Uncertainty was presented using cost-effectiveness planes and acceptability curves. Results Most sequential testing strategies resulted in higher proportions of correctly classified women and lower costs than parallel testing strategies. For different willingness to pay thresholds, the most cost-effective strategies were: 1) performing a dipstick after a positive history for thresholds below €10 per additional correctly classified patient, 2) performing both a history and dipstick for thresholds between €10 and €17 per additional correctly classified patient, 3) performing a dipstick if history was negative, followed by a sediment if the dipstick was negative for thresholds between €17 and €118 per additional correctly classified patient, 4) performing a dipstick if history was negative, followed by a dipslide if the dipstick was negative for thresholds above €118 per

  15. Cost-effectiveness of different strategies for diagnosis of uncomplicated urinary tract infections in women presenting in primary care.

    PubMed

    Bosmans, Judith E; Coupé, Veerle M H; Knottnerus, Bart J; Geerlings, Suzanne E; Moll van Charante, Eric P; Ter Riet, Gerben

    2017-01-01

    Uncomplicated Urinary Tract Infections (UTIs) are common in primary care resulting in substantial costs. Since antimicrobial resistance against antibiotics for UTIs is rising, accurate diagnosis is needed in settings with low rates of multidrug-resistant bacteria. To compare the cost-effectiveness of different strategies to diagnose UTIs in women who contacted their general practitioner (GP) with painful and/or frequent micturition between 2006 and 2008 in and around Amsterdam, The Netherlands. This is a model-based cost-effectiveness analysis using data from 196 women who underwent four tests: history, urine stick, sediment, dipslide, and the gold standard, a urine culture. Decision trees were constructed reflecting 15 diagnostic strategies comprising different parallel and sequential combinations of the four tests. Using the decision trees, for each strategy the costs and the proportion of women with a correct positive or negative diagnosis were estimated. Probabilistic sensitivity analysis was used to estimate uncertainty surrounding costs and effects. Uncertainty was presented using cost-effectiveness planes and acceptability curves. Most sequential testing strategies resulted in higher proportions of correctly classified women and lower costs than parallel testing strategies. For different willingness to pay thresholds, the most cost-effective strategies were: 1) performing a dipstick after a positive history for thresholds below €10 per additional correctly classified patient, 2) performing both a history and dipstick for thresholds between €10 and €17 per additional correctly classified patient, 3) performing a dipstick if history was negative, followed by a sediment if the dipstick was negative for thresholds between €17 and €118 per additional correctly classified patient, 4) performing a dipstick if history was negative, followed by a dipslide if the dipstick was negative for thresholds above €118 per additional correctly classified patient

  16. Accountability Practices in the History of Danish Primary Public Education from the 1660s to the Present

    ERIC Educational Resources Information Center

    Ydesen, Christian; Andreasen, Karen E.

    2014-01-01

    This paper focuses on primary education accountability as a concept and as an organizational practice in the history of Danish public education. Contemporary studies of education policy often address questions of accountability, but the manifestations of school accountability differ significantly between different national settings. Furthermore,…

  17. HFE C282Y/H63D compound heterozygotes are at low risk of hemochromatosis-related morbidity.

    PubMed

    Gurrin, Lyle C; Bertalli, Nadine A; Dalton, Gregory W; Osborne, Nicholas J; Constantine, Clare C; McLaren, Christine E; English, Dallas R; Gertig, Dorota M; Delatycki, Martin B; Nicoll, Amanda J; Southey, Melissa C; Hopper, John L; Giles, Graham G; Anderson, Gregory J; Olynyk, John K; Powell, Lawrie W; Allen, Katrina J

    2009-07-01

    The risk of hemochromatosis-related morbidity is unknown among HFE compound heterozygotes (C282Y/H63D). We used a prospective population-based cohort study to estimate the prevalence of elevated iron indices and hemochromatosis-related morbidity for compound heterozygotes. In all, 31,192 subjects of northern European descent were genotyped for HFE C282Y and H63D. An HFE-genotype stratified random sample of 1,438 subjects, followed for an average of 12 years to a mean age of 65 years, completed questionnaires and gave blood. Clinical examinations were blinded to HFE genotype. A total of 180 (84 males) clinically examined C282Y/H63D participants were compared with 330 (149 males) controls with neither HFE mutation; 132 (65 males) and 270 (122 males), respectively, had serum iron measures at both timepoints. Mean serum ferritin (SF) and transferrin saturation (TS) were significantly greater for male and female compound heterozygotes than for wild-types at baseline and follow-up (all P < 0.02) except for females who were premenopausal at baseline, where SF was similar in both genotype groups. For subjects with serum measures from both baseline and follow-up, mean SF and TS levels did not change significantly for men or for postmenopausal women, but for premenopausal women SF levels increased from 43 to 109 microg/L for compound heterozygotes and from 35 to 64 microg/L for wild-types (both P < 0.001). Male and female compound heterozygotes had a similar prevalence of hemochromatosis-related morbidity to wild-types. One of 82 males and zero of 95 females had documented iron overload-related disease. For male compound heterozygotes, mean iron indices do not change during middle age but for female compound heterozygotes menopause results in increased mean SF. Although compound heterozygotes might maintain elevated iron indices during middle age, documented iron overload-related disease is rare.

  18. A European allele map of the C282Y mutation of hemochromatosis: Celtic versus Viking origin of the mutation?

    PubMed

    Lucotte, Gérard; Dieterlen, Florent

    2003-01-01

    The aim of this new meta-analysis (to the end of 2002) is to compile the Y allele frequencies of the C282Y mutation of hereditary hemochromatosis (HFE gene) for 63 European populations, representing a total of 10,708 unrelated people concerning control samples. A new allele map of C282Y frequencies in Europe was constructed. The highest European frequencies are observed in the Celtic populations in Ireland, in the United Kingdom, and in France, but elevated frequencies are also observed in Scandinavia.

  19. GPs' understanding and practice of safety netting for potential cancer presentations: a qualitative study in primary care.

    PubMed

    Evans, Julie; Ziebland, Sue; MacArtney, John I; Bankhead, Clare R; Rose, Peter W; Nicholson, Brian D

    2018-05-08

    Safety netting is a diagnostic strategy used in UK primary care to ensure patients are monitored until their symptoms or signs are explained. Despite being recommended in cancer diagnosis guidelines, little evidence exists about which components are effective and feasible in modern-day primary care. To understand the reality of safety netting for cancer in contemporary primary care. A qualitative study of GPs in Oxfordshire primary care. In-depth interviews with a purposive sample of 25 qualified GPs were undertaken. Interviews were recorded and transcribed verbatim, and analysed thematically using constant comparison. GPs revealed uncertainty about which aspects of clinical practice are considered safety netting. They use bespoke personal strategies, often developed from past mistakes, without knowledge of their colleagues' practice. Safety netting varied according to the perceived risk of cancer, the perceived reliability of each patient to follow advice, GP working patterns, and time pressures. Increasing workload, short appointments, and a reluctance to overburden hospital systems or create unnecessary patient anxiety have together led to a strategy of selective active follow-up of patients perceived to be at higher risk of cancer or less able to act autonomously. This left patients with low-risk-but-not-no-risk symptoms of cancer with less robust or absent safety netting. GPs would benefit from clearer guidance on which aspects of clinical practice contribute to effective safety netting for cancer. Practice systems that enable active follow-up of patients with low-risk-but-not-no-risk symptoms, which could represent malignancy, could reduce delays in cancer diagnosis without increasing GP workload. © British Journal of General Practice 2018.

  20. Contrast-enhanced [18F] fluorodeoxyglucose-positron emission tomography-computed tomography as an initial imaging modality in patients presenting with metastatic malignancy of undefined primary origin.

    PubMed

    Jain, Avani; Srivastava, Madhur Kumar; Pawaskar, Alok Suresh; Shelley, Simon; Elangovan, Indirani; Jain, Hasmukh; Pandey, Somnath; Kalal, Shilpa; Amalachandran, Jaykanth

    2015-01-01

    To evaluate the advantages of contrast enhanced F-18-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-contrast enhanced CT [CECT]) when used as an initial imaging modality in patients presenting with metastatic malignancy of undefined primary origin (MUO). A total of 243 patients with fine needle aspiration cytology/biopsy proven MUO were included in this prospective study. Patients who were thoroughly evaluated for primary or primary tumor was detected by any other investigation were excluded from the analysis. Totally, 163 patients with pathological diagnosis of malignancy but no apparent sites of the primary tumor were finally selected for analysis. The site of probable primary malignancy suggested by PET-CECT was confirmed by biopsy/follow-up. PET-CECT suggested probable site of primary in 128/163 (78.52%) patients. In 30/35 remaining patients, primary tumor was not detected even after extensive work-up. In 5 patients, where PET-CECT was negative, primary was found on further extensive investigations or follow-up. The sensitivity, specificity, positive predictive value and negative predictive value of the study were 95.76%, 66.67%, 88.28% and 85.71% respectively. F-18 FDG PET-CECT aptly serves the purpose of initial imaging modality owing to high sensitivity, negative and positive predictive value. PET-CECT not only surveys the whole body for the primary malignancy but also stages the disease accurately. Use of contrast improves the diagnostic utility of modality as well as help in staging of the primary tumor. Although benefits of using PET-CECT as initial diagnostic modality are obvious from this study, there is a need for a larger study comparing conventional methods for diagnosing primary in patients with MUO versus PET-CECT.

  1. Contrast-enhanced [18F] fluorodeoxyglucose-positron emission tomography-computed tomography as an initial imaging modality in patients presenting with metastatic malignancy of undefined primary origin

    PubMed Central

    Jain, Avani; Srivastava, Madhur Kumar; Pawaskar, Alok Suresh; Shelley, Simon; Elangovan, Indirani; Jain, Hasmukh; Pandey, Somnath; Kalal, Shilpa; Amalachandran, Jaykanth

    2015-01-01

    Background: To evaluate the advantages of contrast enhanced F-18-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-contrast enhanced CT [CECT]) when used as an initial imaging modality in patients presenting with metastatic malignancy of undefined primary origin (MUO). Materials and Methods: A total of 243 patients with fine needle aspiration cytology/biopsy proven MUO were included in this prospective study. Patients who were thoroughly evaluated for primary or primary tumor was detected by any other investigation were excluded from the analysis. Totally, 163 patients with pathological diagnosis of malignancy but no apparent sites of the primary tumor were finally selected for analysis. The site of probable primary malignancy suggested by PET-CECT was confirmed by biopsy/follow-up. Results: PET-CECT suggested probable site of primary in 128/163 (78.52%) patients. In 30/35 remaining patients, primary tumor was not detected even after extensive work-up. In 5 patients, where PET-CECT was negative, primary was found on further extensive investigations or follow-up. The sensitivity, specificity, positive predictive value and negative predictive value of the study were 95.76%, 66.67%, 88.28% and 85.71% respectively. Conclusions: F-18 FDG PET-CECT aptly serves the purpose of initial imaging modality owing to high sensitivity, negative and positive predictive value. PET-CECT not only surveys the whole body for the primary malignancy but also stages the disease accurately. Use of contrast improves the diagnostic utility of modality as well as help in staging of the primary tumor. Although benefits of using PET-CECT as initial diagnostic modality are obvious from this study, there is a need for a larger study comparing conventional methods for diagnosing primary in patients with MUO versus PET-CECT. PMID:26170563

  2. The cost-effectiveness of screening for hereditary hemochromatosis in Germany: a remodeling study.

    PubMed

    Rogowski, Wolf H

    2009-01-01

    Genetic tests for hereditary hemochromatosis (HH) are currently included in the German ambulatory care reimbursement scheme but only for symptomatic individuals and the offspring of HH patients. This study synthesizes the most current evidence to examine whether screening in the broader population is cost-effective and to identify the best choice of initial and follow-up screening tests. A probabilistic decision-analytic model was constructed to calculate cost per life year gained (LYG) for HH screening among male Caucasians aged 30. Three strategies were considered in both the general population and male offspring of HH patients: phenotypic (transferrin saturation, TS), genotypic (C282Y mutation), and sequential (genotype if TS is elevated) screening. The incremental cost-effectiveness of sequential screening among male offspring, sequential population-wide screening, and genotypic screening is 41000, 124000, and 161000 Eero/LYG, respectively. All other strategies were subject to simple or extended dominance. The results are subject to high uncertainty. The most influential parameters in the deterministic one-way sensitivity analysis are discounting of life years gained and the adherence of patients to preventive phlebotomy. The current German policy of only screening at-risk individuals is consistent with health economic decision making based on typically accepted thresholds. However, conducting the DNA test after the first elevated TS result is more cost-effective than waiting for a second TS result as recommended by the German guidelines. Further empirical work regarding adherence to long-term prevention recommendations and explicit and well-justified guidance for the choice of discount rates in German economic evaluation are needed.

  3. Hemochromatosis Enhances Tumor Progression via Upregulation of Intracellular Iron in Head and Neck Cancer

    PubMed Central

    Lenarduzzi, Michelle; Hui, Angela B. Y.; Yue, Shijun; Ito, Emma; Shi, Wei; Williams, Justin; Bruce, Jeff; Sakemura-Nakatsugawa, Noriko; Xu, Wei; Schimmer, Aaron; Liu, Fei-Fei

    2013-01-01

    Introduction Despite improvements in treatment strategies for head and neck squamous cell carcinoma (HNSCC), outcomes have not significantly improved; highlighting the importance of identifying novel therapeutic approaches to target this disease. To address this challenge, we proceeded to evaluate the role of iron in HNSCC. Experimental Design Expression levels of iron-related genes were evaluated in HNSCC cell lines using quantitative RT-PCR. Cellular phenotypic effects were assessed using viability (MTS), clonogenic survival, BrdU, and tumor formation assays. The prognostic significance of iron-related proteins was determined using immunohistochemistry. Results In a panel of HNSCC cell lines, hemochromatosis (HFE) was one of the most overexpressed genes involved in iron regulation. In vitro knockdown of HFE in HNSCC cell lines significantly decreased hepcidin (HAMP) expression and intracellular iron level. This in turn, resulted in a significant decrease in HNSCC cell viability, clonogenicity, DNA synthesis, and Wnt signalling. These cellular changes were reversed by re-introducing iron back into HNSCC cells after HFE knockdown, indicating that iron was mediating this phenotype. Concordantly, treating HNSCC cells with an iron chelator, ciclopirox olamine (CPX), significantly reduced viability and clonogenic survival. Finally, patients with high HFE expression experienced a reduced survival compared to patients with low HFE expression. Conclusions Our data identify HFE as potentially novel prognostic marker in HNSCC that promotes tumour progression via HAMP and elevated intracellular iron levels, leading to increased cellular proliferation and tumour formation. Hence, these findings suggest that iron chelators might have a therapeutic role in HNSCC management. PMID:23991213

  4. Analysis of HFE and non-HFE gene mutations in Brazilian patients with hemochromatosis.

    PubMed

    Bittencourt, Paulo Lisboa; Marin, Maria Lúcia Carnevale; Couto, Cláudia Alves; Cançado, Eduardo Luiz Rachid; Carrilho, Flair José; Goldberg, Anna Carla

    2009-01-01

    Approximately one-half of Brazilian patients with hereditary hemochromatosis (HH) are neither homozygous for the C282Y mutation nor compound heterozygous for the H63D and C282Y mutations that are associated with HH in Caucasians. Other mutations have been described in the HFE gene as well as in genes involved in iron metabolism, such as transferrin receptor 2 (TfR2) and ferroportin 1 (SCL40A1). To evaluate the role of HFE, TfR2 and SCL40A1 mutations in Brazilian subjects with HH. Nineteen male subjects (median age 42 [range: 20-72] years) with HH were evaluated using the Haemochromatosis StripAssay A. This assay is capable of detecting twelve HFE mutations, which are V53M, V59M, H63D, H63H, S65C, Q127H, P160delC, E168Q, E168X, W169X, C282Y and Q283, four TfR2 mutations, which are E60X, M172K, Y250X, AVAQ594-597del, and two SCL40A1 mutations, which are N144H and V162del. In our cohort, nine (47%) patients were homozygous for the C282Y mutation, two (11%) were heterozygous for the H63D mutation, and one each (5%) was either heterozygous for C282Y or compound heterozygous for C282Y and H63D. No other mutations in the HFE, TfR2 or SCL40A1 genes were observed in the studied patients. One-third of Brazilian subjects with the classical phenotype of HH do not carry HFE or other mutations that are currently associated with the disease in Caucasians. This observation suggests a role for other yet unknown mutations in the aforementioned genes or in other genes involved in iron homeostasis in the pathogenesis of HH in Brazil.

  5. Hyperferritinemia increases the risk of hyperuricemia in HFE-hereditary hemochromatosis.

    PubMed

    Flais, Jérémy; Bardou-Jacquet, Edouard; Deugnier, Yves; Coiffier, Guillaume; Perdriger, Aleth; Chalès, Gérard; Ropert, Martine; Loréal, Olivier; Guggenbuhl, Pascal

    2017-05-01

    Hyperuricemia is becoming increasingly frequent in the population, and is known to be sometimes the cause of gout. The impact of uric acid is still not clearly understood, however. The iron metabolism may interact with the uric acid metabolism. The aim of this study was to examine the relationship between the serum uric acid and serum ferritin levels in a cohort of hemochromatosis patients who were homozygous for the HFE p.Cys282Tyr mutation. 738 patients with the HFE gene mutation Cys282Tyr in the homozygous state were included in the study. The variables measured during the initial evaluation were compared in univariate analysis by Student's t test. In multivariate analysis, linear stepwise regression was used. In the group of hyperuricemic patients, ferritinemia was significantly higher than in the group of non-hyperuricemic patients (1576.7±1387.4μg/l vs. 1095.63±1319.24μg/l, P<0.005). With multivariate analysis, only ferritin and BMI independently explained the uricemia (R 2 =0.258) after adjustment for age, glycemia and CRP. The correlation between uricemia and log(ferritin) with partial regression correlation coefficients was 0.307 (P<0.01). The increase in uricemia is associated with the increase in ferritin in a population of patients who were homozygous for the HFE gene mutation p.Cys282Tyr and this independently of factors commonly associated with hyperuricemia. The increase in uric acid associated with hyperferritinemia, could be a response to the visceral toxicity of excess non-transferrin bound iron linked to oxidative stress via the antioxidant properties of uric acid. Copyright © 2016 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  6. Hereditary hemochromatosis is characterized by a clinically definable arthropathy that correlates with iron load.

    PubMed

    Carroll, G J; Breidahl, W H; Bulsara, M K; Olynyk, J K

    2011-01-01

    To determine the frequency and character of arthropathy in hereditary hemochromatosis (HH) and to investigate the relationship between this arthropathy, nodal interphalangeal osteoarthritis, and iron load. Participants were recruited from the community by newspaper advertisement and assigned to diagnostic confidence categories for HH (definite/probable or possible/unlikely). Arthropathy was determined by use of a predetermined clinical protocol, radiographs of the hands of all participants, and radiographs of other joints in which clinical criteria were met. An arthropathy considered typical for HH, involving metacarpophalangeal joints 2-5 and bilateral specified large joints, was observed in 10 of 41 patients with definite or probable HH (24%), all of whom were homozygous for the C282Y mutation in the HFE gene, while only 2 of 62 patients with possible/unlikely HH had such an arthropathy (P=0.0024). Arthropathy in definite/probable HH was more common with increasing age and was associated with ferritin concentrations>1,000 μg/liter at the time of diagnosis (odds ratio 14.0 [95% confidence interval 1.30-150.89], P=0.03). A trend toward more episodes requiring phlebotomy was also observed among those with arthropathy, but this was not statistically significant (odds ratio 1.03 [95% confidence interval 0.99-1.06], P=0.097). There was no significant association between arthropathy in definite/probable HH and a history of intensive physical labor (P=0.12). An arthropathy consistent with that commonly attributed to HH was found to occur in 24% of patients with definite/probable HH. The association observed between this arthropathy, homozygosity for C282Y, and serum ferritin concentrations at the time of diagnosis suggests that iron load is likely to be a major determinant of arthropathy in HH and to be more important than occupational factors. Copyright © 2011 by the American College of Rheumatology.

  7. Presence of hemochromatosis-associated mutations in Hispanic patients with iron overload.

    PubMed

    Nieves-Santiago, Paul; Cancel, Dilany; Canales, Dialma; Toro, Doris H

    2011-09-01

    To determine the characteristics of the Puerto Rico Veteran population with iron overload in terms of demographic features, clinical manifestations, and the presence of hereditary hemochromatosis (HH) mutations, and to compare such characteristics in patients with and without HH mutations. A retrospective study was conducted in patients with iron overload (transferrin saturation > or = 45%) who were tested for HH mutations from January 2003 to June 2007. Data collected included age, gender, body mass index, hemoglobin level, platelet count, ferritin level, transferrin saturation, ceruloplasmin, alfa-1 antitrypsin, anti-nuclear antibodies, aspartate aminotransferase, alanine aminotransferase, alfa-fetoprotein, viral hepatitis profile, imaging studies, and comorbid conditions. Patients were grouped according to the results of the commercially available HH DNA mutation analysis as homozygote, heterozygote, compound heterozygote, or negative. 94 patients were studied. Most patients were male (90/94); the mean age was 60 years. Of the study group, 36% (34/94) was found positive for HH mutations. The most common mutation was H63D, which was found in 85% (29/34) of patients; 4 homozygotes and 25 heterozygotes. C282Y mutation was identified in only 12% (4/34) of patients, of which one was homozygote. A compound heterozygote (C282Y/ H63D) was also identified. After analyzing the data for confounding factors, 6 of 29 heterozygotes had no other risk factors for liver disease other than the H63D mutation. The predominance of H63D mutations in our population deserves further investigation since it considerably differs from other studied populations with iron overload in which C282Y is the most common mutation.

  8. H63D mutation in hemochromatosis alters cholesterol metabolism and induces memory impairment.

    PubMed

    Ali-Rahmani, Fatima; Grigson, Patricia S; Lee, Sang; Neely, Elizabeth; Connor, James R; Schengrund, Cara-Lynne

    2014-06-01

    The H63D variant of the hemochromatosis (HFE) gene, when expressed in carriers of the apolipoprotein E4 allele, is implicated as a risk factor for earlier onset of Alzheimer's disease (AD). We tested the hypothesis that like expression of apolipoprotein E4, expression of H63D-HFE disrupts cholesterol metabolism contributing to an increase in neurodegeneration and memory deficits. Analysis of SH-SY5Y human neuroblastoma cells transfected to stably express either wild type- (WT) or H63D-HFE indicated about a 50% reduction in cholesterol content in cells expressing H63D-HFE. This was accompanied by a significant decrease in expression of 3-hydroxy-3-methyl-glutaryl-CoA reductase, and a significant increase in expression of cholesterol 24-hydroxylase. Consistent with these studies, H67D-HFE (orthologous to human H63D-HFE) knock-in mice, showed a greater age dependent decline in brain cholesterol than WT-HFE animals and changes in expression of proteins regulating cholesterol metabolism. Brains of aged H67D-HFE mice also exhibited a significant decrease in expression of synapse proteins and a significant increase in caspase-3 expression relative to WT-HFE controls. H67D-HFE mice also had a greater reduction in brain volume and poorer recognition and spatial memory than WT-HFE mice, symptoms associated with AD. These results indicate that the alterations in cholesterol metabolism associated with expression of H63D-HFE may contribute to the development of AD. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Hemochromatosis (HFE) gene mutations and response to chloroquine in porphyria cutanea tarda.

    PubMed

    Stölzel, Ulrich; Köstler, Erich; Schuppan, Detlef; Richter, Matthias; Wollina, Uwe; Doss, Manfred O; Wittekind, Christian; Tannapfel, Andrea

    2003-03-01

    To examine the role of hemochromatosis (HFE) gene mutations, which are associated with porphyria cutanea tarda (PCT), in the therapeutic response to chloroquine. We retrospectively analyzed a database (Excel version 2001 [Microsoft Excel, Redmond, Wash]; date range of search, 1985-1999) of chloroquine-treated patients with PCT on whether HFE mutations (C282Y and H63D) might have influenced the clinical response, urinary porphyrin excretion, liver enzyme activities, and serum iron markers. Serum samples and corresponding complete sets of data before and after therapy were available in 62 of 207 patients with PCT who were treated exclusively with chloroquine. Academic teaching hospital. For treatment, low-dose chloroquine diphosphate, 125 to 250 mg twice weekly, was used during a median time of 16 months (range, 12-26 months). Of the 62 German patients with PCT, 37 (60%) carries HFE mutations. Chloroquine therapy was accompanied by clinical remission and reduced urinary porphyrin excretion (P<.001) in the 24 patients (39%) with HFE wild type as well as in 35 HFE heterozygous patients with PCT (56%). Decreases of serum iron markers following chloroquine therapy were limited to patients with PCT and HFE wild type. All patients homozygous for the C282Y mutation (3 [5%] of 62) had high serum iron, ferritin, and transferrin saturation and failed to respond to chloroquine treatment. The therapeutic response to chloroquine was not compromised by C282Y heterozygosity and compound heterozygosity of HFE mutations. Because HFE C282Y homozygotes (+/+) did not respond to chloroquine and a decrease in serum iron concentration was limited to patients with PCT and HFE wild type, phlebotomy should be first-line therapy in patients with PCT and HFE mutations.

  10. Primary Angioplasty for Cardiac Allograft Vasculopathy Presenting as ST-Elevation Acute Myocardial Infarction during Endomyocardial Biopsy

    PubMed Central

    Nascimento, Bruno Ramos; Gomes, Thalles Oliveira; Borges, Júlio César; Athayde, Guilherme Rafael Sant'Anna; de Andrade, Sílvio Amadeu; Moreira, Maria da Consolação Vieira

    2013-01-01

    Cardiac allograft vasculopathy is still a major issue, with significative mortality in heart transplant patients, and the best therapeutic options are not yet established. The progressively higher survival rates after transplantation have made it a major concern. This is a case report about a patient who underwent cardiac transplantation due to chagasic cardiomiopathy. During an endomyocardial biopsy more than 2 years after the transplant, the patient arrested in ventricular fibrillation, with ST-elevation in anterior leads after defibrillation. The angiography showed total occlusion of proximal left anterior descending artery, promptly treated with primary angioplasty, with excellent angiographic and clinical results. PMID:24066253

  11. [Extracorporeal membrane oxygenation in primary graft dysfunction in a paediatric double lung transplant: presentation of a case].

    PubMed

    López-Cantero, M; Grisolía, A L; Vicente, R; Moreno, I; Ramos, F; Porta, J; Torregrosa, S

    2014-04-01

    Primary graft dysfunction is a leading cause of morbimortality in the immediate postoperative period of patients undergoing lung transplantation. Among the treatment options are: lung protective ventilatory strategies, nitric oxide, lung surfactant therapy, and supportive treatment with extracorporeal membrane oxygenation (ECMO) as a bridge to recovery of lung function or re-transplant. We report the case of a 9-year-old girl affected by cystic fibrosis who underwent double-lung transplantation complicated with a severe primary graft dysfunction in the immediate postoperative period and refractory to standard therapies. Due to development of multiple organ failure, it was decided to insert arteriovenous ECMO catheters (pulmonary artery-right atrium). The postoperative course was satisfactory, allowing withdrawal of ECMO on the 5th post-surgical day. Currently the patient survives free of rejection and with an excellent quality of life after 600 days of follow up. Copyright © 2012 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

  12. You can't treat what you don't diagnose: An analysis of the recognition of somatic presentations of depression and anxiety in primary care.

    PubMed

    Gates, Kristin; Petterson, Stephen; Wingrove, Peter; Miller, Benjamin; Klink, Kathleen

    2016-12-01

    Research suggests that 13-25% of primary care patients who present with physical complaints have underlying depression or anxiety. The goal of this paper is to quantify and compare the frequency of the diagnosis of depression and anxiety in patients with a somatic reason for visit among primary care physicians across disciplines. Data obtained from the National Ambulatory Medical Care Survey (NAMCS) from 2002 to 2010 was used to quantify primary care patients with somatic presentations who were given a diagnosis of depression or anxiety. The Patient Health Questionnaire (PHQ)-15, Somatic Symptom Scale, and the Child Behavior Checklist for Ages 6-18 were used to define what constituted a somatic reason for visit in this study. Of the patients presenting with a somatic reason for visit in this nationally representative survey, less than 4% of patents in family or internal medicine were diagnosed with depression or anxiety. Less than 1% of patients were diagnosed with depression or anxiety in pediatrics or obstetrics and gynecology. Less than 2% of patients with somatic reasons for visit in any primary care specialty had documented screening for depression. The rates of diagnosis of depression and anxiety in patents presenting with somatic reasons for visit were significantly less than the prevalence reported in the literature across primary care disciplines. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  13. Churg-Strauss syndrome presenting with acute kidney injury in a case of primary focal segmental glomerulosclerosis.

    PubMed

    Patil, Sachin B; Vanikar, Aruna V; Gumber, Manoj R; Kute, Vivek B; Shah, Pankaj R; Patel, Himanshu V; Trivedi, Hargovind L

    2014-01-01

    Churg-Strauss syndrome (CSS) also called allergic granulomatosis and angiitis is a multisystem disorder. Churg-Strauss syndrome is defined as an eosinophil-rich, granulomatous inflammation involving the respiratory tract, along with necrotizing vasculitis affecting small- to medium-sized vessels, and is associated with asthma and eosinophilia. Renal involvement in CSS varies from 26 to 88 % but is usually of mild to moderate stage, and advanced renal failure is uncommon. We encountered an unusual case of 27-year-old man with asthma and primary focal segmental glomerulosclerosis diagnosed as CSS showing myeloperoxidase anti-neutrophil cytoplasmic antibody-associated acute kidney injury with crescentic glomerulonephritis. Patient responded to steroid and cyclophosphamide. Over a follow-up of 2 months, he has no hematuria/eosinophilia and serum creatinine of 2.3 mg/dL has decreased to 1.7 mg/dL.

  14. Autoimmune Conditions in 235 Hemochromatosis Probands with HFE C282Y Homozygosity and Their First-Degree Relatives

    PubMed Central

    Barton, James C.; Barton, J. Clayborn

    2015-01-01

    We performed a retrospective study of autoimmune conditions (ACs) in 235 hemochromatosis probands at diagnosis by analyzing age, sex, ACs, history of first-degree family members with ACs (FH), diabetes, heavy ethanol consumption, elevated serum ALT/AST, nonalcoholic fatty liver disease, viral hepatitis, cirrhosis, iron removed to achieve iron depletion (QFe), and positivity for human leukocyte antigen (HLA) haplotypes A∗01, B∗08; A∗02, B∗44; A∗03, B∗07; A∗03, B∗14; and A∗29, B∗44. There were 138 men (58.7%). Median followup was 19.6 y. One or more of 19 ACs were diagnosed in each of 35 probands (14.9%). Prevalences of Hashimoto's thyroiditis, rheumatoid arthritis, and ankylosing spondylitis were 8.1% (95% CI: [5.1, 12.5]), 1.7% [0.6, 4.6], and 0.0085 [0.0015, 0.0337], respectively. Eighteen probands (7.7%) had a FH. Eight probands with ACs had 9 family members with ACs. In a logistic regression, ACs were less likely in men (odds ratio (OR) 0.3 [0.1, 0.6]) and more likely in probands with a FH (OR 4.1 [1.4, 11.8]). Overall ACs risk was not significantly associated with QFe or HLA haplotypes. Estimated survival of probands with and without ACs did not differ significantly. We conclude that ACs are common in hemochromatosis probands, especially women and probands with a FH. PMID:26504855

  15. Deferasirox in patients with iron overload secondary to hereditary hemochromatosis: results of a 1-yr Phase 2 study.

    PubMed

    Cançado, Rodolfo; Melo, Murilo R; de Moraes Bastos, Roberto; Santos, Paulo C J L; Guerra-Shinohara, Elivira M; Chiattone, Carlos; Ballas, Samir K

    2015-12-01

    This open-label, prospective, phase 2 study evaluated the safety and efficacy of deferasirox (10 ± 5 mg/kg/d) in patients with hereditary hemochromatosis (HH) and iron overload refractory to or intolerant of phlebotomy. Ten patients were enrolled and all completed the 12-month treatment period. There were significant decreases from baseline to end of study (i.e., 12 months) in median serum ferritin (P < 0.001), mean transferrin saturation (P < 0.05), median liver iron concentration (P < 0.001), and mean alanine aminotransferase (P < 0.05). The median time to achieve serum ferritin reduction ≥50% compared to baseline was 7.53 months. The most common adverse events were mild, transient diarrhea (n = 5) and nausea (n = 2). No patient experienced an increase in serum creatinine that exceeded the upper limit of normal. These data confirm that deferasirox was well tolerated and effective in reducing iron burden in patients with hereditary hemochromatosis and could be a safe alternative to phlebotomy in selected patients. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Diabetes in first-degree family members: a predictor of type 2 diabetes in 159 nonscreening Alabama hemochromatosis probands with HFE C282Y homozygosity.

    PubMed

    Barton, James C; Barton, J Clayborn; Acton, Ronald T

    2014-01-01

    OBJECTIVE We sought to identify predictors of diabetes diagnosed before hemochromatosis. RESEARCH DESIGN AND METHODS We studied these 16 variables in 159 nonscreening hemochromatosis probands with HFE C282Y homozygosity: age; sex; BMI; diabetes reports in first-degree family members (dichotomous); heavy ethanol consumption; cigarette smoking; elevated serum alanine aminotransferase/aspartate aminotransferase levels; nonalcoholic fatty liver; chronic viral hepatitis; cirrhosis; hand arthropathy; iron removed by phlebotomy; and positivity for HLA-A*01, B*08; A*03, B*07; and A*03, B*14 haplotypes. We performed univariable and multivariable analyses. RESULTS Twenty-three probands (14.5%) had diabetes; 19 were men. Each of the 23 probands had type 2 diabetes. Mean BMI was greater in probands with diabetes (31.7 ± 8.5 [SD] kg/m(2) vs. 27.6 ± 5.1 kg/m(2); P = 0.032). Reports of any first-degree family member with diabetes were more prevalent in probands with than in probands without diabetes (69.6 vs. 17.6%; P < 0.0001). In probands with diabetes, the odds ratio (OR) of maternal diabetes was 6.7 (95% CI 2.3-19.7; P = 0.0005) and of sibling diabetes was 11.7 (3.0-45.5; P = 0.0004). In a logistic regression model, predictors of diabetes at hemochromatosis diagnosis in 159 probands were diabetes reports in family members (OR 8.5 [95% CI 2.9-24.8]; P < 0.0001) and BMI (1.1 [1.0-1.2]; P = 0.049). This model explained 26.0% of total deviance contributing to diabetes. CONCLUSIONS In nonscreening hemochromatosis probands with HFE C282Y homozygosity, a heritable factor(s) increases the risk of diabetes diagnosed before hemochromatosis.

  17. Isolated orbital mass as the primary presentation of a triple-hit lymphoma transformed from a systemic follicular lymphoma.

    PubMed

    Zhou, Xiao Yi; Lu, Xinyan; Raparia, Kirtee; Chen, Yi-Hua

    2018-06-01

    Triple-hit lymphoma is a highly aggressive B-cell lymphoma. We report a case of triple-hit lymphoma transformed from systemic follicular lymphoma (FL) after 9-year remission and presented primarily as an isolated orbital mass without systemic symptoms or lymphadenopathy. A 58-year-old female presented with intermittent vertical binocular diplopia, left upper eyelid swelling and pain and was found to have a 2.9 cm orbital mass. Histological section revealed a CD10-positive large B-cell lymphoma, consistent with transformation of FL. Fluorescent in situ hybridization (FISH) analysis demonstrated rearrangements involving C-MYC, BCL-2 and BCL-6 genes, indicating a high grade, triple-hit lymphoma. Triple-hit lymphoma transformed from a low-grade lymphoma may initially present as an isolated orbital mass without systemic evidence of transformation. Early recognition of double or triple-hit lymphomas is important since these patients require aggressive chemotherapy.

  18. Lung Adenocarcinoma with Anaplastic Lymphoma Kinase (ALK) Rearrangement Presenting as Carcinoma of Unknown Primary Site: Recognition and Treatment Implications.

    PubMed

    Hainsworth, John D; Anthony Greco, F

    Molecular cancer classifier assays are being used with increasing frequency to predict tissue of origin and direct site-specific therapy for patients with carcinoma of unknown primary site (CUP). We postulated some CUP patients predicted to have non-small-cell lung cancer (NSCLC) by molecular cancer classifier assay may have anaplastic lymphoma kinase (ALK) rearranged tumors, and benefit from treatment with ALK inhibitors. We retrospectively reviewed CUP patients who had the 92-gene molecular cancer classifier assay (CancerTYPE ID; bioTheranostics, Inc.) performed on tumor biopsies to identify patients predicted to have NSCLC. Beginning in 2011, we have tested these patients for ALK rearrangements and epidermal growth factor receptor (EGFR) activating mutations, based on the proven therapeutic value of these targets in NSCLC. We identified CUP patients with predicted NSCLC who were subsequently found to have ALK rearrangements. NSCLC was predicted by the molecular cancer classifier assay in 37 of 310 CUP patients. Twenty-one of these patients were tested for ALK rearrangements, and four had an EML4-ALK fusion gene detected. The diagnosis of lung cancer was strongly suggested in only one patient prior to molecular testing. One patient received ALK inhibitor treatment and has had prolonged benefit. We report on patients with lung adenocarcinoma and ALK rearrangements originally diagnosed as CUP who were identified using a molecular cancer classifier assay. Although ALK inhibitors treatment experience is limited, this newly identifiable group of lung cancer patients should be considered for therapy according to guidelines for stage IV ALK-positive NSCLC.

  19. Lung Adenocarcinoma with Anaplastic Lymphoma Kinase (ALK) Rearrangement Presenting as Carcinoma of Unknown Primary Site: Recognition and Treatment Implications.

    PubMed

    Hainsworth, John D; Anthony Greco, F

    2016-03-01

    Molecular cancer classifier assays are being used with increasing frequency to predict tissue of origin and direct site-specific therapy for patients with carcinoma of unknown primary site (CUP). We postulated some CUP patients predicted to have non-small-cell lung cancer (NSCLC) by molecular cancer classifier assay may have anaplastic lymphoma kinase (ALK) rearranged tumors, and benefit from treatment with ALK inhibitors. We retrospectively reviewed CUP patients who had the 92-gene molecular cancer classifier assay (CancerTYPE ID; bioTheranostics, Inc.) performed on tumor biopsies to identify patients predicted to have NSCLC. Beginning in 2011, we have tested these patients for ALK rearrangements and epidermal growth factor receptor (EGFR) activating mutations, based on the proven therapeutic value of these targets in NSCLC. We identified CUP patients with predicted NSCLC who were subsequently found to have ALK rearrangements. NSCLC was predicted by the molecular cancer classifier assay in 37 of 310 CUP patients. Twenty-one of these patients were tested for ALK rearrangements, and four had an EML4-ALK fusion gene detected. The diagnosis of lung cancer was strongly suggested in only one patient prior to molecular testing. One patient received ALK inhibitor treatment and has had prolonged benefit. We report on patients with lung adenocarcinoma and ALK rearrangements originally diagnosed as CUP who were identified using a molecular cancer classifier assay. Although ALK inhibitors treatment experience is limited, this newly identifiable group of lung cancer patients should be considered for therapy according to guidelines for stage IV ALK-positive NSCLC.

  20. Nalidixic Acid-Resistant Salmonella enterica Serotype Typhi Presenting as a Primary Psoas Abscess: Case Report and Review of the Literature

    PubMed Central

    Shakespeare, William A.; Davie, Daniel; Tonnerre, Claude; Rubin, Michael A.; Strong, Michael; Petti, Cathy A.

    2005-01-01

    We report an unusual case of Salmonella enterica serotype Typhi presenting as a primary psoas abscess. The isolate tested susceptible to ciprofloxacin but resistant to nalidixic acid in vitro, a pattern associated with fluoroquinolone therapeutic failures. We review the literature for serovar Typhi psoas abscess in the absence of bacteremia and discuss the importance of identifying isolates with reduced susceptibility to fluoroquinolones. PMID:15695728

  1. An Uncommon Presentation of a Metachronous Testicular Primary Nonseminoma and Seminoma Separated by Two Decades and a Testicular Cancer Literature Review.

    PubMed

    Buck, Dennis Andrew; Smith, Tristan Dean; Montana, Wilbur Nelson

    2017-01-01

    Testicular cancer is the most common malignancy in men aged 15-40 years [Bols et al.: Philadelphia, Wolters Kluwer, Lippincott Williams & Wilkins, 2011]. Its incidence comprises 0.8% of all male cancers worldwide, with a mortality rate of 0.1%. The incidence has nearly doubled from 1975 to 2007 leading to the concern of environmental causes [Thomas: Am J Epidemiol 2013; 178: 1240-1245]. Testicular cancer presents as a painless testicular mass without transillumination. Testicular cancer is subcategorized under germ cell testicular cancer or sex cord-stromal tumors. Of the germ cell tumors, approximately 90% originate in the testis, with the other 10% being extragonadal [Bols et al.: Philadelphia, Wolters Kluwer, Lippincott Williams & Wilkins, 2011]. Typically, if a patient presents with a testicular mass and is 50 years old or older, the diagnosis of a primary lymphoma is considered until proven otherwise [Bols et al.: Philadelphia, Wolters Kluwer, Lippincott Williams & Wilkins, 2011]. Germ cell testicular cancer is further divided into the subtypes of seminomatous and nonseminomatous; each presents with a unique histology and differing treatment implications. Given the uniqueness of our patient's metachronous second testicular primary, we sought to compare our case findings to available historic publications. We sought to address the issues of the incidence of a second primary testicular malignancy with regard to varying histology, age of incidence, and timing of a second primary testicular cancer, the presence of bowel involvement, and finally a brief discussion of testosterone replacement therapy. A review of our case presents several unique factors. The above varying literature has shown our patient to have met the odds of a contralateral testicular primary development in that he had a nonseminomatous primary, followed by a second testicular primary seminoma. Our patient exceeded the 15-year cumulative risk of contralateral metachronous testicular cancer of 1

  2. Delay in presentation and diagnosis of adult primary intracranial neoplasms in a tropical teaching hospital: a pilot study.

    PubMed

    Idowu, O E; Apemiye, R A

    2009-08-01

    Sixty-three adult patients with intracranial neoplasms were studied prospectively over a 2 year period. The various factors related to pre-presentation symptoms interval (PSI) and pre-diagnostic interval (PI) were noted. The mean age at presentation for all patients was 46.8 years (range 18-72 years, median 46 years). Meningiomas (30%), Pituitary tumours (18%), High-grade gliomas (14%) and craniopharyngiomas (8%) were the most common brain tumours. The median PSI of all patients was 2 year (range 2 months-5 years) with a PI of 4 weeks (range 0-8 months). The PSI and PI were longer for women with a statistical significance between the PSI and gender (p=0.016). The tumour grade was significantly correlated with PSI (p=0.000) and PI (p=0.043). Late presentation and diagnosis were due to cultural and religious beliefs compounded by self medication and financial constraint. There is the need for widespread mass enlightenment, improvement in accessibility and affordability of neuroimaging facilities coupled with subsidization of treatment.

  3. Primary biliary cirrhosis-specific antimitochondrial antibodies in neonatal haemochromatosis.

    PubMed

    Smyk, Daniel S; Mytilinaiou, Maria G; Grammatikopoulos, Tassos; Knisely, A S; Mieli-Vergani, Giorgina; Bogdanos, Dimitrios P; Vergani, Diego

    2013-01-01

    Neonatal hemochromatosis (NH) is characterised by severe liver injury and extrahepatic siderosis sparing the reticuloendothelial system. Its aetiology is obscure, although it has been proposed as an alloimmune disease, resulting from immunological reaction to self-antigens (alloantigens) which the body recognizes as foreign. We studied an infant with NH and his mother whose sera contained antimitochondrial antibody (AMA), the hallmark of primary biliary cirrhosis (PBC). To investigate the origin of AMA in the infant, we studied isotype distributions in serum from the mother and infant. Serum samples were obtained at diagnosis of NH, after liver transplantation (LT; age 1 month), and over the ensuing 17 months. At NH diagnosis, infant and maternal serum contained AMA of the IgG isotype, predominantly of the G3 and G1 subclasses. AMA strongly reacted against the pyruvate dehydrogenase complex E2 subunit (PDC-E2), the major PBC-specific AMA autoantigen. Anti-PDC-E2 responses in both infant and mother declined over time, being present 2 months after LT (mother and child) and absent 10 months later (mother) and 17 months later (child). The association of maternally transferred IgG1 and IgG3 subclass AMA with the appearance of liver damage in an infant with NH may suggest a causal link between antibody and liver damage.

  4. Presentation of self and symptoms in primary care consultations involving patients from non-English speaking backgrounds.

    PubMed

    Roberts, Celia; Sarangi, Srikant; Moss, Becky

    2004-01-01

    This paper draws on the PLEDGE research project (Patients with Limited English and Doctors in General Practice) 1 The Patients with Limited English and Doctors in General Practice (PLEDGE) project was funded by Sir Siegmund Warburg's Voluntary Settlement (2001-2003). The research team was: Celia Roberts, Roger Jones, Becky Moss, Srikant Sarangi and Val Wass. which has a database of 232 video-recorded interactions from GP surgeries in South East London. We focus on the opening episodes-the first opportunity the patient has to report on why they have come to see the doctor-to explore some of the contrasts in self presentation and the interactional work that doctors do when faced with the unexpected. Patients who speak a local London or standard variety of English present three aspects: a description of symptoms, the context in which they occurred, and an affective or epistemic stance. These 'micro discourse routines' are accomplished interactionally through the design of figure/ground relationships, framing and metacommunication and presentation of the 'moral self'. Although some patients from non-English speaking backgrounds use broadly similar 'micro discourse routines', the majority configure the relationship between medically salient facts, adequate contextual information and the stance which conveys the 'moral self' in different and apparently less 'orderly' ways. So openings often become protracted and harder work interactionally for both sides. While conversation analytic studies and communication skills textbooks represent the medical consultations as orderly, we suggest that such apparent orderliness must, at least, be partly the result of ironing out linguistic and cultural diversity. Interactional sociolinguistic analysis is used to shed light on the design of these routines and to provide analytic frameworks for doctors in reflecting on their own practice in ways which challenge patient-centred models.

  5. The impact of primary care on emergency department presentation and hospital admission with pneumonia: a case–control study of preschool-aged children

    PubMed Central

    Emery, Diane P; Milne, Tania; Gilchrist, Catherine A; Gibbons, Megan J; Robinson, Elizabeth; Coster, Gregor D; Forrest, Christopher B; Harnden, Anthony; Mant, David; Grant, Cameron C

    2015-01-01

    Background: In children, community-acquired pneumonia is a frequent cause of emergency department (ED) presentation and hospital admission. Quality primary care may prevent some of these hospital visits. Aims: The aim of this study was to identify primary care factors associated with ED presentation and hospital admission of preschool-aged children with community-acquired pneumonia. Methods: A case–control study was conducted by enrolling three groups: children presenting to the ED with pneumonia and admitted (n=326), or discharged home (n=179), and well-neighbourhood controls (n=351). Interviews with parents and primary care staff were conducted and health record review was performed. The association of primary care factors with ED presentation and hospital admission, controlling for available confounding factors, was determined using logistic regression. Results: Children were more likely to present to the ED with pneumonia if they did not have a usual general practitioner (GP) (odds ratio (OR)=2.50, 95% confidence interval (CI)=1.67–3.70), their GP worked ⩽20 h/week (OR=1.86, 95% CI=1.10–3.13) or their GP practice lacked an immunisation recall system (OR=5.44, 95% CI=2.26–13.09). Lower parent ratings for continuity (OR=1.63, 95% CI=1.01–2.62), communication (OR=2.01, 95% CI=1.29–3.14) and overall satisfaction (OR=2.16, 95% CI=1.34–3.47) increased the likelihood of ED presentation. Children were more likely to be admitted when antibiotics were prescribed in primary care (OR=2.50, 95% CI=1.43–4.55). Hospital admission was less likely if children did not have a usual GP (OR=0.22, 95% CI=0.11–0.40) or self-referred to the ED (OR=0.48, 95% CI=0.26–0.89). Conclusions: Accessible and continuous primary care is associated with a decreased likelihood of preschool-aged children with pneumonia presenting to the ED and an increased likelihood of hospital admission, implying more appropriate referral. Lower parental satisfaction is associated with an

  6. Large mass affecting retroperitoneal great vessels: a rare presentation of a cancer of unknown primary with diagnostic dilemma and challenged surgical intervention.

    PubMed

    Stakia, Paraskevi; Lagos, Panagiotis; Gourgiotis, Stavros; Tzilalis, Vasilios D; Aloizos, Stavros; Salemis, Nikolaos S

    2009-01-01

    Cancers of unknown primary site (CUPs) consist of a clinical entity which accounts for 3-5% of all solid tumor patients. They are metastatic solid tumors whose fundamental characteristic is the absence of identifiable site of the primary tumor. We report the case of a completely asymptomatic 34-year-old man with a palpated huge mass found incidentally in the left abdomen. All the investigations were normal. During the operation, a large mass was identified 2 cm below the left renal artery which was displacing and encompassing the great retroperitoneal vessels and the left ureter. A complete resection of the mass was performed while the histological examination revealed a solitary retroperitoneal lymph node categorized as metastatic adenocarcinoma of unknown primary site. It is essential to assess the high incidence of patients with cancer who present with CUP. Early surgical excision of the metastatic lesion followed by adjuvant combination chemotherapy should be considered for patients with only a single site of malignancy.

  7. The Southern French registry of genetic hemochromatosis: a tool for determining clinical prevalence of the disorder and genotype penetrance.

    PubMed

    Aguilar-Martinez, Patricia; Bismuth, Michael; Blanc, François; Blanc, Pierre; Cunat, Severine; Dereure, Olivier; Dujols, Pierre; Giansily-Blaizot, Muriel; Jorgensen, Christian; Konate, Amadou; Larrey, Dominique; Le Quellec, Alain; Mura, Thibault; Raingeard, Isabelle; Ramos, Jeanne; Renard, Eric; Rousseau, Florence; Schved, Jean-François; Picot, Marie-Christine

    2010-04-01

    Despite great progress in understanding the mechanisms underlying genetic hemochromatosis, data on the prevalence and the penetrance of the disorder are conflicting. A registry of patients with genetic hemochromatosis was established in the South of France and a regional health network was developed to allow the inclusion of all the diagnosed patients. C282Y homozygous patients classified in stages 2 (biological iron overload), 3 and 4 (clinical manifestations of iron overload, stage 4 being the more severe) according to the classification of the French National Authority for Health were included in the registry over a 6-year period. A total of 352 symptomatic C282Y homozygotes were identified, resulting in a total prevalence of 1.83 per 10,000 (95% CI: 1.63 to 2.02) in subjects over 20 years and 2.40 per 10,000 (95% CI, 2.15 to 2.65) among subjects of European descent. Among Europeans, the total calculated penetrance was 15.8% in stage 2 or higher, 12.1% in stage 3 or 4 and 2.9% in stage 4. The penetrance was slightly higher in males (18.7%) than in females (13.2%). It was 19.9% for individuals over 40 years of age (24.1% and 16.3% in males and females, respectively) with a maximum of 31% in subjects between 50 and 54 years old. Among 249 patients with complete records, 24% were in stage 2, the majority (58%) were in stage 3, and 18% in stage 4. There was a higher proportion of males, and excessive alcohol intake was more prevalent in stage 4 than in stages 2 and 3 combined. A French Mediterranean regional hemochromatosis registry with strict inclusion criteria is a useful tool for characterizing the history of this disease, particularly for the most severely affected patients, as defined by the disease severity classification. The total prevalence of symptomatic C282Y homozygotes in the region was found to be low. However, clinical penetrance (stages 3 and 4) was not negligible.

  8. The Southern French registry of genetic hemochromatosis: a tool for determining clinical prevalence of the disorder and genotype penetrance

    PubMed Central

    Aguilar-Martinez, Patricia; Bismuth, Michael; Blanc, François; Blanc, Pierre; Cunat, Severine; Dereure, Olivier; Dujols, Pierre; Giansily-Blaizot, Muriel; Jorgensen, Christian; Konate, Amadou; Larrey, Dominique; Le Quellec, Alain; Mura, Thibault; Raingeard, Isabelle; Ramos, Jeanne; Renard, Eric; Rousseau, Florence; Schved, Jean-François; Picot, Marie-Christine

    2010-01-01

    Background Despite great progress in understanding the mechanisms underlying genetic hemochromatosis, data on the prevalence and the penetrance of the disorder are conflicting. Design and Methods A registry of patients with genetic hemochromatosis was established in the South of France and a regional health network was developed to allow the inclusion of all the diagnosed patients. C282Y homozygous patients classified in stages 2 (biological iron overload), 3 and 4 (clinical manifestations of iron overload, stage 4 being the more severe) according to the classification of the French National Authority for Health were included in the registry over a 6-year period. Results A total of 352 symptomatic C282Y homozygotes were identified, resulting in a total prevalence of 1.83 per 10,000 (95% CI: 1.63 to 2.02) in subjects over 20 years and 2.40 per 10,000 (95% CI, 2.15 to 2.65) among subjects of European descent. Among Europeans, the total calculated penetrance was 15.8% in stage 2 or higher, 12.1% in stage 3 or 4 and 2.9% in stage 4. The penetrance was slightly higher in males (18.7%) than in females (13.2%). It was 19.9% for individuals over 40 years of age (24.1% and 16.3% in males and females, respectively) with a maximum of 31% in subjects between 50 and 54 years old. Among 249 patients with complete records, 24% were in stage 2, the majority (58%) were in stage 3, and 18% in stage 4. There was a higher proportion of males, and excessive alcohol intake was more prevalent in stage 4 than in stages 2 and 3 combined. Conclusions A French Mediterranean regional hemochromatosis registry with strict inclusion criteria is a useful tool for characterizing the history of this disease, particularly for the most severely affected patients, as defined by the disease severity classification. The total prevalence of symptomatic C282Y homozygotes in the region was found to be low. However, clinical penetrance (stages 3 and 4) was not negligible. PMID:20145272

  9. A heterogeneous population of nuclear-encoded mitochondrial mRNAs is present in the axons of primary sympathetic neurons.

    PubMed

    Aschrafi, Armaz; Kar, Amar N; Gale, Jenna R; Elkahloun, Abdel G; Vargas, Jose Noberto S; Sales, Naomi; Wilson, Gabriel; Tompkins, Miranda; Gioio, Anthony E; Kaplan, Barry B

    2016-09-01

    Mitochondria are enriched in subcellular regions of high energy consumption, such as axons and pre-synaptic nerve endings. Accumulating evidence suggests that mitochondrial maintenance in these distal structural/functional domains of the neuron depends on the "in-situ" translation of nuclear-encoded mitochondrial mRNAs. In support of this notion, we recently provided evidence for the axonal targeting of several nuclear-encoded mRNAs, such as cytochrome c oxidase, subunit 4 (COXIV) and ATP synthase, H+ transporting and mitochondrial Fo complex, subunit C1 (ATP5G1). Furthermore, we showed that axonal trafficking and local translation of these mRNAs plays a critical role in the generation of axonal ATP. Using a global gene expression analysis, this study identified a highly diverse population of nuclear-encoded mRNAs that were enriched in the axon and presynaptic nerve terminals. Among this population of mRNAs, fifty seven were found to be at least two-fold more abundant in distal axons, as compared with the parental cell bodies. Gene ontology analysis of the nuclear-encoded mitochondrial mRNAs suggested functions for these gene products in molecular and biological processes, including but not limited to oxidoreductase and electron carrier activity and proton transport. Based on these results, we postulate that local translation of nuclear-encoded mitochondrial mRNAs present in the axons may play an essential role in local energy production and maintenance of mitochondrial function. Published by Elsevier B.V.

  10. Childhood respiratory illness presentation and service utilisation in primary care: a six-year cohort study in Wellington, New Zealand, using natural language processing (NLP) software.

    PubMed

    Dowell, Anthony; Darlow, Ben; Macrae, Jayden; Stubbe, Maria; Turner, Nikki; McBain, Lynn

    2017-08-01

    To identify childhood respiratory tract-related illness presentation rates and service utilisation in primary care by interrogating free text and coded data from electronic medical records. Retrospective cohort study. Data interrogation used a natural language processing software inference algorithm. 36 primary care practices in New Zealand. Data analysed from January 2008 to December 2013. The records from 77 582 children enrolled were reviewed over a 6-year period to estimate the presentation of childhood respiratory illness and service utilisation. This cohort represents 268 919 person-years of data and over 650 000 unique consultations. Childhood respiratory illness presentation rate to primary care practice, with description of seasonal and yearly variation. Respiratory conditions constituted 46% of all child-general practitioner consultations with a stable year-on-year pattern of seasonal peaks. Upper respiratory tract infection was the most common respiratory category accounting for 21.0% of all childhood consultations, followed by otitis media (12.2%), wheeze-related illness (9.7%), throat infection (7.4%) and lower respiratory tract infection (4.4%). Almost 70% of children presented to their general practitioner with at least one respiratory condition in their first year of life; this reduced to approximately 25% for children aged 10-17. This is the first study to assess the primary care incidence and service utilisation of childhood respiratory illness in a large primary care cohort by interrogating electronic medical record free text. The study identified the very high primary care workload related to childhood respiratory illness, especially during the first 2 years of life. These data can enable more effective planning of health service delivery. The findings and methodology have relevance to many countries, and the use of primary care 'big data' in this way can be applied to other health conditions. © Article author(s) (or their employer

  11. The Relationship Between Preoperative and Primary Care Blood Pressure Among Veterans Presenting from Home for Surgery. Is There Evidence for Anesthesiologist-Initiated Blood Pressure Referral?

    PubMed Central

    Schonberger, Robert B.; Burg, Matthew M.; Holt, Natalie; Lukens, Carrie L.; Dai, Feng; Brandt, Cynthia

    2011-01-01

    SBP≥146mmHg had 95.9% estimated specificity (95% CI 94.4 to 97.0) for identifying subsequent primary care SBP≥140mmHg and estimated sensitivity of 26.8% (95% CI 22.0 to 32.0). A similarly high specificity using a single DOS SBP required a threshold SBP≥160mmHg, for which estimated specificity was 95.2% (95% CI 94.2 to 96.1). For DBP, a presenting DOS DBP≥92mmHg had 95.7% specificity (95% CI 94.8 to 96.4) for subsequent primary care DBP≥90mmHg with a sensitivity of 18.8% (95% CI 14.4 to 24.0). Conclusion A small bias toward higher DOS blood pressures relative to subsequent primary care measurements was observed. DOS factors predicted only a small proportion of the observed variation. Accounting for the observed bias, a two-stage SBP threshold and a single-reading DBP threshold were highly specific though insensitive for identifying subsequent primary care blood pressure elevation. PMID:22075017

  12. Proton Pump Inhibitors Decrease Phlebotomy Need in HFE Hemochromatosis: Double-Blind Randomized Placebo-Controlled Trial.

    PubMed

    Vanclooster, Annick; van Deursen, Cees; Jaspers, Reggy; Cassiman, David; Koek, Ger

    2017-09-01

    Phlebotomy constitutes the established treatment for HFE-related hemochromatosis. Retrospective studies have suggested proton pump inhibitors (PPIs) reduce the need for phlebotomy in this population. We conducted a randomized controlled trial to prove this. Thirty p.C282Y homozygous patients were randomly allocated to PPI (pantoprazole 40 mg/day) or placebo for 12 months. Phlebotomies were performed when serum ferritin was > 100 μg/L. Phlebotomy need turned out to be significantly lower in patients taking PPI (P = .0052). PPI treatment significantly reduces the need for phlebotomies in p.C282Y homozygous patients. In view of the known long-term safety profile of PPI, they can be a valuable addition to standard therapy. Clinicaltrials.gov: NCT01524757. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  13. [The effectiveness of endonasal electrophoresis of neuroprotective agents used in the rehabilitative treatment of the patients presenting with primary open angle glaucoma].

    PubMed

    Nazarova, G A; Konchugova, T V; Iurova, O V; Sichinava, N V; Turova, E A; Rassulova, M A; Morozova, N E

    2013-01-01

    The objective of the present study was to estimate the effectiveness of the peptide drug cortexin used to treat primary open angle glaucoma. It was shown that endonasal electrophoresis of cortexin resulted in more pronounced positive changes in the dynamics of clinical, functional, perimetric, and electrophysiological characteristics compared with intramuscular administration of the same drug to the patients of the control group. This difference was apparent both immediately after the termination of the treatment and during the long-term follow-up.

  14. Autoimmune Conditions in 235 Hemochromatosis Probands with HFE C282Y Homozygosity and Their First-Degree Relatives.

    PubMed

    Barton, James C; Barton, J Clayborn

    2015-01-01

    We performed a retrospective study of autoimmune conditions (ACs) in 235 hemochromatosis probands at diagnosis by analyzing age, sex, ACs, history of first-degree family members with ACs (FH), diabetes, heavy ethanol consumption, elevated serum ALT/AST, nonalcoholic fatty liver disease, viral hepatitis, cirrhosis, iron removed to achieve iron depletion (QFe), and positivity for human leukocyte antigen (HLA) haplotypes A (∗) 01, B (∗) 08; A (∗) 02, B (∗) 44; A (∗) 03, B (∗) 07; A (∗) 03, B (∗) 14; and A (∗) 29, B (∗) 44. There were 138 men (58.7%). Median followup was 19.6 y. One or more of 19 ACs were diagnosed in each of 35 probands (14.9%). Prevalences of Hashimoto's thyroiditis, rheumatoid arthritis, and ankylosing spondylitis were 8.1% (95% CI: [5.1, 12.5]), 1.7% [0.6, 4.6], and 0.0085 [0.0015, 0.0337], respectively. Eighteen probands (7.7%) had a FH. Eight probands with ACs had 9 family members with ACs. In a logistic regression, ACs were less likely in men (odds ratio (OR) 0.3 [0.1, 0.6]) and more likely in probands with a FH (OR 4.1 [1.4, 11.8]). Overall ACs risk was not significantly associated with QFe or HLA haplotypes. Estimated survival of probands with and without ACs did not differ significantly. We conclude that ACs are common in hemochromatosis probands, especially women and probands with a FH.

  15. A rare case report of simultaneous presentation of myopathy, Addison's disease, primary hypoparathyroidism, and Fanconi syndrome in a child diagnosed with Kearns-Sayre syndrome.

    PubMed

    Tzoufi, Meropi; Makis, Alexandros; Chaliasos, Nikolaos; Nakou, Iliada; Siomou, Ekaterini; Tsatsoulis, Agathoklis; Zikou, Anastasia; Argyropoulou, Maria; Bonnefont, Jean Paul; Siamopoulou, Antigone

    2013-04-01

    Kearns-Sayre syndrome (KSS) is a rare mitochondrial DNA deletion syndrome defined as the presence of ophthalmoplegia, pigmentary retinopathy, onset less than age 20 years, and one of the following: cardiac conduction defects, cerebellar syndrome, or cerebrospinal fluid protein above 100 mg/dl. KSS may affect many organ systems causing endocrinopathies, encephalomyopathy, sensorineural hearing loss, and renal tubulopathy. Clinical presentation at diagnosis is quite heterogeneous and, usually, few organs are affected with progression to generalized disease early in adulthood. We present the case of a boy with KSS presenting at the age of 5 years with myopathy, Addison's disease, primary hypoparathyroidism, and Fanconi syndrome. The proper replacement treatment along with the administration of mitochondrial metabolism-improving agents had a brief ameliorating effect, but gradual severe multisystemic deterioration was inevitable over the next 5 years. This report highlights the fact that in case of simultaneous presentation of polyendocrinopathies and renal disease early in childhood, KSS should be considered.

  16. Influenza A Virus Infection of Human Primary Dendritic Cells Impairs Their Ability to Cross-Present Antigen to CD8 T Cells

    PubMed Central

    Smed-Sörensen, Anna; Chalouni, Cécile; Chatterjee, Bithi; Cohn, Lillian; Blattmann, Peter; Nakamura, Norihiro; Delamarre, Lélia; Mellman, Ira

    2012-01-01

    Influenza A virus (IAV) infection is normally controlled by adaptive immune responses initiated by dendritic cells (DCs). We investigated the consequences of IAV infection of human primary DCs on their ability to function as antigen-presenting cells. IAV was internalized by both myeloid DCs (mDCs) and plasmacytoid DCs but only mDCs supported viral replication. Although infected mDCs efficiently presented endogenous IAV antigens on MHC class II, this was not the case for presentation on MHC class I. Indeed, cross-presentation by uninfected cells of minute amounts of endocytosed, exogenous IAV was ∼300-fold more efficient than presentation of IAV antigens synthesized by infected cells and resulted in a statistically significant increase in expansion of IAV-specific CD8 T cells. Furthermore, IAV infection also impaired cross-presentation of other exogenous antigens, indicating that IAV infection broadly attenuates presentation on MHC class I molecules. Our results suggest that cross-presentation by uninfected mDCs is a preferred mechanism of antigen-presentation for the activation and expansion of CD8 T cells during IAV infection. PMID:22412374

  17. Full-text publication rate of abstracts presented at the Japan Primary Care Association Annual Meetings (2010-2012): a retrospective observational study.

    PubMed

    Komagamine, Junpei; Yabuki, Taku

    2018-06-22

    To determine the publication rate of abstracts presented at the Japan Primary Care Association Annual Meetings and the factors associated with publication. A retrospective observational study. All abstracts presented at the Japan Primary Care Association Annual Meetings (2010-2012). Publication rates were determined by searching the MEDLINE database for full-text articles published by September 2017. Data on presentation format (oral vs poster), affiliation of the first author, number of authors, number of involved institutions, journal of publication and publication date were abstracted. Of the 1003 abstracts evaluated, 38 (3.8%, 95% CI 2.6% to 5.0%) were subsequently published in peer-reviewed journals indexed in the MEDLINE database. The median time to publication was 15.5 months (IQR, 9.3-29.3 months). More than 95% of published abstracts were published within 4 years. The publications appeared in 23 different journals (21 English-language journals and two Japanese-language journals). Based on univariate analysis using binary logistic regression, publication was more frequent for oral presentations (7.3%vs2.0% for poster presentations; OR 3.91,95% CI 1.98 to 7.75), and for first authors affiliated with university-associated institutions (6.4%vs2.4% for first authors affiliated with non-university-associated institutions; OR 2.75,95% CI 1.42 to 5.30). Based on multivariate analysis, oral presentation and first author affiliation with a university-associated institution were still the only independent predictive factors for publication (adjusted OR 3.50(95% CI 1.72 to 7.12) and adjusted OR 2.35(95% CI 1.19 to 4.63), respectively). Even among 151 abstracts presented orally by first authors affiliated with a university-associated institution, only 18 abstracts (11.9%) were subsequently published in peer-reviewed journals. The publication rate of abstracts presented at the Japan Primary Care Association Annual Meetings was extremely low. Further studies are

  18. Whooping cough in school age children presenting with persistent cough in UK primary care after introduction of the preschool pertussis booster vaccination: prospective cohort study.

    PubMed

    Wang, Kay; Fry, Norman K; Campbell, Helen; Amirthalingam, Gayatri; Harrison, Timothy G; Mant, David; Harnden, Anthony

    2014-06-24

    To estimate the prevalence and clinical severity of whooping cough (pertussis) in school age children presenting with persistent cough in primary care since the introduction and implementation of the preschool pertussis booster vaccination. Prospective cohort study (November 2010 to December 2012). General practices in Thames Valley, UK. 279 children aged 5 to 15 years who presented in primary care with a persistent cough of two to eight weeks' duration. Exclusion criteria were cough likely to be caused by a serious underlying medical condition, known immunodeficiency or immunocompromise, participation in another clinical research study, and preschool pertussis booster vaccination received less than one year previously. Evidence of recent pertussis infection based on an oral fluid anti-pertussis toxin IgG titre of at least 70 arbitrary units. Cough frequency was measured in six children with laboratory confirmed pertussis. 56 (20%, 95% confidence interval 16% to 25%) children had evidence of recent pertussis infection, including 39 (18%, 13% to 24%) of 215 children who had been fully vaccinated. The risk of pertussis was more than three times higher (21/53; 40%, 26% to 54%) in children who had received the preschool pertussis booster vaccination seven years or more previously than in those who had received it less than seven years previously (20/171; 12%, 7% to 17%). The risk of pertussis was similar between children who received five and three component preschool pertussis booster vaccines (risk ratio for five component vaccine 1.14, 0.64 to 2.03). Four of six children in whom cough frequency was measured coughed more than 400 times in 24 hours. Pertussis can still be found in a fifth of school age children who present in primary care with persistent cough and can cause clinically significant cough in fully vaccinated children. These findings will help to inform consideration of the need for an adolescent pertussis booster vaccination in the United Kingdom. UK

  19. In-hospital organization of primary care of patients presenting a life-threatening emergency: A French national survey in 32 university hospitals.

    PubMed

    Quintard, Hervé; Severac, Mathilde; Martin, Claude; Ichai, Carole

    2015-08-01

    The development of specialized units dedicated to life-threatening management has demonstrated to improve the prognosis of patients requiring such treatments. However, apart those focused on trauma and stroke, networks are still lacking in France. Despite, the implementation of standardisation of practices and guidelines, particularly in prehospital care, in-hospital clinical practices at admission remain heterogenous. This survey aimed to assess the structural and human organization of teaching hospitals in France concerning the primary in-hospital care for critically ill patients. A questionnaire of 45 items was sent by e-mail to 32 teaching hospitals between January and March 2013. It included information related to the description of the emergency department, of ICUs, and both structural and human organizations for primary in-hospital care of life-threatening patients. Seventy-five percent of teaching hospitals answered to the survey. Seven hundred to 1400 patients were admitted to emergency units per week and among them 10 to 20 were admitted for critically ill conditions. These latter were addressed in a specialized room of the emergency unit (Service d'admission des urgences vitales [SAUV]) in 40% of hospitals and in specialized room in ICU in 18% of cases. Intensivists were involved in 50% of hospitals, emergency physicians in 26% and it was mixed in 24% of hospitals. This survey is the first to assess the in-hospital organization of primary care for instable and life-threatening patients in France. Our results confirmed the extreme heterogeneity of structural and human organizations for primary in-hospital care of patients presenting at least one organ failure. Thus, a consensus is probably needed to homogenize and improve our practices. Copyright © 2015 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.

  20. Variation in promptness of presentation among 10,297 patients subsequently diagnosed with one of 18 cancers: Evidence from a National Audit of Cancer Diagnosis in Primary Care

    PubMed Central

    Keeble, Stuart; Abel, Gary A; Saunders, Catherine L; McPhail, Sean; Walter, Fiona M; Neal, Richard D; Rubin, Gregory P; Lyratzopoulos, Georgios

    2014-01-01

    Cancer awareness public campaigns aim to shorten the interval between symptom onset and presentation to a doctor (the ‘patient interval’). Appreciating variation in promptness of presentation can help to better target awareness campaigns. We explored variation in patient intervals recorded in consultations with general practitioners among 10,297 English patients subsequently diagnosed with one of 18 cancers (bladder, brain, breast, colorectal, endometrial, leukaemia, lung, lymphoma, melanoma, multiple myeloma, oesophageal, oro-pharyngeal, ovarian, pancreatic, prostate, renal, stomach, and unknown primary) using data from of the National Audit of Cancer Diagnosis in Primary Care (2009–2010). Proportions of patients with ‘prompt’/‘non-prompt’ presentation (0–14 or 15+ days from symptom onset, respectively) were described and respective odds ratios were calculated by multivariable logistic regression. The overall median recorded patient interval was 10 days (IQR 0–38). Of all patients, 56% presented promptly. Prompt presentation was more frequent among older or housebound patients (p < 0.001). Prompt presentation was most frequent for bladder and renal cancer (74% and 70%, respectively); and least frequent for oro-pharyngeal and oesophageal cancer (34% and 39%, respectively, p <.001). Using lung cancer as reference, the adjusted odds ratios of non-prompt presentation were 2.26 (95% confidence interval 1.57–3.25) and 0.42 (0.34–0.52) for oro-pharyngeal and bladder cancer, respectively. Sensitivity analyses produced similar findings. Routinely recorded patient interval data reveal considerable variation in the promptness of presentation. These findings can help to prioritise public awareness initiatives and research focusing on symptoms of cancers associated with greater risk of non-prompt presentation, such as oro-pharyngeal and oesophageal cancer. What's new? A critical aspect of cancer diagnosis is how promptly patients consult a doctor after

  1. Development of a prediction tool for patients presenting with acute cough in primary care: a prognostic study spanning six European countries.

    PubMed

    Bruyndonckx, Robin; Hens, Niel; Verheij, Theo Jm; Aerts, Marc; Ieven, Margareta; Butler, Christopher C; Little, Paul; Goossens, Herman; Coenen, Samuel

    2018-05-01

    Accurate prediction of the course of an acute cough episode could curb antibiotic overprescribing, but is still a major challenge in primary care. The authors set out to develop a new prediction rule for poor outcome (re-consultation with new or worsened symptoms, or hospital admission) in adults presenting to primary care with acute cough. Data were collected from 2604 adults presenting to primary care with acute cough or symptoms suggestive of lower respiratory tract infection (LRTI) within the Genomics to combat Resistance against Antibiotics in Community-acquired LRTI in Europe (GRACE; www.grace-lrti.org) Network of Excellence. Important signs and symptoms for the new prediction rule were found by combining random forest and logistic regression modelling. Performance to predict poor outcome in acute cough patients was compared with that of existing prediction rules, using the models' area under the receiver operator characteristic curve (AUC), and any improvement obtained by including additional test results (C-reactive protein [CRP], blood urea nitrogen [BUN], chest radiography, or aetiology) was evaluated using the same methodology. The new prediction rule, included the baseline Risk of poor outcome, Interference with daily activities, number of years stopped Smoking (> or <45 years), severity of Sputum, presence of Crackles, and diastolic blood pressure (> or <85 mmHg) (RISSC85). Though performance of RISSC85 was moderate (sensitivity 62%, specificity 59%, positive predictive value 27%, negative predictive value 86%, AUC 0.63, 95% confidence interval [CI] = 0.61 to 0.67), it outperformed all existing prediction rules used today (highest AUC 0.53, 95% CI = 0.51 to 0.56), and could not be significantly improved by including additional test results (highest AUC 0.64, 95% CI = 0.62 to 0.68). The new prediction rule outperforms all existing alternatives in predicting poor outcome in adult patients presenting to primary care with acute cough and could not be

  2. Population-based analysis of the frequency of HFE gene polymorphisms: Correlation with the susceptibility to develop hereditary hemochromatosis.

    PubMed

    Katsarou, Martha-Spyridoula; Latsi, Rosana; Papasavva, Maria; Demertzis, Nikolaos; Kalogridis, Thodoris; Tsatsakis, Aristides M; Spandidos, Demetrios A; Drakoulis, Nikolaos

    2016-07-01

    Hereditary hemochromatosis (HH) is an autosomal recessive genetic disease, characterized by increased dietary iron absorption. Due to the absence of an effective excretory mechanism, the excess iron in the body may accumulate resulting in toxic effects. The HFE gene also affects the activity of hepcidin, a hormone which acts as a negative regulator of iron metabolism. In this study, we performed a population-based analysis of the distribution of three hemochromatosis-related polymorphisms in the HFE gene (rs1800562, rs1799945 and rs1800730). DNA from 1,446 non‑related individuals of Greek ethnicity was collected and analyzed, either from whole blood or buccal swabs. The frequency distribution of these HFE gene polymorphisms was then determined. The results revealed that in our Greek population cohort (gr) the frequencies of each polymorphism were as follows: rs1800562: GG (wild‑type)=97.0%, GA=1.5%, AA=1.5%; rs1799945: CC (wild‑type)=74.4%, CG=23.4%, GG=2.2%; rs1800730: AA (wild‑type)=98.1%, AT=1.5% and TT=0.4%. No association between the HFE polymorphisms rs1800562, rs1799945 and rs1800730 and gender could be established. As regards the rs1800562 polymorphism, the A allele (mutant) was ~1.8‑fold more frequent in the European population (eur) than in the Greek population [(gr)=2,3%<(eur)=4%]. As for the rs1799945 polymorphism, the G allele (mutant) was 1.2‑fold more frequent in the European population than in the Greek population [(gr)=13,9%<(eur)=17%]. As regards the rs1800730 polymorphism, the T allele (mutant) was ~1.7‑fold more frequent in the European population than in the Greek population [(gr)=1.2%<(eur)=2%]. However, these pathogenic mutations were found more frequently in the Greek population compared to the global population (gl) [rs1800562: (gl)=1%<(gr)=2,3%; rs1799945: (gl)=7%<(gr)=13,9%; rs1800730: (gl)=<1%<(gr)=1.2%]. This suggests that the Greek population may differ genetically from the northern European population

  3. [Effectiveness of therapeutic erythrocytapheresis to achieve iron depletion in hereditary type 1 hemochromatosis: report of 30 cases].

    PubMed

    Poullin, P; Lefèvre, P A

    2011-12-01

    Weekly phlebotomy schedule is commonly recommended to achieve iron depletion in hereditary hemochromatosis (HH). However, in patients with severe iron overload, more than 2 years may be required, leading to fatigue and lack of compliance. For more than 10 years, we have used erythrocytapheresis (EA) as an alternative treatment. To assess the number of EA to achieve iron depletion and the duration of the iron depletion therapy as well of the tolerance, we retrospectively analysed the data of newly diagnosed hemochromatosis patients, homozygote for the C282Y mutation, followed in our department between 2001 and 2007. EA were performed using a discontinuous or a continuous flow cell separators. The protocol consisted in a bimonthly EA until normalisation of the serum ferritin, with the aim of reducing the patient's hematocrit between 32-35% at the end of each session. Then we performed monthly EA until complete desaturation, defined as serum ferritin concentration below 50 μg/L and transferrin saturation below 40%. Thirty patients were included (23 male, mean age 52 years, range 25-78) and 625 procedures analyzed. The mean volume of removed erythrocytes in each procedure was 416.4 mL (range 150-948), which equals to 374 mg of removed iron. Iron depletion (ferritin < 50 μg/L) was achieved after 11 months with 20 sessions (range 14-78). No serious adverse reactions or citrate toxicity were observed during and after the apheresis procedures. No specific fatigue was reported during the iron depletion therapy. Patient compliance was 100%. Clinical improvement was noted in 12 out of 18 of symptomatic patients. We conclude that HH patients treated with bimonthly EA achieved iron depletion in less than 1 year under good condition of tolerance. These data support the use of EA in patients with a severe iron overload, since it may reduce the number of the procedures as well as the duration of the iron depletion therapy. Copyright © 2011 Elsevier Masson SAS. All rights

  4. HFE Cys282Tyr homozygotes with serum ferritin concentrations below 1000 microg/L are at low risk of hemochromatosis.

    PubMed

    Allen, Katrina J; Bertalli, Nadine A; Osborne, Nicholas J; Constantine, Clare C; Delatycki, Martin B; Nisselle, Amy E; Nicoll, Amanda J; Gertig, Dorota M; McLaren, Christine E; Giles, Graham G; Hopper, John L; Anderson, Gregory J; Olynyk, John K; Powell, Lawrie W; Gurrin, Lyle C

    2010-09-01

    Hemochromatosis gene (HFE)-associated hereditary hemochromatosis (HH) is a genetic predisposition to iron overload and subsequent signs and symptoms of disease that potentially affects approximately 80,000 persons in Australia and almost 1 million persons in the United States. Most clinical cases are homozygous for the Cys282Tyr (C282Y) mutation in the HFE gene, with serum ferritin (SF) concentration >1000 microg/L as the strongest predictor of cirrhosis. The optimal treatment regimen for those with SF concentrations above the normal range but <1000 microg/L is unknown. We assessed HFE mutations in a prospective cohort of 31,192 participants of northern European descent, aged 40-69 years. An HFE-stratified random sample of 1438 participants including all C282Y homozygotes with iron studies 12 years apart were examined by physicians blinded to participants' HFE genotype. All previously undiagnosed C282Y homozygotes (35 male, 67 female) and all HFE wild-types (131 male, 160 female) with baseline and follow-up SF concentrations <1000 microg/L were assessed for HH-associated signs and symptoms including abnormal second/third metacarpophalangeal joints (MCP2/3), raised liver enzymes, hepatomegaly, and self-reported liver disease, fatigue, diabetes mellitus, and use of arthritis medication. The prevalence of HH-associated signs and symptoms was similar for C282Y homozygotes and HFE wild-types for both normal and moderately elevated SF concentrations. The maximum prevalence difference between HFE genotype groups with moderately elevated SF was 11% (MCP2/3, 95% confidence interval = -6%, 29%; P = 0.22) and for normal SF was 6% (arthritis medicine use, 95% confidence interval = -3%, 16%; P = 0.11). Previously undiagnosed C282Y homozygotes with SF concentrations that remain below 1000 microg/L are at low risk of developing HH-associated signs and symptoms at an age when disease would be expected to have developed. These observations have implications for the management of C

  5. Dimensional analysis of depressive, anxious and somatic symptoms presented by primary care patients and their relationship with ICD-11 PHC proposed diagnoses.

    PubMed

    Ziebold, Carolina; Goldberg, David P; Reed, Geoffrey M; Minhas, Fareed; Razzaque, Bushra; Fortes, Sandra; Robles, Rebeca; Lam, Tai Pong; Bobes, Julio; Iglesias, Celso; Cogo-Moreira, Hugo; García, José Ángel; Mari, Jair J

    2018-06-04

    A study conducted as part of the development of the Eleventh International Classification of Mental Disorders for Primary Health Care (ICD-11 PHC) provided an opportunity to test the relationships among depressive, anxious and somatic symptoms in PHC. Primary care physicians participating in the ICD-11 PHC field studies in five countries selected patients who presented with somatic symptoms not explained by known physical pathology by applying a 29-item screening on somatic complaints that were under study for bodily stress disorder. Patients were interviewed using the Clinical Interview Schedule-Revised and assessed using two five-item scales that measure depressive and anxious symptoms. Structural models of anxious-depressive symptoms and somatic complaints were tested using a bi-factor approach. A total of 797 patients completed the study procedures. Two bi-factor models fit the data well: Model 1 had all symptoms loaded on a general factor, along with one of three specific depression, anxiety and somatic factors [x2 (627) = 741.016, p < 0.0011, RMSEA = 0.015, CFI = 0.911, TLI = 0.9]. Model 2 had a general factor and two specific anxious depression and somatic factors [x2 (627) = 663.065, p = 0.1543, RMSEA = 0.008, CFI = 0.954, TLI = 0.948]. These data along with those of previous studies suggest that depressive, anxious and somatic symptoms are largely different presentations of a common latent phenomenon. This study provides support for the ICD-11 PHC conceptualization of mood disturbance, especially anxious depression, as central among patients who present multiple somatic symptoms.

  6. QRS Score at Presentation Electrocardiogram Is Correlated With Infarct Size and Mortality in ST-Segment Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention.

    PubMed

    Shiomi, Hiroki; Kosuge, Masami; Morimoto, Takeshi; Watanabe, Hiroki; Taniguchi, Tomohiko; Nakatsuma, Kenji; Toyota, Toshiaki; Yamamoto, Erika; Shizuta, Satoshi; Tada, Tomohisa; Furukawa, Yutaka; Nakagawa, Yoshihisa; Ando, Kenji; Kadota, Kazushige; Kimura, Kazuo; Kimura, Takeshi

    2017-07-25

    In ST-segment elevation myocardial infarction (STEMI), QRS score at presentation ECG may reflect the progression of infarction and facilitate prediction of the degree of myocardial salvage achieved by reperfusion therapy.Methods and Results:Admission electrocardiogram (ECG) was studied in 2,607 patients with STEMI undergoing primary percutaneous coronary intervention (PCI) within 24 h of symptom onset. Patients were classified into 3 groups according to QRS score: low (0-3, n=1,227), intermediate (4-7, n=810), and high (≥8, n=570). An increase of infarct size estimated by median peak creatine phosphokinase was observed as QRS score increased (low score, 1,836 IU/L; inter-quartile range (IQR), 979-3,190 IU/L; intermediate score, 2,488 IU/L; IQR, 1,126-4,640 IU/L; high score, 3,454 IU/L; IQR, 1,759-5,639 IU/L; P<0.001). Higher QRS score was associated with higher long-term mortality (low, intermediate, and high score, 15.6%, 19.7%, and 23.7% at 5 years, respectively; log-rank P<0.001). The positive relationship of QRS score with mortality was consistently seen when stratified by infarct location. The association of high QRS score with increased mortality was most remarkably seen in patients with early (≤2 h) presentation (low, intermediate, and high score: 16.7%, 16.6%, and 28.1% at 5 years, respectively; log-rank P<0.001). Higher QRS score at presentation ECG was associated with larger infarct size, and higher long-term mortality in patients with STEMI undergoing primary PCI. QRS score appears to be important in the early risk stratification for STEMI.

  7. Whooping cough in school age children presenting with persistent cough in UK primary care after introduction of the preschool pertussis booster vaccination: prospective cohort study

    PubMed Central

    Fry, Norman K; Campbell, Helen; Amirthalingam, Gayatri; Harrison, Timothy G; Mant, David; Harnden, Anthony

    2014-01-01

    Objective To estimate the prevalence and clinical severity of whooping cough (pertussis) in school age children presenting with persistent cough in primary care since the introduction and implementation of the preschool pertussis booster vaccination. Design Prospective cohort study (November 2010 to December 2012). Setting General practices in Thames Valley, UK. Participants 279 children aged 5 to 15 years who presented in primary care with a persistent cough of two to eight weeks’ duration. Exclusion criteria were cough likely to be caused by a serious underlying medical condition, known immunodeficiency or immunocompromise, participation in another clinical research study, and preschool pertussis booster vaccination received less than one year previously. Main outcome measures Evidence of recent pertussis infection based on an oral fluid anti-pertussis toxin IgG titre of at least 70 arbitrary units. Cough frequency was measured in six children with laboratory confirmed pertussis. Results 56 (20%, 95% confidence interval 16% to 25%) children had evidence of recent pertussis infection, including 39 (18%, 13% to 24%) of 215 children who had been fully vaccinated. The risk of pertussis was more than three times higher (21/53; 40%, 26% to 54%) in children who had received the preschool pertussis booster vaccination seven years or more previously than in those who had received it less than seven years previously (20/171; 12%, 7% to 17%). The risk of pertussis was similar between children who received five and three component preschool pertussis booster vaccines (risk ratio for five component vaccine 1.14, 0.64 to 2.03). Four of six children in whom cough frequency was measured coughed more than 400 times in 24 hours. Conclusions Pertussis can still be found in a fifth of school age children who present in primary care with persistent cough and can cause clinically significant cough in fully vaccinated children. These findings will help to inform consideration of the

  8. Risk factors for methicillin-resistant Staphylococcal aureus skin and soft tissue infections presenting in primary care: a South Texas Ambulatory Research Network (STARNet) study.

    PubMed

    Parchman, Michael L; Munoz, Abel

    2009-01-01

    To examine skin and soft tissue infections presenting at 4 primary care clinics and assess if historical risk factors and examination findings were associated with a positive methicillin-resistant Staphylococcus aureus (MRSA) culture. During the 10-month observational study (April 2007 through January 2008), physicians in 5 practices across South Texas collected history, physical examination findings, culture results, and antibiotic(s) prescribed for all patients presenting with a skin or soft tissue infection. Analyses were conducted to determine the relationship between historical indicators, location of lesions, and examination findings with a positive MRSA culture. Across 4 practices, 164 cases of skin and soft tissue infections were collected during 10 months. Of the 94 with a culture, 63 (67%) were MRSA positive. Patients working in or exposed to a health care setting were more likely to have a culture positive for MRSA, as were those presenting with an abscess. MRSA-positive lesions were also significantly smaller in size. Because of the high prevalence of MRSA skin and soft tissue infections among patients presenting to family physicians, presumptive treatment for MRSA may be indicated. However, increasing levels of resistance to current antibiotics is concerning and warrants development of alternative management strategies.

  9. Co-stimulatory function in primary germinal center responses: CD40 and B7 are required on distinct antigen-presenting cells.

    PubMed

    Watanabe, Masashi; Fujihara, Chiharu; Radtke, Andrea J; Chiang, Y Jeffrey; Bhatia, Sumeena; Germain, Ronald N; Hodes, Richard J

    2017-09-04

    T cell-dependent germinal center (GC) responses require coordinated interactions of T cells with two antigen-presenting cell (APC) populations, B cells and dendritic cells (DCs), in the presence of B7- and CD40-dependent co-stimulatory pathways. Contrary to the prevailing paradigm, we found unique cellular requirements for B7 and CD40 expression in primary GC responses to vaccine immunization with protein antigen and adjuvant: B7 was required on DCs but was not required on B cells, whereas CD40 was required on B cells but not on DCs in the generation of antigen-specific follicular helper T cells, antigen-specific GC B cells, and high-affinity class-switched antibody production. There was, in fact, no requirement for coexpression of B7 and CD40 on the same cell in these responses. Our findings support a substantially revised model for co-stimulatory function in the primary GC response, with crucial and distinct contributions of B7- and CD40-dependent pathways expressed by different APC populations and with important implications for understanding how to optimize vaccine responses or limit autoimmunity. This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.

  10. The prevalence, pattern and clinical presentation of developmental dental hard-tissue anomalies in children with primary and mix dentition from Ile-Ife, Nigeria.

    PubMed

    Temilola, Dada Oluwaseyi; Folayan, Morenike Oluwatoyin; Fatusi, Olawunmi; Chukwumah, Nneka Maureen; Onyejaka, Nneka; Oziegbe, Elizabeth; Oyedele, Titus; Kolawole, Kikelomo Adebanke; Agbaje, Hakeem

    2014-10-16

    The study of dental anomalies is important because it generates information that is important for both the anthropological and clinical management of patients. The objective of this study is to determine the prevalence and pattern of presentation of dental hard-tissue developmental anomalies in the mix dentition of children residing in Ile-Ife, a suburban region of Nigeria. Information on age, sex and socioeconomic status was collected from 1,036 children aged four months to 12 years through a household survey. Clinical examination was conducted to assess the presence of dental anomalies. Associations between age, sex, socioeconomic status, prevalence, and pattern of presentation of the developmental hard-tissue dental anomalies were determined. Two hundred and seventy six (26.6%) children had dental anomalies. Of these, 23.8% had one anomaly, 2.5% had two anomalies, and 0.3% had more than two anomalies. Of the children with anomalies, 49.3%were male, 50.7%were female, and 47.8%, 28.6% and 23.6% were children from low, middle and high socioeconomic classes, respectively. More anomalies were seen in permanent than primary dentition. Anomalies of tooth structure were most prevalent (16.1%); anomalies which affect tooth number were least prevalent (1.3%). Dens evaginatus, peg-shaped lateral, macrodontia, and talon cusp were more prevalent in the permanent dentition, and dens evaginatus peg-shaped lateral and macrodontia were more prevalent in the maxilla. There were significantly more macrodontia anomalies in males and in children of high socioeconomic status. This large survey of dental hard-tissue anomalies found in the primary dentition and mixed dentition of children in Nigeria provides anthropological and clinical data that may aid the detection and management of dental problems of children in Nigeria.

  11. High Rates of Subsequent Asymptomatic Sexually Transmitted Infections and Risky Sexual Behavior in Patients Initially Presenting With Primary Human Immunodeficiency Virus-1 Infection.

    PubMed

    Braun, Dominique L; Marzel, Alex; Steffens, Daniela; Schreiber, Peter W; Grube, Christina; Scherrer, Alexandra U; Kouyos, Roger D; Günthard, Huldrych F

    2018-02-10

    Knowledge of the risk factors of individuals with an asymptomatic sexually transmitted infection (STI) is essential for implementation of targeted STI screening strategies. Between June 2015 and January 2017, an STI screening was offered to all participants in the Zurich Primary human immunodeficiency virus (HIV)-1 Infection study. Patients were tested for gonorrhea, chlamydia, syphilis, and hepatitis C virus (HCV). Of 214 participants, 174 (81%) were screened at least once. Most patients were men who have sex with men (MSM) (87.4%). Presenting with a primary HIV infection was associated with higher odds for later risky sexual behavior, as compared with presenting in the chronic phase (odds ratio [OR], 5.58; 95% confidence interval [CI], 3.68-8.8). In total, 79 STIs were detected, reflecting a high period prevalence of 33.3% (58 of 174 patients). Sixty-six percent of patients (52 of 79) were asymptomatic. Most common STIs were chlamydia (50.6%; 40 of 79 patients), gonorrhea (25.3%; 20 of 79), and syphilis (19%; 15 of 79). In a multivariable model, engaging in insertive (OR, 6.48; 95% CI, 1.14-36.76) or both insertive and receptive (4.61; 1.01-20.96) anal intercourse, STI symptoms (3.4; 1.68-6.89), and condomless sex (2.06; 1.14-3.74) were positively correlated with a positive screening result. The hazard of an incident STI increased with the presence of STI symptoms (hazard ratio, 3.03; 95% CI, 1.17-7.84) and any recent drug use (2.63; 1-6.9). A trimonthly STI screening including asymptomatic individuals should be considered in this population, particularly in MSM who report sexual risk behavior. NCT 00537966. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  12. Maternal hemochromatosis gene H63D single-nucleotide polymorphism and lead levels of placental tissue, maternal and umbilical cord blood

    SciTech Connect

    Kayaalti, Zeliha, E-mail: kayaalti@ankara.edu.tr; Kaya-Akyüzlü, Dilek; Söylemez, Esma

    Human hemochromatosis protein (HFE), a major histocompatibility complex class I-like integral membrane protein, participates in the down regulation of intestinal iron absorption by binding to transferrin receptor (TR). HFE competes with transferrin-bound iron for the TR and thus reduces uptake of iron into cells. On the other hand, a lack of HFE increases the intestinal absorption of iron similarly to iron deficiency associated with increasing in absorption and deposition of lead. During pregnancy, placenta cannot prevent transfer lead to the fetus; even low-level lead poisoning causes neurodevelopmental toxicity in children. The aim of this study was to determine the associationmore » between the maternal HFE H63D single-nucleotide polymorphism and lead levels in placental tissue, maternal blood and umbilical cord bloods. The study population comprised 93 mother–placenta pairs. Venous blood from mother was collected to investigate lead levels and HFE polymorphism that was detected by standard PCR–RFLP technique. Cord bloods and placentas were collected for lead levels which were analyzed by dual atomic absorption spectrometer system. The HFE H63D genotype frequencies of mothers were found as 75.3% homozygote typical (HH), 23.6% heterozygote (HD) and 1.1% homozygote atypical (DD). Our study results showed that the placental tissue, umbilical cord and maternal blood lead levels of mothers with HD+DD genotypes were significantly higher than those with HH genotype (p<0.05). The present study indicated for the first time that mothers with H63D gene variants have higher lead levels of their newborn's placentas and umbilical cord bloods. - Highlights: • Mothers with H63D gene variants have higher lead levels of their newborn's umbilical cord blood. • Unborn child of women with HD+DD genotypes may be at increased risk of internal exposure to lead. • Maternal HFE status may have an effect on increased placenta, maternal and cord blood lead levels. • Maternal

  13. The impact of training in problem-based interviewing on the detection and management of psychological problems presenting in primary care.

    PubMed Central

    Scott, J; Jennings, T; Standart, S; Ward, R; Goldberg, D

    1999-01-01

    BACKGROUND: The vast majority of mental health problems present to primary care teams. However, rates of under-diagnosis remain worryingly high. This study explores a GP-centred approach to these issues. AIM: To examine the impact of training in problem-based interviewing (BPI) on the detection and management of psychological problems in primary care. METHOD: The detection and management of psychological problems by 10 general practitioners (GPs) who had received PBI training 12 months earlier was compared with that of 10 control GPs matched for age, sex, clinical experience, and practice setting; and had originally applied for, but had not been able to attend, BPI training. Consecutive attendees at one randomly selected surgery undertaken by each GP were invited to participate in the study. Two hundred and eighty patients living in Newcastle upon Tyne met inclusion criteria and gave informed consent. The presence or absence of psychological problems was assessed using patient self-ratings on the 28-item version of the General Health Questionnaire (GHQ) and blind independent observer ratings of the brief Present State Examination (PSE). Patient satisfaction with interviews was rated using the Medical Interview Satisfaction Scale (MISS). After each consultation, the GPs (blind to subjective and observer ratings) recorded their assessment and management of the patients' problems on a Practice Activity Card (PAC). RESULTS: In comparison with control GPs, index GPs demonstrated significantly greater sensitivity in the detection of psychological problems in the GHQ-PAC ratings. The absolute decrease in misdiagnosis of GHQ cases was 9% and of PSE cases was 15%. Patients meeting GHQ criteria for caseness were more likely to be prescribed psychotropic medication by an index GP than compared with a control GP. Length of interview did not differ between the groups and mean scores on the MISS suggested that patients attending PBI-trained GPs, compared with control GPs, were

  14. Incomplete ileus and hemafecia as the presenting features of multi-organ involved primary systemic AL amyloidosis: a rare case report.

    PubMed

    Tian, Li; Tang, Anliu; Zhang, Xian; Mei, Zhen; Liu, Fen; Li, Jingbo; Li, Xiayu; Ai, Feiyan; Wang, Xiaoyan; Shen, Shourong

    2017-06-05

    AL Amyloidosis is known to be a systemic disease affecting multiple organs and tissue while it's rare that patients present with gastrointestinal symptoms at first and later develop multiple-organ dysfuction. Clinical signs are not specific and the diagnosis is rarely given before performing immunofixation and endoscopy with multiple biopsies. We would like to emphasize the value of precise diagnostic process of AL amyloidosis. In this case report, we describe a 56-year-old man who presented with recurrent periumbilical pain for 4 months and gradually worsened over a month. After a series of tests, he was finally diagnosed with primary systemic AL amyloidosis. He was treated with a chemotherapy regimen (Melphalan, dexamethasone and thalidomide) achieving a good clinical response. On account of the high misdiagnosis rate, establishing the most precise diagnosis in first time with typing amyloidogenic protein becomes increasingly vital. Although the presenting feature is usually nonspecific, AL amyloidosis ought to be considered when multiple organs are involved in a short period.

  15. Incidental primary mediastinal choriocarcinoma diagnosed by endobronchial ultrasound-guided fine needle aspiration in a patient presenting with transient ischemic attack and stroke.

    PubMed

    Francischetti, Ivo M B; Cajigas, Antonio; Suhrland, Mark; Farinhas, Joaquim M; Khader, Samer

    2017-08-01

    We describe a case of a 41-year old male patient with no significant prior medical history who presents with symptoms of Transient Ischemic Attack and stroke. Magnetic Resonance Imaging (MRI) of the brain identified areas of ischemia in the left side, and angiography showed occlusion of the left Medial Cerebral Artery (MCA). Cardiac Transthoracic Echocardiogram (TTE) for stroke evaluation incidentally noted a mediastinal abnormality leading to cancer work-up. Computer Tomography (CT) and 18 F-fluorodeoxyglucose (FDG) PET-CT scan of the chest incidentally revealed an avid 6 cm paraesophagial/subcarinal mass. Further diagnostic work-up with endoscopic and endobronchial ultra sound (EBUS)-guided fine needle aspiration (FNA) of the mass yielded a cytology diagnosis of Germ Cell Tumor (GCT), with choriocarcinoma component. Additionally, high plasma levels of β-human chorionic gonadotrophin (β-HCG) were detected with no evidence of testicular tumor. This exceedingly rare presentation for a primary mediastinal choriocarcinoma underscores the importance of complete investigation of young patients presenting with neurological symptoms compatible with ischemic events. Diagn. Cytopathol. 2017;45:738-743. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  16. Variable presentation of primary hyperoxaluria type 1 in 2 patients homozygous for a novel combined deletion and insertion mutation in exon 8 of the AGXT gene.

    PubMed

    von Schnakenburg, C; Hulton, S A; Milford, D V; Roper, H P; Rumsby, G

    1998-01-01

    Two unrelated patients of Pakistani origin presented with primary hyperoxaluria type 1 (PH1) at 4 months and 3 years of age, respectively. While the younger patient failed to thrive and suffered from early renal failure, the older one showed a relatively benign history with urolithiasis as the main feature of the disease. In both patients the diagnosis was confirmed by assessment of alanine:glyoxylate aminotransferase catalytic and immunoreactivity in liver biopsy specimens. The underlying genetic defect was found to be a combined deletion and insertion in exon 8 which alters the reading frame of the protein. The nucleotide change introduces a Stu1 restriction site which facilitated typing of additional family members. Both patients and a further affected brother were homozygous for this mutation, while their parents were heterozygous for it. This mutation is the first deletion/insertion identified in PH1. Although rare in our PH1 patient cohort (2.5% of alleles), the finding of 2 homozygous apparently unrelated individuals of the same ethnic origin suggests that it may prove worthwhile to screen other Asian patients for this mutation. These PH1 cases present further evidence that factors other than genotype contribute significantly to the clinical presentation and severity of PH1.

  17. Effect of olfactory manganese exposure on anxiety-related behavior in a mouse model of iron overload hemochromatosis

    PubMed Central

    Ye, Qi; Kim, Jonghan

    2015-01-01

    Manganese in excess promotes unstable emotional behavior. Our previous study showed that olfactory manganese uptake into the brain is altered in Hfe−/− mice, a model of iron overload hemochromatosis, suggesting that Hfe deficiency could modify the neurotoxicity of airborne manganese. We determined anxiety-related behavior and monoaminergic protein expression after repeated intranasal instillation of MnCl2 to Hfe−/− mice. Compared with manganese-instilled wild-type mice, Hfe−/− mice showed decreased manganese accumulation in the cerebellum. Hfe−/− mice also exhibited increased anxiety with decreased exploratory activity and elevated dopamine D1 receptor and norepinephrine transporter in the striatum. Moreover, Hfe deficiency attenuated manganese-associated impulsivity and modified the effect of manganese on the expression of tyrosine hydroxylase, vesicular monoamine transporter and serotonin transporter. Together, our data indicate that loss of HFE function alters manganese-associated emotional behavior and further suggest that HFE could be a potential molecular target to alleviate affective disorders induced by manganese inhalation. PMID:26189056

  18. In Situ Proximity Ligation Assays Indicate That Hemochromatosis Proteins Hfe and Transferrin Receptor 2 (Tfr2) Do Not Interact

    PubMed Central

    Rishi, Gautam; Crampton, Emily M.; Wallace, Daniel F.; Subramaniam, V. Nathan

    2013-01-01

    The hemochromatosis associated proteins HFE and Transferrin Receptor 2 (TFR2) have been shown to be important for the proper regulation of hepcidin. A number of in vitro studies using transient overexpression systems have suggested that an interaction between HFE and TFR2 is required for the regulation of hepcidin. This model of iron sensing which centers upon the requirement for an interaction between HFE and TFR2 has recently been questioned with in vivo studies in mice from our laboratory and others which suggest that Hfe and Tfr2 can regulate hepcidin independently of each other. To re-examine the postulated interaction between Hfe and Tfr2 we developed a novel expression system in which both proteins are stably co-expressed and used the proximity ligation assay to examine the interactions between Hfe, Tfr1 and Tfr2 at a cellular level. We were able to detect the previously described interaction between Hfe and Tfr1, and heterodimers between Tfr1 and Tfr2; however no interaction between Hfe and Tfr2 was observed in our system. The results from this study indicate that Hfe and Tfr2 do not interact with each other when they are stably expressed at similar levels. Furthermore, these results support in vivo studies which suggest that Hfe and Tfr2 can independently regulate hepcidin. PMID:24155934

  19. Effects of strain and age on hepatic gene expression profiles in murine models of HFE-associated hereditary hemochromatosis.

    PubMed

    Lee, Seung-Min; Loguinov, Alexandre; Fleming, Robert E; Vulpe, Christopher D

    2015-01-01

    Hereditary hemochromatosis is an iron overload disorder most commonly caused by a defect in the HFE gene. While the genetic defect is highly prevalent, the majority of individuals do not develop clinically significant iron overload, suggesting the importance of genetic modifiers. Murine hfe knockout models have demonstrated that strain background has a strong effect on the severity of iron loading. We noted that hepatic iron loading in hfe-/- mice occurs primarily over the first postnatal weeks (loading phase) followed by a timeframe of relatively static iron concentrations (plateau phase). We thus evaluated the effects of background strain and of age on hepatic gene expression in Hfe knockout mice (hfe-/-). Hepatic gene expression profiles were examined using cDNA microarrays in 4- and 8-week-old hfe-/- and wild-type mice on two different genetic backgrounds, C57BL/6J (C57) and AKR/J (AKR). Genes differentially regulated in all hfe-/- mice groups, compared with wild-type mice, including those involved in cell survival, stress and damage responses and lipid metabolism. AKR strain-specific changes in lipid metabolism genes and C57 strain-specific changes in cell adhesion and extracellular matrix protein genes were detected in hfe-/- mice. Mouse strain and age are each significantly associated with hepatic gene expression profiles in hfe-/- mice. These affects may underlie or reflect differences in iron loading in these mice.

  20. The global prevalence of HFE and non-HFE hemochromatosis estimated from analysis of next-generation sequencing data.

    PubMed

    Wallace, Daniel F; Subramaniam, V Nathan

    2016-06-01

    The prevalence of HFE-related hereditary hemochromatosis (HH) among European populations has been well studied. There are no prevalence data for atypical forms of HH caused by mutations in HFE2, HAMP, TFR2, or SLC40A1. The purpose of this study was to estimate the population prevalence of these non-HFE forms of HH. A list of HH pathogenic variants in publically available next-generation sequence (NGS) databases was compiled and allele frequencies were determined. Of 161 variants previously associated with HH, 43 were represented among the NGS data sets; an additional 40 unreported functional variants also were identified. The predicted prevalence of HFE HH and the p.Cys282Tyr mutation closely matched previous estimates from similar populations. Of the non-HFE forms of iron overload, TFR2-, HFE2-, and HAMP-related forms are predicted to be rare, with pathogenic allele frequencies in the range of 0.00007 to 0.0005. Significantly, SLC40A1 variants that have been previously associated with autosomal-dominant ferroportin disease were identified in several populations (pathogenic allele frequency 0.0004), being most prevalent among Africans. We have, for the first time, estimated the population prevalence of non-HFE HH. This methodology could be applied to estimate the population prevalence of a wide variety of genetic disorders.Genet Med 18 6, 618-626.

  1. High-Performance Multiplex SNP Analysis of Three Hemochromatosis-Related Mutations With Capillary Array Electrophoresis Microplates

    PubMed Central

    Medintz, Igor; Wong, Wendy W.; Berti, Lorenzo; Shiow, Lawrence; Tom, Jennifer; Scherer, James; Sensabaugh, George; Mathies, Richard A.

    2001-01-01

    An assay is described for high-throughput single nucleotide polymorphism (SNP) genotyping on a microfabricated capillary array electrophoresis (CAE) microchip. The assay targets the three common variants at the HFE locus associated with the genetic disease hereditary hemochromatosis (HHC). The assay employs allele-specific PCR (ASPCR) for the C282Y (845g->a), H63D (187c->g), and S65C (193a->t) variants using fluorescently-labeled energy-transfer (ET) allele-specific primers. Using a 96-channel radial CAE microplate, the labeled ASPCR products generated from 96 samples in a reference Caucasian population are simultaneously separated with single-base-pair resolution and genotyped in under 10 min. Detection is accomplished with a laser-excited rotary four-color fluorescence scanner. The allele-specific amplicons are differentiated on the basis of both their size and the color of the label emission. This study is the first demonstration of the combined use of ASPCR with ET primers and microfabricated radial CAE microplates to perform multiplex SNP analyses in a clinically relevant population. PMID:11230165

  2. Iron overload in a murine model of hereditary hemochromatosis is associated with accelerated progression of osteoarthritis under mechanical stress.

    PubMed

    Camacho, A; Simão, M; Ea, H-K; Cohen-Solal, M; Richette, P; Branco, J; Cancela, M L

    2016-03-01

    Hereditary hemochromatosis (HH) is a disease caused by mutations in the Hfe gene characterised by systemic iron overload and associated with an increased prevalence of osteoarthritis (OA) but the role of iron overload in the development of OA is still undefined. To further understand the molecular mechanisms involved we have used a murine model of HH and studied the progression of experimental OA under mechanical stress. OA was surgically induced in the knee joints of 10-week-old C57BL6 (wild-type) mice and Hfe-KO mice. OA progression was assessed using histology, micro CT, gene expression and immunohistochemistry at 8 weeks after surgery. Hfe-KO mice showed a systemic iron overload and an increased iron accumulation in the knee synovial membrane following surgery. The histological OA score was significantly higher in the Hfe-KO mice at 8 weeks after surgery. Micro CT study of the proximal tibia revealed increased subchondral bone volume and increased trabecular thickness. Gene expression and immunohistochemical analysis showed a significant increase in the expression of matrix metallopeptidase 3 (MMP-3) in the joints of Hfe-KO mice compared with control mice at 8 weeks after surgery. HH was associated with an accelerated development of OA in mice. Our findings suggest that synovial iron overload has a definite role in the progression of HH-related OA. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  3. Motivational interviewing interactions and the primary health care challenges presented by smokers with low motivation to stop smoking: a conversation analysis.

    PubMed

    Codern-Bové, Núria; Pujol-Ribera, Enriqueta; Pla, Margarida; González-Bonilla, Javier; Granollers, Silvia; Ballvé, José L; Fanlo, Gemma; Cabezas, Carmen

    2014-11-26

    Research indicates that one third of smokers have low motivation to stop smoking. The purpose of the study was to use Conversational Analysis to enhance understanding of the process in Motivational Interviewing sessions carried out by primary care doctors and nurses to motivate their patients to quit smoking. The present study is a substudy of the Systematic Intervention on Smoking Habits in Primary Health Care Project (Spanish acronym: ISTAPS). Motivational interviewing sessions with a subset of nine participants (two interview sessions were conducted with two of the nine) in the ISTAPS study who were current smokers and scored fewer than 5 points on the Richmond test that measures motivation to quit smoking were videotaped and transcribed. A total of 11 interviews conducted by five primary health care professionals in Barcelona, Spain, were analysed. Qualitative Content Analysis was used to develop an analytical guide for coding transcriptions. Conversation Analysis allowed detailed study of the exchange of words during the interaction. Motivational Interviewing sessions had three phases: assessment, reflection on readiness to change, and summary. The interaction was constructed during an office visit, where interactional dilemmas arise and can be resolved in various ways. Some actions by professionals (use of reiterations, declarations, open-ended questions) helped to construct a framework of shared relationship; others inhibited this relationship (focusing on risks of smoking, clinging to the protocol, and prematurely emphasizing change). Some professionals tended to resolve interactional dilemmas (e.g., resistance) through a confrontational or directive style. Interactions that did not follow Motivational Interviewing principles predominated in seven of the interviews analysed. Conversational analysis showed that the complexity of the intervention increases when a health professional encounters individuals with low motivation for change, and interactional

  4. Characteristics and respiratory risk profile of children aged less than 5 years presenting to an urban, Aboriginal-friendly, comprehensive primary health practice in Australia.

    PubMed

    Hall, Kerry K; Chang, Anne B; Anderson, Jennie; Dunbar, Melissa; Arnold, Daniel; O'Grady, Kerry-Ann F

    2017-07-01

    There are no published data on factors impacting on acute respiratory illness (ARI) among urban Indigenous children. We describe the characteristics and respiratory risk profile of young urban Indigenous children attending an Aboriginal-friendly primary health-care practice. We conducted a cross-sectional analysis of data collected at baseline in a cohort study investigating ARI in urban Indigenous children aged less than 5 years registered with an Aboriginal primary health-care service. Descriptive analyses of epidemiological, clinical, environmental and cultural factors were performed. Logistic regression was undertaken to examine associations between child characteristics and the presence of ARI at baseline. Between February 2013 and October 2015, 180 Indigenous children were enrolled; the median age was 18.4 months (7.7-35), 51% were male. A total of 40 (22%) children presented for a cough-related illness; however, ARI was identified in 33% of all children at the time of enrolment. A total of 72% of children were exposed to environmental tobacco smoke. ARI at baseline was associated with low birthweight (adjusted odds ratio (aOR) 2.54, 95% confidence interval (CI) 1.08-5.94), a history of eczema (aOR 2.67, 95% CI 1.00-7.15) and either having a family member from the Stolen Generation (aOR 3.47, 95% CI 1.33-9.03) or not knowing this family history (aOR 3.35, 95% CI 1.21-9.26). We identified an urban community of children of high socio-economic disadvantage and who have excessive exposure to environmental tobacco smoke. Connection to the Stolen Generation or not knowing the family history may be directly impacting on child health in this community. Further research is needed to understand the relationship between cultural factors and ARI. © 2017 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

  5. Mutations in HAMP and HJV genes and their impact on expression of clinical hemochromatosis in a cohort of 100 Spanish patients homozygous for the C282Y mutation of HFE gene.

    PubMed

    Altès, Albert; Bach, Vanessa; Ruiz, Angels; Esteve, Anna; Felez, Jordi; Remacha, Angel F; Sardà, M Pilar; Baiget, Montserrat

    2009-10-01

    Most hereditary hemochromatosis (HH) patients are homozygous for the C282Y mutation of the HFE gene. Nevertheless, penetrance of the disease is very variable. In some patients, penetrance can be mediated by concomitant mutations in other iron master genes. We evaluated the clinical impact of hepcidin (HAMP) and hemojuvelin mutations in a cohort of 100 Spanish patients homozygous for the C282Y mutation of the HFE gene. HAMP and hemojuvelin mutations were evaluated in all patients by bidirectional direct cycle sequencing. Phenotype-genotype interactions were evaluated. A heterozygous mutation of the HAMP gene (G71D) was found in only one out of 100 cases. Following, we performed a study of several members of that family, and we observed several members had a digenic inheritance of the C282Y mutation of the HFE gene and the G71D mutation of the HAMP gene. This mutation in the HAMP gene did not modify the phenotype of the individuals who were homozygous for the C282Y mutation. One other patient presented a new polymorphism in the hemojuvelin gene, without consequences in iron load or clinical course of the disease. In conclusion, HAMP and hemojuvelin mutations are rare among Spanish HH patients, and their impact in this population is not significant.

  6. Primary Papillary Serous Carcinoma of the Fallopian Tube Presenting as a Vaginal Mass: A Case Report and Review of the Literature.

    PubMed

    Kadour-Peero, Einav; Sagi-Dain, Lena; Cohen, Gil; Korobochka, Roman; Agbarya, Abed; Bejar, Jacob; Sagi, Shlomi

    2018-05-07

    BACKGROUND There is now evidence to support that some cases of high-grade serous papillary carcinoma arise from the fallopian tubes rather than the ovaries. Common symptoms at presentation include abdominal pain and swelling, vomiting, altered bowel habit and urinary symptoms. To our knowledge, this is the first case of serous papillary carcinoma presenting as a vaginal mass lesion. CASE REPORT A 41-year-old woman was referred to the Bnai-Zion Medical Center with the main complaint of irregular vaginal bleeding, vaginal mucous discharge, and suspected pelvic mass. Physical examination showed a soft, painless mass, measuring about 10 cm in diameter located mainly in the recto-vaginal septum, but not involving the uterus. Ultrasound examination showed no abnormal ovarian or uterine findings. Transvaginal biopsies of the mass showed a poorly differentiated serous papillary carcinoma of ovarian, tubal, or peritoneal origin. The physical examination and imaging findings strongly indicated an inoperable tumor, and the patient was treated with neoadjuvant (pre-surgical) chemotherapy. Pre-operative computed tomography (CT) imaging showed the partial involvement of the colon, and so surgical treatment included total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, partial vaginectomy, anterior rectal resection, and lymph node dissection. Histopathology of the surgical specimens showed a poorly differentiated serous carcinoma originating from the fimbria of the right fallopian tube. CONCLUSIONS To the best of our knowledge, this is the first report to describe primary fallopian tube papillary serous carcinoma presenting as a vaginal mass. Therefore, physicians should be aware of this possible diagnosis.

  7. Impact of travel time and rurality on presentation and outcomes of symptomatic colorectal cancer: a cross-sectional cohort study in primary care.

    PubMed

    Murage, Peninah; Murchie, Peter; Bachmann, Max; Crawford, Michael; Jones, Andy

    2017-07-01

    Several studies have reported a survival disadvantage for rural dwellers who develop colorectal cancer, but the underlying mechanisms remain obscure. Delayed presentation to GPs may be a contributory factor, but evidence is lacking. To examine the association between rurality and travel time on diagnosis and survival of colorectal cancer in a cohort from northeast Scotland. The authors used a database linking GP records to routine data for patients diagnosed between 1997 and 1998, and followed up to 2011. Primary outcomes were alarm symptoms, emergency admissions, stage, and survival. Travel time in minutes from patients to GP was estimated. Logistic and Cox regression were used to model outcomes. Interaction terms were used to determine if travelling time impacted differently on urban versus rural patients. Rural patients and patients travelling farther to the GP had better 3-year survival. When the travel outcome associations were explored using interaction terms, the associations differed between rural and urban areas. Longer travel in urban areas significantly reduced the odds of emergency admissions (odds ratio [OR] 0.62, P <0.05), and increased survival (hazard ratio 0.75, P <0.05). Longer travel also increased the odds of presenting with alarm symptoms in urban areas; this was nearly significant (OR 1.34, P = 0.06). Presence of alarm symptoms reduced the likelihood of emergency admissions (OR 0.36, P <0.01). Living in a rural area, and travelling farther to a GP in urban areas, may reduce the likelihood of emergency admissions and poor survival. This may be related to how patients present with alarm symptoms. © British Journal of General Practice 2017.

  8. Health check-ups and family screening allow detection of hereditary hemochromatosis with less advanced liver fibrosis and survival comparable with the general population.

    PubMed

    Aleman, Soo; Endalib, Sanam; Stål, Per; Lööf, Lars; Lindgren, Stefan; Sandberg-Gertzén, Hanna; Almer, Sven; Olsson, Sigvard; Danielsson, Ake; Wallerstedt, Sven; Hultcrantz, Rolf

    2011-09-01

    The information concerning the morbidity and mortality of hereditary hemochromatosis is based primarily on clinical cohorts of symptomatic patients. The major aim of this study was to analyze the long-term prognosis for Swedish patients with this condition, with respect to both clinical features and survival, in relation to the route by which the disease was detected. 373 patients with hemochromatosis detected through routine health check-ups (n = 153), family screening (n = 44), symptoms of arthralgia (n = 23), investigation of other diseases/symptoms (n = 108) or signs of liver disease (n = 45) were monitored for a mean period of 11.9 ± 5.8 years. The degree of liver fibrosis and survival were analyzed. Overall survival among these patients was not significantly different from that of a matched normal population. The patients diagnosed through health check-ups and family screening were detected at an earlier age and had the highest rate of survival. Liver biopsy at the time of diagnosis revealed cirrhosis in 9% of those detected through the health check-ups and 5% in the case of family screening, compared with 13% for the group with arthralgia, 17% for other diseases/symptoms and 42% for liver disease. Health check-ups and family screening allow detection of hereditary hemochromatosis at an earlier age and with less advanced liver fibrosis, although a few of these patients have already developed cirrhosis. Our study indicates that iron indices should be included in health check-ups, and if abnormal, should lead to further investigation.

  9. A Case of Acute Budd-Chiari Syndrome Complicating Primary Antiphospholipid Syndrome Presenting as Acute Abdomen and Responding to Tight Anticoagulant Therapy.

    PubMed

    Chinen, Naofumi; Koyama, Yasushi; Sato, Shinji; Suzuki, Yasuo

    2016-01-01

    A 34-year-old woman with primary antiphospholipid syndrome was admitted to the Gastroenterology Department of our hospital with fever, acute abdomen, watery diarrhea, and extremely high levels of inflammatory parameters. She had a history of left lower limb deep vein thrombosis and pulmonary embolism and was taking warfarin potassium. Acute gastroenteritis was suspected and an antibiotic was administered, but symptoms progressed. Abdominal ultrasonography showed occlusion of the left hepatic vein and the middle hepatic vein and her D-dimer level was high. Accordingly, Budd-Chiari syndrome was diagnosed and high-dose intravenous infusion of heparin was initiated. Her abdominal symptoms improved and the levels of inflammatory parameters and D-dimer decreased rapidly. It is known that antiphospholipid syndrome can be complicated by Budd-Chiari syndrome that usually occurs as subacute or chronic onset, but acute onset is rare. It is difficult to diagnose acute Budd-Chiari syndrome complicating antiphospholipid syndrome and this complication generally has a poor outcome. However, the present case can get early diagnosis and successful treatment with tight anticoagulant therapy.

  10. Patients with primary biliary cholangitis and fatigue present with depressive symptoms and selected cognitive deficits, but with normal attention performance and brain structure.

    PubMed

    Zenouzi, Roman; von der Gablentz, Janina; Heldmann, Marcus; Göttlich, Martin; Weiler-Normann, Christina; Sebode, Marcial; Ehlken, Hanno; Hartl, Johannes; Fellbrich, Anja; Siemonsen, Susanne; Schramm, Christoph; Münte, Thomas F; Lohse, Ansgar W

    2018-01-01

    In primary biliary cholangitis (PBC) fatigue is a major clinical challenge of unknown etiology. By demonstrating that fatigue in PBC is associated with an impaired cognitive performance, previous studies have pointed out the possibility of brain abnormalities underlying fatigue in PBC. Whether structural brain changes are present in PBC patients with fatigue, however, is unclear. To evaluate the role of structural brain abnormalities in PBC patients severely affected from fatigue we, therefore, performed a case-control cerebral magnetic resonance imaging (cMRI) study and correlated changes of white and grey brain matter with the cognitive and attention performance. 20 female patients with PBC and 20 female age-matched controls were examined in this study. The assessment of fatigue, psychological symptoms, cognitive and attention performance included clinical questionnaires, established cognition tests and a computerized test battery of attention performance. T1-weighted cMRI and diffusion tensor imaging (DTI) scans were acquired with a 3 Tesla scanner. Structural brain alterations were investigated with voxel-based morphometry (VBM) and DTI analyses. Results were correlated to the cognitive and attention performance. Compared to healthy controls, PBC patients had significantly higher levels of fatigue and associated psychological symptoms. Except for an impairment of verbal fluency, no cognitive or attention deficits were found in the PBC cohort. The VBM and DTI analyses revealed neither major structural brain abnormalities in the PBC cohort nor correlations with the cognitive and attention performance. Despite the high burden of fatigue and selected cognitive deficits, the attention performance of PBC patients appears to be comparable to healthy people. As structural brain alterations do not seem to be present in PBC patients with fatigue, fatigue in PBC must be regarded as purely functional. Future studies should evaluate, whether functional brain changes

  11. Presentation and role of transplantation in adult patients with type 1 primary hyperoxaluria and the I244T AGXT mutation: Single-center experience.

    PubMed

    Lorenzo, V; Alvarez, A; Torres, A; Torregrosa, V; Hernández, D; Salido, E

    2006-09-01

    Primary hyperoxaluria type 1 (PH1) is a rare genetic disorder characterized by allelic and clinical heterogeneity. We aim to describe the presentation and full single-center experience of the management of PH1 patients bearing the mutation described in our community (I244T mutation+polymorphism P11L). Since 1983, 12 patients with recurrent renal lithiasis have been diagnosed with PH1 and renal failure in the Canary Islands, Spain. Diagnostic confirmation was based on the presence of oxalosis in undecalcified bone or kidney allograft biopsy, reduced alanine:glyoxylate aminotransferase activity in liver biopsy, and blood DNA analysis. Patients underwent different treatment modalities depending on individual clinical circumstances and therapeutic possibilities at the time of diagnosis: hemodialysis, isolated kidney, simultaneous liver-kidney, or pre-emptive liver transplantation. In all cases, the presentation of advanced renal disease was relatively late (>13 years) and no cases were reported during lactancy or childhood. The eight patients treated with hemodialysis or isolated kidney transplantation showed unfavorable evolution leading to death over a variable period of time. In contrast, the four patients undergoing liver transplantation (three liver+kidney and one pre-emptive liver alone) showed favorable long-term allograft and patient survival (up to 12 years follow-up). In conclusion, in this PH1 population, all bearing the I244T mutation, the development of end-stage renal disease was distinctive during late adolescence or adulthood. Our long-term results support pre-emptive liver transplantation at early stages of renal failure, and kidney-liver transplantation for those with advanced renal disease.

  12. Hemochromatosis (HFE) gene mutations and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

    PubMed

    Agudo, Antonio; Bonet, Catalina; Sala, Núria; Muñoz, Xavier; Aranda, Núria; Fonseca-Nunes, Ana; Clavel-Chapelon, Françoise; Boutron-Ruault, Marie Christine; Vineis, Paolo; Panico, Salvatore; Palli, Domenico; Tumino, Rosario; Grioni, Sara; Quirós, J Ramón; Molina, Esther; Navarro, Carmen; Barricarte, Aurelio; Chamosa, Saioa; Allen, Naomi E; Khaw, Kay-Tee; Bueno-de-Mesquita, H Bas; Siersema, Peter D; Numans, Mattijs E; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Kaaks, Rudof; Canzian, Federico; Boeing, Heiner; Meidtner, Karina; Johansson, Mattias; Sund, Malin; Manjer, Jonas; Overvad, Kim; Tjonneland, Anne; Lund, Eiliv; Weiderpass, Elisabete; Jenab, Mazda; Fedirko, Veronika; Offerhaus, G Johan A; Riboli, Elio; González, Carlos A; Jakszyn, Paula

    2013-06-01

    Hereditary hemochromatosis (HH) is a strong risk factor for hepatocellular cancer, and mutations in the HFE gene associated with HH and iron overload may be related to other tumors, but no studies have been reported for gastric cancer (GC). A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC), including 365 incident gastric adenocarcinoma and 1284 controls matched by center, sex, age and date of blood collection. Genotype analysis was performed for two functional polymorphisms (C282Y/rs1800562 and H63D/rs1799945) and seven tagSNPs of the HFE genomic region. Association with all gastric adenocarcinoma, and according to anatomical localization and histological subtype, was assessed by means of the odds ratio (OR) and 95% confidence interval (CI) estimated by unconditional logistic regression adjusted for the matching variables. We observed a significant association for H63D with OR (per rare allele) of 1.32 (CI = 1.03-1.69). In subgroup analyses, the association was stronger for non-cardia anatomical subsite (OR = 1.60, CI = 1.16-2.21) and intestinal histological subtype (OR = 1.82, CI = 1.27-2.62). Among intestinal cases, two tagSNPs (rs1572982 and rs6918586) also showed a significant association that disappeared after adjustment for H63D. No association with tumors located in the cardia or with diffuse subtype was found for any of the nine SNPs analyzed. Our results suggest that H63D variant in HFE gene seems to be associated with GC risk of the non-cardia region and intestinal type, possibly due to its association with iron overload although a role for other mechanisms cannot be entirely ruled out.

  13. The Effect of the Hemochromatosis (HFE) Genotype on Lead Load and Iron Metabolism among Lead Smelter Workers

    PubMed Central

    Fan, Guangqin; Du, Guihua; Li, Huijun; Lin, Fen; Sun, Ziyong; Yang, Wei; Feng, Chang; Zhu, Gaochun; Li, Yanshu; Chen, Ying; Jiao, Huan; Zhou, Fankun

    2014-01-01

    Background Both an excess of toxic lead (Pb) and an essential iron disorder have been implicated in many diseases and public health problems. Iron metabolism genes, such as the hemochromatosis (HFE) gene, have been reported to be modifiers for lead absorption and storage. However, the HFE gene studies among the Asian population with occupationally high lead exposure are lacking. Objectives To explore the modifying effects of the HFE genotype (wild-type, H63D variant and C282Y variant) on the Pb load and iron metabolism among Asian Pb-workers with high occupational exposure. Methods Seven hundred and seventy-one employees from a lead smelter manufacturing company were tested to determine their Pb intoxication parameters, iron metabolic indexes and identify the HFE genotype. Descriptive and multivariate analyses were conducted. Results Forty-five H63D variant carriers and no C282Y variant carrier were found among the 771 subjects. Compared with subjects with the wild-type genotype, H63D variant carriers had higher blood lead levels, even after controlling for factors such as age, sex, marriage, education, smoking and lead exposure levels. Multivariate analyses also showed that the H63D genotype modifies the associations between the blood lead levels and the body iron burden/transferrin. Conclusions No C282Y variant was found in this Asian population. The H63D genotype modified the association between the lead and iron metabolism such that increased blood lead is associated with a higher body iron content or a lower transferrin in the H63D variant. It is indicated that H63D variant carriers may be a potentially highly vulnerable sub-population if they are exposed to high lead levels occupationally. PMID:24988074

  14. The effect of the hemochromatosis (HFE) genotype on lead load and iron metabolism among lead smelter workers.

    PubMed

    Fan, Guangqin; Du, Guihua; Li, Huijun; Lin, Fen; Sun, Ziyong; Yang, Wei; Feng, Chang; Zhu, Gaochun; Li, Yanshu; Chen, Ying; Jiao, Huan; Zhou, Fankun

    2014-01-01

    Both an excess of toxic lead (Pb) and an essential iron disorder have been implicated in many diseases and public health problems. Iron metabolism genes, such as the hemochromatosis (HFE) gene, have been reported to be modifiers for lead absorption and storage. However, the HFE gene studies among the Asian population with occupationally high lead exposure are lacking. To explore the modifying effects of the HFE genotype (wild-type, H63D variant and C282Y variant) on the Pb load and iron metabolism among Asian Pb-workers with high occupational exposure. Seven hundred and seventy-one employees from a lead smelter manufacturing company were tested to determine their Pb intoxication parameters, iron metabolic indexes and identify the HFE genotype. Descriptive and multivariate analyses were conducted. Forty-five H63D variant carriers and no C282Y variant carrier were found among the 771 subjects. Compared with subjects with the wild-type genotype, H63D variant carriers had higher blood lead levels, even after controlling for factors such as age, sex, marriage, education, smoking and lead exposure levels. Multivariate analyses also showed that the H63D genotype modifies the associations between the blood lead levels and the body iron burden/transferrin. No C282Y variant was found in this Asian population. The H63D genotype modified the association between the lead and iron metabolism such that increased blood lead is associated with a higher body iron content or a lower transferrin in the H63D variant. It is indicated that H63D variant carriers may be a potentially highly vulnerable sub-population if they are exposed to high lead levels occupationally.

  15. Great Issues in American History: A Compilation of Primary Sources Related to Issues That Have Occupied the Attention of the American People from Colonial Days to the Present. Oregon ASCD Curriculum Bulletin, Vol. 30, No. 333.

    ERIC Educational Resources Information Center

    Nance, Elizabeth

    This publication is a compilation of primary source materials related to issues that have occupied the attention of the American people from colonial days to the present. It is intended for use at the secondary level. A prologue contains creation stories and poems on the origins of the world and man. Documentation of the primary sources is…

  16. Effect of pH on the stability of hemochromatosis factor E: a combined spectroscopic and molecular dynamics simulation-based study.

    PubMed

    Khan, Parvez; Shandilya, Ashutosh; Jayaram, B; Islam, Asimul; Ahmad, Faizan; Hassan, Md Imtaiyaz

    2017-05-01

    Hereditary hemochromatosis is an iron overburden condition, which is mainly governed by hereditary hemochromatosis factor E (HFE), a member of major histocompatibility complex class I. To understand the effect of pH on the structure and stability of HFE, we have cloned, expressed, and purified the HFE in the bacterial system and performed circular dichroism, fluorescence, and absorbance measurements at a wide pH range (pH 3.0-11.0). We found that HFE remains stable in the pH range 7.5-11.0 and gets completely acid denatured at low pH values. In this work, we also analyzed the contribution of salt bridges to the stability of HFE. We further performed molecular dynamics simulations for 80 ns at different pH values. An excellent agreement was observed between results from biophysical and MD simulation studies. At lower pH, HFE undergoes denaturation and may be driven toward a degradation pathway, such as ubiquitination. Hence, HFE is not available to bind again with transferrin receptor1 to negatively regulate iron homeostasis. Further we postulated that, might be low pH of cancerous cells helps them to meet their high iron requirement.

  17. Clinical course, characteristics and prognostic indicators in patients presenting with back and leg pain in primary care. The ATLAS study protocol

    PubMed Central

    2012-01-01

    qualitative enquiries, to describe the course, health care usage, patients' experiences and prognostic indicators in an adult population presenting in primary care with LBP and leg pain with or without nerve root involvement. PMID:22264273

  18. Patatin-like phospholipase domain containing-3 gene I148M polymorphism, steatosis, and liver damage in hereditary hemochromatosis

    PubMed Central

    Valenti, Luca; Maggioni, Paolo; Piperno, Alberto; Rametta, Raffaela; Pelucchi, Sara; Mariani, Raffaella; Dongiovanni, Paola; Fracanzani, Anna Ludovica; Fargion, Silvia

    2012-01-01

    AIM: To investigate whether the patatin-like phospholipase domain containing-3 gene (PNPLA3) I148M polymorphism is associated with steatosis, fibrosis stage, and cirrhosis in hereditary hemochromatosis (HH). METHODS: We studied 174 consecutive unrelated homozygous for the C282Y HFE mutation of HH (C282Y+/+ HH) patients from Northern Italy, for whom the presence of cirrhosis could be determined based on histological or clinical criteria, without excessive alcohol intake (< 30/20 g/d in males or females) or hepatitis B virus and hepatitis C virus viral hepatitis. Steatosis was evaluated in 123 patients by histology (n = 100) or ultrasound (n = 23). The PNPLA3 rs738409 single nucleotide polymorphism, encoding for the p.148M protein variant, was genotyped by a Taqman assay (assay on demand, Applied Biosystems). The association of the PNPLA3 I148M protein variant (p.I148M) with steatosis, fibrosis stage, and cirrhosis was evaluated by logistic regression analysis. RESULTS: PNPLA3 genotype was not associated with metabolic parameters, including body mass index (BMI), the presence of diabetes, and lipid levels, but the presence of the p.148M variant at risk was independently associated with steatosis [odds ratio (OR) 1.84 per p.148M allele, 95% confidence interval (CI): 1.05-3.31; P = 0.037], independently of BMI and alanine aminotransaminase (ALT) levels. The p.148M variant was also associated with higher aspartate aminotransferase (P = 0.0014) and ALT levels (P = 0.017) at diagnosis, independently of BMI and the severity of iron overload. In patients with liver biopsy, the 148M variant was independently associated with the severity (stage) of fibrosis (estimated coefficient 0.56 ± 0.27, P = 0.041). In the overall series of patients, the p.148M variant was associated with cirrhosis in lean (P = 0.049), but not in overweight patients (P = not significant). At logistic regression analysis, cirrhosis was associated with BMI ≥ 25 (OR 1.82, 95% CI: 1.02-3.55), ferritin

  19. Sick-leave decisions for patients with severe subjective health complaints presenting in primary care: A cross-sectional study in Norway, Sweden, and Denmark

    PubMed Central

    2013-01-01

    Abstract Objectives The primary objective of this study was to explore whether general practitioners (GPs) in Norway, Sweden, and Denmark make similar or different decisions regarding sick leave for patients with severe subjective health complaints (SHC). The secondary objective was to investigate if patient diagnoses, the reasons attributed for patient complaints, and GP demographics could explain variations in sick leave decisions. Design A cross-sectional study. Method Video vignettes of GP consultations with nine different patients. Subjects 126 GPs in Norway, Sweden, and Denmark. Setting Primary care in Norway, Sweden, and Denmark. Main outcome measure Sick leave decisions made by GPs. Results “Psychological” diagnoses in Sweden were related to lower odds ratio (OR) of granting sick leave than in Norway (OR = 0.07; 95% CI = 0.01–0.83) Assessments of patient health, the risk of deterioration, and their ability to work predicted sick leave decisions. Specialists in general medicine grant significantly fewer sick leaves than non-specialists. Conclusion Sick-leave decisions made by GPs in the three countries were relatively similar. However, Swedish GPs were more reluctant to grant sick leave for patients with “psychological” diagnoses. Assessments regarding health-related factors were more important than diagnoses in sick-leave decisions. Specialist training may be of importance for sick-leave decisions. PMID:24164371

  20. Gender, socioeconomic position, revascularization procedures and mortality in patients presenting with STEMI and NSTEMI in the era of primary PCI. Differences or inequities?

    PubMed

    Gnavi, Roberto; Rusciani, Raffaella; Dalmasso, Marco; Giammaria, Massimo; Anselmino, Monica; Roggeri, Daniela Paola; Roggeri, Alessandro

    2014-10-20

    Several studies have reported gender and socioeconomic differences in the use of revascularization procedures in patients with acute myocardial infarction. However, it is not clear whether these differences influence patients' survival. Moreover, most of the studies neither considered STEMI and NSTEMI separately, nor included primary PCI, which nowadays is the treatment of choice in case of AMI. In an unselected population of patients admitted to hospital with a first episode of STEMI and NSTEMI we examined gender and socioeconomic differences in the use of cardiac invasive procedures and in one-year mortality. Subjects hospitalized with a first episode of STEMI (n=3506) or NSTEMI (n=2286) were selected from the Piedmont (Italy) hospital discharge database. We considered the percentage of patients undergoing PCI, primary PCI and CABG, and in-hospital mortality. Out of hospital mortality was calculated through record linkage with the regional register. The relation between outcomes and gender or educational level was investigated using appropriate multivariate regression models adjusting for available confounders. After adjustment for age, comorbidity and hospital characteristics, women and low educated patients had a lower probability of undergoing revascularization procedures. However, neither in-hospital, nor 30-day, nor 1-year mortality showed gender or social disparities. Despite gender and socioeconomic differences in the use of revascularization, no differences emerged in in-hospital and 1-year mortality. These findings could suggest that patients are differently, but equitably, treated; differences are more likely due to an inability to fully adjust for clinical conditions rather than to a selection process at admission. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. Primary Murine CD4+ T Cells Fail to Acquire the Ability to Produce Effector Cytokines When Active Ras Is Present during Th1/Th2 Differentiation

    PubMed Central

    Janardhan, Sujit V.; Marks, Reinhard; Gajewski, Thomas F.

    2014-01-01

    Constitutive Ras signaling has been shown to augment IL-2 production, reverse anergy, and functionally replace many aspects of CD28 co-stimulation in CD4+ T cells. These data raise the possibility that introduction of active Ras into primary T cells might result in improved functionality in pathologic situations of T cell dysfunction, such as cancer or chronic viral infection. To test the biologic effects of active Ras in primary T cells, CD4+ T cells from Coxsackie-Adenovirus Receptor Transgenic mice were transduced with an adenovirus encoding active Ras. As expected, active Ras augmented IL-2 production in naive CD4+ T cells. However, when cells were cultured for 4 days under conditions to promote effector cell differentiation, active Ras inhibited the ability of CD4+ T cells to acquire a Th1 or Th2 effector cytokine profile. This differentiation defect was not due to deficient STAT4 or STAT6 activation by IL-12 or IL-4, respectively, nor was it associated with deficient induction of T-bet and GATA-3 expression. Impaired effector cytokine production in active Ras-transduced cells was associated with deficient demethylation of the IL-4 gene locus. Our results indicate that, despite augmenting acute activation of naïve T cells, constitutive Ras signaling inhibits the ability of CD4+ T cells to properly differentiate into Th1/Th2 effector cytokine-producing cells, in part by interfering with epigenetic modification of effector gene loci. Alternative strategies to potentiate Ras pathway signaling in T cells in a more regulated fashion should be considered as a therapeutic approach to improve immune responses in vivo. PMID:25397617

  2. Differing impact of the deletion of hemochromatosis-associated molecules HFE and transferrin receptor-2 on the iron phenotype of mice lacking bone morphogenetic protein 6 or hemojuvelin.

    PubMed

    Latour, Chloé; Besson-Fournier, Céline; Meynard, Delphine; Silvestri, Laura; Gourbeyre, Ophélie; Aguilar-Martinez, Patricia; Schmidt, Paul J; Fleming, Mark D; Roth, Marie-Paule; Coppin, Hélène

    2016-01-01

    Hereditary hemochromatosis, which is characterized by inappropriately low levels of hepcidin, increased dietary iron uptake, and systemic iron accumulation, has been associated with mutations in the HFE, transferrin receptor-2 (TfR2), and hemojuvelin (HJV) genes. However, it is still not clear whether these molecules intersect in vivo with bone morphogenetic protein 6 (BMP6)/mothers against decapentaplegic (SMAD) homolog signaling, the main pathway up-regulating hepcidin expression in response to elevated hepatic iron. To answer this question, we produced double knockout mice for Bmp6 and β2-microglobulin (a surrogate for the loss of Hfe) and for Bmp6 and Tfr2, and we compared their phenotype (hepcidin expression, Bmp/Smad signaling, hepatic and extrahepatic tissue iron accumulation) with that of single Bmp6-deficient mice and that of mice deficient for Hjv, alone or in combination with Hfe or Tfr2. Whereas the phenotype of Hjv-deficient females was not affected by loss of Hfe or Tfr2, that of Bmp6-deficient females was considerably worsened, with decreased Smad5 phosphorylation, compared with single Bmp6-deficient mice, further repression of hepcidin gene expression, undetectable serum hepcidin, and massive iron accumulation not only in the liver but also in the pancreas, the heart, and the kidneys. These results show that (1) BMP6 does not require HJV to transduce signal to hepcidin in response to intracellular iron, even if the loss of HJV partly reduces this signal, (2) another BMP ligand can replace BMP6 and significantly induce hepcidin expression in response to extracellular iron, and (3) BMP6 alone is as efficient at inducing hepcidin as the other BMPs in association with the HJV/HFE/TfR2 complex; they provide an explanation for the compensatory effect of BMP6 treatment on the molecular defect underlying Hfe hemochromatosis in mice. © 2015 by the American Association for the Study of Liver Diseases.

  3. Increased Retinal Expression of the Pro-Angiogenic Receptor GPR91 via BMP6 in a Mouse Model of Juvenile Hemochromatosis.

    PubMed

    Arjunan, Pachiappan; Gnanaprakasam, Jaya P; Ananth, Sudha; Romej, Michelle A; Rajalakshmi, Veeranan-Karmegam; Prasad, Puttur D; Martin, Pamela M; Gurusamy, Mariappan; Thangaraju, Muthusamy; Bhutia, Yangzom D; Ganapathy, Vadivel

    2016-04-01

    Hemochromatosis, an iron-overload disease, occurs as adult and juvenile types. Mutations in hemojuvelin (HJV), an iron-regulatory protein and a bone morphogenetic protein (BMP) coreceptor, underlie most of the juvenile type. Hjv(-/-) mice accumulate excess iron in retina and exhibit aberrant vascularization and angiomas. A succinate receptor, GPR91, is pro-angiogenic in retina. We hypothesized that Hjv(-/-) retinas have increased BMP signaling and increased GPR91 expression as the basis of angiomas. Expression of GPR91 was examined by qPCR, immunofluorescence, and Western blot in wild-type and Hjv(-/-) mouse retinas and pRPE cells. Influence of excess iron and BMP6 on GPR91 expression was investigated in ARPE-19 cells, and wild-type and Hjv(-/-) pRPE cells. Succinate was used to activate GPR91 and determine the effects of GPR91 signaling on VEGF expression. Signaling of BMP6 was studied by the expression of Smad1/5/8 and pSmad4, and the BMP-target gene Id1. The interaction of pSmad4 with GPR91 promoter was studied by ChIP. Expression of GPR91 was higher in Hjv(-/-) retinas and RPE than in wild-type counterparts. Unexpectedly, BMP signaling was increased, not decreased, in Hjv(-/-) retinas and RPE. Bone morphogenetic protein 6 induced GPR91 in RPE, suggesting that increased BMP signaling in Hjv(-/-) retinas was likely responsible for GPR91 upregulation. Exposure of RPE to excess iron and succinate as well as BMP6 and succinate increased VEGF expression. Bone morphogenetic protein 6 promoted the interaction of pSmad4 with GPR91 promoter in RPE. G-protein-coupled receptor 91 is a BMP6 target and Hjv deletion enhances BMP signaling in retina, thus underscoring a role for excess iron and hemochromatosis in abnormal retinal vascularization.

  4. Histogram Analysis of Apparent Diffusion Coefficients for Occult Tonsil Cancer in Patients with Cervical Nodal Metastasis from an Unknown Primary Site at Presentation.

    PubMed

    Choi, Young Jun; Lee, Jeong Hyun; Kim, Hye Ok; Kim, Dae Yoon; Yoon, Ra Gyoung; Cho, So Hyun; Koh, Myeong Ju; Kim, Namkug; Kim, Sang Yoon; Baek, Jung Hwan

    2016-01-01

    To explore the added value of histogram analysis of apparent diffusion coefficient (ADC) values over magnetic resonance (MR) imaging and fluorine 18 ((18)F) fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) for the detection of occult palatine tonsil squamous cell carcinoma (SCC) in patients with cervical nodal metastasis from a cancer of an unknown primary site. The institutional review board approved this retrospective study, and the requirement for informed consent was waived. Differences in the bimodal histogram parameters of the ADC values were assessed among occult palatine tonsil SCC (n = 19), overt palatine tonsil SCC (n = 20), and normal palatine tonsils (n = 20). One-way analysis of variance was used to analyze differences among the three groups. Receiver operating characteristic curve analysis was used to determine the best differentiating parameters. The increased sensitivity of histogram analysis over MR imaging and (18)F-FDG PET/CT for the detection of occult palatine tonsil SCC was evaluated as added value. Histogram analysis showed statistically significant differences in the mean, standard deviation, and 50th and 90th percentile ADC values among the three groups (P < .0045). Occult palatine tonsil SCC had a significantly higher standard deviation for the overall curves, mean and standard deviation of the higher curves, and 90th percentile ADC value, compared with normal palatine tonsils (P < .0167). Receiver operating characteristic curve analysis showed that the standard deviation of the overall curve best delineated occult palatine tonsil SCC from normal palatine tonsils, with a sensitivity of 78.9% (15 of 19 patients) and a specificity of 60% (12 of 20 patients). The added value of ADC histogram analysis was 52.6% over MR imaging alone and 15.8% over combined conventional MR imaging and (18)F-FDG PET/CT. Adding ADC histogram analysis to conventional MR imaging can improve the detection sensitivity for occult

  5. Involvement of substance P present in primary afferent neurones in modulation of cutaneous blood flow in the instep of rat hind paw.

    PubMed Central

    Yonehara, N.; Chen, J. Q.; Imai, Y.; Inoki, R.

    1992-01-01

    1. The participation of small-diameter afferent fibres in the microcirculatory haemodynamics of cutaneous tissue was examined by studies on the effects of antidromic stimulation of primary afferent neurones on cutaneous blood flow (CBF) and tachykinin release into the subcutaneous space in the instep of the hind paw of rats. 2. Antidromic stimulation of the sectioned sciatic nerve induced a biphasic flow response, an initial transient decrease followed by an increase, with no alteration in the blood pressure. 3. Neither phase was affected by pretreatment with phentolamine (0.1 mg kg-1, i.a.), propranolol (0.5 mg kg-1, i.a.), atropine (0.5 mg kg-1, i.a.), methysergide (0.5 mg kg-1, i.a.) or mepyramine (10 mg kg-1, i.a.) plus cimetidine (10 mg kg-1, i.a.), but both were significantly inhibited by pretreatment with capsaicin (50 mg kg-1, s.c.). 4. Spantide (1-2 mumol kg-1, i.a.), a substance P (SP) antagonist, reduced the basal CBF, and also inhibited both phases of the biphasic flow response evoked by antidromic stimulation of the sectioned sciatic nerve. 5. Intra-arterial infusion of SP (0.5 mumol kg-1, i.a.) induced a biphasic flow response similar to that elicited by antidromic stimulation of the sectioned sciatic nerve. 6. Antidromic stimulation of the sectioned sciatic nerve caused a marked increase in SP release into the subcutaneous perfusate of the instep of the rat hind paw, but no detectable increase in neurokinin A release.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1382777

  6. Learning about Hereditary Hemochromatosis

    MedlinePlus

    ... New Horizons and Research Patient Management Policy and Ethics Issues Quick Links for Patient Care Education All About ... Genome Exhibition Talking Glossary: English Talking Glossary: Español Issues ... Contacts Media Resources NHGRI-Related News Journal Articles ...

  7. Use of human antigen presenting cell gene array profiling to examine the effect of human T-cell leukemia virus type 1 Tax on primary human dendritic cells.

    PubMed

    Ahuja, Jaya; Kampani, Karan; Datta, Suman; Wigdahl, Brian; Flaig, Katherine E; Jain, Pooja

    2006-02-01

    Human T-cell leukemia virus type 1 (HTLV-1) is etiologically linked to adult T-cell leukemia and a progressive demyelinating disorder termed HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). One of the most striking features of the immune response in HAM/TSP centers on the expansion of HTLV-1-specific CD8(+) cytotoxic T lymphocyte (CTL) compartment in the peripheral blood and cerebrospinal fluid. More than 90% of the HTLV-1-specific CTLs are directed against the viral Tax (11-19) peptide implying that Tax is available for immune recognition by antigen presenting cells, such as dendritic cells (DCs). DCs obtained from HAM/TSP patients have been shown to be infected with HTLV-1 and exhibit rapid maturation. Therefore, we hypothesized that presentation of Tax peptides by activated DCs to naIve CD8(+) T cells may play an important role in the induction of a Tax-specific CTL response and neurologic dysfunction. In this study, a pathway-specific antigen presenting cell gene array was used to study transcriptional changes induced by exposure of monocyte-derived DCs to extracellular HTLV-1 Tax protein. Approximately 100 genes were differentially expressed including genes encoding toll-like receptors, cell surface receptors, proteins involved in antigen uptake and presentation and adhesion molecules. The differential regulation of chemokines and cytokines characteristic of functional DC activation was also observed by the gene array analyses. Furthermore, the expression pattern of signal transduction genes was also significantly altered. These results have suggested that Tax-mediated DC gene regulation might play a critical role in cellular activation and the mechanisms resulting in HTLV-1-induced disease.

  8. Catastrophic cerebral antiphospholipid syndrome presenting as cerebral infarction with haemorrhagic transformation after sudden withdrawal of warfarin in a patient with primary antiphospholipid syndrome

    PubMed Central

    Wani, Abdul Majid; Hussain, Waleed Mohd; Mejally, Mousa Ali Al; Ali, Khaled Shawkat; Raja, Sadeya Hanif; Maimani, Wael Al; Bafaraj, Mazen G; Bashraheel, Ashraf; Akhtar, Mubeena; Khoujah, Amer Mohd

    2010-01-01

    Catastrophic antiphospholipid syndrome (APS) is caused by thrombotic vascular occlusions that affect both small and large vessels, producing ischaemia in the affected organs. The “catastrophic” variant of the antiphospholipid syndrome (cAPS) develops over a short period of time. Although patients with cAPS represent <1% of all patients with APS, they are usually life threatening with a 50% mortality rate. A strong association with concomitant infection is thought to act as the main trigger of microthromboses in cAPS. Several theories have been proposed to explain these physiopathological features. Some of them suggest the possibility of molecular mimicry between components of infectious microorganisms and natural anticoagulants, which might be involved in the production of cross-reacting antiphospholipid antibodies. We present a case of catastrophic cerebral APS characterised by massive temporal lobe infarction and subsequent haemorrhagic transformation after sudden withdrawal of warfarin. PMID:22242060

  9. Congenital primary adrenal insufficiency and selective aldosterone defects presenting as salt-wasting in infancy: a single center 10-year experience.

    PubMed

    Bizzarri, Carla; Olivini, Nicole; Pedicelli, Stefania; Marini, Romana; Giannone, Germana; Cambiaso, Paola; Cappa, Marco

    2016-08-02

    Salt-wasting represents a relatively common cause of emergency admission in infants and may result in life-threatening complications. Neonatal kidneys show low glomerular filtration rate and immaturity of the distal nephron leading to reduced ability to concentrate urine. A retrospective chart review was conducted for infants hospitalized in a single Institution from 1(st) January 2006 to 31(st) December 2015. The selection criterion was represented by the referral to the Endocrinology Unit for hyponatremia (serum sodium <130 mEq/L) of suspected endocrine origin at admission. Fifty-one infants were identified. In nine infants (17.6 %) hyponatremia was related to unrecognized chronic gastrointestinal or renal salt losses or reduced sodium intake. In 10 infants (19.6 %) hyponatremia was related to central nervous system diseases. In 19 patients (37.3 %) the final diagnosis was congenital adrenal hyperplasia (CAH). CAH was related to 21-hydroxylase deficiency in 18 patients, and to 3β-Hydroxysteroid dehydrogenase (3βHSD) deficiency in one patient. Thirteen patients (25.5 %) were affected by different non-CAH salt-wasting forms of adrenal origin. Four familial cases of X-linked adrenal hypoplasia congenita due to NROB1 gene mutation were identified. Two unrelated girls showed aldosterone synthase deficiency due to mutation of the CYP11B2 gene. Two unrelated infants were affected by familial glucocorticoid deficiency due to MC2R gene mutations. One girl showed pseudohypoaldosteronism related to mutations of the SCNN1G gene encoding for the epithelial sodium channel. Transient pseudohypoaldosteronism was identified in two patients with renal malformations. In two infants the genetic aetiology was not identified. Emergency management of infants presenting with salt wasting requires correction of water losses and treatment of electrolyte imbalances. Nevertheless, the differential diagnosis may be difficult in emergency settings, and sometimes hospitalized infants

  10. Primary percutaneous coronary intervention for patients presenting with ST-segment elevation myocardial infarction: process improvement in a rural ST-segment elevation myocardial infarction receiving center.

    PubMed

    Niles, Nathaniel W; Conley, Sheila M; Yang, Rayson C; Vanichakarn, Pantila; Anderson, Tamara A; Butterly, John R; Robb, John F; Jayne, John E; Yanofsky, Norman N; Proehl, Jean A; Guadagni, Donald F; Brown, Jeremiah R

    2010-01-01

    Rural ST-segment elevation myocardial infarction (STEMI) care networks may be particularly disadvantaged in achieving a door-to-balloon time (D2B) of less than or equal to 90 minutes recommended in current guidelines. ST-ELEVATION MYOCARDIAL INFARCTION PROCESS UPGRADE PROJECT: A multidisciplinary STEMI process upgrade group at a rural percutaneous coronary intervention center implemented evidence-based strategies to reduce time to electrocardiogram (ECG) and D2B, including catheterization laboratory activation triggered by either a prehospital ECG demonstrating STEMI or an emergency department physician diagnosing STEMI, single-call catheterization laboratory activation, catheterization laboratory response time less than or equal to 30 minutes, and prompt data feedback. An ongoing regional STEMI registry was used to collect process time intervals, including time to ECG and D2B, in a consecutive series of STEMI patients presenting before (group 1) and after (group 2) strategy implementation. Significant reductions in time to first ECG in the emergency department and D2B were seen in group 2 compared with group 1. Important improvement in the process of acute STEMI patient care was accomplished in the rural percutaneous coronary intervention center setting by implementing evidence-based strategies. Copyright © 2010 Elsevier Inc. All rights reserved.

  11. A 3-Year-Old Girl with Recurrent Infections and Autoimmunity due to a STAT1 Gain-of-Function Mutation: The Expanding Clinical Presentation of Primary Immunodeficiencies.

    PubMed

    Aldave Becerra, Juan Carlos; Cachay Rojas, Enrique

    2017-01-01

    We report a 3-year-old Peruvian girl, born to non-consanguineous parents. At the age of 8 months, she had a severe pneumonia complicated with empyema that required thoracic drainage and mechanical ventilation. Although no microorganisms were isolated, the patient recovered with broad-spectrum antibiotics. Since that date, she has presented multiple episodes of pneumonia and recurrent episodes of bronchospasm. At 1 year 5 months of age, the patient began with recurrent episodes of oropharyngeal, vaginal, and skin candidiasis, which improved transiently after using oral azole drugs. At 2.5 years of age, she was admitted with lupus-like syndrome, including serositis, hemolytic anemia, thrombocytopenia, and positive antinuclear (1:80) and dsDNA (1:10) autoantibodies. Available immunologic testing was not contributory. Imaging studies revealed bilateral ethmoidal sinusitis and mild hepatomegaly. Bone marrow analysis did not showed evidence of leukemia or myelodysplasia, while renal biopsy concluded mild mesangial proliferation. Genetic studies revealed a pathogenic heterozygous signal transducer and activator of transcription 1 gain-of-function mutation (WT/P293L). The clinical status and lung function of the patient has worsened progressively. She has not achieved an optimal response to therapy, including high-dose intravenous immunoglobulin, GM-CSF, prophylactic antibiotics and antifungal drugs, so we plan to perform hematopoietic stem cell transplantation.

  12. Prevalence of C282Y, H63D, and S65C mutations in hereditary HFE-hemochromatosis gene in Lithuanian population.

    PubMed

    Kucinskas, Laimutis; Juzenas, Simonas; Sventoraityte, Jurgita; Cedaviciute, Ruta; Vitkauskiene, Astra; Kalibatas, Vytenis; Kondrackiene, Jurate; Kupcinskas, Limas

    2012-04-01

    HFE-hemochromatosis is a common autosomal recessive disease caused by HFE gene mutations and characterized as iron overload and failure of different organs. The aim of this study was to determine the prevalence of C282Y (c.845 G>A), H63D (c.187 C>G), and S65C (c.193A>T) alleles of HFE gene in the Lithuanian population. One thousand and eleven healthy blood donors of Lithuanian nationality were examined in four different ethnic Lithuanian regions to determine HFE gene alleles and genotype frequencies. The samples of DNA were analyzed for the presence of restriction fragment length polymorphism and validated by DNA sequencing. Among 1,011 blood donors tested, the frequency of C282Y, H63D, and S65C alleles were 2.6%, 15.9%, and 1.9%, respectively. One third of the tested subjects (n = 336) had at least one of the C282Y or H63D HFE gene mutations. The screening of Lithuanian blood donors has detected 13 (1.3%) subjects with a genotype C282Y/C282Y or C282Y/H63D responsible for the development of HFE-hemochromatosis. The prevalence of C282Y mutation was significantly higher among the inhabitants of Zemaitija (Somogitia) at the Baltic Sea area (5.9%) in comparison to the regions of continental part of Lithuania (2.4% in Dzukija, 2.3% in Aukstaitija, and 2% in Suvalkija, p < 0.05). These data support the hypothesis that the p.C282Y mutation originated from Scandinavia and spread with the Vikings along the Baltic Sea coast. The first epidemiological investigation of HFE gene mutations in ethnic Lithuanians showed that the frequencies of H63D, C282Y, and S65C of HFE gene alleles are similar to the other North-Eastern Europeans, especially in the Baltic region (Estonia, Latvia), Poland, and part of Russia (Moscow region).

  13. Increased Retinal Expression of the Pro-Angiogenic Receptor GPR91 via BMP6 in a Mouse Model of Juvenile Hemochromatosis

    PubMed Central

    Arjunan, Pachiappan; Gnanaprakasam, Jaya P.; Ananth, Sudha; Romej, Michelle A.; Rajalakshmi, Veeranan-Karmegam; Prasad, Puttur D.; Martin, Pamela M.; Gurusamy, Mariappan; Thangaraju, Muthusamy; Bhutia, Yangzom D.; Ganapathy, Vadivel

    2016-01-01

    Purpose Hemochromatosis, an iron-overload disease, occurs as adult and juvenile types. Mutations in hemojuvelin (HJV), an iron-regulatory protein and a bone morphogenetic protein (BMP) coreceptor, underlie most of the juvenile type. Hjv−/− mice accumulate excess iron in retina and exhibit aberrant vascularization and angiomas. A succinate receptor, GPR91, is pro-angiogenic in retina. We hypothesized that Hjv−/− retinas have increased BMP signaling and increased GPR91 expression as the basis of angiomas. Methods Expression of GPR91 was examined by qPCR, immunofluorescence, and Western blot in wild-type and Hjv−/− mouse retinas and pRPE cells. Influence of excess iron and BMP6 on GPR91 expression was investigated in ARPE-19 cells, and wild-type and Hjv−/− pRPE cells. Succinate was used to activate GPR91 and determine the effects of GPR91 signaling on VEGF expression. Signaling of BMP6 was studied by the expression of Smad1/5/8 and pSmad4, and the BMP-target gene Id1. The interaction of pSmad4 with GPR91 promoter was studied by ChIP. Results Expression of GPR91 was higher in Hjv−/− retinas and RPE than in wild-type counterparts. Unexpectedly, BMP signaling was increased, not decreased, in Hjv−/− retinas and RPE. Bone morphogenetic protein 6 induced GPR91 in RPE, suggesting that increased BMP signaling in Hjv−/− retinas was likely responsible for GPR91 upregulation. Exposure of RPE to excess iron and succinate as well as BMP6 and succinate increased VEGF expression. Bone morphogenetic protein 6 promoted the interaction of pSmad4 with GPR91 promoter in RPE. Conclusions G-protein-coupled receptor 91 is a BMP6 target and Hjv deletion enhances BMP signaling in retina, thus underscoring a role for excess iron and hemochromatosis in abnormal retinal vascularization. PMID:27046124

  14. The diagnosis of urinary tract infections in young children (DUTY): protocol for a diagnostic and prospective observational study to derive and validate a clinical algorithm for the diagnosis of UTI in children presenting to primary care with an acute illness.

    PubMed

    Downing, Harriet; Thomas-Jones, Emma; Gal, Micaela; Waldron, Cherry-Ann; Sterne, Jonathan; Hollingworth, William; Hood, Kerenza; Delaney, Brendan; Little, Paul; Howe, Robin; Wootton, Mandy; Macgowan, Alastair; Butler, Christopher C; Hay, Alastair D

    2012-07-19

    Urinary tract infection (UTI) is common in children, and may cause serious illness and recurrent symptoms. However, obtaining a urine sample from young children in primary care is challenging and not feasible for large numbers. Evidence regarding the predictive value of symptoms, signs and urinalysis for UTI in young children is urgently needed to help primary care clinicians better identify children who should be investigated for UTI. This paper describes the protocol for the Diagnosis of Urinary Tract infection in Young children (DUTY) study. The overall study aim is to derive and validate a cost-effective clinical algorithm for the diagnosis of UTI in children presenting to primary care acutely unwell. DUTY is a multicentre, diagnostic and prospective observational study aiming to recruit at least 7,000 children aged before their fifth birthday, being assessed in primary care for any acute, non-traumatic, illness of ≤ 28 days duration. Urine samples will be obtained from eligible consented children, and data collected on medical history and presenting symptoms and signs. Urine samples will be dipstick tested in general practice and sent for microbiological analysis. All children with culture positive urines and a random sample of children with urine culture results in other, non-positive categories will be followed up to record symptom duration and healthcare resource use. A diagnostic algorithm will be constructed and validated and an economic evaluation conducted.The primary outcome will be a validated diagnostic algorithm using a reference standard of a pure/predominant growth of at least >103, but usually >105 CFU/mL of one, but no more than two uropathogens.We will use logistic regression to identify the clinical predictors (i.e. demographic, medical history, presenting signs and symptoms and urine dipstick analysis results) most strongly associated with a positive urine culture result. We will then use economic evaluation to compare the cost

  15. The diagnosis of urinary tract infections in young children (DUTY): protocol for a diagnostic and prospective observational study to derive and validate a clinical algorithm for the diagnosis of UTI in children presenting to primary care with an acute illness

    PubMed Central

    2012-01-01

    Background Urinary tract infection (UTI) is common in children, and may cause serious illness and recurrent symptoms. However, obtaining a urine sample from young children in primary care is challenging and not feasible for large numbers. Evidence regarding the predictive value of symptoms, signs and urinalysis for UTI in young children is urgently needed to help primary care clinicians better identify children who should be investigated for UTI. This paper describes the protocol for the Diagnosis of Urinary Tract infection in Young children (DUTY) study. The overall study aim is to derive and validate a cost-effective clinical algorithm for the diagnosis of UTI in children presenting to primary care acutely unwell. Methods/design DUTY is a multicentre, diagnostic and prospective observational study aiming to recruit at least 7,000 children aged before their fifth birthday, being assessed in primary care for any acute, non-traumatic, illness of ≤ 28 days duration. Urine samples will be obtained from eligible consented children, and data collected on medical history and presenting symptoms and signs. Urine samples will be dipstick tested in general practice and sent for microbiological analysis. All children with culture positive urines and a random sample of children with urine culture results in other, non-positive categories will be followed up to record symptom duration and healthcare resource use. A diagnostic algorithm will be constructed and validated and an economic evaluation conducted. The primary outcome will be a validated diagnostic algorithm using a reference standard of a pure/predominant growth of at least >103, but usually >105 CFU/mL of one, but no more than two uropathogens. We will use logistic regression to identify the clinical predictors (i.e. demographic, medical history, presenting signs and symptoms and urine dipstick analysis results) most strongly associated with a positive urine culture result. We will then use economic evaluation

  16. Morbidity and mortality in first-degree relatives of C282Y homozygous probands with clinically detected haemochromatosis compared with the general population: the HEmochromatosis FAmily Study (HEFAS).

    PubMed

    Jacobs, E M G; Hendriks, J C M; Marx, J J M; van Deursen, C Th B M; Kreeftenberg, H G; de Vries, R A; Stalenhoef, A F H; Verbeek, A L M; Swinkels, D W

    2007-12-01

    Family screening has been suggested as a sophisticated model for the early detection of HFE-related hereditary haemochromatosis (HH). However, until now, controlled studies on the morbidity and mortality in families with HH are lacking. Data on iron parameters, morbidity and mortality were collected from 224 dutch C282Y-homozygous probands with clinically overt HH and 735 of their first-degree family members, all participating in the HEmochromatosis fAmily study (HEfAs). These data were compared with results obtained from an age- and gender-matched normal population. HEfAs and controls filled in similar questionnaires on demographics, lifestyle factors, health, morbidity and mortality. A significantly higher proportion of the HEfAs first-degree family members reported to be diagnosed with haemochromatosis-related diseases: 45.7 vs 19.4% of the matched normal population (McNemar p<0.001). Mortality among siblings, children and parents in the HEFAS population was similar to that in the relatives of matched control. In this study we show that, morbidity among first-degree family members of C282Y-homozygous probands previously diagnosed with clinically proven HH is higher than that in an age- and gender-matched normal population. Further studies are needed to definitely connect these increase morbidity figures to increase prevalenc of the C282Y mutated HFE-gene and elevated serum iron indices.

  17. The efficiency of therapeutic erythrocytapheresis compared to phlebotomy: a mathematical tool for predicting response in hereditary hemochromatosis, polycythemia vera, and secondary erythrocytosis.

    PubMed

    Evers, Dorothea; Kerkhoffs, Jean-Louis; Van Egmond, Liane; Schipperus, Martin R; Wijermans, Pierre W

    2014-06-01

    Recently, therapeutic erythrocytapheresis (TE) was suggested to be more efficient in depletion of red blood cells (RBC) compared to manual phlebotomy in the treatment of hereditary hemochromatosis (HH), polycythemia vera (PV), and secondary erythrocytosis (SE). The efficiency rate (ER) of TE, that is, the increase in RBC depletion achieved with one TE cycle compared to one phlebotomy procedure, can be calculated based on estimated blood volume (BV), preprocedural hematocrit (Hct(B)), and delta-hematocrit (ΔHct). In a retrospective evaluation of 843 TE procedures (in 45 HH, 33 PV, and 40 SE patients) the mean ER was 1.86 ± 0.62 with the highest rates achieved in HH patients. An ER of 1.5 was not reached in 37.9% of all procedures mainly concerning patients with a BV below 4,500 ml. In 12 newly diagnosed homozygous HH patients, the induction phase duration was medially 38.4 weeks (medially 10.5 procedures). During the maintenance treatment of HH, PV, and SE, the interval between TE procedures was medially 13.4 weeks. This mathematical model can help select the proper treatment modality for the individual patient. Especially for patients with a large BV and high achievable ΔHct, TE appears to be more efficient than manual phlebotomy in RBC depletion thereby potentially reducing the numbers of procedures and expanding the interprocedural time period for HH, PV, and SE. © 2013 Wiley Periodicals, Inc.

  18. Primary extranodal marginal zone lymphoma of the uvea associated with massive diffuse epibulbar extension and focal infiltration of the optic nerve and meninges, clinically presented as uveitis masquerade syndrome: a case report.

    PubMed

    Rasić, D M; Stanković, Z; Terzić, T; Kovacević, D; Koturović, Z; Marković, V

    2010-09-01

    To report a clinical, histopathological and immunohistochemical findings in a case of primary extranodal marginal zone lymphoma of the uvea associated with massive diffuse extraocular episcleral extension and focal infiltration of the optic nerve and meninges, clinically presented as longstanding uveitis masquerade syndrome. Interventional case reports with histopathological correlation. We describe a 80-year-old male patient with a 3-year history of chronic recurrent hypertensive (pan) uveitis associated with ocular pain, unresponsive to topical and systemic anti-inflammatory, immunosuppressive, antibiotic/antiviral and antiglaucomatous therapy. Because the eye was not salvageable with conservative treatment, enucleation of blind and painful eye was performed. Findings from histopathological and immunohistochemistry examination of the enucleated eye showed an extranodal marginal zone lymphoma of the uveal tract with massive epibulbar extension and optic nerve and meningeal penetration. During almost 3 years of clinical course and 6 months after the enucleation, there were no systemic manifestations of lymphoma, and patient has not required subsequent treatment. Primary lymphoproliferative lesions of the uvea, comprising the iris, ciliary body and choroid are very rare, associated with epibulbar extension extremely and with optic nerve and menigeal penetration exceptionally. Despite its rarity, primary lymphoma of the uvea should be included in the differential diagnosis particularly in older patients with longstanding recurrent uveitis.

  19. Presentation Annotated

    NASA Technical Reports Server (NTRS)

    Ditto, Thomas

    2017-01-01

    This Report is not the latest word on an old idea but the first word on a new one. The new idea reverses the old one, the axiom that the best primary objective for an astronomical telescope exhibits the least chromatic aberration. That axiomatic distinction goes back to a young Isaac Newton who knew from experiments with prisms and mirrors in the 1660's that magnification with a reflection primary was completely free of the dispersion he saw with refraction. The superiority of reflection primary objectives for eyeball or photographic viewing is now considered obvious. It was this piece of wisdom on achromatic primary objectives that led to the dominance of the parabolic mirror as the means to collect star light. Newton was aware of the problem when he introduced his telescope to the scientific world in 1670.This Report is not the latest word on an old idea but the first word on a new one. The new idea reverses the old one, the axiom that the best primary objective for an astronomical telescope exhibits the least chromatic aberration. That axiomatic distinction goes back to a young Isaac Newton who knew from experiments with prisms and mirrors in the 1660's that magnification with a reflection primary was completely free of the dispersion he saw with refraction. The superiority of reflection primary objectives for eyeball or photographic viewing is now considered obvious. Actually, Newton's design innovation was in a secondary mirror, a plane mirror far more easily fabricated than Gregory's embodiment of 1663 which required two curved mirrors.

  20. Prognostic implications of Q waves at presentation in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: An analysis of the HORIZONS-AMI study.

    PubMed

    Kosmidou, Ioanna; Redfors, Björn; Crowley, Aaron; Gersh, Bernard; Chen, Shmuel; Dizon, José M; Embacher, Monica; Mehran, Roxana; Ben-Yehuda, Ori; Mintz, Gary S; Stone, Gregg W

    2017-11-01

    Presence of Q waves on the presenting electrocardiogram (ECG) in patients with ST-segment elevation myocardial infarction (STEMI) has been associated with worse prognosis; however, whether the prognostic value of Q waves is influenced by baseline characteristics and/or rapidity of revascularization based on the guideline-based metric of door-to-balloon time remains unknown. We hypothesized that Q waves in the presenting ECG will be predictive of long term mortality regardless of time to reperfusion. The Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial enrolled 3602 patients with STEMI undergoing primary percutaneous coronary intervention. We stratified patients without prior history of myocardial infarction or coronary revascularization according to presence or absence of pathological Q waves on their presenting ECG. Associations between Q waves, death, and cardiovascular outcomes within 3 years were assessed using Cox proportional hazards regression. Among 2723 patients with evaluable ECGs, 1084 (39.8%) had Q waves on their presenting ECG. Male sex and time from symptom onset to balloon inflation were independent predictors of presence of Q waves. Patients with Q waves had higher adjusted risks of all-cause death (adjusted hazard ratio: 1.45, 95% confidence interval: 1.02-2.05, P = 0.04) and cardiac death (adjusted hazard ratio: 1.72, 95% confidence interval: 1.08-2.72, P = 0.02). The association between Q waves and cardiac death was consistent regardless of sex, diabetes status, target vessel, or door-to-balloon time (P interaction > 0.4 for all). Presence of Q waves on the presenting ECG in patients undergoing primary percutaneous coronary intervention due to STEMI is an independent predictor of mortality and adds prognostic value, regardless of sex or rapidity of revascularization. © 2017 Wiley Periodicals, Inc.

  1. Percutaneous excretion of iron and ferritin (through Al-hijamah) as a novel treatment for iron overload in beta-thalassemia major, hemochromatosis and sideroblastic anemia.

    PubMed

    El Sayed, Salah Mohamed; Abou-Taleb, Ashraf; Mahmoud, Hany Salah; Baghdadi, Hussam; Maria, Reham A; Ahmed, Nagwa Sayed; Nabo, Manal Mohamed Helmy

    2014-08-01

    Iron overload is a big challenge when treating thalassemia (TM), hemochromatosis and sideroblastic anemia. It persists even after cure of TM with bone marrow transplantation. Iron overload results from increased iron absorption and repeated blood transfusions causing increased iron in plasma and interstitial fluids. Iron deposition in tissues e.g. heart, liver, endocrine glands and others leads to tissue damage and organ dysfunction. Iron chelation therapy and phlebotomy for iron overload have treatment difficulties, side effects and contraindications. As mean iron level in skin of TM patients increases by more than 200%, percutaneous iron excretion may be beneficial. Wet cupping therapy (WCT) is a simple, safe and economic treatment. WCT is a familiar treatment modality in some European countries and in Chinese hospitals in treating different diseases. WCT was reported to clear both blood plasma and interstitial spaces from causative pathological substances (CPS). Standard WCT method is Al-hijamah (cupping, puncturing and cupping, CPC) method of WCT that was reported to clear blood and interstitial fluids better than the traditional WCT (puncturing and cupping method, PC method of WCT). In other word, traditional WCT may be described as scarification and suction method (double S technique), while Al-hijamah may be described as suction, scarification and suction method (triple S technique). Al-hijamah is a more comprehensive treatment modality that includes all steps and therapeutic benefits of traditional dry cupping therapy and WCT altogether according to the evidence-based Taibah mechanism (Taibah theory). During the first cupping step of Al-hijamah, a fluid mixture is collected inside skin uplifting due to the effect of negative pressure inside sucking cups. This fluid mixture contains collected interstitial fluids with CPS (iron, ferritin and hemolyzed RBCs in thalassemia), filtered fluids (from blood capillaries) with iron and hemolyzed blood cells (hemolyzed

  2. 'Can he have the test for bipolar, doctor? His dad's got it': exploring the potential of general practitioners to work with children and young people presenting in primary care with common mental health problems - a clinical initiative.

    PubMed

    Roberts, Jane H; Bernard, Paul M

    2012-06-01

    Background General practitioners (GPs) play a key role in assessing and managing adult mental health problems, but this input is not seen in their management of child and adolescent mental health. Mental health problems in 5-19-year-olds are common, yet detection rates in primary care are low. The symptoms of most adult diagnoses of mental health problems are present by mid-adolescence, yet the typical time from onset to diagnosis is 5-15 years. The role of general practice in this area has been underexplored. Aim This pilot study explores the potential of GPs to respond to common mental health problems in children and adolescents. Design Children and young people who would have ordinarily been referred to Child and Adolescent Mental Health Services (CAMHS) were seen in a GP setting. In a UK general practice surgery serving a disadvantaged population. Method Children and young people were seen for an initial biopsychosocial assessment and formulation of the presenting concerns. GP-based interventions were offered as appropriate or referred to CAMHS. Results Data from the first 50 children (2-19 years) are presented. Twenty younger children (10 years and under) and 30 older children (11 years and above) were seen. Eighteen referrals were made to CAMHS. GP interventions included watchful waiting, brief behavioural interventions, non-directive counselling, brief cognitive- behavioural therapy (CBT) and liaison with colleagues in education, CAMHS and the voluntary sector. Conclusion This clinical pilot demonstrates that with adequate time, access to supervision and practice support, children and young people experiencing emotional and behavioural problems associated with common mental health issues can be helped in primary care.

  3. ‘Can he have the test for bipolar, doctor? His dad's got it’: exploring the potential of general practitioners to work with children and young people presenting in primary care with common mental health problems – a clinical initiative

    PubMed Central

    2012-01-01

    Background General practitioners (GPs) play a key role in assessing and managing adult mental health problems, but this input is not seen in their management of child and adolescent mental health. Mental health problems in 5–19-year-olds are common, yet detection rates in primary care are low. The symptoms of most adult diagnoses of mental health problems are present by mid-adolescence, yet the typical time from onset to diagnosis is 5–15 years. The role of general practice in this area has been underexplored. Aim This pilot study explores the potential of GPs to respond to common mental health problems in children and adolescents. Design Children and young people who would have ordinarily been referred to Child and Adolescent Mental Health Services (CAMHS) were seen in a GP setting. In a UK general practice surgery serving a disadvantaged population. Method Children and young people were seen for an initial biopsychosocial assessment and formulation of the presenting concerns. GP-based interventions were offered as appropriate or referred to CAMHS. Results Data from the first 50 children (2–19 years) are presented. Twenty younger children (10 years and under) and 30 older children (11 years and above) were seen. Eighteen referrals were made to CAMHS. GP interventions included watchful waiting, brief behavioural interventions, non-directive counselling, brief cognitive– behavioural therapy (CBT) and liaison with colleagues in education, CAMHS and the voluntary sector. Conclusion This clinical pilot demonstrates that with adequate time, access to supervision and practice support, children and young people experiencing emotional and behavioural problems associated with common mental health issues can be helped in primary care. PMID:23730336

  4. Profound Morphological Changes in the Erythrocytes and Fibrin Networks of Patients with Hemochromatosis or with Hyperferritinemia, and Their Normalization by Iron Chelators and Other Agents

    PubMed Central

    Pretorius, Etheresia; Bester, Janette; Vermeulen, Natasha; Lipinski, Boguslaw; Gericke, George S.; Kell, Douglas B.

    2014-01-01

    It is well-known that individuals with increased iron levels are more prone to thrombotic diseases, mainly due to the presence of unliganded iron, and thereby the increased production of hydroxyl radicals. It is also known that erythrocytes (RBCs) may play an important role during thrombotic events. Therefore the purpose of the current study was to assess whether RBCs had an altered morphology in individuals with hereditary hemochromatosis (HH), as well as some who displayed hyperferritinemia (HF). Using scanning electron microscopy, we also assessed means by which the RBC and fibrin morphology might be normalized. An important objective was to test the hypothesis that the altered RBC morphology was due to the presence of excess unliganded iron by removing it through chelation. Very striking differences were observed, in that the erythrocytes from HH and HF individuals were distorted and had a much greater axial ratio compared to that accompanying the discoid appearance seen in the normal samples. The response to thrombin, and the appearance of a platelet-rich plasma smear, were also markedly different. These differences could largely be reversed by the iron chelator desferal and to some degree by the iron chelator clioquinol, or by the free radical trapping agents salicylate or selenite (that may themselves also be iron chelators). These findings are consistent with the view that the aberrant morphology of the HH and HF erythrocytes is caused, at least in part, by unliganded (‘free’) iron, whether derived directly via raised ferritin levels or otherwise, and that lowering it or affecting the consequences of its action may be of therapeutic benefit. The findings also bear on the question of the extent to which accepting blood donations from HH individuals may be desirable or otherwise. PMID:24416376

  5. The value of signs, symptoms and plasma heart-type fatty acid-binding protein (H-FABP) in evaluating patients presenting with symptoms possibly matching acute coronary syndrome: background and methods of a diagnostic study in primary care.

    PubMed

    Willemsen, Robert T A; Buntinx, Frank; Winkens, Bjorn; Glatz, Jan F; Dinant, Geert Jan

    2014-12-12

    Chest complaints presented to a general practitioner (GP) are frequently caused by diseases which have advantageous outcomes. However, in some cases, acute coronary syndrome (ACS) is present (1.5-22% of cases). The patient's signs, symptoms and electrocardiography results are insufficient diagnostic tools to distinguish mild disease from ACS. Therefore, most patients presenting chest complaints are referred to secondary care facilities where ACS is then ruled out in a majority of patients (78%). Recently, a point of care test for heart-type fatty acid-binding protein (H-FABP) using a low cut-off value between positive and negative of 4 ng/ml has become available. We aim to study the role of this point of care device in triage of patients presenting chest complaints possibly due to ACS, in primary care. Our research protocol is presented in this article. Results are expected in 2015. Participating GPs will register signs and symptoms in all patients presenting chest complaints possibly due to ACS. Point of care H-FABP testing will also be performed. Our study will be a derivation study to identify signs and symptoms that, combined with point of care H-FABP testing, can be part of an algorithm to either confirm or rule out ACS. The diagnostic value for ACS of this algorithm in general practice will be determined. A safe diagnostic elimination of ACS by application of the algorithm can be of significant clinical relevance. Improved triage and thus reduction of the number of patients with chest complaints without underlying ACS, that are referred to secondary care facilities, could lead to a substantial cost reduction. ClinicalTrials.gov, NCT01826994, accepted April 8th 2013.

  6. Is CDX2 immunostaining useful for delineating anorectal from penile/vulvar squamous cancer in the setting of squamous cell carcinoma with clinically unknown primary site presenting with histologically confirmed inguinal lymph node metastasis?

    PubMed

    Gunia, Sven; Koch, Stefan; May, Matthias

    2013-02-01

    Penile, vulvar and anal squamous cell carcinomas (SCCs) share histomorphological overlap and are prone to lymphatic dissemination into inguinal nodes. Anal SCCs might derive from the anorectal zone (ARZ), anal transitional zone, squamous zone or from perianal skin. These anatomically distinct zones differ in terms of their embryological development. We sought to investigate the role of caudal-related homeobox 2 (CDX2), a homeobox gene implicated in the development and anterior/posterior pattern specification from duodenum to rectum including the ARZ, in terms of narrowing the possible sites of origin to be considered in the setting of SCC with unknown primary presenting with histologically confirmed inguinal lymph node metastasis. By immunohistochemistry (IHC) employing a panel of antibodies directed against CK5/6, CK7, CK20, p63, p16, CEA and CDX2, we compared 89 penile, 11 vulvar and eight anal SCCs with respect to their staining profiles. Moreover, anal SCCs were subjected to in situ hybridisation (ISH) for high-risk human papillomavirus (HPV) subtypes. By IHC, CDX2 expression was observed in 2/8 anal SCCs (25%) while being absent from all penile and vulvar SCCs examined. High-risk HPV subtypes were detected by ISH in all anal SCCs examined, which were uniformly p16-positive by IHC. CDX2 might be valuable in terms of narrowing the possible sites of origin to be considered in the setting of SCC with unknown primary presenting with inguinal lymph node metastasis. However, despite its favourable specificity, the diagnostic benefit achieved by this observation is limited by the low sensitivity.

  7. Delivery presentations

    MedlinePlus

    ... Labor - delivery presentation; Occiput posterior; Occiput anterior; Brow presentation References Lanni SM, Gherman R, Gonik B. Malpresentations. In: Gabbe SG, Niebyl JR, Simpson JL, et al, eds. Obstetrics: Normal and Problem Pregnancies . 7th ed. Philadelphia, ...

  8. Impact of active and passive smoking as risk factors for asthma and COPD in women presenting to primary care in Syria: first report by the WHO-GARD survey group

    PubMed Central

    Mohammad, Yousser; Shaaban, Rafea; Al-Zahab, Bassam Abou; Khaltaev, Nikolai; Bousquet, Jean; Dubaybo, Basim

    2013-01-01

    Background The burden of chronic respiratory disease (CRD) is alarming. International studies suggest that women with CRD are undersurveyed and underdiagnosed by physicians worldwide. It is unclear what the prevalence of CRD is in the general population of Syria, particularly among women, since there has never been a survey on CRD in this nation. The purpose of this study was to investigate the impact of different patterns of smoking on CRD in women. Materials and methods We extracted data on smoking patterns and outcome in women from the Global Alliance Against Chronic Respiratory Diseases survey. Using spirometric measurements before and after the use of inhaled bronchodilators, we tracked the frequency of CRD in females active and passive narghile or cigarette smokers presenting to primary care. We administered the questionnaire to 788 randomly selected females seen during 1 week in the fiscal year 2009–2010 in 22 primary care centers in six different regions of Syria. Inclusion criteria were age >6 years, presenting for any medical complaint. In this cross-sectional study, three groups of female subjects were evaluated: active smokers of cigarettes, active smokers of narghiles, and passive smokers of either cigarettes or narghiles. These three groups were compared to a control group of female subjects not exposed to active or passive smoking. Results Exposure to active cigarette smoke but not narghile smoke was associated with doctor-diagnosed chronic obstructive pulmonary disease (COPD). However, neither cigarette nor narghile active smoking was associated with increased incidence of spirometrically diagnosed COPD. Paradoxically, exposure to passive smoking of either cigarettes or narghiles resulted in association with airway obstruction, defined as forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) < 70% according to the Global initiative for chronic Obstructive Lung Disease criteria; association with FEV1 < 80% predicted, evidencing

  9. A phase 1/2, dose-escalation trial of deferasirox for the treatment of iron overload in HFE-related hereditary hemochromatosis.

    PubMed

    Phatak, Pradyumna; Brissot, Pierre; Wurster, Mark; Adams, Paul C; Bonkovsky, Herbert L; Gross, John; Malfertheiner, Peter; McLaren, Gordon D; Niederau, Claus; Piperno, Alberto; Powell, Lawrie W; Russo, Mark W; Stoelzel, Ulrich; Stremmel, Wolfgang; Griffel, Louis; Lynch, Nicola; Zhang, Yiyun; Pietrangelo, Antonello

    2010-11-01

    Hereditary hemochromatosis (HH) is characterized by increased intestinal iron absorption that may result in iron overload. Although phlebotomy is widely practiced, it is poorly tolerated or contraindicated in patients with anemias, severe heart disease, or poor venous access, and compliance can vary. The once-daily, oral iron chelator, deferasirox (Exjade) may provide an alternative treatment option. Patients with HH carrying the HFE gene who were homozygous for the Cys282Tyr mutation, serum ferritin levels of 300-2000 ng/mL, transferrin saturation ≥ 45%, and no known history of cirrhosis were enrolled in this dose-escalation study to characterize the safety and efficacy of deferasirox, comprising a core and an extension phase (each 24 weeks). Forty-nine patients were enrolled and received starting deferasirox doses of 5 (n = 11), 10 (n = 15), or 15 (n = 23) mg/kg/day. Adverse events were generally dose-dependent, the most common being diarrhea, headache, and nausea (n = 18, n = 10, and n = 8 in the core and n = 1, n = 1, and n = 0 in the extension, respectively). More patients in the 15 mg/kg/day than in the 5 or 10 mg/kg/day cohorts experienced increases in alanine aminotransferase and serum creatinine levels during the 48-week treatment period; six patients had alanine aminotransferase > 3 × baseline and greater than the upper limit of normal range, and eight patients had serum creatinine > 33% above baseline and greater than upper limit of normal on two consecutive occasions. After receiving deferasirox for 48 weeks, median serum ferritin levels decreased by 63.5%, 74.8%, and 74.1% in the 5, 10, and 15 mg/kg/day cohorts, respectively. In all cohorts, median serum ferritin decreased to < 250 ng/mL. Deferasirox doses of 5, 10, and 15 mg/kg/day can reduce iron burden in patients with HH. Based on the safety and efficacy results, starting deferasirox at 10 mg/kg/day appears to be most appropriate for further study in this patient population.

  10. A Phase 1/2, Dose-Escalation Trial of Deferasirox for the Treatment of Iron Overload in HFE-Related Hereditary Hemochromatosis

    PubMed Central

    Phatak, Pradyumna; Brissot, Pierre; Wurster, Mark; Adams, Paul C; Bonkovsky, Herbert L; Gross, John; Malfertheiner, Peter; McLaren, Gordon D; Niederau, Claus; Piperno, Alberto; Powell, Lawrie W; Russo, Mark W; Stoelzel, Ulrich; Stremmel, Wolfgang; Griffel, Louis; Lynch, Nicola; Zhang, Yiyun; Pietrangelo, Antonello

    2010-01-01

    Hereditary hemochromatosis (HH) is characterized by increased intestinal iron absorption that may result in iron overload. Although phlebotomy is widely practiced, it is poorly tolerated or contraindicated in patients with anemias, severe heart disease, or poor venous access, and compliance can vary. The once-daily, oral iron chelator, deferasirox (Exjade) may provide an alternative treatment option. Patients with HH carrying the HFE gene who were homozygous for the Cys282Tyr mutation, serum ferritin levels of 300-2000 ng/mL, transferrin saturation ≥45%, and no known history of cirrhosis were enrolled in this dose-escalation study to characterize the safety and efficacy of deferasirox, comprising a core and an extension phase (each 24 weeks). Forty-nine patients were enrolled and received starting deferasirox doses of 5 (n = 11), 10 (n = 15), or 15 (n = 23) mg/kg/day. Adverse events were generally dose-dependent, the most common being diarrhea, headache, and nausea (n = 18, n = 10, and n = 8 in the core and n = 1, n = 1, and n = 0 in the extension, respectively). More patients in the 15 mg/kg/day than in the 5 or 10 mg/kg/day cohorts experienced increases in alanine aminotransferase and serum creatinine levels during the 48-week treatment period; six patients had alanine aminotransferase >3× baseline and greater than the upper limit of normal range, and eight patients had serum creatinine >33% above baseline and greater than upper limit of normal on two consecutive occasions. After receiving deferasirox for 48 weeks, median serum ferritin levels decreased by 63.5%, 74.8%, and 74.1% in the 5, 10, and 15 mg/kg/day cohorts, respectively. In all cohorts, median serum ferritin decreased to <250 ng/mL. Conclusion: Deferasirox doses of 5, 10, and 15 mg/kg/day can reduce iron burden in patients with HH. Based on the safety and efficacy results, starting deferasirox at 10 mg/kg/day appears to be most appropriate for further study in this patient population. (Hepatology

  11. Information Presentation

    NASA Technical Reports Server (NTRS)

    Holden, Kritina; Sandor, A.; Thompson, S. G.; McCann, R. S.; Kaiser, M. K.; Begault, D. R.; Adelstein, B. D.; Beutter, B. R.; Stone, L. S.

    2008-01-01

    The goal of the Information Presentation Directed Research Project (DRP) is to address design questions related to the presentation of information to the crew on flight vehicles, surface landers and habitats, and during extra-vehicular activities (EVA). Designers of displays and controls for exploration missions must be prepared to select the text formats, label styles, alarms, electronic procedure designs, and cursor control devices that provide for optimal crew performance on exploration tasks. The major areas of work, or subtasks, within the Information Presentation DRP are: 1) Controls, 2) Displays, 3) Procedures, and 4) EVA Operations.

  12. Information Presentation

    NASA Technical Reports Server (NTRS)

    Holden, Kritina L.; Thompson, Shelby G.; Sandor, Aniko; McCann, Robert S.; Kaiser, Mary K.; Adelstein, Barnard D.; Begault, Durand R.; Beutter, Brent R.; Stone, Leland S.; Godfroy, Martine

    2009-01-01

    The goal of the Information Presentation Directed Research Project (DRP) is to address design questions related to the presentation of information to the crew. In addition to addressing display design issues associated with information formatting, style, layout, and interaction, the Information Presentation DRP is also working toward understanding the effects of extreme environments encountered in space travel on information processing. Work is also in progress to refine human factors-based design tools, such as human performance modeling, that will supplement traditional design techniques and help ensure that optimal information design is accomplished in the most cost-efficient manner. The major areas of work, or subtasks, within the Information Presentation DRP for FY10 are: 1) Displays, 2) Controls, 3) Procedures and Fault Management, and 4) Human Performance Modeling. The poster will highlight completed and planned work for each subtask.

  13. Conservation Presentation.

    ERIC Educational Resources Information Center

    Friday, Gerald

    2001-01-01

    Introduces a project in which students teach about the importance of recycling and conservation by presenting demonstrations. Includes demonstrations on water, plastic, and other recycling products such as steel. (YDS)

  14. Information Presentation

    NASA Technical Reports Server (NTRS)

    Holden, K.L.; Boyer, J.L.; Sandor, A.; Thompson, S.G.; McCann, R.S.; Begault, D.R.; Adelstein, B.D.; Beutter, B.R.; Stone, L.S.

    2009-01-01

    The goal of the Information Presentation Directed Research Project (DRP) is to address design questions related to the presentation of information to the crew. The major areas of work, or subtasks, within this DRP are: 1) Displays, 2) Controls, 3) Electronic Procedures and Fault Management, and 4) Human Performance Modeling. This DRP is a collaborative effort between researchers at Johnson Space Center and Ames Research Center.

  15. Primary enzyme quantitation

    DOEpatents

    Saunders, G.C.

    1982-03-04

    The disclosure relates to the quantitation of a primary enzyme concentration by utilizing a substrate for the primary enzyme labeled with a second enzyme which is an indicator enzyme. Enzyme catalysis of the substrate occurs and results in release of the indicator enzyme in an amount directly proportional to the amount of primary enzyme present. By quantifying the free indicator enzyme one determines the amount of primary enzyme present.

  16. Risk factors for development of dementia in a unique six-year cohort study. I. An exploratory, pilot study of involvement of the E4 allele of apolipoprotein E, mutations of the hemochromatosis-HFE gene, type 2 diabetes, and stroke.

    PubMed

    Percy, Maire; Somerville, Martin J; Hicks, Mark; Garcia, Angeles; Colelli, Teresa; Wright, Emily; Kitaygorodsky, Julia; Jiang, Amy; Ho, Valerie; Parpia, Alyssa; Wong, Michael K

    2014-01-01

    Risk factors for dementia development are not well-defined. We evaluated several factors alone and in combination in a unique cohort of Caucasian volunteers over an approximately 6-year observation window using a nested case/control design. Factors included: apolipoprotein E (ApoE) gene variants (the E4 allele is the strongest confirmed genetic predisposing factor for Alzheimer's disease), the hemochromatosis-HFE gene mutations (H63D and C282Y), diabetes, and stroke. At study entry, subjects were ≥65 years of age (M ± SD = 73.0 ± 4.9), had an MMSE score ≥24, and no evidence of cerebrovascular disease or current depression. Genotyping was completed on 163 available DNA samples from three different groups at the study end: those who still had normal cognitive function; those who had developed dementia; and those with Mild Cognitive Impairment (MCI). Analyses were interpreted at the 95% confidence level without Bonferroni corrections. In the subgroup with dementia, all cases of diabetes were type 2 and present at study entry, whereas all strokes occurred during the study. The results highlight apparently synergistic interactions between genetic and medical risk factors for dementia development, gender differences in risk factors, and involvement of HFE mutations. Having E4 (i.e., either of E3/4 or E4/4), C282Y, H63D, diabetes, or stroke alone did not attain significance. Significant predisposing factors with post-hoc power ≥80% were: E4 homozygosity (E4/4)males+females, odds ratio (OR) = 56.0); E4+diabetes (males+females, OR = 13.7; E4+H63D+diabetes (females, OR = 52.0); E4+stroke (males, OR = 46.5). The importance of preventing diabetes and stroke to ward off dementia and the possible role of iron dysmetabolism in dementia are discussed.

  17. Overview Presentation

    NASA Technical Reports Server (NTRS)

    Lytle, John

    2001-01-01

    This report provides an overview presentation of the 2000 NPSS (Numerical Propulsion System Simulation) Review and Planning Meeting. Topics include: 1) a background of the program; 2) 1999 Industry Feedback; 3) FY00 Status, including resource distribution and major accomplishments; 4) FY01 Major Milestones; and 5) Future direction for the program. Specifically, simulation environment/production software and NPSS CORBA Security Development are discussed.

  18. The Diagnosis of Urinary Tract infection in Young children (DUTY): a diagnostic prospective observational study to derive and validate a clinical algorithm for the diagnosis of urinary tract infection in children presenting to primary care with an acute illness.

    PubMed

    Hay, Alastair D; Birnie, Kate; Busby, John; Delaney, Brendan; Downing, Harriet; Dudley, Jan; Durbaba, Stevo; Fletcher, Margaret; Harman, Kim; Hollingworth, William; Hood, Kerenza; Howe, Robin; Lawton, Michael; Lisles, Catherine; Little, Paul; MacGowan, Alasdair; O'Brien, Kathryn; Pickles, Timothy; Rumsby, Kate; Sterne, Jonathan Ac; Thomas-Jones, Emma; van der Voort, Judith; Waldron, Cherry-Ann; Whiting, Penny; Wootton, Mandy; Butler, Christopher C

    2016-07-01

    It is not clear which young children presenting acutely unwell to primary care should be investigated for urinary tract infection (UTI) and whether or not dipstick testing should be used to inform antibiotic treatment. To develop algorithms to accurately identify pre-school children in whom urine should be obtained; assess whether or not dipstick urinalysis provides additional diagnostic information; and model algorithm cost-effectiveness. Multicentre, prospective diagnostic cohort study. Children < 5 years old presenting to primary care with an acute illness and/or new urinary symptoms. One hundred and seven clinical characteristics (index tests) were recorded from the child's past medical history, symptoms, physical examination signs and urine dipstick test. Prior to dipstick results clinician opinion of UTI likelihood ('clinical diagnosis') and urine sampling and treatment intentions ('clinical judgement') were recorded. All index tests were measured blind to the reference standard, defined as a pure or predominant uropathogen cultured at ≥ 10(5) colony-forming units (CFU)/ml in a single research laboratory. Urine was collected by clean catch (preferred) or nappy pad. Index tests were sequentially evaluated in two groups, stratified by urine collection method: parent-reported symptoms with clinician-reported signs, and urine dipstick results. Diagnostic accuracy was quantified using area under receiver operating characteristic curve (AUROC) with 95% confidence interval (CI) and bootstrap-validated AUROC, and compared with the 'clinician diagnosis' AUROC. Decision-analytic models were used to identify optimal urine sampling strategy compared with 'clinical judgement'. A total of 7163 children were recruited, of whom 50% were female and 49% were < 2 years old. Culture results were available for 5017 (70%); 2740 children provided clean-catch samples, 94% of whom were ≥ 2 years old, with 2.2% meeting the UTI definition. Among these, 'clinical diagnosis

  19. Investigating Primary Source Literacy

    ERIC Educational Resources Information Center

    Archer, Joanne; Hanlon, Ann M.; Levine, Jennie A.

    2009-01-01

    Primary source research requires students to acquire specialized research skills. This paper presents results from a user study testing the effectiveness of a Web guide designed to convey the concepts behind "primary source literacy". The study also evaluated students' strengths and weaknesses when conducting primary source research. (Contains 3…

  20. An extensive analysis of the hereditary hemochromatosis gene HFE and neighboring histone genes: associations with childhood leukemia.

    PubMed

    Davis, Charronne F; Dorak, M Tevfik

    2010-04-01

    The most common mutation of the HFE gene C282Y has shown a risk association with childhood acute lymphoblastic leukemia (ALL) in Welsh and Scottish case-control studies. This finding has not been replicated outside Britain. Here, we present a thorough analysis of the HFE gene in a panel of HLA homozygous reference cell lines and in the original population sample from South Wales (117 childhood ALL cases and 414 newborn controls). The 21 of 24 variants analyzed were from the HFE gene region extending 52 kb from the histone gene HIST1H1C to HIST1H1T. We identified the single-nucleotide polymorphism (SNP) rs807212 as a tagging SNP for the most common HFE region haplotype, which contains wild-type alleles of all HFE variants examined. This intergenic SNP rs807212 yielded a strong male-specific protective association (per allele OR = 0.38, 95% CI = 0.22-0.64, P (trend) = 0.0002; P = 0.48 in females), which accounted for the original C282Y risk association. In the HapMap project data, rs807212 was in strong linkage disequilibrium with 25 other SNPs spanning 151 kb around HFE. Minor alleles of these 26 SNPs characterized the most common haplotype for the HFE region, which lacked all disease-associated HFE variants. The HapMap data suggested positive selection in this region even in populations where the HFE C282Y mutation is absent. These results have implications for the sex-specific associations observed in this region and suggest the inclusion of rs807212 in future studies of the HFE gene and the extended HLA class I region.

  1. The CHICO (Children's Cough) Trial protocol: a feasibility randomised controlled trial investigating the clinical and cost-effectiveness of a complex intervention to improve the management of children presenting to primary care with acute respiratory tract infection.

    PubMed

    Turnbull, Sophie L; Redmond, Niamh M; Lucas, Patricia; Cabral, Christie; Ingram, Jenny; Hollinghurst, Sandra; Hay, Alastair D; Peters, Tim J; Horwood, Jeremy; Little, Paul; Francis, Nick; Blair, Peter S

    2015-09-15

    While most respiratory tract infections (RTIs) will resolve without treatment, many children will receive antibiotics and some will develop severe symptoms requiring hospitalisation. There have been calls for evidence to reduce uncertainty regarding the identification of children who will and will not benefit from antibiotics. The aim of this feasibility trial is to test recruitment and the acceptance of a complex behavioural intervention designed to reduce antibiotic prescribing, and to inform how best to conduct a larger trial. The CHICO (Children's Cough) trial is a single-centre feasibility cluster randomised controlled trial (RCT) comparing a web-based, within-consultation, behavioural intervention with usual care for children presenting to general practitioner practices with RTI and acute cough. The trial aims to recruit at least 300 children between October 2014 and April 2015, in a single area in South West England. Following informed consent, demographic information will be recorded, and symptoms and signs measured. Parents/carers of recruited children will be followed up on a weekly basis to establish symptom duration, resource use and cost of the illness to the parent until the child's cough has resolved or up to 8 weeks, whichever occurs earlier. A review of medical notes, including clinical history, primary care reconsultations and hospitalisations will be undertaken 2 months after recruitment. The trial feasibility will be assessed by: determining acceptability of the intervention to clinicians and parent/carers; quantifying differential recruitment and follow-up; determining intervention fidelity; the success in gathering the data necessary to conduct a cost-effectiveness analysis; and collecting data about antibiotic prescribing rates to inform the sample size needed for a fully powered RCT. The study was approved by the North West-Haydock Research Ethics Committee, UK (reference number: 14/NW/1034). The findings from this feasibility trial will

  2. The Diagnosis of Urinary Tract infection in Young children (DUTY): a diagnostic prospective observational study to derive and validate a clinical algorithm for the diagnosis of urinary tract infection in children presenting to primary care with an acute illness.

    PubMed Central

    Hay, Alastair D; Birnie, Kate; Busby, John; Delaney, Brendan; Downing, Harriet; Dudley, Jan; Durbaba, Stevo; Fletcher, Margaret; Harman, Kim; Hollingworth, William; Hood, Kerenza; Howe, Robin; Lawton, Michael; Lisles, Catherine; Little, Paul; MacGowan, Alasdair; O'Brien, Kathryn; Pickles, Timothy; Rumsby, Kate; Sterne, Jonathan Ac; Thomas-Jones, Emma; van der Voort, Judith; Waldron, Cherry-Ann; Whiting, Penny; Wootton, Mandy; Butler, Christopher C

    2016-01-01

    BACKGROUND It is not clear which young children presenting acutely unwell to primary care should be investigated for urinary tract infection (UTI) and whether or not dipstick testing should be used to inform antibiotic treatment. OBJECTIVES To develop algorithms to accurately identify pre-school children in whom urine should be obtained; assess whether or not dipstick urinalysis provides additional diagnostic information; and model algorithm cost-effectiveness. DESIGN Multicentre, prospective diagnostic cohort study. SETTING AND PARTICIPANTS Children < 5 years old presenting to primary care with an acute illness and/or new urinary symptoms. METHODS One hundred and seven clinical characteristics (index tests) were recorded from the child's past medical history, symptoms, physical examination signs and urine dipstick test. Prior to dipstick results clinician opinion of UTI likelihood ('clinical diagnosis') and urine sampling and treatment intentions ('clinical judgement') were recorded. All index tests were measured blind to the reference standard, defined as a pure or predominant uropathogen cultured at ≥ 10(5) colony-forming units (CFU)/ml in a single research laboratory. Urine was collected by clean catch (preferred) or nappy pad. Index tests were sequentially evaluated in two groups, stratified by urine collection method: parent-reported symptoms with clinician-reported signs, and urine dipstick results. Diagnostic accuracy was quantified using area under receiver operating characteristic curve (AUROC) with 95% confidence interval (CI) and bootstrap-validated AUROC, and compared with the 'clinician diagnosis' AUROC. Decision-analytic models were used to identify optimal urine sampling strategy compared with 'clinical judgement'. RESULTS A total of 7163 children were recruited, of whom 50% were female and 49% were < 2 years old. Culture results were available for 5017 (70%); 2740 children provided clean-catch samples, 94% of whom were ≥ 2 years old

  3. Primary Intra-aortic Epstein-Barr Virus-Positive Large B-Cell Lymphoma Presenting as Aortic Mural Thrombosis: An Entity Distinct From Intravascular Large B-Cell Lymphoma.

    PubMed

    Nakao, Ryuta; Sakashita, Aki; Omoto, Atsushi; Sato, Osamu; Hino, Yoko; Yanagisawa, Akio; Urata, Yoji

    2017-12-01

    Intravascular selective growth of neoplastic B lymphocytes is a characteristic finding of intravascular large B-cell lymphoma (IVLBCL). However, because neoplastic B cells of IVLBCL grow merely in the lumina of capillaries or small vessels, primary IVLBCL of the great vessels is considered exceptional. To our knowledge, only 2 primary B-cell lymphomas in the lumina of the vena cava have been reported. However, there has been no report of primary B-cell lymphoma with intra-aortic growth. We describe a novel manifestation of primary Epstein-Barr virus-positive large B-cell lymphoma mainly affecting the lumina of the aorta and its major branches in a 76-year-old man. He had a long-term fever that was refractory to antibiotics and aortic mural thrombosis with visceral embolization. Because he had no detectable mass suggesting a malignancy, it was difficult to diagnose while he was alive. He died without anticancer treatment, and the confirmed diagnosis was made at autopsy.

  4. Genetics Home Reference: hereditary hemochromatosis

    MedlinePlus

    ... of sex hormones is evident. Females usually begin menstruation in a normal manner, but menses stop after ... in an autosomal recessive pattern , which means both copies of the gene in each cell have mutations. ...

  5. Hyperthyroidism (primary)

    PubMed Central

    2008-01-01

    Introduction Hyperthyroidism is characterised by high levels of serum thyroxine and triiodothyronine, and low levels of thyroid-stimulating hormone. The main causes of hyperthyroidism are Graves' disease, toxic multinodular goitre, and toxic adenoma. About 20 times more women than men have hyperthyroidism. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments for primary hyperthyroidism? What are the effects of surgical treatments for primary hyperthyroidism? What are the effects of treatments for subclinical hyperthyroidism? We searched: Medline, Embase, The Cochrane Library and other important databases up to June 2007 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 14 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: adding thyroxine to antithyroid drugs (carbimazole, propylthiouracil, and thiamazole), antithyroid drugs (carbimazole, propylthiouracil, and thiamazole), radioactive iodine, and thyroidectomy. PMID:19450325

  6. Hyperthyroidism (primary)

    PubMed Central

    2010-01-01

    Introduction Hyperthyroidism is characterised by high levels of serum thyroxine and triiodothyronine, and low levels of thyroid-stimulating hormone. The main causes of hyperthyroidism are Graves' disease, toxic multinodular goitre, and toxic adenoma. About 20 times more women than men have hyperthyroidism. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments for primary hyperthyroidism? What are the effects of surgical treatments for primary hyperthyroidism? What are the effects of treatments for subclinical hyperthyroidism? We searched: Medline, Embase, The Cochrane Library, and other important databases up to February 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 15 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: adding thyroxine to antithyroid drugs (carbimazole, propylthiouracil, and thiamazole), antithyroid drugs (carbimazole, propylthiouracil, and thiamazole), radioactive iodine, and thyroidectomy. PMID:21418670

  7. Primary amyloidosis

    MedlinePlus

    Amyloidosis - primary; Immunoglobulin light chain amyloidosis ... The cause of primary amyloidosis is not well understood. Genes may play a role. The condition is related to abnormal and excess production of proteins. ...

  8. HFE gene mutations in patients with primary iron overload: is there a significant improvement in molecular diagnosis yield with HFE sequencing?

    PubMed

    Santos, Paulo C J L; Pereira, Alexandre C; Cançado, Rodolfo D; Schettert, Isolmar T; Sobreira, Tiago J P; Oliveira, Paulo S L; Hirata, Rosario D C; Hirata, Mario H; Figueiredo, Maria Stella; Chiattone, Carlos S; Krieger, Jose E; Guerra-Shinohara, Elvira M

    2010-12-15

    Rare HFE variants have been shown to be associated with hereditary hemochromatosis (HH), an iron overload disease. The low frequency of the HFE p.C282Y mutation in HH-affected Brazilian patients may suggest that other HFE-related mutations may also be implicated in the pathogenesis of HH in this population. The main aim was to screen for new HFE mutations in Brazilian individuals with primary iron overload and to investigate their relationship with HH. Fifty Brazilian patients with primary iron overload (transferrin saturation>50% in females and 60% in males) were selected. Subsequent bidirectional sequencing for each HFE exon was performed. The effect of HFE mutations on protein structure were analyzed by molecular dynamics simulation and free binding energy calculations. p.C282Y in homozygosis or in heterozygosis with p.H63D were the most frequent genotypic combinations associated with HH in our sample population (present in 17 individuals, 34%). Thirty-six (72.0%) out of the 50 individuals presented at least one HFE mutation. The most frequent genotype associated with HH was the homozygous p.C282Y mutation (n=11, 22.0%). One novel mutation (p.V256I) was indentified in heterozygosis with the p.H63D mutation. In silico modeling analysis of protein behavior indicated that the p.V256I mutation does not reduce the binding affinity between HFE and β2-microglobulin (β2M) in the same way the p.C282Y mutation does compared with the native HFE protein. In conclusion, screening of HFE through direct sequencing, as compared to p.C282Y/p.H63D genotyping, was not able to increase the molecular diagnosis yield of HH. The novel p.V256I mutation could not be implicated in the molecular basis of the HH phenotype, although its role cannot be completely excluded in HH-phenotype development. Our molecular modeling analysis can help in the analysis of novel, previously undescribed, HFE mutations. Copyright © 2010 Elsevier Inc. All rights reserved.

  9. Longer survival associated with HLA-A*03, B*14 among 212 hemochromatosis probands with HFE C282Y homozygosity and HLA-A and -B typing and haplotyping.

    PubMed

    Barton, James C; Barton, J Clayborn; Acton, Ronald T

    2010-11-01

    Human leukocyte antigen (HLA) haplotypes may influence iron phenotypes in patients with HFE hemochromatosis and could affect survival. We tabulated general characteristics of HLA-A and -B types and haplotypes of HFE C282Y/C282Y probands diagnosed in medical care and analyzed these data to identify HLA survival modifiers. There were 212 probands (130 men, 82 women). Mean follow-up was 12.0 ± 6.4 yr (0.1-41.2 yr; 34 deaths). HLA-A*03 was more prevalent in men (76.9% vs. 61.0% women; P = 0.0129); 35.4% of men and 29.3% of women had A*03, B*07; and 7.7% of men and 8.5% of women had A*03, B*14. Twenty-three probands had cirrhosis; none had A*03, B*14. Positivity for A*03 or A*03, B*07 was not a significant predictor or modifier of survival. In multiple regression analyses, A*03, B*14 predicted longer survival (P = 0.0004). Kaplan-Meier analysis confirmed longer survival in probands with A*03, B*14 (P = 0.0199, log-rank test). After excluding the 23 non-A*03, B*14 probands with cirrhosis, survival of probands with A*03, B*14 was still greater than that of probands without A*03, B*14 (P = 0.0254; log-rank test). Twenty-four years after diagnosis, cumulative survival of probands with and without A*03, B*14 was 100% and 58%, respectively. The percentage of deaths due to iron overload was lower in probands with A*03, B*14 (0% vs. 21.9%; P = 0.0392). In hemochromatosis probands with HFE C282Y/C282Y, survival was longer in those with HLA-A*03, B*14. Earlier age at diagnosis and less severe iron overload in probands with A*03, B*14 could explain this difference. © 2010 John Wiley & Sons A/S.

  10. Primary Macroglobulinemia

    PubMed Central

    Edwards, A. M.; Costopoulous, L. B.; Bell, H. E.

    1964-01-01

    Clinical features presented by a patient with primary macroglobulinemia over a four-year period included cachexia, weight loss, bleeding tendency, anemia, lymphadenopathy, hepatosplenomegaly and recurrent pulmonary bacterial infections. Immunoelectrophoresis demonstrated the presence of a β2 macroglobulin which, on ultracentrifugation, was found to have a sedimentation constant of 14.9 S20, w; this macroglobulin constituted over 40% of the total serum protein. Postmortem findings included the typical “naked” lymphocyte infiltration of the reticuloendothelial system, with septic embolization from a terminal Gram-negative bacteremia, associated with a mesenteric vascular occlusion. A feature of particular interest was the antemortem appearance of gas in the portal venous system, shown on two abdominal scout radiographs taken one and two hours before death. The diagnostic significance of this rare radiologic sign is discussed. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8Fig. 9Fig. 10Fig. 11Fig. 12Fig. 13Fig. 14Fig. 15 PMID:14226112

  11. Sarcoidosis Presenting Addison's Disease.

    PubMed

    Takahashi, Kentaro; Kagami, Shin-Ichiro; Kawashima, Hirotoshi; Kashiwakuma, Daisuke; Suzuki, Yoshio; Iwamoto, Itsuo

    2016-01-01

    We herein describe a second Japanese case of sarcoidosis presenting Addison's disease. A 52-year-old man was diagnosed with sarcoidosis based on clinical and laboratory findings, including bilateral hilar lymphadenopathy and elevated levels of serum angiotensin-converting enzyme and lysozyme, as well as the presence of noncaseating epithelioid granulomas. The patient also exhibited general fatigue, pigmentation, weight loss, hypotension and hyponatremia, suggestive of chronic adrenocortical insufficiency. An endocrine examination confirmed primary adrenocortical insufficiency. This case suggests the direct involvement of sarcoid granuloma in the adrenal glands.

  12. Inside the Primary Classroom.

    ERIC Educational Resources Information Center

    Simon, Brian

    1980-01-01

    Presents some of the findings of the ORACLE research program (Observational Research and Classroom Learning Evaluation), a detailed observational study of teacher-student interaction, teaching styles, and management methods within a sample of primary classrooms. (Editor/SJL)

  13. Primary syphilis (image)

    MedlinePlus

    Syphilis is a sexually transmitted disease caused by the bacterium Treponema pallidum . Primary syphilis presents as a small painless open sore 3 to 6 weeks after exposure. Although the lesion heals within 6 ...

  14. Primary Myelofibrosis

    MedlinePlus

    ... are described below. Chronic myeloproliferative neoplasms sometimes become acute leukemia , in which too many abnormal white blood ... higher. Patients also have an increased risk of acute myeloid leukemia or primary myelofibrosis . Symptoms of polycythemia ...

  15. PRImary care Streptococcal Management (PRISM) study: identifying clinical variables associated with Lancefield group A β-haemolytic streptococci and Lancefield non-Group A streptococcal throat infections from two cohorts of patients presenting with an acute sore throat.

    PubMed

    Little, Paul; Moore, Michael; Hobbs, F D R; Mant, David; McNulty, Cliodna; Williamson, Ian; Cheng, Edith; Stuart, Beth; Kelly, Joanne; Barnett, Jane; Mullee, Mark

    2013-10-25

    To assess the association between features of acute sore throat and the growth of streptococci from culturing a throat swab. Diagnostic cohort. UK general practices. Patients aged 5 or over presenting with an acute sore throat. Patients were recruited for a second cohort (cohort 2, n=517) consecutively after the first (cohort 1, n=606) from similar practices. Predictors of the presence of Lancefield A/C/G streptococci. The clinical score developed from cohort 1 had poor discrimination in cohort 2 (bootstrapped estimate of area under the receiver operator characteristic (ROC) curve (0.65), due to the poor validity of the individual items in the second data set. Variables significant in multivariate analysis in both cohorts were rapid attendance (prior duration 3 days or less; multivariate adjusted OR 1.92 cohort, 1.67 cohort 2); fever in the last 24 h (1.69, 2.40); and doctor assessment of severity (severely inflamed pharynx/tonsils (2.28, 2.29)). The absence of coryza or cough and purulent tonsils were significant in univariate analysis in both cohorts and in multivariate analysis in one cohort. A five-item score based on Fever, Purulence, Attend rapidly (3 days or less), severely Inflamed tonsils and No cough or coryza (FeverPAIN) had moderate predictive value (bootstrapped area under the ROC curve 0.73 cohort 1, 0.71 cohort 2) and identified a substantial number of participants at low risk of streptococcal infection (38% in cohort 1, 36% in cohort 2 scored ≤1, associated with a streptococcal percentage of 13% and 18%, respectively). A Centor score of ≤1 identified 23% and 26% of participants with streptococcal percentages of 10% and 28%, respectively. Items widely used to help identify streptococcal sore throat may not be the most consistent. A modified clinical scoring system (FeverPAIN) which requires further validation may be clinically helpful in identifying individuals who are unlikely to have major pathogenic streptococci.

  16. PRImary care Streptococcal Management (PRISM) study: identifying clinical variables associated with Lancefield group A β-haemolytic streptococci and Lancefield non-Group A streptococcal throat infections from two cohorts of patients presenting with an acute sore throat

    PubMed Central

    Little, Paul; Moore, Michael; Hobbs, F D R; Mant, David; McNulty, Cliodna; Williamson, Ian; Cheng, Edith; Stuart, Beth; Kelly, Joanne; Barnett, Jane; Mullee, Mark

    2013-01-01

    Objective To assess the association between features of acute sore throat and the growth of streptococci from culturing a throat swab. Design Diagnostic cohort. Setting UK general practices. Participants Patients aged 5 or over presenting with an acute sore throat. Patients were recruited for a second cohort (cohort 2, n=517) consecutively after the first (cohort 1, n=606) from similar practices. Main outcome Predictors of the presence of Lancefield A/C/G streptococci. Results The clinical score developed from cohort 1 had poor discrimination in cohort 2 (bootstrapped estimate of area under the receiver operator characteristic (ROC) curve (0.65), due to the poor validity of the individual items in the second data set. Variables significant in multivariate analysis in both cohorts were rapid attendance (prior duration 3 days or less; multivariate adjusted OR 1.92 cohort, 1.67 cohort 2); fever in the last 24 h (1.69, 2.40); and doctor assessment of severity (severely inflamed pharynx/tonsils (2.28, 2.29)). The absence of coryza or cough and purulent tonsils were significant in univariate analysis in both cohorts and in multivariate analysis in one cohort. A five-item score based on Fever, Purulence, Attend rapidly (3 days or less), severely Inflamed tonsils and No cough or coryza (FeverPAIN) had moderate predictive value (bootstrapped area under the ROC curve 0.73 cohort 1, 0.71 cohort 2) and identified a substantial number of participants at low risk of streptococcal infection (38% in cohort 1, 36% in cohort 2 scored ≤1, associated with a streptococcal percentage of 13% and 18%, respectively). A Centor score of ≤1 identified 23% and 26% of participants with streptococcal percentages of 10% and 28%, respectively. Conclusions Items widely used to help identify streptococcal sore throat may not be the most consistent. A modified clinical scoring system (FeverPAIN) which requires further validation may be clinically helpful in identifying individuals who are

  17. Primary acquired cold urticaria.

    PubMed

    Lee, Chyh-Woei; Sheffer, Albert L

    2003-01-01

    Primary acquired cold urticaria (ACU) is the most common type of cold urticaria characterized by rapid onset of pruritic hives, swelling, and possible severe systemic reactions including hypotension and shock after cold exposure. Primary ACU is diagnosed by history of such symptoms, a positive immediate cold-contact stimulation test, and negative laboratory evaluation for underlying systemic disorders. Clinicians should be aware that patients with ACU may be susceptible to life-threatening systemic reactions especially during aquatic activities and that proper patient education is extremely important. This article reviews the clinical presentation, pathogenesis, diagnosis, and management of primary ACU.

  18. Primary intestinal lymphangiectasia.

    PubMed

    Suresh, N; Ganesh, R; Sankar, Janani; Sathiyasekaran, Malathi

    2009-10-01

    Primary intestinal lymphangiectasia (PIL) is a rare disease of intestinal lymphatics presenting with hypoproteinemia, bilateral lower limb edema, ascites, and protein losing enteropathy. We report a series of 4 children from Chennai, India presenting with anasarca, recurrent diarrhea, hypoproteinemia and confirmatory features of PIL on endoscopy and histopathology.

  19. Common founder effects of hereditary hemochromatosis, Wilson´s disease, the long QT syndrome and autosomal recessive deafness caused by two novel mutations in the WHRN and TMC1 genes.

    PubMed

    Olsson, K Sigvard; Wålinder, Olof; Jansson, Ulf; Wilbe, Maria; Bondeson, Marie-Louise; Stattin, Eva-Lena; Raha-Chowdhury, Ruma; Williams, Roger

    2017-01-01

    Genealogy and molecular genetic studies of a Swedish river valley population resulted in a large pedigree, showing that the hereditary hemochromatosis (HH) HFE/p. C282Y mutation is inherited with other recessive disorders such as Wilson´s disease (WND), a rare recessive disorder of copper overload. The population also contain individuals with the Swedish long QT syndrome (LQTS1) founder mutation ( KCNQ1 /p.Y111C) which in homozygotes causes the Jervell & Lange Nielsen syndrome (JLNS) and hearing loss (HL).Aims of the study were to test whether the Swedish long QT founder mutation originated in an ancestral HFE family and if carriers had an increased risk for hemochromatosis (HH), a treatable disorder. We also aimed to identify the pathogenic mutation causing the hearing loss disorder segregating in the pedigree. LQTS patients were asked about their ancestry and possible origin in a HH family. They were also offered a predictive testing for the HFE genotype. Church books were screened for families with hearing loss. One HH family had two members with hearing loss, who underwent molecular genetic analysis of the LQTS founder mutation, connexin 26 and thereafter exome sequencing. Another family with hearing loss in repeat generations was also analyzed for connexin 26 and underwent exome sequencing. Of nine LQTS patients studied, four carried a HFE mutation (two p.C282Y, two p.H63D), none was homozygous. Three LQTS patients confirmed origin in a female founder ( b 1694, identical to AJ b 1694, a HFE pedigree member from the Fax river. Her descent of 44 HH families, included also 29 families with hearing loss (HL) suggesting JLNS. Eleven LQTS probands confirmed origin in a second founder couple (b 1614/1605) in which the woman b 1605 was identical to a HFE pedigree member from the Fjällsjö river. In her descent there were not only 64 HH, six WND families, one JLNS, but also 48 hearing loss families. Most hearing loss was non syndromic and caused by founder effects of

  20. Sample-to-SNP kit: a reliable, easy and fast tool for the detection of HFE p.H63D and p.C282Y variations associated to hereditary hemochromatosis.

    PubMed

    Nielsen, Peter B; Petersen, Maja S; Ystaas, Viviana; Andersen, Rolf V; Hansen, Karin M; Blaabjerg, Vibeke; Refstrup, Mette

    2012-10-01

    Classical hereditary hemochromatosis involves the HFE-gene and diagnostic analysis of the DNA variants HFE p.C282Y (c.845G>A; rs1800562) and HFE p.H63D (c.187C>G; rs1799945). The affected protein alters the iron homeostasis resulting in iron overload in various tissues. The aim of this study was to validate the TaqMan-based Sample-to-SNP protocol for the analysis of the HFE-p.C282Y and p.H63D variants with regard to accuracy, usefulness and reproducibility compared to an existing SNP protocol. The Sample-to-SNP protocol uses an approach where the DNA template is made accessible from a cell lysate followed by TaqMan analysis. Besides the HFE-SNPs other eight SNPs were used as well. These SNPs were: Coagulation factor II-gene F2 c.20210G>A, Coagulation factor V-gene F5 p.R506Q (c.1517G>A; rs121917732), Mitochondria SNP: mt7028 G>A, Mitochondria SNP: mt12308 A>G, Proprotein convertase subtilisin/kexin type 9-gene PCSK9 p.R46L (c.137G>T), Plutathione S-transferase pi 1-gene GSTP1 p.I105V (c313A>G; rs1695), LXR g.-171 A>G, ZNF202 g.-118 G>T. In conclusion the Sample-to-SNP kit proved to be an accurate, reliable, robust, easy to use and rapid TaqMan-based SNP detection protocol, which could be quickly implemented in a routine diagnostic or research facility. Copyright © 2012. Published by Elsevier B.V.

  1. Urinalysis: case presentations for the primary care physician.

    PubMed

    Sharp, Victoria J; Lee, Daniel K; Askeland, Eric J

    2014-10-15

    Urinalysis is useful in diagnosing systemic and genitourinary conditions. In patients with suspected microscopic hematuria, urine dipstick testing may suggest the presence of blood, but results should be confirmed with a microscopic examination. In the absence of obvious causes, the evaluation of microscopic hematuria should include renal function testing, urinary tract imaging, and cystoscopy. In a patient with a ureteral stent, urinalysis alone cannot establish the diagnosis of urinary tract infection. Plain radiography of the kidneys, ureters, and bladder can identify a stent and is preferred over computed tomography. Asymptomatic bacteriuria is the isolation of bacteria in an appropriately collected urine specimen obtained from a person without symptoms of a urinary tract infection. Treatment of asymptomatic bacteriuria is not recommended in nonpregnant adults, including those with prolonged urinary catheter use.

  2. Rare Presentation of a Primary Cutaneous well Differentiated Liposarcoma

    DTIC Science & Technology

    2018-02-16

    Roberts, Capt Jared 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 59th Clinical Research Division 1100 Willford Hall Loop, Bldg 4430 JBSA-Lackland...TX 78236-9908 210-292-7141 9. SPONSORING/MONITORING AGENCY NAME(S) AND ADDRESS(ES) 59th Clinical Research Division 1100 Willford Hall Loop, Bldg...been proposed to aid in identifying lipoblasts. Lipoblasts should have a hyperchromatic indented or sharply scalloped nucleus, a lipid -rich droplets

  3. - 174 G>C IL-6 polymorphism and primary iron overload in male patients.

    PubMed

    Tetzlaff, Walter F; Meroño, Tomás; Botta, Eliana E; Martín, Maximiliano E; Sorroche, Patricia B; Boero, Laura E; Castro, Marcelo; Frechtel, Gustavo D; Rey, Jorge; Daruich, Jorge; Cerrone, Gloria E; Brites, Fernando

    2018-04-14

    Primary iron overload (IO) is commonly associated with mutations in the hereditary hemochromatosis gene (HFE). Nonetheless, other genetic variants may influence the development of IO beyond HFE mutations. There is a single nucleotide polymorphism (SNP) at - 174 G>C of the interleukin (IL)-6 gene which might be associated with primary IO. Our aim was to study the association between the SNP - 174 G>C gene promoter of IL-6 and primary IO in middle-aged male patients. We studied 37 men with primary IO diagnosed by liver histology. Controls were age-matched male volunteers (n = 37). HFE mutations and the SNP - 174 G>C gene promoter of IL-6 were evaluated by PCR-RFLP. Logistic regression was used to evaluate the association between primary IO and SNP - 174 G>C gene promoter of IL-6. Patients and control subjects were in Hardy-Weinberg equilibrium for the SNP - 174 G>C gene promoter of IL-6 (p = 0.17). Significantly different genotype frequencies were observed between patients (43% CC, 43% CG, and 14% GG) and control subjects (10% CC, 41% CG, and 49% GG) (OR = 4.09, 95% CI = 2.06-8.13; p < 0.0001). The multiple logistic regression analysis showed that IO was significantly associated with CC homozygosis in the SNP - 174 G>C gene promoter of IL-6 (OR = 6.3, 95% CI = 1.9-21.4; p < 0.005) in a model adjusted by age and body mass index. In conclusion, CC homozygosis in the SNP - 174 G>C gene promoter of IL-6 can be proposed as one of the gene variants influencing iron accumulation in male adults with HFE mutations. Studies in larger cohorts are warranted.

  4. Refining Presentation Documents with Presentation Schema

    ERIC Educational Resources Information Center

    Obara, Yuki; Kashihara, Akihiro

    2017-01-01

    Presentation is one of the important activities in research to publish research results. When we create presentation documents (P-documents for short), it is important to compose presentation structure (P-structure for short) that represents what to present and how to sequence the contents. To create proper P-documents, we need to learn how to…

  5. STS-69 postflight presentation

    NASA Astrophysics Data System (ADS)

    1995-10-01

    A postflight conference of the STS-69 mission is presented. The flightcrew ('The Dog Team') consisted of Cmdr. David Walker, Pilot Kenneth Cockrell, Payload Cmdr. James Voss, and Mission Specialists James Newman and Michael Gernhardt. The mission's primary objective was the deployment and retrieval of the SPARTAN-201 satellite, which investigated the interaction between the Sun and it's solar wind. Other secondary experiments and shuttle payloads included the Wake Shield Facility (WSF), which grew several layers of semiconductor films, the International Extreme Ultraviolet Hitchhiker (IEH-1), the Capillary Pumped Loop-2/Gas Bridge Assembly (CAPL-2/GBA), several Get Away Specials (GAS) experiments, the Electrolysis Performance Improvement Concept Study (EPICS), the Thermal Energy Storage (TES-2) experiment, the Commercial Generic Bioprocessing Apparatus-7 (CGBA-7), the National Institutes of Health-Cells 4 (NIH-C4) experiment, and the Biological Research in Canister-6 (BRIC-6) experiment. Earth views consisted of Saudi Arabia water wells, uncommon vortices over Oman, the Amazon River, the Bahamas, Somalia, a sunset over the Earth's horizon, and two hurricanes, Luis and Marilyn.

  6. Primary Hyperoxaluria

    PubMed Central

    Harambat, Jérôme; Fargue, Sonia; Bacchetta, Justine; Acquaviva, Cécile; Cochat, Pierre

    2011-01-01

    Primary hyperoxalurias (PH) are inborn errors in the metabolism of glyoxylate and oxalate. PH type 1, the most common form, is an autosomal recessive disorder caused by a deficiency of the liver-specific enzyme alanine, glyoxylate aminotransferase (AGT) resulting in overproduction and excessive urinary excretion of oxalate. Recurrent urolithiasis and nephrocalcinosis are the hallmarks of the disease. As glomerular filtration rate decreases due to progressive renal damage, oxalate accumulates leading to systemic oxalosis. Diagnosis is often delayed and is based on clinical and sonographic findings, urinary oxalate assessment, DNA analysis, and, if necessary, direct AGT activity measurement in liver biopsy tissue. Early initiation of conservative treatment, including high fluid intake, inhibitors of calcium oxalate crystallization, and pyridoxine in responsive cases, can help to maintain renal function in compliant subjects. In end-stage renal disease patients, the best outcomes have been achieved with combined liver-kidney transplantation which corrects the enzyme defect. PMID:21748001

  7. Primary utilization of birch

    Treesearch

    Henry W. Saunders

    1969-01-01

    From an industry point-of-view, procurement of raw material and primary manufacture present problems today and challenges for tomorrow. So that you may become more familiar with the white birch industry and more specifically with Saunders Brothers, I will briefly explain some of the products we manufacture and some of the methods we use to make them. In some ways, we...

  8. Writing for Primary Science

    ERIC Educational Resources Information Center

    Mawby, Tara, Ed.

    2011-01-01

    In this article, two short pieces are presented to show educators just what a good article and a good review could have in them. This article has been written for the purpose of illustrating a good example, but is also representative of the type of content the editors encourage in "Primary Science": practical and active, with images. They also…

  9. Lymphocyte gene expression signatures from patients and mouse models of hereditary hemochromatosis reveal a function of HFE as a negative regulator of CD8+ T-lymphocyte activation and differentiation in vivo.

    PubMed

    Costa, Mónica; Cruz, Eugénia; Oliveira, Susana; Benes, Vladimir; Ivacevic, Tomi; Silva, Maria João; Vieira, Inês; Dias, Francisco; Fonseca, Sónia; Gonçalves, Marta; Lima, Margarida; Leitão, Catarina; Muckenthaler, Martina U; Pinto, Jorge; Porto, Graça

    2015-01-01

    Abnormally low CD8+ T-lymphocyte numbers is characteristic of some patients with hereditary hemochromatosis (HH), a MHC-linked disorder of iron overload. Both environmental and genetic components are known to influence CD8+ T-lymphocyte homeostasis but the role of the HH associated protein HFE is still insufficiently understood. Genome-wide expression profiling was performed in peripheral blood CD8+ T lymphocytes from HH patients selected according to CD8+ T-lymphocyte numbers and from Hfe-/- mice maintained either under normal or high iron diet conditions. In addition, T-lymphocyte apoptosis and cell cycle progression were analyzed by flow cytometry in HH patients. HH patients with low CD8+ T-lymphocyte numbers show a differential expression of genes related to lymphocyte differentiation and maturation namely CCR7, LEF1, ACTN1, NAA50, P2RY8 and FOSL2, whose expression correlates with the relative proportions of naïve, central and effector memory subsets. In addition, expression levels of LEF1 and P2RY8 in memory cells as well as the proportions of CD8+ T cells in G2/M cell cycle phase are significantly different in HH patients compared to controls. Hfe-/- mice do not show alterations in CD8+ T-lymphocyte numbers but differential gene response patterns. We found an increased expression of S100a8 and S100a9 that is most pronounced in high iron diet conditions. Similarly, CD8+ T lymphocytes from HH patients display higher S100a9 expression both at the mRNA and protein level. Altogether, our results support a role for HFE as a negative regulator of CD8+ T-lymphocyte activation. While the activation markers S100a8 and S100a9 are strongly increased in CD8+ T cells from both, Hfe-/- mice and HH patients, a differential profile of genes related to differentiation/maturation of CD8+ T memory cells is evident in HH patients only. This supports the notion that HFE contributes, at least in part, to the generation of low peripheral blood CD8+ T lymphocytes in HH.

  10. Lymphocyte Gene Expression Signatures from Patients and Mouse Models of Hereditary Hemochromatosis Reveal a Function of HFE as a Negative Regulator of CD8+ T-Lymphocyte Activation and Differentiation In Vivo

    PubMed Central

    Costa, Mónica; Cruz, Eugénia; Oliveira, Susana; Benes, Vladimir; Ivacevic, Tomi; Silva, Maria João; Vieira, Inês; Dias, Francisco; Fonseca, Sónia; Gonçalves, Marta; Lima, Margarida; Leitão, Catarina; Muckenthaler, Martina U.; Pinto, Jorge; Porto, Graça

    2015-01-01

    Abnormally low CD8+ T-lymphocyte numbers is characteristic of some patients with hereditary hemochromatosis (HH), a MHC-linked disorder of iron overload. Both environmental and genetic components are known to influence CD8+ T-lymphocyte homeostasis but the role of the HH associated protein HFE is still insufficiently understood. Genome-wide expression profiling was performed in peripheral blood CD8+ T lymphocytes from HH patients selected according to CD8+ T-lymphocyte numbers and from Hfe -/- mice maintained either under normal or high iron diet conditions. In addition, T-lymphocyte apoptosis and cell cycle progression were analyzed by flow cytometry in HH patients. HH patients with low CD8+ T-lymphocyte numbers show a differential expression of genes related to lymphocyte differentiation and maturation namely CCR7, LEF1, ACTN1, NAA50, P2RY8 and FOSL2, whose expression correlates with the relative proportions of naïve, central and effector memory subsets. In addition, expression levels of LEF1 and P2RY8 in memory cells as well as the proportions of CD8+ T cells in G2/M cell cycle phase are significantly different in HH patients compared to controls. Hfe -/- mice do not show alterations in CD8+ T-lymphocyte numbers but differential gene response patterns. We found an increased expression of S100a8 and S100a9 that is most pronounced in high iron diet conditions. Similarly, CD8+ T lymphocytes from HH patients display higher S100a9 expression both at the mRNA and protein level. Altogether, our results support a role for HFE as a negative regulator of CD8+ T-lymphocyte activation. While the activation markers S100a8 and S100a9 are strongly increased in CD8+ T cells from both, Hfe -/- mice and HH patients, a differential profile of genes related to differentiation/maturation of CD8+ T memory cells is evident in HH patients only. This supports the notion that HFE contributes, at least in part, to the generation of low peripheral blood CD8+ T lymphocytes in HH. PMID

  11. Penetrance of Hemochromatosis in HFE Genotypes Resulting in p.Cys282Tyr and p.[Cys282Tyr];[His63Asp] in the eMERGE Network

    PubMed Central

    Gallego, Carlos J.; Burt, Amber; Sundaresan, Agnes S.; Ye, Zi; Shaw, Christopher; Crosslin, David R.; Crane, Paul K.; Fullerton, S. Malia; Hansen, Kris; Carrell, David; Kuivaniemi, Helena; Derr, Kimberly; de Andrade, Mariza; McCarty, Catherine A.; Kitchner, Terrie E.; Ragon, Brittany K.; Stallings, Sarah C.; Papa, Gabriella; Bochenek, Joseph; Smith, Maureen E.; Aufox, Sharon A.; Pacheco, Jennifer A.; Patel, Vaibhav; Friesema, Elisha M.; Erwin, Angelika Ludtke; Gottesman, Omri; Gerhard, Glenn S.; Ritchie, Marylyn; Motulsky, Arno G.; Kullo, Iftikhar J.; Larson, Eric B.; Tromp, Gerard; Brilliant, Murray H.; Bottinger, Erwin; Denny, Joshua C.; Roden, Dan M.; Williams, Marc S.; Jarvik, Gail P.

    2015-01-01

    Hereditary hemochromatosis (HH) is a common autosomal-recessive disorder associated with pathogenic HFE variants, most commonly those resulting in p.Cys282Tyr and p.His63Asp. Recommendations on returning incidental findings of HFE variants in individuals undergoing genome-scale sequencing should be informed by penetrance estimates of HH in unselected samples. We used the eMERGE Network, a multicenter cohort with genotype data linked to electronic medical records, to estimate the diagnostic rate and clinical penetrance of HH in 98 individuals homozygous for the variant coding for HFE p.Cys282Tyr and 397 compound heterozygotes with variants resulting in p.[His63Asp];[Cys282Tyr]. The diagnostic rate of HH in males was 24.4% for p.Cys282Tyr homozygotes and 3.5% for compound heterozygotes (p < 0.001); in females, it was 14.0% for p.Cys282Tyr homozygotes and 2.3% for compound heterozygotes (p < 0.001). Only males showed differences across genotypes in transferrin saturation levels (100% of homozygotes versus 37.5% of compound heterozygotes with transferrin saturation > 50%; p = 0.003), serum ferritin levels (77.8% versus 33.3% with serum ferritin > 300 ng/ml; p = 0.006), and diabetes (44.7% versus 28.0%; p = 0.03). No differences were found in the prevalence of heart disease, arthritis, or liver disease, except for the rate of liver biopsy (10.9% versus 1.8% [p = 0.013] in males; 9.1% versus 2% [p = 0.035] in females). Given the higher rate of HH diagnosis than in prior studies, the high penetrance of iron overload, and the frequency of at-risk genotypes, in addition to other suggested actionable adult-onset genetic conditions, opportunistic screening should be considered for p.[Cys282Tyr];[Cys282Tyr] individuals with existing genomic data. PMID:26365338

  12. Spectrophotometry: Past and Present

    NASA Astrophysics Data System (ADS)

    Adelman, Saul J.

    2009-01-01

    I describe the rise of optical region spectrophotometry in the 1960's and 1970's when it achieved a status as a major tool in stellar research through its decline and near demise at present. With absolutely calibrated fluxes and Balmer profiles usually of H-gamma, astronomers used model atmospheres predictions to find both the effective temperatures and surface gravities of many stars. Spectrophotometry as I knew it was photometrically calibrated low dispersion spectroscopy with a typical resolution of order 25 A. A typical data set consists of 10 to 15 values covering most of the optical spectral region. The strengths and shortcomings of the rotating grating scanners are discussed. The accomplishments achieved using spectrophotometric data, which were obtained with instruments using photomultipliers, are reviewed. Extensions to other spectral regions are noted and attempts to use observations from space to calibrate the optical region will be discussed. There are two steps to fully calibrate flux data. The first requires the calibration of the fluxes of one or more standard stars against sources calibrated absolutely in a laboratory. The use of Vega as the primary standard has been both a blessing as it is so bright and a curse especially as modeling it correctly requires treating it as a fast rotating star seen nearly pole-on. At best its calibration has errors of about 1%. The other step is to apply extinction corrections for the Earth's atmosphere and then calibrate the fluxes using the fluxes of standard stars. Now the ASTRA Spectrophotometer promises a revitalization of the use and availability of optical flux data. Its design specifications included solutions to the problems of past optical spectrophotometric instruments.

  13. Spirometry in primary care

    PubMed Central

    Coates, Allan L; Graham, Brian L; McFadden, Robin G; McParland, Colm; Moosa, Dilshad; Provencher, Steeve; Road, Jeremy

    2013-01-01

    Canadian Thoracic Society (CTS) clinical guidelines for asthma and chronic obstructive pulmonary disease (COPD) specify that spirometry should be used to diagnose these diseases. Given the burden of asthma and COPD, most people with these diseases will be diagnosed in the primary care setting. The present CTS position statement was developed to provide guidance on key factors affecting the quality of spirometry testing in the primary care setting. The present statement may also be used to inform and guide the accreditation process for spirometry in each province. Although many of the principles discussed are equally applicable to pulmonary function laboratories and interpretation of tests by respirologists, they are held to a higher standard and are outside the scope of the present statement. PMID:23457669

  14. Primary explosives

    DOEpatents

    Hiskey, Michael A [Los Alamos, NM; Huynh, My Hang V [Los Alamos, NM

    2011-01-25

    The present invention provides a compound of the formula (Cat).sup.+.sub.z[M.sup.++(5-nitro-1H-tetrazolato-N2).sup.-.sub.x(H.sub.2- O).sub.y] where x is 3 or 4, y is 2 or 3, x+y is 6, z is 1 or 2, and M.sup.++ is selected from the group consisting of iron, cobalt, nickel, copper, zinc, chromium, and manganese, and (Cat).sup.+ is selected from the group consisting of ammonium, sodium, potassium, rubidium and cesium. A method of preparing the compound of that formula is also disclosed.

  15. Primary explosives

    DOEpatents

    Hiskey, Michael A [Los Alamos, NM; Huynh, My Hang V [Los Alamos, NM

    2009-03-03

    The present invention provides a compound of the formula (Cat).sup.+.sub.z[M.sup.++(5-nitro-1H-tetrazolato-N2).sup.-.sub.x(H.sub.2- O).sub.y] where x is 3 or 4, y is 2 or 3, x+y is 6, z is 1 or 2, and M.sup.++ is selected from the group consisting of iron, cobalt, nickel, copper, zinc, chromium, and manganese, and (Cat).sup.+ is selected from the group consisting of ammonium, sodium, potassium, rubidium and cesium. A method of preparing the compound of that formula is also disclosed.

  16. Addison's disease presenting with muscle spasm.

    PubMed

    Bhattacharjee, Rana; Sharma, A; Rays, A; Thakur, I; Sarkar, D; Mandal, B; Mookerjee, S K; Chatterjee, S K; Chowdhury, Pradip Roy

    2013-09-01

    Primary hypoadrenalism has various causes and protean manifestation. We report a young female patient who presented with severe muscle spasm as her primary complaint. On evaluation she was found to be a case of Addison's disease secondary to adrenal tuberculosis. Her muscle spasm disappeared rapidly with replacement dose of glucocorticoid.

  17. Malignant presentation of uterine lymphangioleiomyomatosis.

    PubMed

    Szpurek, Dariusz; Szubert, Sebastian; Zielinski, Pawel; Frankowski, Andrzej; Sajdak, Stefan; Moszynski, Rafal

    2015-10-01

    The main aim of this case report was to present the method of diagnosis, management, and the 12-year-follow-up of a patient diagnosed with primary uterine lymphangioleiomyomatosis (LAM). A 47-year-old woman was admitted to the Department of Thoracosurgery due to pulmonary lesions suspected to be metastatic. The potential primary site of the neoplasm was not identified by previous imaging studies and specialist counseling. The patient had a history of total abdominal hysterectomy without ovaries due to a uterine tumor recognized as cellular leiomyoma and left salpingo-oophorectomy due to a solid ovarian tumor also recognized as leiomyoma. She had previously undergone the removal of a left kidney angiomyolipoma. After histopathological examination of the pulmonary lesions and repeated evaluation of the ovarian and uterine tumors, the diagnosis of primary uterine LAM with metastases to the ovary and the lungs was established. Although new metastatic lesions occurred, the patient remained in good condition during the 12-year-follow-up. The history of our patient and review of the literature suggest that although uterine LAM presents malignant features (i.e., metastasis), the disease is long lasting and the patient can be in good condition for a number of years. Copyright © 2015. Published by Elsevier B.V.

  18. Tularaemia presenting as parapharyngeal abscess: case presentation.

    PubMed

    Koc, S; Gürbüzler, L; Yaman, H; Eyibilen, A; Salman, N; Ekici, A

    2012-05-01

    We report an extremely rare case of the oropharyngeal form of tularaemia, causing a parapharyngeal abscess. A 48-year-old woman presented with fever, sore throat, breathing difficulty and a right-sided neck swelling. This mass had previously been treated with penicillin without response, and had already been surgically drained once in another hospital. On physical examination, the tonsils were exudative and hypertrophic and the pharynx was hyperaemic. A fluctuant, 4 × 4 cm mass was seen on endoscopic examination, originating from the left parapharyngeal area and protruding towards the pyriform sinus, and partly obstructing the airway. Microagglutination test antibody titres for Francisella tularensis were positive (1/1280). The patient healed completely after definitive drainage of the abscess and antimicrobial therapy for 14 days (streptomycin, 2 × 1 g intramuscularly). Tularaemia should be considered in the differential diagnosis of patients presenting with tonsillopharyngitis, cervical lymphadenitis and parapharyngeal abscess who do not respond to treatment with penicillin, even if they do not live in an endemic region.

  19. Subpart RR Training Presentations

    EPA Pesticide Factsheets

    EPA has produced the following training presentation(s) for reporters subject to this subpart. Generally, these presentations explain the rule or show how to use the reporting system e-GGRT to submit annual GHG reports to EPA.

  20. Subpart D Training Presentations

    EPA Pesticide Factsheets

    EPA has produced the following training presentation(s) for reporters subject to this subpart. Generally, these presentations explain the rule or show how to use the reporting system e-GGRT to submit annual GHG reports to EPA.

  1. Subpart C Training Presentations

    EPA Pesticide Factsheets

    EPA has produced the following training presentation(s) for reporters subject to this subpart. Generally, these presentations explain the rule or show how to use the reporting system e-GGRT to submit annual GHG reports to EPA.

  2. Subpart X Training Presentations

    EPA Pesticide Factsheets

    EPA has produced the following training presentation(s) for reporters subject to this subpart. Generally, these presentations explain the rule or show how to use the reporting system e-GGRT to submit annual GHG reports to EPA.

  3. Subpart Y Training Presentations

    EPA Pesticide Factsheets

    EPA has produced the following training presentation(s) for reporters subject to this subpart. Generally, these presentations explain the rule or show how to use the reporting system e-GGRT to submit annual GHG reports to EPA.

  4. Subpart P Training Presentations

    EPA Pesticide Factsheets

    EPA has produced the following training presentation(s) for reporters subject to this subpart. Generally, these presentations explain the rule or show how to use the reporting system e-GGRT to submit annual GHG reports to EPA.

  5. Subpart T Training Presentations

    EPA Pesticide Factsheets

    EPA has produced the following training presentation(s) for reporters subject to this subpart. Generally, these presentations explain the rule or show how to use the reporting system e-GGRT to submit annual GHG reports to EPA.

  6. Subpart A Training Presentations

    EPA Pesticide Factsheets

    EPA has produced the following training presentation(s) for reporters subject to this subpart. Generally, these presentations explain the rule or show how to use the reporting system e-GGRT to submit annual GHG reports to EPA.

  7. Subpart QQ Training Presentations

    EPA Pesticide Factsheets

    EPA has produced the following training presentation(s) for reporters subject to this subpart. Generally, these presentations explain the rule or show how to use the reporting system e-GGRT to submit annual GHG reports to EPA.

  8. Subpart OO Training Presentations

    EPA Pesticide Factsheets

    EPA has produced the following training presentation(s) for reporters subject to this subpart. Generally, these presentations explain the rule or show how to use the reporting system e-GGRT to submit annual GHG reports to EPA.

  9. Subpart Q Training Presentations

    EPA Pesticide Factsheets

    EPA has produced the following training presentation(s) for reporters subject to this subpart. Generally, these presentations explain the rule or show how to use the reporting system e-GGRT to submit annual GHG reports to EPA.

  10. Subpart L Training Presentations

    EPA Pesticide Factsheets

    EPA has produced the following training presentation(s) for reporters subject to this subpart. Generally, these presentations explain the rule or show how to use the reporting system e-GGRT to submit annual GHG reports to EPA.

  11. Subpart AA Training Presentations

    EPA Pesticide Factsheets

    EPA has produced the following training presentation(s) for reporters subject to this subpart. Generally, these presentations explain how to use the reporting system e-GGRT to submit annual GHG reports to EPA.

  12. Subpart W Training Presentations

    EPA Pesticide Factsheets

    EPA has produced the following training presentation(s) for reporters subject to this subpart. Generally, these presentations explain the rule or show how to use the reporting system e-GGRT to submit annual GHG reports to EPA.

  13. Subpart HH Training Presentations

    EPA Pesticide Factsheets

    EPA has produced the following training presentation(s) for reporters subject to this subpart. Generally, these presentations explain the rule or show how to use the reporting system e-GGRT to submit annual GHG reports to EPA.

  14. Subpart TT Training Presentations

    EPA Pesticide Factsheets

    EPA has produced the following training presentation(s) for reporters subject to this subpart. Generally, these presentations explain the rule or show how to use the reporting system e-GGRT to submit annual GHG reports to EPA.

  15. Subpart UU Training Presentations

    EPA Pesticide Factsheets

    EPA has produced the following training presentation(s) for reporters subject to this subpart. Generally, these presentations explain the rule or show how to use the reporting system e-GGRT to submit annual GHG reports to EPA.

  16. Subpart V Training Presentations

    EPA Pesticide Factsheets

    EPA has produced the following training presentation(s) for reporters subject to this subpart. Generally, these presentations explain the rule or show how to use the reporting system e-GGRT to submit annual GHG reports to EPA.

  17. Subpart Z Training Presentations

    EPA Pesticide Factsheets

    EPA has produced the following training presentation(s) for reporters subject to this subpart. Generally, these presentations explain the rule or show how to use the reporting system e-GGRT to submit annual GHG reports to EPA.

  18. Subpart DD Training Presentations

    EPA Pesticide Factsheets

    EPA has produced the following training presentation(s) for reporters subject to this subpart. Generally, these presentations explain the rule or show how to use the reporting system e-GGRT to submit annual GHG reports to EPA.

  19. Subpart N Training Presentations

    EPA Pesticide Factsheets

    EPA has produced the following training presentation(s) for reporters subject to this subpart. Generally, these presentations explain the rule or show how to use the reporting system e-GGRT to submit annual GHG reports to EPA.

  20. Subpart PP Training Presentations

    EPA Pesticide Factsheets

    EPA has produced the following training presentation(s) for reporters subject to this subpart. Generally, these presentations explain the rule or show how to use the reporting system e-GGRT to submit annual GHG reports to EPA.

  1. Subpart MM Training Presentations

    EPA Pesticide Factsheets

    EPA has produced the following training presentation(s) for reporters subject to this subpart. Generally, these presentations explain the rule or show how to use the reporting system e-GGRT to submit annual GHG reports to EPA.

  2. Subpart S Training Presentations

    EPA Pesticide Factsheets

    EPA has produced the following training presentation(s) for reporters subject to this subpart. Generally, these presentations explain the rule or show how to use the reporting system e-GGRT to submit annual GHG reports to EPA.

  3. Subpart G Training Presentations

    EPA Pesticide Factsheets

    EPA has produced the following training presentation(s) for reporters subject to this subpart. Generally, these presentations explain the rule or show how to use the reporting system e-GGRT to submit annual GHG reports to EPA.

  4. Subpart SS Training Presentations

    EPA Pesticide Factsheets

    EPA has produced the following training presentation(s) for reporters subject to this subpart. Generally, these presentations explain the rule or show how to use the reporting system e-GGRT to submit annual GHG reports to EPA.

  5. Subpart NN Training Presentations

    EPA Pesticide Factsheets

    EPA has produced the following training presentation(s) for reporters subject to this subpart. Generally, these presentations explain the rule or show how to use the reporting system e-GGRT to submit annual GHG reports to EPA.

  6. Subpart FF Training Presentations

    EPA Pesticide Factsheets

    EPA has produced the following training presentation(s) for reporters subject to this subpart. Generally, these presentations explain the rule or show how to use the reporting system e-GGRT to submit annual GHG reports to EPA.

  7. Subpart I Training Presentations

    EPA Pesticide Factsheets

    EPA has produced the following training presentation(s) for reporters subject to this subpart. Generally, these presentations explain the rule or show how to use the reporting system e-GGRT to submit annual GHG reports to EPA.

  8. Subpart II Training Presentations

    EPA Pesticide Factsheets

    EPA has produced the following training presentation(s) for reporters subject to this subpart. Generally, these presentations explain the rule or show how to use the reporting system e-GGRT to submit annual GHG reports to EPA.

  9. Subpart H Training Presentations

    EPA Pesticide Factsheets

    EPA has produced the following training presentation(s) for reporters subject to this subpart. Generally, these presentations explain the rule or show how to use the reporting system e-GGRT to submit annual GHG reports to EPA.

  10. Serum ferritin concentrations and body iron stores in a multicenter, multiethnic primary-care population

    PubMed Central

    Gordeuk, Victor R.; Reboussin, David M.; McLaren, Christine E.; Barton, James C.; Acton, Ronald T.; McLaren, Gordon D.; Harris, Emily L.; Reiss, Jacob A.; Adams, Paul C.; Speechley, Mark; Phatak, Pradyumna D.; Sholinsky, Phyliss; Eckfeldt, John H.; Chen, Wen-Pin; Passmore, Leah; Dawkins, Fitzroy W.

    2013-01-01

    How often elevated serum ferritin in primary-care patients reflects increased iron stores (normally 0.8 g in men, 0.4 g in women) is not known. The Hereditary Hemochromatosis and Iron Overload Screening (HEIRS) study screened 101,168 primary-care participants (44% Caucasians, 27% African-Americans, 14% Asians/Pacific Islanders, 13% Hispanics, 2% others). Follow-up clinical evaluation was performed in 302 of 333 HFE C282Y homozygotes regardless of iron measures and 1,375 of 1,920 nonhomozygotes with serum ferritin >300 μg/L (men), >200 μg/L (women) and transferrin saturation >50% (men), >45% (women). Quantitative phlebotomy was conducted in 122 of 175 C282Y homozygotes and 122 of 1,102 nonhomozygotes with non-transfusional serum ferritin elevation at evaluation. The estimated prevalence in the Caucasian population of C282Y homozygotes with serum ferritin >900 μg/L at evaluation was 20 per 10,000 men and 4 per 10,000 women; this constellation was predictive of iron stores >4 g in men and >2 g in women. The estimated prevalence per 10,000 of non-C282Y homozygotes with serum ferritin >900 μg/L at evaluation was 7 among Caucasians, 13 among Hispanics, 20 among African Americans, and 38 among Asians and Pacific Islanders, and this constellation was predictive of iron stores >2 g but <4 g. In conclusion, serum ferritin >900 μg/L after initial elevations of both serum ferritin and transferrin saturation is predictive of mildly increased iron stores in multiple ethnic populations regardless of HFE genotype. Serum ferritin >900 μg/L in male C282Y homozygotes is predictive of moderately increased iron stores. PMID:18429050

  11. Renewable Electricity Futures (Presentation)

    SciTech Connect

    Mai, T.

    2012-08-01

    This presentation summarizes findings of NREL's Renewable Electricity Futures study, published in June 2012. RE Futures investigated the challenges and impacts of achieving very high renewable electricity generation levels in the contiguous United States by 2050. This presentation was presented in a Wind Powering America webinar on August 15, 2012 and is now available through the Wind Powering America website.

  12. Make Your Presentation Powerful

    ERIC Educational Resources Information Center

    Palmer, Erik

    2015-01-01

    "I was planning on doing a lot of work today during your presentation, but I couldn't get anything done. I just had to pay attention!" The author received this unexpected feedback from a teacher at the end of a presentation he gave, and although he considered it a compliment, it made him reflect on the dire state of presentations in…

  13. Presenting Food Science Effectively

    ERIC Educational Resources Information Center

    Winter, Carl K.

    2016-01-01

    While the need to present food science information effectively is viewed as a critical competency for food scientists by the Institute of Food Technologists, most food scientists may not receive adequate training in this area. Effective presentations combine both scientific content and delivery mechanisms that demonstrate presenter enthusiasm for…

  14. Rotating Poster Presentations

    ERIC Educational Resources Information Center

    Lagares, Manuel; Reisenleutner, Sandra

    2017-01-01

    Oral presentations are a common practice in foreign language classes, often used to assess students' speaking skills. Usually, the presentations are delivered by students in front of the class, often with PowerPoint slides or Prezi as support. However, frequently the audience does not engage with the presentation and thus, the benefits of this…

  15. Presentation skills for nurses.

    PubMed

    Foulkes, Mark

    2015-02-20

    This article emphasises the importance of effective presentation skills. Such skills allow nurses to share knowledge and expertise and to communicate clearly in a range of workplace scenarios. Nurses are increasingly being asked to present in formal and informal situations, such as conferences, poster presentations, job interviews, case reports and ward-based teaching. This article explores the principles underpinning the development of these skills, discusses the situations in which they could be applied and demonstrates how nurses might improve and develop as presenters.

  16. The Primary Teacher's Survival Guide.

    ERIC Educational Resources Information Center

    Heyda, Pamela A.

    This guide for primary school teachers presents commonly asked questions and answers. Chapter 1, "How Do I Set Up My Classroom?" discusses desk and furniture arrangement. Chapter 2, "How Do I Survive the First Days of School?" offers tips for meeting and greeting students, establishing routines, and presenting activities.…

  17. Renewable Electricity Futures (Presentation)

    SciTech Connect

    Hand, M. M.

    2012-08-01

    This presentation library summarizes findings of NREL's Renewable Electricity Futures study, published in June 2012. RE Futures investigated the challenges and impacts of achieving very high renewable electricity generation levels in the contiguous United States by 2050. It was presented in a webinar given by the California Energy Commission.

  18. Renewable Electricity Futures (Presentation)

    SciTech Connect

    Mai, T.

    2012-08-01

    This presentation summarizes findings of NREL's Renewable Electricity Futures study, published in June 2012. RE Futures investigated the challenges and impacts of achieving very high renewable electricity generation levels in the contiguous United States by 2050. It was presented in a Power Systems Engineering Research Center webinar on September 4, 2012.

  19. Renewable Electricity Futures (Presentation)

    SciTech Connect

    Hand, M.; Mai, T.

    2012-08-01

    This presentation library summarizes findings of NREL's Renewable Electricity Futures study, published in June 2012. RE Futures investigated the challenges and impacts of achieving very high renewable electricity generation levels in the contiguous United States by 2050. It was presented in an Union of Concerned Scientists webinar on June 12, 2012.

  20. Renewable Electricity Futures (Presentation)

    SciTech Connect

    Hand, M.

    2012-10-01

    This presentation library summarizes findings of NREL's Renewable Electricity Futures study, published in June 2012. RE Futures investigated the challenges and impacts of achieving very high renewable electricity generation levels in the contiguous United States by 2050. It is being presented at the Utility Variable-Generation Integration Group Fall Technical Workshop on October 24, 2012.

  1. The Upside of Presentism

    ERIC Educational Resources Information Center

    Fendler, Lynn

    2008-01-01

    Presentism is generally regarded as a necessary evil in historiography. This paper explores the upside of that inevitability. Using a philosophical approach to discourse analysis in the tradition of new cultural history, the paper distinguishes between a strategic use of presentism on the one hand, and a rationalistic approach to history on the…

  2. Unusual presentation of sunburn.

    PubMed

    Verma, Gopalkrishna G; Dave, Dhaval; Byrne, Eileen

    2008-10-01

    We present three cases of sunburn to the head, presenting with oedema of the face in children aged 6, 9 and 13 years. Oedema was predominantly on the forehead and temporal region; a direct effect of gravity was associated with erythema of the scalp. Sunburn healed without any complications.

  3. Making Presentations. ERIC Topical Bibliography and Commentary.

    ERIC Educational Resources Information Center

    Smith, Carl B., Ed.

    This topical bibliography and commentary consists of research summaries which address the challenges of creating an effective public presentation. The research articles discussed in the bibliography/commentary are geared toward teaching students to better present information with an emphasis on the primary importance of content above empty…

  4. Reactivated Moraxella osteitis presenting as granulomatous disease.

    PubMed

    Sendi, P; Meier, R; Sonderegger, B; Bonel, H M; Schäfer, S C; Vögelin, E

    2014-11-01

    Granulomatous infections are commonly associated with mycobacteria, brucellosis, actinomycosis, nocardiosis, spirochetes, and fungi. Rarely, granuloma formation is a host response to other bacterial infection. Osteomyelitis and osteitis that reactivate many years after the primary episode is a known phenomenon. A reactivation that presents as a granulomatous disease is rare. We present a case of reactivated osteitis due to Moraxella osloensis with consecutive granuloma formation.

  5. Primary obstructive megaureter.

    PubMed

    Sripathi, V; King, P A; Thomson, M R; Bogle, M S

    1991-07-01

    Twenty-three children with primary obstructive megaureters presented between 1978 and 1988 to the Princess Margaret Hospital for Children in Perth. Twenty-eight ureters were treated. Urinary infections were the presenting feature in 14 children. The obstructive segment was transvesically excised. Histopathologic examination of the distal, intramural ureter showed fibromuscular disarray with a relative increase in fibrous tissue and reduction of musculature in all specimens. Twenty-two ureters were tapered by excision and all 28 were reimplanted using an antireflux technique. Seventeen children were followed for an average of 3 years. Seven children showed renal growth, reduction in ureteric size by greater than 2 cm, improvement in glomerular filtration rate by more than 10%, no obstruction on reflux, and no infections in postoperative period. Four children showed all the above but suffered one or more infections after the operation. Of the remaining 6 children, 3 had postoperative obstruction and 3 had vesicoureteric reflux.

  6. [Chronic daily headache: clinical presentation].

    PubMed

    Krymchantowski, A V; Moreira Filho, P F

    2000-06-01

    Chronic daily headache (CDH) represents a group of any headache disorder that occurs on a daily or near daily basis, for longer than 6 months. Even though it is a common problem, it is not a well defined disorder, resulting in controversies regarding its identification, description and approach. Three hundred patients, 232 women and 68 men, ages 16 to 86 (mean 38 years old for the women and 42 for the men), attending a headache center and fulfilling the proposed criteria for CDH (Silberstein et al.) and presenting headache 28 days per month were retrospectively studied. The clinical features allowed the primary headache diagnosis, before the transformation into daily presentation as: transformed migraine (TM ) in 271 patients (90,3%), chronic tension-type headache (CTTH) in 26 patients (8,7%) and new daily persistent headache (NDPH) in 3 patients (1%). Among the TM patients, the most observed presentation was pressure or tightening, bilateral fronto-temporal, moderate non-continuous headache, with a progressive onset. The association with nausea and phonophobia was demonstrated in 60% and 32% of the patients respectively. The association with photophobia and sleep disturbances, as well as the occurrence of intermittent headache attacks, was different among male and female patients. With regard to the CTTH patients, pressure or tightening, bilateral fronto-temporal, moderate non-continuous headache, with sleep disturbances and no associated symptoms, was the predominant presentation.

  7. Renewable Electricity Futures (Presentation)

    SciTech Connect

    Mai, T.

    2012-11-01

    This presentation summarizes findings of NREL's Renewable Electricity Futures study, published in June 2012. RE Futures investigated the challenges and impacts of achieving very high renewable electricity generation levels in the contiguous United States by 2050.

  8. Renewable Electricity Futures (Presentation)

    SciTech Connect

    Hand, M. M.

    2012-09-01

    This presentation summarizes findings of NREL's Renewable Electricity Futures study, published in June 2012. RE Futures investigated the challenges and impacts of achieving very high renewable electricity generation levels in the contiguous United States by 2050.

  9. Renewable Electricity Futures (Presentation)

    SciTech Connect

    Mai, T.

    2013-04-01

    This presentation summarizes findings of NREL's Renewable Electricity Futures study, published in June 2012. RE Futures investigated the challenges and impacts of achieving very high renewable electricity generation levels in the contiguous United States by 2050.

  10. Renewable Electricity Futures (Presentation)

    SciTech Connect

    Mai, T.

    2012-10-01

    This presentation library summarizes findings of NREL's Renewable Electricity Futures study, published in June 2012. RE Futures investigated the challenges and impacts of achieving very high renewable electricity generation levels in the contiguous United States by 2050.

  11. UTM Weather Presentation

    NASA Technical Reports Server (NTRS)

    Chan, William N.; Kopardekar, Parimal H.; Carmichael, Bruce; Cornman, Larry

    2017-01-01

    Presentation highlighting how weather affected UAS operations during the UTM field tests. Research to develop UAS weather translation models with a description of current and future work for UTM weather.

  12. Recorded ICR Overview Presentations

    EPA Pesticide Factsheets

    This presentation provides a brief overview of the applicability of the EPA’s Plywood and Composite Wood Products Information Collection Request, or “ICR,” for facilities that produce kiln‐dried lumber.

  13. Renewable Electricity Futures (Presentation)

    SciTech Connect

    Hand, M. M.

    2012-08-01

    This presentation library summarizes findings of NREL's Renewable Electricity Futures study, published in June 2012. RE Futures investigated the challenges and impacts of achieving very high renewable electricity generation levels in the contiguous United States by 2050. It was presented to the 2012 Western Conference of Public Service Commissioners, during their June, 2012, meeting. The Western Conference of Public Service Commissioners is a regional association within the National Association of Regulatory Utility Commissioners (NARUC).

  14. Blade Testing Trends (Presentation)

    SciTech Connect

    Desmond, M.

    2014-08-01

    As an invited guest speaker, Michael Desmond presented on NREL's NWTC structural testing methods and capabilities at the 2014 Sandia Blade Workshop held on August 26-28, 2014 in Albuquerque, NM. Although dynamometer and field testing capabilities were mentioned, the presentation focused primarily on wind turbine blade testing, including descriptions and capabilities for accredited certification testing, historical methodology and technology deployment, and current research and development activities.

  15. Stellar Presentations (Abstract)

    NASA Astrophysics Data System (ADS)

    Young, D.

    2015-12-01

    (Abstract only) The AAVSO is in the process of expanding its education, outreach and speakers bureau program. powerpoint presentations prepared for specific target audiences such as AAVSO members, educators, students, the general public, and Science Olympiad teams, coaches, event supervisors, and state directors will be available online for members to use. The presentations range from specific and general content relating to stellar evolution and variable stars to specific activities for a workshop environment. A presentation—even with a general topic—that works for high school students will not work for educators, Science Olympiad teams, or the general public. Each audience is unique and requires a different approach. The current environment necessitates presentations that are captivating for a younger generation that is embedded in a highly visual and sound-bite world of social media, twitter and U-Tube, and mobile devices. For educators, presentations and workshops for themselves and their students must support the Next Generation Science Standards (NGSS), the Common Core Content Standards, and the Science Technology, Engineering and Mathematics (STEM) initiative. Current best practices for developing relevant and engaging powerpoint presentations to deliver information to a variety of targeted audiences will be presented along with several examples.

  16. The Coming Primary Care Revolution.

    PubMed

    Ellner, Andrew L; Phillips, Russell S

    2017-04-01

    The United States has the most expensive, technologically advanced, and sub-specialized healthcare system in the world, yet it has worse population health status than any other high-income country. Rising healthcare costs, high rates of waste, the continued trend towards chronic non-communica