WorldWideScience

Sample records for hereditary gastrointestinal polyposis

  1. Gastrointestinal polyposis in Cowden disease

    Kullnig, P.; Steiner, H.; Porsch, G.; Smolle, J.

    1987-01-01

    A case of Cowden disease (multiple hamartoma syndrome) with marked gastrointestinal polyposis is presented. The differential diagnosis of gastrointestinal polyposis syndromes is discussed. (orig.) [de

  2. Recurrent gastrointestinal hemorrhage in treatment with dasatinib in a patient showing SMAD4 mutation with acute lymphoblastic leukemia Philadelphia positive and juvenile polyposis hereditary hemorrhagic telangiectasia syndrome

    Chiara Sartor

    2013-07-01

    Full Text Available We report a case of a patient affected by juvenile polyposis and hereditary hemorrhagic telangiectasia linked to a SMAD4 mutation who developed acute lymphoblastic leukemia positive for the Philadelphia chromosome translocation and with a complex karyotype. During the treatment with the tyrosine kinase inhibitor dasatinib the patient presented recurrent severe gastrointestinal hemorrhages linked to the genetic background and aggravated by thrombocytopenia.

  3. Multiple lymphomatous polyposis of the gastrointestinal tract

    Maria Isete Fares Franco

    Full Text Available CONTEXT: Gastrointestinal multiple lymphomatous polyposis is a rare type of malignant lymphoma that has aggressive biological behavior, early systemic dissemination and poor prognosis. It is considered to be a manifestation of non-Hodgkin lymphoma and represents the gastrointestinal counterpart of mantle cell nodal lymphoma. OBJECTIVE: A case of gastrointestinal multiple lymphomatous polyposis is presented and the anatomopathological, clinical, diagnostic and treatment aspects of this unusual neoplasia are discussed. CASE REPORT: The patient was a 59-year-old white male with a complaint of asthenia, night sweating, alteration in intestinal habit and weight loss over the preceding two months. The physical examination showed pallid mucosa and a palpable mass in the epigastrium and mesogastrium. Endoscopy of the upper digestive tract showed the presence of gastric and duodenal polyps. An opaque enema showed multiple polypoid lesions, especially in the cecum. A rectal biopsy revealed infiltration of the mucosa and submucosa by diffuse lymphoma consisting of small cleaved cells. Immunohistochemical study showed lymphocytes that expressed the antibody CD20 (L-26 and light-chain kappa (k immunoglobulin, but not light-chain lambda (l immunoglobulin. The patient presented a condition of acute intestinal obstruction with the presence of a mesenteric mass formed by agglutinated lymph nodes that surrounded the proximal ileum, thereby obstructing its lumen. He was submitted to a segmental enterectomy and gastrotomy with excisional biopsies of the gastric polypoid lesions. After two cycles of chemotherapy there was a worsening of the general state, with an increase in the dimensions of the abdominal masses and sepsis, accompanied by progressive respiratory insufficiency, leading to death.

  4. Hereditary non-polyposis colorectal cancer : Identification of mutation carriers and assessing pathogenicity of mutations

    Niessen, RC; Sijmons, RH; Berends, MJW; Ou, J; Hofstra, RNW; Kleibeuker, JH

    2004-01-01

    Hereditary non-polyposis colorectal cancer (HNPCC), also referred to as Lynch syndrome, is an autosomal dominantly inherited disorder that is characterized by susceptibility to colorectal cancer and extracolonic malignancies, in particular endometrial cancer. HNPCC is caused by pathogenic mutations

  5. The tumour spectrum in hereditary non-polyposis colorectal cancer: a study of 24 kindreds in the Netherlands

    Vasen, H. F.; Offerhaus, G. J.; den Hartog Jager, F. C.; Menko, F. H.; Nagengast, F. M.; Griffioen, G.; van Hogezand, R. B.; Heintz, A. P.

    1990-01-01

    The hereditary colonic cancer syndrome without polyposis, hereditary non-polyposis colorectal cancer (HNPCC), is usually divided into 2 main categories: hereditary site-specific colorectal cancer (Lynch syndrome I) and colorectal cancer in association with other forms of cancer (Lynch syndrome II).

  6. Copy Number Variation in Hereditary Non-Polyposis Colorectal Cancer

    Garry N. Hannan

    2013-09-01

    Full Text Available Hereditary non-polyposis colorectal cancer (HNPCC is the commonest form of inherited colorectal cancer (CRC predisposition and by definition describes families which conform to the Amsterdam Criteria or reiterations thereof. In ~50% of patients adhering to the Amsterdam criteria germline variants are identified in one of four DNA Mismatch repair (MMR genes MLH1, MSH2, MSH6 and PMS2. Loss of function of any one of these genes results in a failure to repair DNA errors occurring during replication which can be most easily observed as DNA microsatellite instability (MSI—a hallmark feature of this disease. The remaining 50% of patients without a genetic diagnosis of disease may harbour more cryptic changes within or adjacent to MLH1, MSH2, MSH6 or PMS2 or elsewhere in the genome. We used a high density cytogenetic array to screen for deletions or duplications in a series of patients, all of whom adhered to the Amsterdam/Bethesda criteria, to determine if genomic re-arrangements could account for a proportion of patients that had been shown not to harbour causative mutations as assessed by standard diagnostic techniques. The study has revealed some associations between copy number variants (CNVs and HNPCC mutation negative cases and further highlights difficulties associated with CNV analysis.

  7. Clinical definition of hereditary non-polyposis colorectal cancer : A search for the impossible?

    Berends, MJW; Wu, Y; Sijmons, RH; Hofstra, RMW; van der Zee, AGJ; Buys, CHCM; Kleibeuker, JH

    2001-01-01

    Hereditary non-polyposis colorectal cancer is an autosomal dominant inherited disorder that predisposes its carriers to an almost 100% lifetime risk of cancer, in particular colorectal and endometrial cancer. Germline mutations, resulting in a deficient DNA mismatch repair system. are responsible

  8. Hereditary mixed polyposis syndrome due to a BMPR1A mutation.

    O'Riordan, J M

    2010-06-01

    The conditions Juvenile Polyposis Syndrome (JPS) and Hereditary Mixed Polyposis Syndrome (HMPS) are associated with an increased risk of colorectal carcinoma. The genetic mechanisms which explain these conditions have until recently been poorly understood. Recent interest has focused on the transforming growth factor (TGF)-beta signalling pathway and, in particular, on mutations in the SMAD4 gene. However, not all cases of JPS and HMPS have mutations in SMAD4 and focus has now shifted to other components of the TGF-beta pathway to clarify the genetic mechanisms involved in these conditions. In this report, we describe the significance of a bone morphogenetic protein receptor type 1A gene mutation in an Irish family.

  9. Hereditary non-polyposis colorectal cancer: clinical features and survival. Results from the Danish HNPCC register

    Myrhøj, T; Bisgaard, M L; Bernstein, Inge Thomsen

    1997-01-01

    BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) is a dominantly inherited syndrome characterized by the development of colorectal cancer (CRC) and other carcinomas. Our aim was to evaluate tumour parameters and survival in HNPCC. METHODS: One hundred and eight Danish HNPCC patients...... were compared with 870 patients with sporadic colorectal cancer. RESULTS: The median age at CRC diagnosis was 41 years in the HNPCC group. HNPCC patients had significantly more carcinomas located to the right colon (68% against 49% in controls), more synchromous tumours (7% versus 1%), more...

  10. HEREDITARY NON-POLYPOSIS COLORECTAL CANCER (LYNCH SYNDROME PADA WANITA UMUR 16 TAHUN

    Asril Zahari

    2011-09-01

    Full Text Available AbstrakKanker kolorektal menduduki peringkat ketiga jenis kanker yang paling sering terjadi di dunia. Sekitar 3% kasus kanker kolorektal merupakan jenis hereditary non polyposis colorectal cancer (HNPCC/Lynch syndrome, yang sering muncul pada usia muda. Dilaporkan satu kasus di rumah sakit Dr. M. Djamil Padang, wanita berumur 16 tahun dengan keluhan nyeri perut kanan bawah. Didapatkan riwayat penyakit serupa pada kakek, bibi pasien dan enam anggota keluarga yang lain. Pada pemeriksaan fisik abdomen teraba massa dengan konsistensi keras dan terfiksir. Pada kolonoskopi dan biopsi ditemukan tumor jenis adenocarcinoma colon moderatly differentiated di fleksura hepatika dan polip di kolon sigmoid. Berdasarkan kriteria Amsterdam pasien didiagnosa Lynch syndrome. Pada Pasien dilakukan subtotal kolektomi, anastomose ileorectal dan kemoterapi ajuvan. Identifikasi genetik sedang dikerjakan untuk melihat adanya kelainan genetik pada pasien. Pasien melakukan skrining berkala untuk mencegah kanker HNPCC jenis yang lain.Kata kunci : Hereditary non polyposis colorectal cancer, Lynch syndrome, Microsatellite instability, skrining.AbstractCarcinoma colorectal is the third most common type of cancer that occurs in the world. About 2% -3% of cases of colorectal cancer is hereditary non-polyposis colorectal cancer (HNPCC/Lynch syndrome, which often appear at a young age. Amsterdam and Bethesda criteria have been used to identify patients with Lynch syndrome.one case was reported at the Dr. M. Djamil Padang hospital, a 16-year-old girl with right lower abdominal pain. Obtained a history of similar disease in grandparents, aunts and six other family members. On physical examination found palpable fixed abdominal mass with hard consistency in the lower right abdomen. At colonoscopy and biopsy found a moderatly differentiated adenocarcinoma colon type at the hepatic flexure and the sigmoid colon polyp. Based on the Amsterdam criteria, patients diagnosed with HNPCC

  11. Hamartomatous polyposis syndromes

    Jelsig, Anne Marie; Qvist, Niels; Brusgaard, Klaus

    2014-01-01

    Hamartomatous Polyposis Syndromes (HPS) are genetic syndromes, which include Peutz-Jeghers syndrome, Juvenile polyposis syndrome, PTEN hamartoma tumour syndrome (Cowden Syndrom, Bannayan-Riley-Ruvalcaba and Proteus Syndrome) as well as hereditary mixed polyposis syndrome. Other syndromes such as ......Hamartomatous Polyposis Syndromes (HPS) are genetic syndromes, which include Peutz-Jeghers syndrome, Juvenile polyposis syndrome, PTEN hamartoma tumour syndrome (Cowden Syndrom, Bannayan-Riley-Ruvalcaba and Proteus Syndrome) as well as hereditary mixed polyposis syndrome. Other syndromes...

  12. Presymptomatic diagnosis using a deletion of a single codon in families with hereditary non-polyposis colorectal cancer

    Ripa, Rasmus S.; Katballe, Niels; Wikman, Friedrik P.

    2005-01-01

    The diagnosis of hereditary non-polyposis colorectal cancer (HNPCC) is often confirmed by a mutation in one of several mismatch-repair genes, in particular MLH1, MSH2 and MSH6. Presymptomatic diagnosis requires the identification of a mutation causing the disease. Three different deletions...

  13. Juvenile polyposis syndrome: An unusual case report of anemia and gastrointestinal bleeding in young infant.

    Hsiao, Yi-Han; Wei, Chin-Hung; Chang, Szu-Wen; Chang, Lung; Fu, Yu-Wei; Lee, Hung-Chang; Liu, Hsuan-Liang; Yeung, Chun-Yan

    2016-09-01

    Juvenile polyposis syndrome, a rare disorder in children, is characterized with multiple hamartomatous polyps in alimentary tract. A variety of manifestations include bleeding, intussusception, or polyp prolapse. In this study, we present an 8-month-old male infant of juvenile polyposis syndrome initially presenting with chronic anemia. To the best of our knowledge, this is the youngest case reported in the literature. We report a rare case of an 8-month-old male infant who presented with chronic anemia and gastrointestinal bleeding initially. Panendoscopy and abdominal computed tomography showed multiple polyposis throughout the entire alimentary tract leading to intussusception. Technetium-99m-labeled red blood cell (RBC) bleeding scan revealed the possibility of gastrointestinal tract bleeding in the jejunum. Histopathological examination on biopsy samples showed Peutz-Jeghers syndrome was excluded, whereas the diagnosis of juvenile polyposis syndrome was established. Enteroscopic polypectomy is the mainstay of the treatment. However, polyps recurred and occupied the majority of the gastrointestinal tract in 6 months. Supportive management was given. The patient expired for severe sepsis at the age of 18 months. Juvenile polyposis syndrome is an inherited disease, so it is not possible to prevent it. Concerning of its poor outcome and high mortality rate, it is important that we should increase awareness and education of the parents at its earliest stages.

  14. MSI-Testing in Hereditary Non-Polyposis Colorectal Carcinoma (HNPCC

    Annegret Müller

    2004-01-01

    Full Text Available Genomic instability at simple repeated sequences, termed microsatellite instability (MSI, plays an important role in the analysis of sporadic and hereditary colon cancers. In hereditary non-polyposis colorectal cancer syndrome (HNPCC more than 90% of cases show MSI, whereas only 10–15% of sporadic colorectal cancers do so. Thus, microsatellite analysis is commonly used as the first diagnostic screening test for HNPCC. In 1997, an international collaborative workshop sponsored by the National Cancer Institute (NCI proposed a set of guidelines for MSI-testing to improve reliability and reproducibility of the analysis as well to allow comparisons between different studies and different laboratories. In this review we assess the value of current protocols forMSI-testing and discuss some diagnostic pitfalls. Our findings support continued use of the MSI marker panel recommended in 1997. Additionally, MSI-testing should be improved by use of microdissection, which helps to identify additional patients with MSI due to enrichment of tumor cells and therefore increased sensitivity. In our view, immunohistochemical staining for mismatch repair protein expression is not a substitute for MSI-analysis but complements MSI screening and helps direct further testing. In summary, MSI-analysis is a highly sensitive and reliable screening method for HNPCC, that requires a well-equipped laboratory as well as an experienced pathologist. Integration of family history and histo-pathological features is also critical.

  15. Hereditary non-polyposis colorectal cancer/Lynch syndrome in three dimensions.

    Kravochuck, Sara E; Church, James M

    2017-12-01

    Hereditary non-polyposis colorectal cancer (HNPCC) is defined by family history, and Lynch syndrome (LS) is defined genetically. However, universal tumour testing is now increasingly used to screen for patients with defective mismatch repair. This mixing of the results of family history, tumour testing and germline testing produces multiple permutations and combinations that can foster confusion. We wanted to clarify hereditary colorectal cancer using the three dimensions of classification: family history, tumour testing and germline testing. Family history (Amsterdam I or II criteria versus not Amsterdam criteria) was used to define patients and families with HNPCC. Tumour testing and germline testing were then performed to sub-classify patients and families. The permutations of these classifications are applied to our registry. There were 234 HNPCC families: 129 had LS of which 55 were three-dimensional Lynch (family history, tumour testing and germline testing), 66 were two-dimensional Lynch and eight were one-dimensional Lynch. A total of 10 families had tumour Lynch (tumours with microsatellite instability or loss of expression of a mismatch repair protein but an Amsterdam-negative family and negative germline testing), five were Lynch like (Amsterdam-positive family, tumours with microsatellite instability or loss of expression of a mismatch repair protein on immunohistochemistry but negative germline testing), 26 were familial colorectal cancer type X and 95 were HNPCC. Hereditary colorectal cancer can be confusing. Sorting families in three dimensions can clarify the confusion and may direct further testing and, ultimately, surveillance. © 2016 Royal Australasian College of Surgeons.

  16. Molecular Analysis: Microsatellite Instability and Loss of Heterozygosity of Tumor Suppressor Gene in Hereditary Non-Polyposis Colorectal Cancer (HNPCC

    Vesna Hadžiavdić

    2009-02-01

    Full Text Available HNPCC (Hereditary non-polyposis colorectal cancer development is caused by mutation of genes included in system of mismatch repair genes. The mutation exists at 60% of patients in hMSH2 gene, 30% in hMLH1 and 10% both in hPMS1and hPMS2 genes. RER+ exists in about 90% in hereditary non-polyposis colorectal cancer and about 15-28% in sporadic cancers.The purpose of the study was to determine highly sensitive microsatellite markers which can be fast and efficient way of microsatellite screening for detection of HNPCC patients. Moreover, we have analysed the loss of heterozygosity of tumour suppressor genes which could have the diagnostic value in detection of HPNCC patients.

  17. Gastrointestinal bleeding in patients with hereditary hemorrhagic telangiectasia

    Kjeldsen, A D; Kjeldsen, J

    2000-01-01

    Gastrointestinal bleeding occurs in a number of patients with hereditary hemorrhagic telangiectasia (HHT) and may lead to a high transfusion need. The aim of this study was to estimate the occurrence and severity of gastrointestinal bleeding in a geographically well defined HHT population....

  18. Psychological impact of genetic testing for hereditary non-polyposis colorectal cancer.

    Meiser, B; Collins, V; Warren, R; Gaff, C; St John, D J B; Young, M-A; Harrop, K; Brown, J; Halliday, J

    2004-12-01

    The psychological impact of predictive genetic testing for hereditary non-polyposis colorectal cancer (HNPCC) was assessed in 114 individuals (32 carriers and 82 non-carriers) attending familial cancer clinics, using mailed self-administered questionnaires prior to, 2 weeks, 4 months and 12 months after carrier status disclosure. Compared to baseline, carriers showed a significant increase in mean scores for intrusive and avoidant thoughts about colorectal cancer 2 weeks (t = 2.49; p = 0.014) and a significant decrease in mean depression scores 2 weeks post-notification of result (t = -3.98; p depression scores 2 weeks, 4 months and 12 months post-notification. Significant decreases from baseline for mean state anxiety scores were also observed for non-carriers 2 weeks post-notification (t = -3.99; p < 0.001). These data indicate that predictive genetic testing for HNPCC leads to psychological benefits amongst non-carriers, and no adverse psychological outcomes were observed amongst carriers.

  19. Molecular genetic approach for screening of hereditary non-polyposis colorectal cancer

    Metka Ravnik-Glavač

    2005-07-01

    Full Text Available Background: The main goal of knowledge concerning human diseases is to transfer as much as possible useful information into clinical applications. Hereditary non-polyposis colorectal cancer (HNPCC is the most common autosomal dominant inherited predisposition for colorectal cancer, accounting for 1–2% of all bowel cancer. The only way to diagnose HNPCC is by a family history consistent with the disease defined by International Collaborative Group on HNPCC (Amsterdam criteria I and II. The main molecular cause of HNPCC is a constitutional mutation in one of the mismatch repair (MMR genes. Since HNPCC mutations have been detected also in families that did not fulfil the Amsterdam criteria, molecular genetic characteristics of HNPCC cancers have been proposed as valuable first step in HNPCC identification. Microsatellite instability is present in about 90% of cancers of HNPCC patients. However, of all MSI colorectal cancers 80– 90% are sporadic. Several molecular mechanisms have been uncovered that enable distinguishing to some extent between sporadic and HNPCC cancers with MSI including hypermethylation of hMLH1 promoter and frequent mutations in BAX and TGFBR2 in sporadic CRC with MSI-H.Conclusions: The determination of MSI status and careful separation of MSI positive colorectal cancer into sporadic MSIL, sporadic MSI-H, and HNPCC MSI-H followed by mutation detection in MMR genes is important for prevention, screening and management of colorectal cancer. In some studies we and others have already shown that large-scale molecular genetic analysis for HNPCC can be done and is sensitive enough to approve population screening. Population screening includes also colonoscopy which is restricted only to the obligate carriers of the mutation. This enables that the disease is detected in earlier stages which would greatly decrease medical treatment costs and most importantly decrease mortality. In Slovenia we have started population screening based

  20. Screening for susceptibility genes in hereditary non-polyposis colorectal cancer.

    Yu, Li; Yin, Bo; Qu, Kaiying; Li, Jingjing; Jin, Qiao; Liu, Ling; Liu, Chunlan; Zhu, Yuxing; Wang, Qi; Peng, Xiaowei; Zhou, Jianda; Cao, Peiguo; Cao, Ke

    2018-06-01

    In the present study, hereditary non-polyposis colorectal cancer (HNPCC) susceptibility genes were screened for using whole exome sequencing in 3 HNPCC patients from 1 family and using single nucleotide polymorphism (SNP) genotyping assays in 96 other colorectal cancer and control samples. Peripheral blood was obtained from 3 HNPCC patients from 1 family; the proband and the proband's brother and cousin. High-throughput sequencing was performed using whole exome capture technology. Sequences were aligned against the HAPMAP, dbSNP130 and 1,000 Genome Project databases. Reported common variations and synonymous mutations were filtered out. Non-synonymous single nucleotide variants in the 3 HNPCC patients were integrated and the candidate genes were identified. Finally, SNP genotyping was performed for the genes in 96 peripheral blood samples. In total, 60.4 Gb of data was retrieved from the 3 HNPCC patients using whole exome capture technology. Subsequently, according to certain screening criteria, 15 candidate genes were identified. Among the 96 samples that had been SNP genotyped, 92 were successfully genotyped for 15 gene loci, while genotyping for HTRA1 failed in 4 sporadic colorectal cancer patient samples. In 12 control subjects and 81 sporadic colorectal cancer patients, genotypes at 13 loci were wild-type, namely DDX20, ZFYVE26, PIK3R3, SLC26A8, ZEB2, TP53INP1, SLC11A1, LRBA, CEBPZ, ETAA1, SEMA3G, IFRD2 and FAT1 . The CEP290 genotype was mutant in 1 sporadic colorectal cancer patient and was wild-type in all other subjects. A total of 5 of the 12 control subjects and 30 of the 81 sporadic colorectal cancer patients had a mutant HTRA1 genotype. In all 3 HNPCC patients, the same mutant genotypes were identified at all 15 gene loci. Overall, 13 potential susceptibility genes for HNPCC were identified, namely DDX20, ZFYVE26, PIK3R3, SLC26A8, ZEB2, TP53INP1, SLC11A1, LRBA, CEBPZ, ETAA1, SEMA3G, IFRD2 and FAT1 .

  1. Presymptomatic diagnosis using a deletion of a single codon in families with hereditary non-polyposis colorectal cancer

    Ripa, R S; Katballe, N; Wikman, F P

    2005-01-01

    The diagnosis of hereditary non-polyposis colorectal cancer (HNPCC) is often confirmed by a mutation in one of several mismatch-repair genes, in particular MLH1, MSH2 and MSH6. Presymptomatic diagnosis requires the identification of a mutation causing the disease. Three different deletions......, identified after mutation screening of MSH2 and MLH1. All patients in the families were haplotyped using markers flanking the MSH2 gene. The haplotypes revealed that the five families with high probability descended from only two founders. The N596del segregated with the HNPCC phenotype with lod scores of 3.......2 and 2.0 at the recombination fraction of 0.0 in the two founder families. Sequencing of MSH2 and MLH1 did not reveal other pathogenic mutations, and N596del was not identified in 50 healthy controls. The mutation has previously been found expressed in mRNA, and is located in a conserved domain...

  2. Hereditary non-polyposis colorectal cancer is predicted to contribute towards colorectal cancer in young South African blacks

    M. Ramsay

    2009-12-01

    Full Text Available A disproportionately large number of young (<50 years black patients present with colorectal cancer (CRC in South Africa. Although a phenomenon previously described elsewhere in Africa, its specificmolecular basis,whether sporadic or hereditary, has not been established. Molecular analysis of these tumours could link them to the features known to be associated with specific types of hereditary colorectal cancer, specifically through examination of levels of microsatellite instability, promoter methylation and the presence or absence of KRAS and BRAF mutations. The molecular features of cancer tissue samples from 44 CRC cases of black and white patients in South Africa were accordingly retrospectively analysed without knowledge of family history. Compared with samples from older blacks (>50 years, those from young black patients presented more often with a low methylation phenotype (CIMP-L and high levels of microsatellite instability (MSI-H. Furthermore, as determined by real-time PCR using probe technology, the tissues from35%of young blacks showed mutations within exon 1 of the KRAS gene. The BRAF-V600E mutation was only evident in the case of a single young black patient. Based on these results it seems likely that a proportion of CRC cases in young black patients from South Africa develop through the accumulation of mutations resulting in a mismatch repair deficiency linked to MSI-H and, possibly, germline mutations in the mismatch repair genes. The features in these patients are consistent with a diagnosis of the Hereditary Non-Polyposis Colorectal Cancer (HNPCC syndrome. This finding has important implications for patient management and suggests that family members may be at high risk for CRC.

  3. Hereditary Colorectal Tumors: A Literature Review on MUTYH-Associated Polyposis

    Micaella Kantor

    2017-01-01

    Full Text Available MAP (MUTYH-associated polyposis is a syndrome, described in 2002, which is associated with colorectal adenomas, with enhanced colorectal carcinogenesis. This review synthesizes the available literature on MAP and outlines its pathogenesis, association with colorectal tumorigenesis, screening, treatment, and the subtle differences between it and its close cousins—FAP and AFAP. The preponderance of data is collected using MAP guidelines. However, although AFAP and MAP appear similar, potentially important distinctions exist, warranting targeted diagnostic criteria and treatment approaches. We suggest that it may be prudent to screen for MAP earlier than in current clinical practice, as it has been shown that sequence variants are associated with more severe disease, presenting with an earlier onset of colorectal cancer. Finally, we issue a call-to-action for much-needed further data to establish clear clinical and diagnostic criteria.

  4. Feasibility and diagnostic utility of video capsule endoscopy for the detection of small bowel polyps in patients with hereditary polyposis syndromes.

    Schulmann, Karsten; Hollerbach, Stephan; Kraus, Katja; Willert, Jörg; Vogel, Tilman; Möslein, Gabriela; Pox, Christian; Reiser, Markus; Reinacher-Schick, Anke; Schmiegel, Wolff

    2005-01-01

    At present, surveillance of premalignant small bowel polyps in hereditary polyposis syndromes has a number of limitations. Capsule endoscopy (CE) is a promising new method to endoscopically assess the entire length of the small bowel. We prospectively examined 40 patients with hereditary polyposis syndromes (29 familial adenomatous polyposis (FAP), 11 Peutz-Jeghers syndrome (PJS)). Results were compared with push-enteroscopy (PE) results in FAP and with esophagogastroduodenoscopy, PE, (MR)-enteroclysis, and surgical specimen in PJS patients. A total of 76% of the patients with FAP with duodenal adenomas (n = 21) had additional adenomas in the proximal jejunum that could be detected by CE and PE. Moreover, 24% of these FAP patients had further polyps in the distal jejunum or ileum that could only be detected by CE. In contrast, in FAP patients without duodenal polyps (n = 8), jejunal or ileal polyps occurred rarely (12%). CE detected polyps in 10 of 11 patients with PJS, a rate superior to all other reference procedures employed. Importantly, the findings of CE had immediate impact on further clinical management in all PJS patients. Our results suggest that CE may be of clinical value in selected patients with FAP, whereas in PJS, CE could be used as first line surveillance procedure.

  5. Microsatellite instability analysis in hereditary non-polyposis colon cancer using the Bethesda consensus panel of microsatellite markers in the absence of proband normal tissue

    Dourisboure Ricardo J

    2006-01-01

    Full Text Available Abstract Background Hereditary non-polyposis colon cancer (HNPCC is an autosomal dominant syndrome predisposing to the early development of various cancers including those of colon, rectum, endometrium, ovarium, small bowel, stomach and urinary tract. HNPCC is caused by germline mutations in the DNA mismatch repair genes, mostly hMSH2 or hMLH1. In this study, we report the analysis for genetic counseling of three first-degree relatives (the mother and two sisters of a male who died of colorectal adenocarcinoma at the age of 23. The family fulfilled strict Amsterdam-I criteria (AC-I with the presence of extracolonic tumors in the extended pedigree. We overcame the difficulty of having a proband post-mortem non-tumor tissue sample for MSI testing by studying the alleles carried by his progenitors. Methods Tumor MSI testing is described as initial screening in both primary and metastasis tumor tissue blocks, using the reference panel of 5 microsatellite markers standardized by the National Cancer Institute (NCI for the screening of HNPCC (BAT-25, BAT-26, D2S123, D5S346 and D17S250. Subsequent mutation analysis of the hMLH1 and hMSH2 genes was performed. Results Three of five microsatellite markers (BAT-25, BAT-26 and D5S346 presented different alleles in the proband's tumor as compared to those inherited from his parents. The tumor was classified as high frequency microsatellite instability (MSI-H. We identified in the HNPCC family a novel germline missense (c.1864C>A mutation in exon 12 of hMSH2 gene, leading to a proline 622 to threonine (p.Pro622Thr amino acid substitution. Conclusion This approach allowed us to establish the tumor MSI status using the NCI recommended panel in the absence of proband's non-tumor tissue and before sequencing the obligate carrier. According to the Human Gene Mutation Database (HGMD and the International Society for Gastrointestinal Hereditary Tumors (InSiGHT Database this is the first report of this mutation.

  6. MUTYH Associated Polyposis (MAP)

    Poulsen, Marie Louise Mølgaard; Bisgaard, M L

    2008-01-01

    Adenomatous Polyposis (FAP) and to a lesser extend Lynch Syndrome, which are caused by germline mutations in the APC and Mismatch Repair (MMR) genes, respectively.Here we review research findings regarding MUTYH interactions, genotypic and phenotypic characteristics of MAP, as well as surveillance......MUTYH Associated Polyposis (MAP), a Polyposis predisposition caused by biallelic mutations in the Base Excision Repair (BER) gene MUTYH, confers a marked risk of colorectal cancer (CRC). The MAP phenotype is difficult to distinguish from other hereditary CRC syndromes. Especially from Familial...

  7. Hereditary Mixed Polyposis Syndrome

    ... to Content ASCO.org Conquer Cancer Foundation ASCO Journals Donate eNews Signup f Cancer.net on Facebook t Cancer.net on Twitter q Cancer.net on YouTube g Cancer.net on Google Menu Home Types of Cancer Navigating Cancer Care Coping With Cancer Research and Advocacy Survivorship Blog About ...

  8. Pulmonary sclerosing hemangioma in a 21-year-old male with metastatic hereditary non-polyposis colorectal cancer: Report of a case

    Angele Martin K

    2011-06-01

    Full Text Available Abstract Background Pulmonary sclerosing hemangioma (SH is a rare tumor of the lung predominantly affecting Asian women in their fifth decade of life. SH is thought to evolve from primitive respiratory epithelium and mostly shows benign biological behavior; however, cases of lymph node metastases, local recurrence and multiple lesions have been described. Case Presentation We report the case of a 21-year-old Caucasian male with a history of locally advanced and metastatic rectal carcinoma (UICC IV; pT4, pN1, M1(hep that was eventually identified as having hereditary non-polyposis colorectal cancer (HNPCC, Lynch syndrome. After neoadjuvant chemotherapy followed by low anterior resection, adjuvant chemotherapy and metachronous partial hepatectomy, he was admitted for treatment of newly diagnosed bilateral pulmonary metastases. Thoracic computed tomography showed a homogenous, sharply marked nodule in the left lower lobe. We decided in favor of atypical resection followed by systematic lymphadenectomy. Histopathological analysis revealed the diagnosis of SH. Conclusions Cases have been published with familial adenomatous polyposis (FAP and simultaneous SH. FAP, Gardner syndrome and Li-Fraumeni syndrome, however, had been ruled out in the present case. To the best of our knowledge, this is the first report describing SH associated with Lynch syndrome.

  9. The gastrointestinal manifestation of constitutional mismatch repair deficiency syndrome: from a single adenoma to polyposis-like phenotype and early onset cancer.

    Levi, Z; Kariv, R; Barnes-Kedar, I; Goldberg, Y; Half, E; Morgentern, S; Eli, B; Baris, H N; Vilkin, A; Belfer, R G; Niv, Y; Elhasid, R; Dvir, R; Abu-Freha, N; Cohen, S

    2015-11-01

    Data on the clinical presentation of constitutional mismatch repair deficiency syndrome (CMMRD) is accumulating. However, as the extraintestinal manifestations are often fatal and occur at early age, data on the systematic evaluation of the gastrointestinal tract is scarce. Here we describe 11 subjects with verified biallelic carriage and who underwent colonoscopy, upper endoscopy and small bowel evaluation. Five subjects were symptomatic and in six subjects the findings were screen detected. Two subjects had colorectal cancer and few adenomatous polyps (19, 20 years), three subjects had polyposis-like phenotype (13, 14, 16 years), four subjects had few adenomatous polyps (8, 12-14 years) and two subjects had no polyps (both at age 6). Of the three subjects in the polyposis-like group, two subjects had already developed high-grade dysplasia or cancer and one subject had atypical juvenile polyps suggesting juvenile polyposis. Three out of the five subjects that underwent repeated exams had significant findings during short interval. The gastrointestinal manifestations of CMMRD are highly dependent upon age of examination and highly variable. The polyps may also resemble juvenile polyposis. Intensive surveillance according to current guidelines is mandatory. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Familial adenomatous polyposis

    Rozen Paul

    2009-10-01

    Full Text Available Abstract Familial adenomatous polyposis (FAP is characterized by the development of many tens to thousands of adenomas in the rectum and colon during the second decade of life. FAP has an incidence at birth of about 1/8,300, it manifests equally in both sexes, and accounts for less than 1% of colorectal cancer (CRC cases. In the European Union, prevalence has been estimated at 1/11,300-37,600. Most patients are asymptomatic for years until the adenomas are large and numerous, and cause rectal bleeding or even anemia, or cancer develops. Generally, cancers start to develop a decade after the appearance of the polyps. Nonspecific symptoms may include constipation or diarrhea, abdominal pain, palpable abdominal masses and weight loss. FAP may present with some extraintestinal manifestations such as osteomas, dental abnormalities (unerupted teeth, congenital absence of one or more teeth, supernumerary teeth, dentigerous cysts and odontomas, congenital hypertrophy of the retinal pigment epithelium (CHRPE, desmoid tumors, and extracolonic cancers (thyroid, liver, bile ducts and central nervous system. A less aggressive variant of FAP, attenuated FAP (AFAP, is characterized by fewer colorectal adenomatous polyps (usually 10 to 100, later age of adenoma appearance and a lower cancer risk. Some lesions (skull and mandible osteomas, dental abnormalities, and fibromas on the scalp, shoulders, arms and back are indicative of the Gardner variant of FAP. Classic FAP is inherited in an autosomal dominant manner and results from a germline mutation in the adenomatous polyposis (APC gene. Most patients (~70% have a family history of colorectal polyps and cancer. In a subset of individuals, a MUTYH mutation causes a recessively inherited polyposis condition, MUTYH-associated polyposis (MAP, which is characterized by a slightly increased risk of developing CRC and polyps/adenomas in both the upper and lower gastrointestinal tract. Diagnosis is based on a

  11. Juvenile polyposis syndrome

    Hsiao, Yi-Han; Wei, Chin-Hung; Chang, Szu-Wen; Chang, Lung; Fu, Yu-Wei; Lee, Hung-Chang; Liu, Hsuan-Liang; Yeung, Chun-Yan

    2016-01-01

    Abstract Background: Juvenile polyposis syndrome, a rare disorder in children, is characterized with multiple hamartomatous polyps in alimentary tract. A variety of manifestations include bleeding, intussusception, or polyp prolapse. In this study, we present an 8-month-old male infant of juvenile polyposis syndrome initially presenting with chronic anemia. To the best of our knowledge, this is the youngest case reported in the literature. Methods: We report a rare case of an 8-month-old male infant who presented with chronic anemia and gastrointestinal bleeding initially. Panendoscopy and abdominal computed tomography showed multiple polyposis throughout the entire alimentary tract leading to intussusception. Technetium-99m-labeled red blood cell (RBC) bleeding scan revealed the possibility of gastrointestinal tract bleeding in the jejunum. Histopathological examination on biopsy samples showed Peutz-Jeghers syndrome was excluded, whereas the diagnosis of juvenile polyposis syndrome was established. Results: Enteroscopic polypectomy is the mainstay of the treatment. However, polyps recurred and occupied the majority of the gastrointestinal tract in 6 months. Supportive management was given. The patient expired for severe sepsis at the age of 18 months. Conclusion: Juvenile polyposis syndrome is an inherited disease, so it is not possible to prevent it. Concerning of its poor outcome and high mortality rate, it is important that we should increase awareness and education of the parents at its earliest stages. PMID:27631205

  12. Hereditary familial polyposis and Gardner's syndrome: contribution of the odonto-stomatology examination in its diagnosis and a case description.

    Chimenos-Küstner, Eduardo; Pascual, Montserrat; Blanco, Ignacio; Finestres, Fernando

    2005-01-01

    Familial Adenomatous Polyposis (FAP) and its phenotype variant, Gardner's syndrome, constitute a rare autosomal dominant inherited disorder. They are characterised by the development, generally during the second and third decades of life, of multiple adenomatous polyps in the colon and rectum. These polyps have a high risk of subsequently becoming malignant, which normally occurs in the third and fourth decades of life. The phenotypical features of FAP can be very variable. As well as colorectal polyps, these individuals can present with extra-colonic symptoms, among which are particularly: gastro-duodenal polyps, dermoid and epidermoid cysts, desmoid tumours, congenital hypertrophy of the retinal pigment epithelium, disorders of the maxillary and skeletal bones and dental anomalies. In this paper the most important aspects of this syndrome are reviewed, showing an example based on a well documented clinical case. The importance of odonto-stomatological examinations should be pointed out, among others, as a means of reaching a presumptive diagnosis, whose confirmation is vital to the patient.

  13. Een jongeman met intestinale polyposis en epistaxis

    Menko, Fred H.; Jacobs, Maarten A. J. M.; Mager, Johannes J.; Nicolaï, Jan J.; Mensenkamp, Arjen R.; Aalfs, Cora M.

    2014-01-01

    Germline mutations in the SMAD4 gene lead to both juvenile polyposis syndrome and hereditary haemorrhagic telangiectasia (HHT). A 23-year-old man underwent colectomy with ileo-anal pouch anastomosis at the age of 12 due to colorectal juvenile polyposis. At follow-up, recurrent juvenile polyps in the

  14. Guidelines for the clinical management of familial adenomatous polyposis (FAP)

    Vasen, H.F.; Moslein, G.; Alonso, A.

    2008-01-01

    BACKGROUND: Familial adenomatous polyposis (FAP) is a well-described inherited syndrome, which is responsible for cancer (CRC) cases. The syndrome is characterised by the development of hundreds to thousands of adenomas in the colorectum. Almost all patients will develop CRC...... if they are not identified and treated at an early stage. The syndrome is inherited as an autosomal dominant trait and caused by mutations in the APC gene. Recently, a second gene has been identified that also gives rise to colonic adenomatous polyposis, although the phenotype is less severe than typical FAP. The gene...... is the MUTYH gene and the inheritance is autosomal recessive. In April 2006 and February 2007, a workshop was organised in Mallorca by European experts on hereditary gastrointestinal cancer aiming to establish guidelines for the clinical management of FAP and to initiate collaborative studies. Thirty...

  15. Germ line mutations of mismatch repair genes in hereditary nonpolyposis colorectal cancer patients with small bowel cancer: International Society for Gastrointestinal Hereditary Tumours Collaborative Study

    Park, Jae-Gahb; Kim, Duck-Woo; Hong, Chang Won

    2006-01-01

    PURPOSE: The aim of study was to determine the clinical characteristics and mutational profiles of the mismatch repair genes in hereditary nonpolyposis colorectal cancer (HNPCC) patients with small bowel cancer (SBC). EXPERIMENTAL DESIGN: A questionnaire was mailed to 55 members of the Internatio......PURPOSE: The aim of study was to determine the clinical characteristics and mutational profiles of the mismatch repair genes in hereditary nonpolyposis colorectal cancer (HNPCC) patients with small bowel cancer (SBC). EXPERIMENTAL DESIGN: A questionnaire was mailed to 55 members...... of the International Society for Gastrointestinal Hereditary Tumours, requesting information regarding patients with HNPCC-associated SBC and germ line mismatch repair gene mutations. RESULTS: The study population consisted of 85 HNPCC patients with identified mismatch repair gene mutations and SBCs. SBC was the first...... HNPCC-associated malignancy in 14 of 41 (34.1%) patients for whom a personal history of HNPCC-associated cancers was available. The study population harbored 69 different germ line mismatch repair gene mutations, including 31 mutations in MLH1, 34 in MSH2, 3 in MSH6, and 1 in PMS2. We compared...

  16. [A young man with intestinal polyposis and epistaxis

    Menko, F.H.; Jacobs, M.A.; Mager, J.J.; Nicolai, J.J.; Mensenkamp, A.R.; Aalfs, C.M.

    2014-01-01

    BACKGROUND: Germline mutations in the SMAD4 gene lead to both juvenile polyposis syndrome and hereditary haemorrhagic telangiectasia (HHT). CASE DESCRIPTION: A 23-year-old man underwent colectomy with ileo-anal pouch anastomosis at the age of 12 due to colorectal juvenile polyposis. At follow-up,

  17. Wireless capsule endoscopy in adolescents with familial adenomatous polyposis.

    Cavallo, Debora; Ballardini, Giovanni; Ferrari, Andrea; Delconte, Gabriele; Signoroni, Stefano; Sala, Paola; Chiaravalli, Stefano; Massimino, Maura; Bertario, Lucio; Vitellaro, Marco

    2016-01-01

    Guidelines for surveillance in patients with familial adenomatous polyposis (FAP) recommend mutation carriers to undergo periodic colorectal examination starting in the early teens. Performing colonoscopy in children may lead to complications. Wireless capsule endoscopy (WCE) has been introduced recently to evaluate both the upper and lower gastrointestinal tract, and seems suitable as a first screening examination for adolescents. The aim of this study was to evaluate the pros and cons of WCE. This was a retrospective review of a single institution database of adolescent patients with FAP identified through the Hereditary Colorectal Tumor Registry between 2007 and 2013. The main outcomes were identification of upper and lower gastrointestinal tract polyps, tolerance of the examination, and number and size of polyps. Of 46 adolescent patients with FAP, 14 (30.4%) patients carrying adenomatous polyposis coli gene (APC) mutation, 6 male and 8 female, age (median, range) 12 (10-17) years, body mass index 19 (13-24), underwent WCE as first screening examination. The examination was completed in 13 patients (93.3%). Wireless capsule endoscopy identified the duodenal papilla in 4 patients and colonic and rectal polyps in all 13 patients. In 7 patients, fewer than 25 polyps were identified. No complications were recorded related to the use of the video capsule. Wireless capsule endoscopy is feasible and well-tolerated as a first screening examination in adolescent patients. It cannot be used as alternative to the colonoscopy, but could improve compliance with colonoscopy, and increase early adherence to a surveillance program.

  18. Sensitivity to mitomycin-C and radiation of cells derived from patients with familial colon polyposis: an autosomal dominant hereditary disease

    Ban, Sadayuki; Iida, Shozo; Tamura, Taizo.

    1984-04-01

    This study was undertaken to investigate the sensitivity to mitomycin-C (MMC) of skin fibroblasts derived from patients with adenomatosis coli (AC), especially familial colon polyposis. The sensitivity to X rays and ultraviolet rays of AC cells cultured at RERF was similar to that of normal human diploid cells. However, there were large individual differences in sensitivity to MMC. DNA elongation in cells sensitive to MMC was found to be inhibited after MMC treatment. Sites highly sensitive to MMC were considered to be involved in the initial stages of DNA synthesis. (author)

  19. A Comparison Between Denaturing Gradient Gel Electrophoresis and Denaturing High Performance Liquid Chromatography in Detecting Mutations in Genes Associated with Hereditary Non-Polyposis Colorectal Cancer (HNPCC and the Identification of 9 New Mutations Previously Unidentified by DGGE

    Meldrum Cliff J

    2003-12-01

    Full Text Available Abstract Denaturing high performance liquid chromatography is a relatively new method by which heteroduplex structures formed during the PCR amplification of heterozygote samples can be rapidly identified. The use of this technology for mutation detection in hereditary non-polyposis colorectal cancer (HNPCC has the potential to appreciably shorten the time it takes to analyze genes associated with this disorder. Prior to acceptance of this method for screening genes associated with HNPCC, assessment of the reliability of this method should be performed. In this report we have compared mutation and polymorphism detection by denaturing gradient gel electrophoresis (DGGE with denaturing high performance liquid chromatography (DHPLC in a set of 130 families. All mutations/polymorphisms representing base substitutions, deletions, insertions and a 23 base pair inversion were detected by DHPLC whereas DGGE failed to identify four single base substitutions and a single base pair deletion. In addition, we show that DHPLC has been used for the identification of 5 different mutations in exon 7 of hMSH2 that could not be detected by DGGE. From this study we conclude that DHPLC is a more effective and rapid alternative to the detection of mutations in hMSH2 and hMLH1 with the same or better accuracy than DGGE. Furthermore, this technique offers opportunities for automation, which have not been realised for the majority of other methods of gene analysis.

  20. Gastrointestinal manifestations of hereditary angioedema diagnosed by ultrasound in the emergency department.

    Riguzzi, Christine; Losonczy, Lia; Teismann, Nathan; Herring, Andrew A; Nagdev, Arun

    2014-11-01

    Abdominal angioedema is a less recognized type of angioedema, which can occur in patients with hereditary angioedema (HAE). The clinical signs may range from subtle, diffuse abdominal pain and nausea, to overt peritonitis. We describe two cases of abdominal angioedema in patients with known HAE that were diagnosed in the emergency department by point-of-care (POC) ultrasound. In each case, the patient presented with isolated abdominal complaints and no signs of oropharyngeal edema. Findings on POC ultrasound included intraperitoneal free fluid and bowel wall edema. Both patients recovered uneventfully after receiving treatment. Because it can be performed rapidly, requires no ionizing radiation, and can rule out alternative diagnoses, POC ultrasound holds promise as a valuable tool in the evaluation and management of patients with HAE.

  1. Gastrointestinal Manifestations of Hereditary Angioedema Diagnosed by Ultrasound in the Emergency Department

    Christine Riguzzi

    2014-11-01

    Full Text Available Abdominal angioedema is a less recognized type of angioedema, which can occur in patients with hereditary angioedema (HAE. The clinical signs may range from subtle, diffuse abdominal pain and nausea, to overt peritonitis. We describe two cases of abdominal angioedema in patients with known HAE that were diagnosed in the emergency department by point-of-care (POC ultrasound. In each case, the patient presented with isolated abdominal complaints and no signs of oropharyngeal edema. Findings on POC ultrasound included intraperitoneal free fluid and bowel wall edema. Both patients recovered uneventfully after receiving treatment. Because it can be performed rapidly, requires no ionizing radiation,and can rule out alternative diagnoses, POC ultrasound holds promise as a valuable tool in the evaluation and management of patients with HAE. [West J Emerg Med. 2014;15(7:-0.

  2. Sporadic diffuse segmental interstitial cell of Cajal hyperplasia harbouring two gastric gastrointestinal stromal tumours (GIST mimicking hereditary GIST syndromes

    Mafalda Costa Neves

    2015-01-01

    Conclusion: We describe a diffuse form of sporadic ICC hyperplasia harbouring multifocal GISTs, mimicking diffuse ICC hyperplasia in hereditary GIST syndromes. Detection of somatic c-KIT exon 11 mutation ruled out a hereditary disorder.

  3. Mutación fundadora en una familia argentina con cáncer colorrectal hereditario Detection of a founder mutation in an Argentine family with hereditary non polyposis colorectal cancer

    Laura Gómez

    2010-02-01

    Full Text Available El cáncer colorrectal hereditario no poliposo (CCHNP se relaciona con mutaciones en los genes reparadores de ADN (MLH1, MSH2 y MSH6. La mayoría de estas alteraciones son familia-específicas y su detección suele requerir la secuenciación completa de los genes relacionados. Se detectó una mutación puntual (2269-2270insT en el último codón del gen MLH1 en familias de un área del norte de Italia (Reggio Emilia y su origen se considera debido a un efecto fundador. En este trabajo presentamos una familia mendocina con CCHNP portadora de la misma mutación, cuyos ancestros eran oriundos de Reggio Emilia. Para la detección de la mutación se diseñó una estrategia basada en PCR y posterior corte enzimático. La mutación fue hallada en tres integrantes de la familia estudiada, dos de los cuales no presentaban sintomatología clínica. Estos pacientes fueron seguidos preventivamente mediante colonoscopias. La metodología utilizada en nuestro laboratorio fue específica y sensible para la detección de una mutación previamente registrada y permitió realizar el diagnóstico genético molecular en el país, evitando el envío de muestras al extranjero. Es de importancia destacar que el diagnóstico genético pre-sintomático de cáncer hereditario, enfocado desde un grupo multidisciplinario de profesionales, permite un mejor seguimiento y apoyo a las familias afectadas.Hereditary non polyposis colorectal cancer (HNPCC has been related to mutations in the DNA mismatch repair genes (MLH1, MSH2 y MSH6. Mutation detection analysis requires the complete sequencing of these genes, given the high frequency of family-specific alterations. A point mutation (2269- 2270insT in the last codon of the MLH1 gene has been detected in families from a northern region of Italy (Reggio Emilia.Given that this alteration was registered only in people from this region, it has been considered a founder mutation. In this work, we present an Argentine HNPCC family

  4. Genetics Home Reference: hereditary hemorrhagic telangiectasia

    ... Central OMIM: JUVENILE POLYPOSIS/HEREDITARY HEMORRHAGIC TELANGIECTASIA SYNDROME McDonald J, Bayrak-Toydemir P, Pyeritz RE. Hereditary hemorrhagic ... 10.1097/GIM.0b013e3182136d32. Review. Citation on PubMed McDonald J, Wooderchak-Donahue W, VanSant Webb C, Whitehead ...

  5. Sulindac treatment in hereditary non-pollyposis colorectal cancer

    Rijcken, Fleur E. M.; Hollema, Harry; van der Zee, Ate G. J.; van der Sluis, Tineke; Ek, Wytske Boersma-van; Kleibeuker, Jan H.

    Non-steroidal anti-inflammatory drugs, e.g. sulindac have been extensively studied for chemoprevention in familial adenomatous polyposis, but not in hereditary non-polyposis colorectal cancer (HNPCC). We evaluated these effects in HNPCC using surrogate end-points for cancer risk. In a randomised

  6. Juvenile polyposis syndrome

    Hsiao, Yi-Han; Wei, Chin-Hung; Chang, Szu-Wen; Chang, Lung; Fu, Yu-Wei; Lee, Hung-Chang; Liu, Hsuan-Liang; Yeung, Chun-Yan

    2016-01-01

    Abstract Background: Juvenile polyposis syndrome, a rare disorder in children, is characterized with multiple hamartomatous polyps in alimentary tract. A variety of manifestations include bleeding, intussusception, or polyp prolapse. In this study, we present an 8-month-old male infant of juvenile polyposis syndrome initially presenting with chronic anemia. To the best of our knowledge, this is the youngest case reported in the literature. Methods: We report a rare case of an 8-month-old male...

  7. Hereditary haemorrhagic telangiectasia

    Kjeldsen, A D; Vase, P; Green, A

    1999-01-01

    Hereditary haemorrhagic telangiectasia (HHT) is a dominantly inherited disease characterized by telangiectatic lesions. The disease manifestations are variable and include epistaxis, gastrointestinal bleeding, pulmonary arteriovenous malformations and cerebral arteriovenous malformations. Early...

  8. MUTYH-Associated Polyposis: The Irish Experience

    McVeigh, TP

    2016-11-01

    MUTYH is involved in DNA damage repair. Bi-allelic MUTYH mutations predispose to polyposis and gastrointestinal malignancies, distinct genetically from autosomal dominant familial adenomatous polyposis coli. Two common European MUTYH mutations account for 90% of MUTYH-associated polyposis (MAP). We aimed to examine the incidence of MAP in Ireland. A retrospective cohort study was undertaken. Patients undergoing MUTYH testing from 2003-2016 were identified by searching electronic databases using terms "MUTYH" and "MYH". Phenotypic and genotypic details were obtained by chart review. Bi-allelic mutations were confirmed in 26 individuals (17 families), of whom 16 (62%) developed colorectal malignancies, and 22(85%) polyposis. Eleven families had bi-allelic status for one\\/both common European mutations. Regional variation was noted, with over-representation of bi-allelic mutation carriers in the South-west of Ireland. MAP is under-diagnosed in Ireland. Increased awareness is required to facilitate appropriate identification and surveillance of bi-allelic mutation carriers for colorectal pathology.

  9. Review: Clinical aspects of hereditary DNA Mismatch repair gene mutations

    Sijmons, Rolf H.; Hofstra, Robert M. W.

    Inherited mutations of the DNA Mismatch repair genes MLH1, MSH2, MSH6 and PMS2 can result in two hereditary tumor syndromes: the adult-onset autosomal dominant Lynch syndrome, previously referred to as Hereditary Non-Polyposis Colorectal Cancer (HNPCC) and the childhood-onset autosomal recessive

  10. [Surgical aspects of indications and techniques for adenomatous polyposis variants].

    Möslein, Gabriela

    2016-08-01

    Due to the advances in molecular genetic diagnostics of adenomatous polyposis variants, identification of patients with a genetic predisposition and their at risk relatives is becoming increasingly important in clinical practice. Precise knowledge of the specific risk profile is gaining significance especially for surgeons and requires a clinically differentiated approach in order to correctly identify the indications for prophylactic surgery. In this article reference will be made to the technical details of the pouch operation rather than the decision-making process per se, since this has become common knowledge for specialized colorectal surgeons. Besides the more commonly known polyposis syndromes, such as familial adenomatous polyposis (FAP), surgeons should nowadays at least be able to clinically distinguish between attenuated and classical variants of FAP, be aware of MUTYH-associated polyposis (MAP) and also the new polyposis syndrome polymerase proofreading-associated polyposis (PPAP). Surgeons should be familiar with the specific indications and extent of surgery for prophylactic organ removal in the lower gastrointestinal tract in order to be able to competently advise patients.

  11. Rapidly progressive adenomatous polyposis in a patient with germline mutations in both the APC and MLH1 genes: the worst of two worlds.

    Scheenstra, R; Rijcken, FE; Koornstra, JJ; Hollema, H; Fodde, R; Menko, F.H.; Sijmons, RH; Bijleveld, CM; Kleibeuker, J.H.

    2003-01-01

    The two most common inherited forms of colorectal cancer are familial adenomatous polyposis and hereditary non-polyposis colorectal cancer. Simultaneous inheritance of both an APC gene mutation and a mismatch repair gene (for example, MLH1) mutation has never been described. In the present case

  12. Expanding the genotype-phenotype spectrum in hereditary colorectal cancer by gene panel testing

    Rohlin, Anna; Rambech, Eva; Kvist, Anders

    2017-01-01

    Hereditary syndromes causing colorectal cancer include both polyposis and non-polyposis syndromes. Overlapping phenotypes between the syndromes have been recognized and this make targeted molecular testing for single genes less favorable, instead there is a gaining interest for multi-gene panel...

  13. Familial adenomatous polyposis.

    Burn, J; Chapman, P D; Eastham, E J

    1994-01-01

    Abstract Familial adenomatous polyposis (FAP) is characterized by the development of many tens to thousands of adenomas in the rectum and colon during the second decade of life. FAP has an incidence at birth of about 1/8,300, it manifests equally in both sexes, and accounts for less than 1% of colorectal cancer (CRC) cases. In the European Union, prevalence has been estimated at 1/11,300-37,600. Most patients are asymptomatic for years until the adenomas are large and numerous, and cause rect...

  14. Prophylactic colectomy for hyperplastic polyposis.

    Doran, D

    2011-03-01

    Hyperplastic polyposis (HP) is important to recognise as it increases the risk of adenomata which may develop dysplastic change or frank adenocarcinoma. We present the case of a 58-year-old woman with HP.

  15. Hereditary colorectal cancer diagnostics

    Klarskov, Louise; Holck, Susanne; Bernstein, Inge

    2012-01-01

    BackgroundThe hereditary non-polyposis colorectal cancer (HNPCC) subset of tumours can broadly be divided into tumours caused by an underlying mismatch-repair gene mutation, referred to as Lynch syndrome, and those that develop in families with similar patterns of heredity but without disease......-predisposing germline mismatch repair mutations, referred to as familial colorectal cancer type X (FCCTX). Recognition of HNPCC-associated colorectal cancers is central since surveillance programmes effectively reduce morbidity and mortality. The characteristic morphological features linked to Lynch syndrome can aid...... in the identification of this subset, whereas the possibility to use morphological features as an indicator of FCCTX is uncertain.Objective and methodsTo perform a detailed morphological evaluation of HNPCC-associated colorectal cancers and demonstrate significant differences between tumours associated with FCCTX...

  16. Gastric tumours in hereditary cancer syndromes: clinical features, molecular biology and strategies for prevention.

    Sereno, María; Aguayo, Cristina; Guillén Ponce, Carmen; Gómez-Raposo, César; Zambrana, Francisco; Gómez-López, Miriam; Casado, Enrique

    2011-09-01

    Gastric cancer is the major cause of cancer-related deaths worldwide. The majority of them are classified as sporadic, whereas the remaining 10% exhibit familial clustering. Hereditary diffuse gastric cancer (HDGC) syndrome is the most important condition that leads to hereditary gastric cancer. However, other hereditary cancer syndromes, such as hereditary non-polyposis colorectal cancer, familial adenomatous polyposis, Peutz-Jeghers syndrome, Li-Fraumeni syndrome and hereditary breast and ovarian cancer, entail a higher risk compared to the general population for developing this kind of neoplasia. In this review, we describe briefly the most important aspects related to clinical features, molecular biology and strategies for prevention in hereditary gastric associated to different cancer syndromes.

  17. Familial Adenomatous Polyposis (FAP and Other Polyposis Syndromes

    Scott Rodney J

    2003-12-01

    Full Text Available Abstract There have been significant advances in our knowledge about the molecular changes that precede and accompany the development of inherited predispositions to colorectal cancer. In this review the clinical relationship to the molecular changes associated with the polyposis syndromes is presented. The aim is to put into context the diverse findings that have been shown to be associated with the development of colorectal cancer in persons who harbor a predisposition to develop disease at unusually early ages. The main focus will be on familial adenomatous polyposis as it serves as a model disease and is the most extensively studied of all of the polyposis syndromes. In addition some information is provided that explains the relationship between a germline change in one gene and what consequences that can have for a particular cell and the development of disease.

  18. Broad phenotypic spectrum in familial adenomatous polyposis; from early onset and severe phenotypes to late onset of attenuated polyposis with the first manifestation at age 72

    Nilbert, Mef; Kristoffersson, Ulf; Ericsson, Mats

    2008-01-01

    ABSTRACT: Background Familial adenomatous polyposis (FAP) is typically characterized by multiple colonic polyps and frequent extracolonic features. Whereas the number of colonic polyps has been linked to the APC gene mutation, possible genotype-phenotype correlations largely remain to be defined...... of extracolonic manifestations was identified in most of these individuals. Two sisters with an insertion in codon 528 (c.1582_1583insGC) both showed severe phenotypes with classical polyposis, upper gastrointestinal polyps and thyroid cancer. A woman with a 3'APC mutation (c.5030_5031insAA) developed colon...

  19. Laparoscopic Restorative Total Proctocolectomy With Ileal Pouch Anal Anastomosis for Familial Adenomatous Polyposis

    Palanivelu, C.; Jani, Kalpesh; Sendhilkumar, K.; Parthasarathi, R.; Senthilnathan, P.; Maheshkumar, G.

    2008-01-01

    Background: Familial adenomatous polyposis is a hereditary disease characterized by the presence of thousands of colonic adenomas, which, if untreated, invariably undergo malignant transformation. Because this disease manifests at a young age, the laparoscopic approach to perform surgery would be desirable due to its cosmetic benefits. We describe our experience with this procedure and review the literature on the topic. Methods: This is a case series of 15 patients who underwent restorative ...

  20. [Hereditary colorectal cancer : An update on genetics and entities in terms of differential diagnosis].

    Rau, T T; Dawson, H; Hartmann, A; Rüschoff, J

    2017-05-01

    The pathologist can contribute to recognizing hereditary causes of colorectal cancer via morphology. By identifying so-called index patients, it is possible to take preventive measures in affected families. The precise definition of the clinical presentation and the histopathological phenotype help to narrow the spectrum of expected genetic alterations. Novelties within Lynch syndrome include the recognition of EPCAM as a fifth gene locus, as well as the newly defined Lynch-like syndrome with evidence of somatic mismatch repair (MMR) mutations. With regard to polyposis-associated syndromes, the spectrum of polyps, whether serrated, hamartomatous or classic adenoma, is of crucial importance. The resulting differential diagnosis includes (attenuated) familial adenomatous polyposis ([a]FAP), MUTYH-associated polyposis (MAP), polymerase proofreading-associated polyposis (PPAP), phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS), Peutz-Jeghers syndrome and juvenile polyposis, each with a specific genetic background.

  1. Drug therapy for hereditary cancers

    Imyanitov Evgeny N

    2011-08-01

    Full Text Available Abstract Tumors arising in patients with hereditary cancer syndromes may have distinct drug sensitivity as compared to their sporadic counterparts. Breast and ovarian neoplasms from BRCA1 or BRCA2 mutation carriers are characterized by deficient homologous recombination (HR of DNA, that makes them particularly sensitive to platinum compounds or inhibitors of poly (ADP-ribose polymerase (PARP. Outstandingly durable complete responses to high dose chemotherapy have been observed in several cases of BRCA-related metastatic breast cancer (BC. Multiple lines of evidence indicate that women with BRCA1-related BC may derive less benefit from taxane-based treatment than other categories of BC patients. There is virtually no reports directly assessing drug response in hereditary colorectal cancer (CRC patients; studies involving non-selected (i.e., both sporadic and hereditary CRC with high-level microsatellite instability (MSI-H suggest therapeutic advantage of irinotecan. Celecoxib has been approved for the treatment of familial adenomatous polyposis (FAP. Hereditary medullary thyroid cancers (MTC have been shown to be highly responsive to a multitargeted tyrosine kinase inhibitor vandetanib, which exerts specific activity towards mutated RET receptor. Given the rapidly improving accessibility of DNA analysis, it is foreseen that the potential predictive value of cancer-associated germ-line mutations will be increasingly considered in the future studies.

  2. Genetic profiles distinguish different types of hereditary ovarian cancer

    Domanska, Katarina; Malander, Susanne; Staaf, Johan

    2010-01-01

    (HBOC) syndrome and the hereditary non-polyposis colorectal cancer (HNPCC) syndrome. Genome-wide array comparative genomic hybridization was applied to 12 HBOC associated tumors with BRCA1 mutations and 8 HNPCC associated tumors with mismatch repair gene mutations with 24 sporadic ovarian cancers......Heredity represents the strongest risk factor for ovarian cancer with disease predisposing mutations identified in 15% of the tumors. With the aim to identify genetic classifiers for hereditary ovarian cancer, we profiled hereditary ovarian cancers linked to the hereditary breast and ovarian cancer...... that HBOC and HNPCC associated ovarian cancer develop along distinct genetic pathways and genetic profiles can thus be applied to distinguish between different types of hereditary ovarian cancer....

  3. The adenomatous polyposis coli protein.

    Näthke, I S

    1999-01-01

    Mutations in the adenomatous polyposis coli (APC) gene are associated with most colorectal cancers. The APC protein has been implicated in many aspects of tumour development. This article will discuss recent data suggesting that APC may have multiple functions in the cell. First, APC is a component of the Wnt signalling pathway; second, APC may have a role in cell migration; finally, APC may regulate proliferation and apoptosis.

  4. A case series of intestinal adenomatous polyposis of unidentified etiology; a late effect of irradiation?

    Rigter, Lisanne Sara; Kallenberg, Frank G. J.; Bastiaansen, Barbara; Os, Theo A. M. van; Leeuwen, Floor E. van; Leerdam, Monique Esther van; Dekker, Evelien

    2016-01-01

    In a large number of patients with multiple gastrointestinal adenomatous polyps, no causal germline mutation can be found. Non-genetic factors may contribute to the development of adenomatous polyps in these unexplained polyposis patients. In the development of gastrointestinal cancer, prior exposure to abdominal radiotherapy has been identified as such a factor, as it increases the gastrointestinal cancer risk in cancer survivors. A relationship of radiotherapy with intestinal polyposis, however, has not yet been described. Despite the increased cancer risk, these cancer survivors do not receive gastrointestinal screening recommendations. This case series describes three patients with adenomatous polyposis after abdominal radiotherapy. Patient 1 was diagnosed with testicular cancer at the age of 31 and was treated with hemicastration, radiotherapy and chemotherapy. Thirty-nine years later, he was diagnosed with more than 30 colonic adenomas. Additionally, gastroduodenoscopy revealed a well-differentiated adenocarcinoma in the antrum of the stomach. Patient 2 was diagnosed with a nephroblastoma at the age of 10, which was resected and treated with radiotherapy and chemotherapy. At age 36, a rectal adenocarcinoma was diagnosed and treated by radiotherapy and a total mesorectal excision. During 11 years of surveillance endoscopies, 21 colonic adenomas and three duodenal adenomas were detected. Patient 3 was diagnosed with Hodgkin lymphoma at the age of 20 and treated with radiotherapy, followed by chemotherapy for a recurrence 3 years later. At age 62, a subtotal colectomy was performed because of colonic polyposis: 36 adenomas were detected. During screening gastro-duodenoscopy, three duodenal adenomas were detected. In all three patients, germline analysis did not reveal a mutation in the APC and MYH genes. The gastric and rectal cancer were both microsatellite stable. This report describes three patients with adenomatous polyposis, of which two developed a

  5. Gardner syndrome associated with multiple osteomas, intestinal polyposis, and epidermoid cysts

    Koh, Kwang Joon; Park, Ha Na; Kim, Kyoung A [Dept. of Oral and Maxillofacial Radiology, School of Dentistry and Institute of Oral Bioscience, Chonbuk National University, Jeonju (Korea, Republic of)

    2016-12-15

    Gardner syndrome is known as a variant of familial adenomatous polyposis. This syndrome is characterized by multiple intestinal polyposes, osteomas, and epidermoid cysts. In addition, dental abnormalities include an increased frequency of multiple odontomas, as well as supernumerary and impacted teeth. The authors report the case of a 7-year-old male patient with Gardner syndrome. Radiographic findings revealed multiple osteomas in both sides of the maxilla, multiple diffuse enostoses in both jaws, and a complex odontoma in the left mandibular body. Two years later, multiple epidermoid cysts on the scalp were found. Since this patient was suspected to have Gardner syndrome, the authors recommended gastrointestinal endoscopy to check for intestinal polyposis. Gastrointestinal endoscopic examination revealed multiple polyposes in the upper gastrointestinal tract and fundus of the stomach. As a result, the final diagnosis was Gardner syndrome.

  6. [Consensus on clinical diagnosis, treatment and pedigree management of hereditary colorectal cancer in China].

    2018-01-23

    Hereditary colorectal cancer can be divded into two categories based on the presence or absence of polyps. The first category is characterized by the development of polyposis, which includes familial adenomatous polyposis (FAP); The second category is nonpolyposis colorectal cancer, which is represented by Lynch syndrome. "Consensus on clinical diagnosis, treatment and pedigree management of hereditary colorectal cancer in China" developed by the Genetics Group of the Committee of Colorectal Cancer, Chinese Anti-cancer Association, is composed of three sections, including hereditary nonpolyposis syndrome, polyposis syndrome as well as genetic evaluation of hereditary colorectal cancer. The consensus aims to provide recommendations on management of the respective hereditary syndromes in terms of definition, clinical and pathological features, diagnostic standards, treatment, and follow-ups. In addition to describing diagnostic and treatment strategies, prophylactic treatment as well as genetic screening and pedigree monitoring is highly recommended. Through the establishment of this expert consensus, we hope to promote better understanding of hereditary colorectal cancer for clinicians and encourage standardized treatment through multidisciplinery approaches, eventually improving clinical treatment and pedigree management of hereditary colorectal cancer in China.

  7. Hereditary angioedema

    ... disease; HAE- Hereditary angioedema; Kallikrein inhibitor-HAE: bradykinin receptor antagonist-HAE; C1-inhibitors-HAE; Hives-HAE ... aunt, uncle, or grandparent. Dental procedures, sickness (including colds and the flu), and surgery may trigger HAE ...

  8. Hereditary Diffuse Gastric Cancer

    ... Hereditary Diffuse Gastric Cancer Request Permissions Hereditary Diffuse Gastric Cancer Approved by the Cancer.Net Editorial Board , 10/2017 What is hereditary diffuse gastric cancer? Hereditary diffuse gastric cancer (HDGC) is a rare ...

  9. Low-level APC mutational mosaicism is the underlying cause in a substantial fraction of unexplained colorectal adenomatous polyposis cases.

    Spier, Isabel; Drichel, Dmitriy; Kerick, Martin; Kirfel, Jutta; Horpaopan, Sukanya; Laner, Andreas; Holzapfel, Stefanie; Peters, Sophia; Adam, Ronja; Zhao, Bixiao; Becker, Tim; Lifton, Richard P; Perner, Sven; Hoffmann, Per; Kristiansen, Glen; Timmermann, Bernd; Nöthen, Markus M; Holinski-Feder, Elke; Schweiger, Michal R; Aretz, Stefan

    2016-03-01

    In 30-50% of patients with colorectal adenomatous polyposis, no germline mutation in the known genes APC, causing familial adenomatous polyposis, MUTYH, causing MUTYH-associated polyposis, or POLE or POLD1, causing polymerase-proofreading-associated polyposis can be identified, although a hereditary aetiology is likely. This study aimed to explore the impact of APC mutational mosaicism in unexplained polyposis. To comprehensively screen for somatic low-level APC mosaicism, high-coverage next-generation sequencing of the APC gene was performed using DNA from leucocytes and a total of 53 colorectal tumours from 20 unrelated patients with unexplained sporadic adenomatous polyposis. APC mosaicism was assumed if the same loss-of-function APC mutation was present in ≥ 2 anatomically separated colorectal adenomas/carcinomas per patient. All mutations were validated using diverse methods. In 25% (5/20) of patients, somatic mosaicism of a pathogenic APC mutation was identified as underlying cause of the disease. In 2/5 cases, the mosaic level in leucocyte DNA was slightly below the sensitivity threshold of Sanger sequencing; while in 3/5 cases, the allelic fraction was either very low (0.1-1%) or no mutations were detectable. The majority of mosaic mutations were located outside the somatic mutation cluster region of the gene. The present data indicate a high prevalence of pathogenic mosaic APC mutations below the detection thresholds of routine diagnostics in adenomatous polyposis, even if high-coverage sequencing of leucocyte DNA alone is taken into account. This has important implications for both routine work-up and strategies to identify new causative genes in this patient group. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  10. Germline variants in Hamartomatous Polyposis Syndrome-associated genes from patients with one or few hamartomatous polyps

    Jelsig, Anne Marie; Brusgaard, Klaus; Hansen, Tine Plato

    2016-01-01

    OBJECTIVE: A subgroup of patients with hamartomatous polyps in the GI tract has a hereditary Hamartomatous Polyposis Syndrome with an increased risk of cancer. The distinction between patients with one or few polyps and patients with a syndrome can be difficult. A pathogenic germline mutation can...... significance of genetic variants can be difficult to interpret. A family history of polyps, cancer, or extraintestinal findings or a minimum of 3-5 polyps seems to be relevant information to include before genetic testing....

  11. Hereditary angioedema.

    Bracho, Francisco A

    2005-11-01

    Hereditary angioedema is an autosomal-dominant deficiency of C1 inhibitor--a serpin inhibitor of kallikrein, C1r, C1s, factor XII, and plasmin. Quantitative or qualitative deficiency of C1 inhibitor leads to the generation of vasoactive mediators, most likely bradykinin. The clinical syndrome is repeated bouts of nonpruritic, nonpitting edema of the face, larynx, extermities, and intestinal viscera. Recently, investigators, physicians, and industry have demonstrated a renewed interest in the biology and treatment of hereditary angioedema. Investigators have generated a C1INH-/- mouse model that has demonstrated the importance of the contact activation system for hereditary angioedema-related vascular permeability. An interactive database of mutations is available electronically. Investigators have continued exploration into mRNA/protein levels. The proceedings of a recent workshop have been impressive in the scope and depth. Clinicians have produced consensus documents and expert reviews. The pharmaceutical industry has initiated clinical trails with novel agents. Hereditary angioedema is often misdiagnosed and poorly treated. Diagnosis requires careful medical and family history and the measurement of functional C1 inhibitor and C4 levels. Attenuated androgens, anti-fibrinolytics, and C1 inhibitor concentrates are used for long-term and preprocedure prophylaxis, but have significant drawbacks. C1 inhibitor concentrates and fresh frozen plasma are available for acute intervention. The mainstays of supportive care are airway monitoring, pain relief, hydration, and control of nausea. New agents such as recombinant C1 inhibitor, kallikrein inhibitors, and bradykinin inhibitors may offer safer and more tolerable treatments.

  12. Causes of death in familial adenomatous polyposis

    Galle, T S; Juel, K; Bülow, S

    1999-01-01

    The prognosis in familial adenomatous polyposis (FAP) has improved over the past decades owing to a reduction in the prevalence of colorectal cancer, resulting from effective early screening. During the same period several polyposis registers have recorded an increasing number of deaths due to du...... to duodenal/periampullary cancer and desmoid tumours. The aim of this study was to examine the causes of death with special emphasis on duodenal/periampullary cancer.......The prognosis in familial adenomatous polyposis (FAP) has improved over the past decades owing to a reduction in the prevalence of colorectal cancer, resulting from effective early screening. During the same period several polyposis registers have recorded an increasing number of deaths due...

  13. Laparoscopic restorative total proctocolectomy with ileal pouch anal anastomosis for familial adenomatous polyposis.

    Palanivelu, C; Jani, Kalpesh; Sendhilkumar, K; Parthasarathi, R; Senthilnathan, P; Maheshkumar, G

    2008-01-01

    Familial adenomatous polyposis is a hereditary disease characterized by the presence of thousands of colonic adenomas, which, if untreated, invariably undergo malignant transformation. Because this disease manifests at a young age, the laparoscopic approach to perform surgery would be desirable due to its cosmetic benefits. We describe our experience with this procedure and review the literature on the topic. This is a case series of 15 patients who underwent restorative proctocolectomy with ileo-anal pouch anastomosis for familial adenomatous polyposis between 2000 and 2007. The salient operative steps are described. There were 9 males and 6 females, 32 to 52 years of age, with an average age of 44.8 years. The median body mass index was 21.5 (range, 17 to 28). Rectal cancer was already present in 4 patients at the time of diagnosis. The median operating time was 225 minutes. Mean blood loss was 60 mL, with none of the patients requiring perioperative blood transfusion. None of the surgeries required conversion to the open approach. Bowel function resumed on the second postoperative day in 12 patients and on the third postoperative day in 3 patients. The median hospital stay was 8 days. Postoperatively, there was no mortality and no serious morbidity. Laparoscopic restorative proctocolectomy with ileal pouch anal anastomosis is a feasible surgery for familial adenomatous polyposis, and considering its cosmetic benefit, is a desirable option for this group of predominantly young patients.

  14. Middle ear function in sinonasal polyposis.

    Bakhshaee, Mehdi; Ardakani, Hossein Payedar; Ghazizadeh, Amir Hossain; Movahed, Rahman; Jarahi, Lida; Rajati, Mohsen

    2016-10-01

    Nasal airway patency has long been considered a major factor in ear health. The aim of this study was to determine the effect of sinonasal polyposis on middle ear and eustachian tube (ET) functionality. Forty-four individuals with polyposis, 23 with non-polyposis nasal obstruction, and 23 healthy controls were enrolled. Demographic, clinical and imaging data of all participants were collected and ET function tests and audiologic tests were performed. Hearing loss (p = 0.02), flat tympanogram (p = 0.02), disturbed Toynbee and Valsalva tests (p = 0.01), and the prevalence of allergy (p = 0.04) and purulent nasal discharge (p polyposis group than the other groups. Regression analysis revealed that infection and allergy have more important roles in ET function than the nasal obstruction. Polyposis could impede ET function; however, it is probably not because of its obstructive nature, but because of the associated increased risk of infection.

  15. Hereditary hemochromatosis

    Stephen A. Geller

    2015-03-01

    Full Text Available Hereditary hemochromatosis (HH is the most commonly identified autosomal recessive genetic disorder in the white population, characterized by increased intestinal iron absorption and secondary abnormal accumulation in parenchymal organs, not infrequently accompanied by functional impairment. This entity is associated with mutations of the HFE gene (located on the short arm of chromosome 6 at location 6p22.2; closely linked to the HLA-A3 locus, which encodes the HFE protein, a membrane protein thought to regulate iron absorption by affecting the interaction between transferrin receptor and transferrin.

  16. The genetic basis of colonic adenomatous polyposis syndromes.

    Talseth-Palmer, Bente A

    2017-01-01

    Colorectal cancer (CRC) is one of the most common forms of cancer worldwide and familial adenomatous polyposis (FAP) accounts for approximately 1% of all CRCs. Adenomatous polyposis syndromes can be divided into; familial adenomatous polyposis (FAP) - classic FAP and attenuated familial adenomatous polyposis (AFAP), MUTYH-associated polyposis (MAP), NTHL1-associated polyposis (NAP) and polymerase proofreading-associated polyposis (PPAP). The polyposis syndromes genetics and clinical manifestation of disease varies and cases with clinical diagnosis of FAP might molecularly show a different diagnosis. This review examines different aspects of the adenomatous polyposis syndromes genetics and clinical manifestation of disease; in addition the genotype-phenotype and modifier alleles of FAP will be discussed. New technology has made it possible to diagnose some of the APC mutation negative patients into their respective syndromes. There still remain many molecularly undiagnosed adenomatous polyposis patients indicating that there remain causative genes to be discovered and with today's technology these are expected to be identified in the near future. The knowledge about the role of modifier alleles in FAP will contribute to improved pre-symptomatic diagnosis and treatment. New novel mutations will continually be discovered in genes already associated with disease and new genes will be discovered that are associated with adenomatous polyposis. The search for modifier alleles in FAP should be made a priority.

  17. Familial adenomatous polyposis. Report of a case

    Barroso Marquez, Lisset; Tusen Toledo, Yunia; Chao Gonzalez, Lissette; Alonso Soto, Jordi

    2009-01-01

    Familial adenomatous polyposis is an inherited disease characterized by the appearance of multiple colorectal adenomas by the teenagers and with an incidence of colorectal cancer approaching 100%. We present herein a 39-years-old man with an atypical form of the disease, an attenuated variant, and we comment the importance of management guidelines for surveillance of the patients and their families

  18. Genetic testing in inherited polyposis syndromes - how and why?

    Lee, G H; Payne, S J; Melville, A; Clark, S K

    2014-08-01

    There have been recent advances in genetic testing enabling accurate diagnosis of polyposis syndromes by identifying causative gene mutations, which is essential in the management of individuals with polyposis syndrome and predictive genetic testing of their extended families. There are some similarities in clinical presentation of various polyposis syndromes, which may pose a challenge to diagnosis. In this review, we discuss the clinical presentation of the main polyposis syndromes and the process of genetic testing, including the latest advancement and future of genetic testing. We aim to reiterate the importance of genetic testing in the management of polyposis syndromes, potential pitfalls associated with genetic testing and recommendations for healthcare professionals involved with the care of polyposis patients. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

  19. Adult T-cell leukemia/lymphoma presenting multiple lymphomatous polyposis

    Akira Hokama; Nobuyuki Takasu; Jiro Fujita; Takeaki Tomoyose; Yu-ichi Yamamoto; Takako Watanabe; Tetsuo Hirata; Fukunori Kinjo; Seiya Kato; Koichi Ohshima; Hiroshi Uezato

    2008-01-01

    Multiple lymphomatous polyposis (HLP) is an unusual form of non-Hodgkin's lymphoma characterized by polyps throughout the gastrointestinal tract. It has been reported that most MLP are observed in cases with mantle cell lymphoma of B-cell type. We herein present a case of a 66-year-old man with adult T-cell leukemia/lymphoma (ATLL). Colonoscopy revealed MLP throughout the colon and histopathological findings of ATLL cell infiltration. The patient died despite combination of chemotherapy. The literature of manifestations of colonic involvement of ATLL is reviewed and the importance of endoscopic evaluation to differentiate ATLL intestinal lesions from opportunistic infectious enterocolitis is discussed.

  20. Familial adenomatous polyposis: from bedside to benchside.

    O'Sullivan, M J

    2012-02-03

    Familial adenomatous polyposis (FAP) is a dominantly inherited cancer-predisposition syndrome with an incidence of between 1:17,000 and 1:5,000. The condition has been causally linked to mutation of the adenomatous polyposis coli (APC) gene located at 5q21. Virtually all mutations in the APC gene are truncating mutations, resulting in loss of function of the APC protein. Spontaneous germline mutation of this gene occurs frequently and accounts for the high incidence of FAP. The gene is somatically mutated at an early point in the colorectal adenoma-carcinoma progression. Somatic mutations of the APC gene are also frequently observed in a variety of other human carcinomas. Isolation of the APC gene has led to the recognition of genotype-phenotype correlations and, together with protein studies, has helped to elucidate the structure and function of the APC protein. This report aims to take the reader from a clinical appreciation to a molecular understanding of FAP.

  1. Sinonasal polyposis: investigation by direct coronal CT

    Drutman, J.; Harnsberger, H.R.; Babbel, R.W.; Sonkens, J.W.; Braby, D.

    1994-01-01

    To demonstrate the typical clinical and CT features of sinonasal polyposis, we reviewed the clinical records and preoperative direct coronal CT scans of 35 patients with surgically proven disease. Symptoms included progressive nasal stuffiness (100 %), rhinorrhea (69 %), facial pain (60 %), headache (43 %) and anosmia (17 %). We found associations with rhinitis (46 %), asthma (29 %) and aspirin sensitivity (9 %). Coronal CT features included polypoid masses in the nasal cavity (91 %), partial or complete pansinus opacification (90 %), enlargement of infundibula (89 %), bony attenuation of the ethmoid trabeculae (63 %) and nasal septum (37 %), opacified ethmoid sinuses with convex lateral walls (51 %) and air-fluid levels (43 %). The latter feature correlated with symptoms and signs of acute sinusitis in only 40 % of patients. Recognition of sinonasal polyposis is important to the endoscopic surgeon since it can be the most troubling sinonasal inflammatory disease to manage due to its aggressive nature and tendency to recur despite appropriate treatment. (orig.)

  2. Attenuated familial adenomatous polyposis and Muir-Torre syndrome linked to compound biallelic constitutional MYH gene mutations.

    Ponti, G; Ponz de Leon, M; Maffei, S; Pedroni, M; Losi, L; Di Gregorio, C; Gismondi, V; Scarselli, A; Benatti, P; Roncari, B; Seidenari, S; Pellacani, G; Varotti, C; Prete, E; Varesco, L; Roncucci, L

    2005-11-01

    Attenuated familial adenomatous polyposis and Muir-Torre syndrome linked to compound biallelic constitutional MYH gene mutations.Peculiar dermatologic manifestations are present in several heritable gastrointestinal disorders. Muir-Torre syndrome (MTS) is a genodermatosis whose peculiar feature is the presence of sebaceous gland tumors associated with visceral malignancies. We describe one patient in whom multiple sebaceous gland tumors were associated with early onset colon and thyroid cancers and attenuated polyposis coli. Her family history was positive for colonic adenomas. She had a daughter presenting with yellow papules in the forehead region developed in the late infancy. Skin and visceral neoplasms were tested for microsatellite instability and immunohistochemical status of mismatch repair (MMR), APC and MYH proteins. The proband colon and skin tumors were microsatellite stable and showed normal expression of MMR proteins. Cytoplasmic expression of MYH protein was revealed in colonic cancer cells. Compound heterozygosity due to biallelic mutations in MYH, R168H and 379delC, was identified in the proband. The 11-year-old daughter was carrier of the monoallelic constitutional mutation 379delC in the MYH gene; in the sister, the R168H MYH gene mutation was detected. This report presents an interesting case of association between MYH-associated polyposis and sebaceous gland tumors. These findings suggest that patients with MTS phenotype that include colonic polyposis should be screened for MYH gene mutations.

  3. Fungal Agents as a Cause of Nasal Polyposis

    Mohammad Nejadkazem

    2015-01-01

    Full Text Available Introduction: Sinonasal polyposis is the most common tumor of nasal cavity and sinuses. Its complications are but not limited to sinusitis, breathing difficulties, hyposmia, anosmia and bone erosion. Methods and materials: A total of 98 patients with sinonasal polyposis were examined for suspicious causative fungal agent. Results: Direct microscopy and culture confirmed fungal agent in 8 patients (8.1% from which 3 cases had Alternaria spp, 1 patient Aspergillus spp, 1 patient Bipolaris spp, and 3 patients yeast. Conclusion: Fungi may be considered as a potential cause of sinonasal polyposis.   Keywords: Sinonasal Polyposis, Rhinosinusitis, Fungi

  4. INCIDENCE OF FUNGAL ELEMENTS IN SINONASAL POLYPOSIS

    Santhosh G. S

    2016-12-01

    Full Text Available BACKGROUND Nasal polyposis is a disease entity characterised by formation of pseudoedema of sinonasal mucus membrane progressing to form polyps. It presents clinically with nasal obstruction and fleshy masses in the nasal cavity. The nasal mucosa reacts to formation of polypi in allergic fungal sinusitis also. The present study is an attempt to demonstrate possible fungal elements from the polypi removed during surgery by KOH study and HPE study. The aim of the study is to find out the incidence of fungal elements in sinonasal polyposis. MATERIALS AND METHODS 50 patients attending the ENT OPD for nasal obstruction and showing polypi on anterior rhinoscopy were selected. All the patients were subjected to surgery and specimens collected were subjected to KOH study and histopathology to demonstrate fungal elements. RESULTS Among 50 patients, the age range was from 9-57 years; mean age- 36.46 years. The male-to-female ratio was 1.5:1. Deviated nasal septum was found in 38% of patients. Among the unilateral cases, 47% were antrochoanal polyps and 53% were ethmoid polyps. Out of 50 patients, only 3 specimens were positive for fungal elements with KOH study and only 2 cases with fungal culture. Thus, the incidence of fungal elements in sinonasal polyposis was 6%. CONCLUSION The incidence of fungal elements in sinonasal polyposis was 6%. Histopathological examination of polypectomy specimen was negative for invasive fungal disease and showed inflammatory changes only. There is no difference in the detection of the presence of fungal by two methods.

  5. Clinical aspects of patients with nasal polyposis

    Crespo, Cassio Caldini

    2009-09-01

    Full Text Available Introduction: The nasal Polyposis is a non-neoplastic chronic inflammatory process of the nasal mucosa. It causes a large impact to the patients' life quality. Objective: To analyze the characteristics of patients with polyposis in the Brazilian population. Method: 50 records of patients followed up in a tertiary hospital and submitted to surgical treatment of nasal polyposis were reviewed. The following variables were analyzed: age, sex, smoking, presence of asthma, presence of AAS intolerance and also the clinical manifestations: anterior and posterior rhinorrhea, nasal obstruction, hyposmia, sneezing and pruritus. The tomographic evaluation system applied was that of Lund-McKay. For statistical analysis we applied the chi-square test with p<0.05. Results: Out of 50 patients evaluated, 28 were male and 22 were female. The mean age range was of 40.8 years. The main clinical manifestation was nasal obstruction in 100% of the patients. In the tomographic evaluation, according to the Lund-McKay system, the average scoring was of 10.9. Discussion: No statistically significant difference was obtained in the patients' general symptoms compared to the patients with asthma or AAS intolerance. The difference in the Lund-McKay score was statistically significant in the populations studied. The symptoms were similar to the frequency of symptoms of other works. Conclusion: We concluded that the main complaint of the patients with nasal polyposis is nasal obstruction, the most affected age is of about 40 years old, without preference of sex. The severity of tomographic findings is higher in patients with asthma and AAS intolerance.

  6. Constitutional MLH1 methylation presenting with colonic polyposis syndrome and not Lynch syndrome.

    Kidambi, Trilokesh D; Blanco, Amie; Van Ziffle, Jessica; Terdiman, Jonathan P

    2016-04-01

    At least one-third of patients meeting clinical criteria for Lynch syndrome will have no germline mutation and constitutional epimutations leading to promoter methylation of MLH1 have been identified in a subset of these patients. We report the first case of constitutional MLH1 promoter methylation associated with a colonic polyposis syndrome in a 39 year-old man with a family history of colorectal cancer (CRC) and a personal history of 21 polyps identified over 8 years as well as the development of two synchronous CRCs over 16 months who was evaluated for a hereditary cancer syndrome. Immunohistochemistry (IHC) of multiple tumors showed absent MLH1 and PMS2 expression, though germline testing with Sanger sequencing and multiplex ligation-dependent probe amplification of these mismatch repair genes (MMR) genes was negative. A next generation sequencing panel of 29 genes also failed to identify a pathogenic mutation. Hypermethylation was identified in MLH1 intron 1 in tumor specimens along with buccal cells and peripheral white blood cells, confirming the diagnosis of constitutional MLH1 promoter methylation. This case highlights that constitutional MLH1 methylation should be considered in the differential diagnosis for a polyposis syndrome if IHC staining shows absent MMR gene expression.

  7. Genetics Home Reference: familial adenomatous polyposis

    ... Rectal Surgeons: Hereditary Colorectal Cancer Registries Colon Cancer Alliance Colorectal Cancer ... This Page Attard TM, Cuffari C, Tajouri T, Stoner JA, Eisenberg MT, Yardley JH, Abraham SC, Perry D, Vanderhoof J, Lynch H. Multicenter ...

  8. APC gene mutations and extraintestinal phenotype of familial adenomatous polyposis

    Giardiello, F. M.; Petersen, G. M.; Piantadosi, S.; Gruber, S. B.; Traboulsi, E. I.; Offerhaus, G. J.; Muro, K.; Krush, A. J.; Booker, S. V.; Luce, M. C.; Laken, S. J.; Kinzler, K. W.; Vogelstein, B.; Hamilton, S. R.

    1997-01-01

    Familial adenomatous polyposis (FAP) is caused by germline mutation of the adenomatous polyposis coli (APC) gene on chromosome 5q. This study assessed genotype-phenotype correlations for extraintestinal lesions in FAP. Mutations of the APC gene were compared with the occurrence of seven

  9. Broad phenotypic spectrum in familial adenomatous polyposis; from early onset and severe phenotypes to late onset of attenuated polyposis with the first manifestation at age 72

    Johannsson Oskar

    2008-11-01

    Full Text Available Abstract Background Familial adenomatous polyposis (FAP is typically characterized by multiple colonic polyps and frequent extracolonic features. Whereas the number of colonic polyps has been linked to the APC gene mutation, possible genotype-phenotype correlations largely remain to be defined for the extracolonic manifestations. Methods Full genomic sequencing combined with multiplex ligation-dependent probe amplification was used to identify APC gene mutations, which were correlated to the clinical presentations. Results 10 novel APC gene mutations were identified in 11 families. A broad spectrum of extracolonic manifestations was identified in most of these individuals. Two sisters with an insertion in codon 528 (c.1582_1583insGC both showed severe phenotypes with classical polyposis, upper gastrointestinal polyps and thyroid cancer. A woman with a 3'APC mutation (c.5030_5031insAA developed colon cancer at age 72 as the first manifestation of attenuated FAP. Conclusion With an increasing number of FAP families diagnosed, a broad and variable tumor spectrum and a high frequency of extracolonic manifestations are gradually recognized. We report novel APC mutations and present two FAP cases that suggest familial aggregation of thyroid cancer and demonstrate the need to consider attenuated FAP also among elderly patients with colon cancer.

  10. Omalizumab a new prospective: a nasal polyposis.

    Cavaliere, C; Begvarfaj, E; Frati, F; Masieri, S

    2018-01-01

    Omalizumab, a monoclonal antibody against IgE, may be effective on nasal polyps, but its use is not currently authorized to treat that disease. We report the cases of three patients who were given omalizumab for asthma after undergoing nasal surgical polypectomy. Although such procedure is frequently followed by polyp recurrence, none of the three patients developed this complication, and in one subject the regression of initial polyp return was registered after starting omalizumab. Our data support the hypothesis that omalizumab may be useful to treat nasal polyposis.

  11. Genetics Home Reference: hereditary pancreatitis

    ... Facebook Twitter Home Health Conditions Hereditary pancreatitis Hereditary pancreatitis Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Hereditary pancreatitis is a genetic condition characterized by recurrent episodes ...

  12. Multidetector-row CT duodenography in familial adenomatous polyposis: a pilot study

    Taylor, S.A.; Halligan, S.; Moore, L.; Saunders, B.P.; Gallagher, M.; Phillips, R.K.S.; Bartram, C.I.

    2004-01-01

    AIM: To investigate the feasibility of using multidetector-row computed tomography (CT) duodenography to stage duodenal polyposis in patients with familial adenomatous polyposis. MATERIALS AND METHODS: Six patients underwent multidetector-row CT duodenography before upper gastrointestinal endoscopy. A single-blinded radiologist used a surface shaded three-dimensional endoluminal fly though and two-dimensional axial and multiplanar reformats to assign a score for maximum polyp size and number based on the Spigelman classification. Comparison was made with the corresponding Spigelman scores obtained from subsequent endoscopy. RESULTS: CT duodenography was technically successful in five of six patients. The CT derived Spigelman score based on maximum polyp size was accurate in all five patients. The CT derived Spigelman score based on polyp number was accurate in only two cases: Polyp number was overestimated in one patient and underestimated in a further two. In retrospect, fine carpeting of tiny duodenal polyps was poorly visualized with CT. CONCLUSIONS: CT duodenography is technically feasible and accurately predicts maximum polyp size but CT estimates of polyp number are relatively inaccurate. CT duodenography potentially has a useful role for duodenal surveillance in those patients intolerant of conventional endoscopy

  13. Brazilian guidelines for the diagnosis and treatment of hereditary angioedema

    Pedro Giavina-Bianchi

    2011-01-01

    Full Text Available Hereditary angioedema is an autosomal dominant disease characterized by edema attacks with multiple organ involvement. It is caused by a quantitative or functional deficiency of the C1 inhibitor, which is a member of the serine protease inhibitor family. Hereditary angioedema is unknown to many health professionals and is therefore an underdiagnosed disease. The causes of death from hereditary angioedema include laryngeal edema with asphyxia. The estimated mortality rate in patients in whom the disease goes undetected and who are therefore incorrectly treated is 25-40%. In addition to edema of the glottis, hereditary angioedema often results in edema of the gastrointestinal tract, which can be incapacitating. Patients with hereditary angioedema may undergo unnecessary surgical interventions because the digestive tract can be the primary or only organ system involved, thus mimicking acute surgical abdomen. It is estimated that patients with hereditary angioedema experience some degree of disability 20-100 days per year. The Experts in Clinical Immunology and Allergy of the "Associação Brasileira de Alergia e Imunopatologia -ASBAI" developed these guidelines for the diagnosis, therapy, and management of hereditary angioedema.

  14. Brazilian guidelines for the diagnosis and treatment of hereditary angioedema.

    Giavina-Bianchi, Pedro; França, Alfeu T; Grumach, Anete S; Motta, Abílio A; Fernandes, Fátima R; Campos, Regis A; Valle, Solange O; Rosário, Nelson A; Sole, Dirceu

    2011-01-01

    Hereditary angioedema is an autosomal dominant disease characterized by edema attacks with multiple organ involvement. It is caused by a quantitative or functional deficiency of the C1 inhibitor, which is a member of the serine protease inhibitor family. Hereditary angioedema is unknown to many health professionals and is therefore an underdiagnosed disease. The causes of death from hereditary angioedema include laryngeal edema with asphyxia. The estimated mortality rate in patients in whom the disease goes undetected and who are therefore incorrectly treated is 25-40%. In addition to edema of the glottis, hereditary angioedema often results in edema of the gastrointestinal tract, which can be incapacitating. Patients with hereditary angioedema may undergo unnecessary surgical interventions because the digestive tract can be the primary or only organ system involved, thus mimicking acute surgical abdomen. It is estimated that patients with hereditary angioedema experience some degree of disability 20-100 days per year. The Experts in Clinical Immunology and Allergy of the "Associação Brasileira de Alergia e Imunopatologia -ASBAI" developed these guidelines for the diagnosis, therapy, and management of hereditary angioedema.

  15. Learning about Hereditary Hemochromatosis

    Skip to main content Learning About Hereditary Hemochromatosis Enter Search Term(s): Español Research Funding An Overview Bioinformatics Current Grants Education and Training Funding Extramural Research ...

  16. Evaluation of management of desmoid tumours associated with familial adenomatous polyposis in Dutch patients

    Nieuwenhuis, M. H.; Mathus-Vliegen, E. M.; Baeten, C. G.; Nagengast, F. M.; van der Bijl, J.; van Dalsen, A. D.; Kleibeuker, J. H.; Dekker, E.; Langers, A. M.; Vecht, J.; Peters, F. T.; van Dam, R.; van Gemert, W. G.; Stuifbergen, W. N.; Schouten, W. R.; Gelderblom, H.; Vasen, H. F. A.

    2011-01-01

    BACKGROUND: The optimal treatment of desmoid tumours is controversial. We evaluated desmoid management in Dutch familial adenomatous polyposis (FAP) patients. METHODS: Seventy-eight FAP patients with desmoids were identified from the Dutch Polyposis Registry. Data on desmoid morphology, management,

  17. Risk of gynecologic cancers in Danish hereditary non-polyposis colorectal cancer families

    Boilesen, Astrid Elisabeth Bruun; Bisgaard, Marie Luise; Bernstein, Inge

    2008-01-01

    , clinical and MMR gene mutation data were retrieved. RESULTS: In a total of 105 cases of endometrial cancer, there was no significant difference in MSH2, MSH6 and MLH1 mutation carrier frequency. Compared to the general population, mutation carriers had a 20 times increase in lifetime risk of endometrial...

  18. Immunopurification of adenomatous polyposis coli (APC) proteins

    2013-01-01

    Background The adenomatous polyposis coli (APC) tumour suppressor gene encodes a 2843 residue (310 kDa) protein. APC is a multifunctional protein involved in the regulation of β-catenin/Wnt signalling, cytoskeletal dynamics and cell adhesion. APC mutations occur in most colorectal cancers and typically result in truncation of the C-terminal half of the protein. Results In order to investigate the biophysical properties of APC, we have generated a set of monoclonal antibodies which enable purification of recombinant forms of APC. Here we describe the characterisation of these anti-APC monoclonal antibodies (APC-NT) that specifically recognise endogenous APC both in solution and in fixed cells. Full-length APC(1–2843) and cancer-associated, truncated APC proteins, APC(1–1638) and APC(1–1311) were produced in Sf9 insect cells. Conclusions Recombinant APC proteins were purified using a two-step affinity approach using our APC-NT antibodies. The purification of APC proteins provides the basis for detailed structure/function analyses of full-length, cancer-truncated and endogenous forms of the protein. PMID:24156781

  19. Subjective Evaluation of Vocal Quality in Nasal Polyposis

    Ziya Saltürk

    2014-12-01

    Full Text Available Aim: Nose is a resonator organ in production of voice. The aim of this study was to evaluate the effects of nasal obstruction caused by nasal polyposis on voice quality subjectively. Methods: Thirty-six patients diagnosed with nasal polyposis were included in the study. The 30-item voice handicap index 30 was used in order to evaluate subjective status of voice. Nasal endoscopy and computed tomography imaging of the paranasal sinuses were performed for each patient. Lund-Kennedy endoscopy scores and Lund-MacKay computed tomography scores were evaluated. Control group composed of 20 healthy subjects. Results: The mean voice handicap score in the patient group was 43.16 (SD 15.53 and it was 2.15 (SD 1.92 in control group. There was a statistically significant difference between the groups (p=0.001. The mean Lund-Kennedy and Lund-Mackay scores were 8.58 (SD 2.5 and 17 (SD 5.52, respectively. It was found that increased severity of nasal polyposis was the cause for decreased satisfaction with voice quality. Conclusion: Nasal obstruction caused by nasal polyposis affects voice quality adversely and as the severity of nasal polyposis increases, satisfaction with voice quality decreases.

  20. Dental anomalies in pediatric patients with familial adenomatous polyposis.

    Septer, Seth; Bohaty, Brenda; Onikul, Robin; Kumar, Vandana; Williams, Karen B; Attard, Thomas M; Friesen, Craig A; Friesen, Lynn Roosa

    2018-04-01

    Familial adenomatous polyposis patients often present with non-malignant extra-intestinal manifestations which include dental anomalies that may be evident prior to the appearance of the colonic adenomas. The aims of this study were to describe the prevalence and type of dental anomalies and the relationships between gene mutations and dental anomalies in these patients. Twenty-two pediatric familial adenomatous polyposis patients and 46 controls, who were age and gender matched participated. Familial adenomatous polyposis patient's had a dental examination with panoramic radiograph and medical record review for age at diagnosis, the presence of the adenomatous polyposis coli gene mutation, and determination of other extra-intestinal manifestations on the body. The control group was identified from a retrospective chart review and selected if there was a current panoramic radiograph. The only significant difference between familial adenomatous polyposis patients and controls were the presence of jaw osteomas and sclerosis (p = .0001). Patients with a mutation in, or upstream of codon 1309 had a higher frequency of osteomas (77.8%) and jaw-bone sclerosis (44.4%), and 77% of these had at least one dental anomaly. This preliminary study showed an association between a genetic variant at, or upstream of codon 1309, and radiographic dental anomalies.

  1. [Rare indication of cephalic duodenopancreatectomy with total gastrectomy--periampullary carcinoma in moderate form of familial adenomatous polyposis].

    Stănciulea, Oana; Preda, Carmen; Herlea, V; Popa, Monica; Ulmeanu, D; Vasilescu, C

    2007-01-01

    We present the case of a 52 years old man, with significant familial history, diagnosed with familial adenomatous polyposis-attenuated form, with no clinical and endoscopic surveillance until 2001 when he was admitted for an upper gastrointestinal haemorrhage episode. Upper gastrointestinal scopy revealed duodenal adenomatous polyps and gastric hyperplastic polyps. The patient underwent duodenopancreatectomy with total gastrectomy. The histopathological exam revealed duodenal G2 adenocarcinoma pT3N0, and gastric hyperplastic polyps with no signs of dysplasia. The surgical procedure was followed by chemotherapy. In 2002 the patient was admitted for rectal bleeding and colonoscopy showed 2 sigmoid polyps, appropriate for endoscopic removal and a poly-lobate polyp in the transverse colon. The patient underwent transverse colectomy (the histopathological exam--in situ carcinoma). March 2003--the patient underwent endoscopic removal for a rectal polyp (histopathological exam: moderate dysplasia). In 2005 was noted a pulmonary nodule, located in the postero-apical segment of upper left lobe, for which left superior lobe resection was performed (the histopathological exam: metastatic adenocarcinoma). In May 2006 was performed an exploratory laparotomy. Intraoperatively were noted: peritoneal carcinomatosis and multiple liver metastasis. The surgical procedure recommended in patients with attenuated form of familial adenomatous polyposis and suspect periampullary lesions is duodenopancreatectomy. The particularity of the case is the association of total gastrectomy for gastric hyperplastic polyps.

  2. Peutz-Jeghers Syndrome Report of one case associated with Gastrointestin Carcinoma

    SHARIAT F.

    1982-07-01

    Full Text Available The peutz-Jeghers syndrome is characterized by an association of gastrointestinal polyposis with rnelain spots on oral mucosa, lips, and skin. This symdrorne is inherited as a simple mendelian autosomal dominant trait. Intussusception is by far the most common complication. Although these polyps are widely regarded as hamartomas and rarely undergo malignant change, they have been reported to be associated with carcinoma of gastrointestin and ovary."nIn the case reported here, the cancer developed from hamartomatous polyps.

  3. Hereditary Hearing Loss.

    Tran, LenhAnh P.; Grundfast, Kenneth M.

    1997-01-01

    This article discusses inheritance patterns in hearing loss, epidemiology, clues to genetic causes, locating genes that cause hereditary disorders, genes related to hearing loss disorders in individuals with Usher syndrome, Waardenburg syndrome, Treacher-Collins syndrome, Branchio-oto-renal and Pendred syndromes, and the significance of finding…

  4. Hereditary periodic fever syndromes

    McDermott, MF; Frenkel, J

    Hereditary periodic fever syndromes are defined by recurrent attacks of generalised inflammation for which no infectious or auto-immune cause can be identified. For most of these disorders, the molecular basis has recently been elucidated. This has opened the prospect of novel therapeutic

  5. Mutation analysis of the adenomatous polyposis coli (APC) gene in Danish patients with familial adenomatous polyposis (FAP)

    Bisgaard, Marie Luise; Ripa, Rasmus S; Bülow, Steffen

    2004-01-01

    Development of one hundred or more adenomas in the colon and rectum is diagnostic for the dominantly inherited, autosomal disease Familial Adenomatous Polyposis (FAP). It is possible to identify a mutation in the Adenomatous Polyposis Coli (APC) gene in approximately 80% of the patients, and almost...... 1,000 different pathogenic mutations have been identified in the APC gene up till now. We report 12 novel and 24' previously described germline APC mutations from 48 unrelated Danish families. Four families with the mutation localized in the 3' region of the gene showed great variance in phenotypic...

  6. Hereditary angioedema: a bradykinin-mediated swelling disorder.

    Björkqvist, Jenny; Sala-Cunill, Anna; Renné, Thomas

    2013-03-01

    Edema is tissue swelling and is a common symptom in a variety of diseases. Edema form due to accumulation of fluids, either through reduced drainage or increased vascular permeability. There are multiple vascular signalling pathways that regulate vessel permeability. An important mediator that increases vascular leak is the peptide hormone bradykinin, which is the principal agent in the swelling disorder hereditary angioedema. The disease is autosomal dominant inherited and presents clinically with recurrent episodes of acute swelling that can be life-threatening involving the skin, the oropharyngeal, laryngeal, and gastrointestinal mucosa. Three different types of hereditary angiodema exist in patients. The review summarises current knowledge on the pathophysiology of hereditary angiodema and focuses on recent experimental and pharmacological findings that have led to a better understanding and new treatments for the disease.

  7. A possible role of stem cells in nasal polyposis

    Klimek, L.; Koennecke, M.; Mullol, J.; Hellings, P. W.; Wang, D. Y.; Fokkens, W.; Gevaert, P.; Wollenberg, B.

    2017-01-01

    Since its discovery, the understanding of stem/progenitor cells raised dramatically in the last decade. Their regenerative potential is important to develop new therapeutic applications, but the identification advanced much faster than our understanding of stem/progenitor cells. In nasal polyposis,

  8. Small bowel endoscopy in familial adenomatous polyposis and Lynch syndrome

    Koornstra, Jan Jacob

    Patients with familial adenomatous polyposis (FAP) and patients with Lynch syndrome have an increased risk of developing small intestinal neoplasia. In both conditions, the lifetime risk to develop small bowel cancer is estimated to be around 5%. In FAP, this risk is associated with the degree of

  9. Lessons from the hepatoblastoma-familial polyposis connection ...

    Background. Approximately one-third of hepatoblastoma (HB) patients have associated congenital abnormalities, but familial recurrence is rare, except in association with familial adenomatous polyposis (FAP). This correlation may be missed if not actively sought, with implications for long-term outcome and management.

  10. Hopefulness predicts resilience after hereditary colorectal cancer genetic testing: a prospective outcome trajectories study

    Chu Annie TW; Bonanno George A; Ho Judy WC; Ho Samuel MY; Chan Emily MS

    2010-01-01

    Abstract Background - Genetic testing for hereditary colorectal cancer (HCRC) had significant psychological consequences for test recipients. This prospective longitudinal study investigated the factors that predict psychological resilience in adults undergoing genetic testing for HCRC. Methods - A longitudinal study was carried out from April 2003 to August 2006 on Hong Kong Chinese HCRC family members who were recruited and offered genetic testing by the Hereditary Gastrointestinal Cancer R...

  11. Combined pulmonary involvement in hereditary lysozyme amyloidosis with associated pulmonary sarcoidosis: a case report.

    McCarthy, Cormac; Deegan, Alexander P; Garvey, John F; McDonnell, Timothy J

    2013-12-17

    Sarcoidosis is a multisystem inflammatory disorder of unknown cause which can affect any organ system. Autosomal dominant lysozyme amyloidosis is a very rare form of hereditary amyloidosis. The Arg64 variant is extraordinarily rare with each family showing a particular pattern of organ involvement, however while Sicca syndrome, gastrointestinal involvement and renal failure are common, lymph node involvement is very rare. In this case report we describe the first reported case of sarcoidosis in association with hereditary lysozyme amyloidosis.

  12. Hereditary breast cancer

    Larsen, Martin J; Thomassen, Mads; Gerdes, Anne-Marie

    2014-01-01

    Pathogenic mutations in BRCA1 or BRCA2 are only detected in 25% of families with a strong history of breast cancer, though hereditary factors are expected to be involved in the remaining families with no recognized mutation. Molecular characterization is expected to provide new insight...... into the tumor biology to guide the search of new high-risk alleles and provide better classification of the growing number of BRCA1/2 variants of unknown significance (VUS). In this review, we provide an overview of hereditary breast cancer, its genetic background, and clinical implications, before focusing...... on the pathologically and molecular features associated with the disease. Recent transcriptome and genome profiling studies of tumor series from BRCA1/2 mutation carriers as well as familial non-BRCA1/2 will be discussed. Special attention is paid to its association with molecular breast cancer subtypes as well...

  13. Hereditary pancreatitis for the endoscopist

    Patel, Milan R.; Eppolito, Amanda L.; Willingham, Field F.

    2013-01-01

    Hereditary pancreatitis shares a majority of clinical and morphologic features with chronic alcoholic pancreatitis, but may present at an earlier age. The term hereditary pancreatitis has primarily been associated with mutations in the serine protease 1 gene (PRSS1) which encodes for cationic trypsinogen. PRSS1 mutations account for approximately 68–81% of hereditary pancreatitis. Mutations in other genes, primarily serine protease inhibitor Kazal type 1 (SPINK1) and the cystic fibrosis trans...

  14. Comparison of Attitudes Regarding Preimplantation Genetic Diagnosis Among Patients with Hereditary Cancer Syndromes

    Rich, Thereasa A.; Liu, Mei; Etzel, Carol J.; Bannon, Sarah A.; Mork, Maureen E.; Ready, Kaylene; Saraiya, Devki S.; Grubbs, Elizabeth G.; Perrier, Nancy D.; Lu, Karen H.; Arun, Banu K.; Woodard, Terri L.; Schover, Leslie R.; Litton, Jennifer K.

    2014-01-01

    Introduction Preimplantation Genetic Diagnosis (PGD) allows couples to avoid having a child with an inherited condition, potentially reducing cancer burden in families with a hereditary cancer predisposition. This study investigated awareness and acceptance of PGD among patients with hereditary cancer syndromes. Methods Questionnaires were mailed to 984 adults with hereditary breast and ovarian cancer, Lynch syndrome, familial adenomatous polyposis, or multiple endocrine neoplasia type 1 or 2. Associations between clinical, demographic, and psychosocial factors and awareness and acceptance of PGD were examined. Results Of 370 respondents (38% return rate), 28% felt their syndrome impacted family planning, 24% were aware of PGD, 72% felt that PGD should be offered, 43% would consider using PGD, and 29% were uncertain. Family experience and syndrome-specific characteristics, such as disease severity, quality of life and availability of medical interventions as well as gender, family planning stage, and religiosity impact perceptions of the acceptability of PGD, though a high level of uncertainty exists. Conclusion Hereditary cancer patients' opinions about the acceptability of PGD are similar to those of genetics and ethical experts. Patients should be told about PGD given that most had not heard of PGD, but feel that PGD should be offered. PMID:24072553

  15. EAMJ Oct Hereditary.indd

    HEREDITARY GINGIVAL FIBROMATOSIS: REPORT OF FAMILY CASE SERIES. E. G. Wagaiyu ... Senior Lecturer, Department of Periodontology/Community and Preventive Dentistry, ... fibrous connective tissue held in chronically inflamed.

  16. Genetics Home Reference: hereditary fructose intolerance

    ... Twitter Home Health Conditions Hereditary fructose intolerance Hereditary fructose intolerance Printable PDF Open All Close All Enable ... to view the expand/collapse boxes. Description Hereditary fructose intolerance is a condition that affects a person's ...

  17. Multidetector CT diagnosis of massive hemobilia due to gallbladder polyposis in a child with metachromatic leukodystrophy

    Wanner, Matthew R.; Karmazyn, Boaz [Indiana University School of Medicine, Riley Hospital for Children, Department of Radiology and Imaging Sciences, Indianapolis, IN (United States); Fan, Rong [Indiana University School of Medicine, Riley Hospital for Children, Department of Pathology and Laboratory Medicine, Indianapolis, IN (United States)

    2015-12-15

    Hemobilia secondary to gallbladder polyposis is rare in children but has been reported in a few children with metachromatic leukodystrophy. We present a case with preoperative multidetector computed tomography (MDCT) diagnosis of massive hemobilia caused by gallbladder polyposis in a patient with metachromatic leukodystrophy. Our report highlights the importance of both awareness of the association of gallbladder polyposis with other syndromes such as metachromatic leukodystrophy as well as the possibility of this entity presenting with life-threatening bleeding. (orig.)

  18. Hereditary angioedema in women

    Bouillet Laurence

    2010-07-01

    Full Text Available Abstract Women with hereditary angioedema (HAE are more likely to be symptomatic that men. Hormonal factors (puberty, contraception, pregnancy,.... play a significant role in the precipitation or worsening of the condition in women. So, combined contraceptive pills are not indicated and progestogen pill must be preferred. During pregnancy, attack rate can increase (38-48% of women. C1Inhibitor concentrate and tranexamic acid can be used during pregnancy. Attenuated androgens for long term prophylaxis are effective but side effects appear more often in female patients. These side effects are dose dependant and can be attenuated by titrating the dose down the lowest effective level.

  19. Hereditary Angioedema in Childhood

    Kjaer, Line; Bygum, Anette

    2012-01-01

    Hereditary angioedema (HAE) is a rare inherited disease that is often difficult to diagnose. We report a case of a 9-year-old boy with a spontaneous mutation causing HAE, diagnosed after a life-threatening episode of angioedema of the head and upper respiratory tract after a 5-year history of r...... of recurrent skin swellings and abdominal pain leading to several hospital admissions. The aim of this report is to direct focus on this rare disease, which can be treated effectively, to diminish morbidity and mortality of children suffering from undiagnosed HAE....

  20. Efficacy of functional endoscopic sinus surgery in recurrent nasal polyposis

    Aslam, S.; Ali, M.; Ahmed, A.; Asghar, A.; Aslam, S.

    2014-01-01

    To analyze the efficacy of FESS in patients with recurrent nasal polyposis in terms of relief of nasal obstruction, improvement in sense of smell and to assess recurrence of disease. Study Design: Descriptive case series. Materials and Method: All patients who underwent FESS (Functional endoscopic sinus surgery) for recurrent nasal polyposis from June 2008 to June 2010 with an average follow up of 06 month were included. Clinical symptoms including nasal obstruction and olfactory disturbance were evaluated using VAS system pre and postoperatively. Preoperatively computed tomography scan was done in all cases to assess extent of disease and surgical anatomy. Results: Following FESS 96% of total patients demonstrated statistically significant improvement in relieving nasal obstruction after 6 months follow up, however improvement in sense of smell was seen in 44% of patients. Recurrence was seen in only 3 (6%) cases at 3rd and 6th month follow up. Conclusion: Functional endoscopy sinus surgery of recurrent nasal polyposis is an effective method of surgery with significant improvement of symptom of nasal obstruction and olfaction with minimal recurrence at 6 month in our centre. Our results were compatible with results attained internationally. (author)

  1. Serrated Polyposis: An Enigmatic Model of Colorectal Cancer Predisposition

    Christophe Rosty

    2011-01-01

    Full Text Available Serrated polyposis has only recently been accepted as a condition which carries an increased personal and familial risk of colorectal cancer. Described over four decades ago, it remains one of the most underrecognized and poorly understood of all the intestinal polyposes. With a variety of phenotypic presentations, it is likely that serrated polyposis represents a group of diseases rather than a single entity. Further, neoplastic progression in serrated polyposis may be associated with premature aging in the normal mucosa, typified by widespread gene promoter hypermethylation. From this epigenetically altered field, arise diverse polyps and cancers which show a range of molecular features. Despite a high serrated polyp count, only one-third of colorectal cancers demonstrate a BRAF V600E mutation, the molecular hallmark of the canonical serrated pathway, suggesting that though multiple serrated polyps act as a marker of an abnormal mucosa, the majority of CRC in these patients arise within lesions other than BRAF-mutated serrated polyps.

  2. French experts report on MUTYH-associated polyposis (MAP).

    Buecher, Bruno; Bonaïti, Catherine; Buisine, Marie-Pierre; Colas, Chrystelle; Saurin, Jean-Christophe

    2012-09-01

    Recent years have been characterised by an improvement in our knowledge of genetic determinism of adenomatous polyposes and by the description in 2002 of a new entity called "MUTYH-associated polyposis" (MAP), related to biallelic mutations of this gene. Its autosomal recessive mode of inheritance contrasts with the autosomal dominant inheritance of the classical "familial adenomatous polyposis" (FAP), associated with an APC germline mutation. Although some phenotypic features may be of value to distinguish these two conditions, their clinical "spectra" largely overlap and the differential diagnosis may be difficult. The purpose of this expertise conducted under the auspices of the French Institut National du Cancer (INCa) was to assess the current state of knowledge on MUTYH-associated polyposis and to establish some recommendations in the field of molecular analysis (indications of tests and analysis strategies for affected patients and their relatives) and of clinical management based on available data in the literature, on the results from the French molecular genetics laboratories performing MUTYH analysis and on the opinions of biologists and clinicians experts (genetic counsellors and gastroenterologists). The risk of colorectal cancer among relatives carrying a monoallelic MUTYH mutation was also studied.

  3. Startle responses in hereditary hyperekplexia

    Tijssen, M. A.; Voorkamp, L. M.; Padberg, G. W.; van Dijk, J. G.

    1997-01-01

    BACKGROUND: Patients with hereditary hyperekplexia have excessive startle responses that are accompanied by transient stiffness and also continuous stiffness in infancy. A point of mutation has been identified for the major form of hereditary hyperekplexia in the gene encoding the alpha 1 subunit of

  4. Startle responses in hereditary hyperekplexia

    Tijssen, MAJ; Voorkamp, LM; Padberg, GW; vanDijk, JG

    Background: Patients with hereditary hyperekplexia have excessive startle responses that are accompanied by transient stiffness and also continuous stiffness in infancy. A point of mutation has been identified for the major form of hereditary hyperekplexia in the gene encoding the alpha 1 subunit of

  5. Splenic arteriovenous malformation manifested by thrombocytopenia in hereditary hemorrhagic telangiectasia: a case report

    Kwon, Hee Jin; Choi, Jong Cheol; Oh, Jong Yeong; Cho, Jin Han; Kang, Myong Jin; Lee, Jin Hwa; Yoon, Seong Kuk; Nam, Kyeong Jin [College of Medicine, Dong-A University, Busan (Korea, Republic of)

    2008-09-15

    Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant inherited disease characterized by epistaxis, telangiectases and visceral arteriovenous malformations (AVMs). The involvement of the gastrointestinal tract, liver, lung and cerebrum for HHT has been described, whereas little is known about AVMs of the spleen. We report here the radiological findings of a case of a splenic AVM manifested by thrombocytopenia in HHT.

  6. Splenic arteriovenous malformation manifested by thrombocytopenia in hereditary hemorrhagic telangiectasia: a case report

    Kwon, Hee Jin; Choi, Jong Cheol; Oh, Jong Yeong; Cho, Jin Han; Kang, Myong Jin; Lee, Jin Hwa; Yoon, Seong Kuk; Nam, Kyeong Jin

    2008-01-01

    Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant inherited disease characterized by epistaxis, telangiectases and visceral arteriovenous malformations (AVMs). The involvement of the gastrointestinal tract, liver, lung and cerebrum for HHT has been described, whereas little is known about AVMs of the spleen. We report here the radiological findings of a case of a splenic AVM manifested by thrombocytopenia in HHT

  7. Hereditary neuromuscular diseases

    Oezsarlak, O. E-mail: ozkan.ozsarlak@uza.be; Schepens, E.; Parizel, P.M.; Goethem, J.W. van; Vanhoenacker, F.; Schepper, A.M. de; Martin, J.J

    2001-12-01

    This article presents the actual classification of neuromuscular diseases based on present expansion of our knowledge and understanding due to genetic developments. It summarizes the genetic and clinical presentations of each disorder together with CT findings, which we studied in a large group of patients with neuromuscular diseases. The muscular dystrophies as the largest and most common group of hereditary muscle diseases will be highlighted by giving detailed information about the role of CT and MRI in the differential diagnosis. The radiological features of neuromuscular diseases are atrophy, hypertrophy, pseudohypertrophy and fatty infiltration of muscles on a selective basis. Although the patterns and distribution of involvement are characteristic in some of the diseases, the definition of the type of disease based on CT scan only is not always possible.

  8. Hereditary spastic paraplegia.

    Blackstone, Craig

    2018-01-01

    The hereditary spastic paraplegias (HSPs) are a heterogeneous group of neurologic disorders with the common feature of prominent lower-extremity spasticity, resulting from a length-dependent axonopathy of corticospinal upper motor neurons. The HSPs exist not only in "pure" forms but also in "complex" forms that are associated with additional neurologic and extraneurologic features. The HSPs are among the most genetically diverse neurologic disorders, with well over 70 distinct genetic loci, for which about 60 mutated genes have already been identified. Numerous studies elucidating the molecular pathogenesis underlying HSPs have highlighted the importance of basic cellular functions - especially membrane trafficking, mitochondrial function, organelle shaping and biogenesis, axon transport, and lipid/cholesterol metabolism - in axon development and maintenance. An encouragingly small number of converging cellular pathogenic themes have been identified for the most common HSPs, and some of these pathways present compelling targets for future therapies. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. The outcome of familial adenomatous polyposis in the absence of a ...

    S Afr Med J 1995; 85: 272-276. Familial adenomatous polyposis (FAP) almost always leads to large-bowel cancer unless prophylactic surgery is performed. The results of treating large numbers of patients with FAP are usually reported from polyposis registries. Such registries have two main functions. Firstly they identify,.

  10. Hereditary chronic pancreatitis

    Mössner Joachim

    2007-01-01

    Full Text Available Abstract Hereditary chronic pancreatitis (HCP is a very rare form of early onset chronic pancreatitis. With the exception of the young age at diagnosis and a slower progression, the clinical course, morphological features and laboratory findings of HCP do not differ from those of patients with alcoholic chronic pancreatitis. As well, diagnostic criteria and treatment of HCP resemble that of chronic pancreatitis of other causes. The clinical presentation is highly variable and includes chronic abdominal pain, impairment of endocrine and exocrine pancreatic function, nausea and vomiting, maldigestion, diabetes, pseudocysts, bile duct and duodenal obstruction, and rarely pancreatic cancer. Fortunately, most patients have a mild disease. Mutations in the PRSS1 gene, encoding cationic trypsinogen, play a causative role in chronic pancreatitis. It has been shown that the PRSS1 mutations increase autocatalytic conversion of trypsinogen to active trypsin, and thus probably cause premature, intrapancreatic trypsinogen activation disturbing the intrapancreatic balance of proteases and their inhibitors. Other genes, such as the anionic trypsinogen (PRSS2, the serine protease inhibitor, Kazal type 1 (SPINK1 and the cystic fibrosis transmembrane conductance regulator (CFTR have been found to be associated with chronic pancreatitis (idiopathic and hereditary as well. Genetic testing should only be performed in carefully selected patients by direct DNA sequencing and antenatal diagnosis should not be encouraged. Treatment focuses on enzyme and nutritional supplementation, pain management, pancreatic diabetes, and local organ complications, such as pseudocysts, bile duct or duodenal obstruction. The disease course and prognosis of patients with HCP is unpredictable. Pancreatic cancer risk is elevated. Therefore, HCP patients should strongly avoid environmental risk factors for pancreatic cancer.

  11. Clinical and ethical implications of genetic counselling in familial adenomatous polyposis Implicaciones clínicas y éticas del consejo genético en la poliposis adenomatosa familiar

    A. Fernández-Suárez

    2005-09-01

    Full Text Available The association of specific genetic disturbances with the development of hereditary cancer helps us to understand the risk of suffering from it, the possibility of an earlier diagnosis, and the treatment and prevention of this disease. Familial adenomatous polyposis (FAP is a pre-neoplastic syndrome characterized by the presence of hundreds of adenomatous polyps in the colon, which develop into a carcinoma. FAP can be diagnosed using sequencing techniques to detect mutations in the germinal line of the APC (adenomatous polyposis coli gene. The genetic diagnostic approach in families with FAP, previously followed up in the Gastrointestinal Clinic, has both advantages and disadvantages, and places us nearer the disease and patient. Disclosing the results of this genetic test entails relevant problems in clinical practice, which affect the health field and raise legal and ethical issues, along with the familial, occupational, and social implications that knowing the genetic status can have on the patient. Genetic analysis is rare in normal clinical practice, which involves errors in the interpretation of the results obtained, and during the process of genetic counselling. Specialized multidisciplinary units are necessary for the management of patients with FAP undergoing analysis and appropriate genetic counselling, thus providing an individualized service. The creation of FAP registers and protocols for this healthcare process should optimize the management of these patients and their families.La asociación de determinadas alteraciones genéticas con la aparición de cáncer hereditario, nos permite conocer el riesgo de padecerlo, posibilitando el diagnóstico precoz, el tratamiento y la prevención de la enfermedad. La poliposis adenomatosa familiar (PAF es un síndrome preneoplásico que se caracteriza por la presencia de cientos de pólipos adenomatosos en colon, que evolucionarán hacia carcinoma. La PAF puede ser diagnosticada mediante t

  12. Constitutional mismatch repair-deficiency syndrome presenting as colonic adenomatous polyposis: clues from the skin.

    Jasperson, K W; Samowitz, W S; Burt, R W

    2011-10-01

    Constitutional mismatch repair-deficiency (CMMR-D) syndrome is an autosomal recessive condition characterized by hematologic malignancies, brain tumors, Lynch syndrome-associated cancers and skin manifestations reminiscent of neurofibromatosis type 1 (NF1). In contrast to Lynch syndrome, CMMR-D syndrome is exceptionally rare, onset typically occurs in infancy or early childhood and, as described in this report, may also present with colonic polyposis suggestive of attenuated familial adenomatous polyposis (AFAP) or MUTYH associated polyposis (MAP). Here we describe two sisters with CMMR-D syndrome due to germline bi-allelic MSH6 mutations. Both sisters are without cancer, are older than typical for this condition, have NF1 associated features and a colonic phenotype suspicious for an attenuated polyposis syndrome. This report highlights the role of skin examinations in leading to an underlying genetic diagnosis in individuals with colonic adenomatous polyposis, but without mutations associated with AFAP or MAP. © 2010 John Wiley & Sons A/S.

  13. CLINICAL APPROACH TO HEREDITARY HEMORRHAGIC TELANGIECTASIA

    Mary Hachmeriyan

    2013-11-01

    Full Text Available Background: Hereditary hemorrhagic telangiectasia (HHT or Rendu-Osler-Weber disease is a rare syndrome, inherited as an autosomal dominant trait with incidence of 1/10000. The clinical manifestations are due to vascular malformations and predisposition to hemorrhages in different organs, the leading symptom being recurrent epistaxis. If diagnosed with HHT, the patient and his relatives and especially children have to be screened for occult vascular malformations.Case report: A 30 years old woman was treated for cerebral stroke, epistaxis, anemia, arterio-venous malformations for over 6 months. Only at this point she was diagnosed with HHT, after noticing the typical mucosal changes. Focused family history revealed symptoms of HHT in her only child, her father, aunt and two cousins The child was screened for occult vascular malformations – attainment of the nasal mucosa, lungs, gastrointestinal system, liver and brain. Pulmonary and gastrointestinal arterio-venous malformations were proven.Conclusion: Any case of recurrent epistaxis should be evaluated for HHT. After confirmation of the diagnosis every patient and close relatives have to be screened for attainment of other organs and followed up in order to prevent severe life threatening complications.

  14. Gastrointestinal tuberculosis.

    Galloway, D J; Scott, R N

    1986-10-01

    In the developed countries gastrointestinal tuberculosis is no longer common in clinical practice. In this setting the importance of the condition lies in the vagaries of its presentation and the fact that it is eminently treatable, usually by a combination of chemotherapy and surgery. The clinical features and complications of gastrointestinal tuberculosis are highlighted by the seven cases which we report. Diagnosis and treatment of this condition is discussed and attention is drawn to the importance of case notification. Clinicians should bear in mind the diagnosis of gastrointestinal tuberculosis when dealing with any patient with non-specific abdominal symptoms.

  15. Hereditary familial vestibular degenerative diseases.

    Sun, J.; Alphen, A.M. van; Wagenaar, M.; Huygen, P.L.M.; Hoogenraad, C.C.; Hasson, T.; Koekkoek, S.K.; Bohne, B.A.; Zeeuw, C.I. de

    2001-01-01

    Identification of genes involved in hereditary vestibular disease is growing at a remarkable pace. Mutant mouse technology can be an important tool for understanding the biological mechanism of human vestibular diseases.

  16. Hereditary forms of breast cancer

    Bella, V.

    2009-01-01

    Breast cancer is the most common oncologic disease in the female population. Besides the sporadic occurrence it occurs in the familial and hereditary form. Persons with the occurrence of positive family anamnesis of breast cancer should be actively investigated. In the indicated cases it is necessary to send the woman to genetic examination. In case that the hereditary form of breast cancer is affirmed it is necessary to examine her family relatives. Women with the hereditary form of breast cancer occur in about 5 – 10 % portion from all women diagnosed with breast cancer. Nowadays we already know that 80 % of hereditary breast cancers are due to germ mutations in BRCA 1 and BRCA 2 gene. Persons with detected gene mutations must be dispensarized in the centres intended for it. (author)

  17. IL-33 activates tumor stroma to promote intestinal polyposis.

    Maywald, Rebecca L; Doerner, Stephanie K; Pastorelli, Luca; De Salvo, Carlo; Benton, Susan M; Dawson, Emily P; Lanza, Denise G; Berger, Nathan A; Markowitz, Sanford D; Lenz, Heinz-Josef; Nadeau, Joseph H; Pizarro, Theresa T; Heaney, Jason D

    2015-05-12

    Tumor epithelial cells develop within a microenvironment consisting of extracellular matrix, growth factors, and cytokines produced by nonepithelial stromal cells. In response to paracrine signals from tumor epithelia, stromal cells modify the microenvironment to promote tumor growth and metastasis. Here, we identify interleukin 33 (IL-33) as a regulator of tumor stromal cell activation and mediator of intestinal polyposis. In human colorectal cancer, IL-33 expression was induced in the tumor epithelium of adenomas and carcinomas, and expression of the IL-33 receptor, IL1RL1 (also referred to as IL1-R4 or ST2), localized predominantly to the stroma of adenoma and both the stroma and epithelium of carcinoma. Genetic and antibody abrogation of responsiveness to IL-33 in the Apc(Min/+) mouse model of intestinal tumorigenesis inhibited proliferation, induced apoptosis, and suppressed angiogenesis in adenomatous polyps, which reduced both tumor number and size. Similar to human adenomas, IL-33 expression localized to tumor epithelial cells and expression of IL1RL1 associated with two stromal cell types, subepithelial myofibroblasts and mast cells, in Apc(Min/+) polyps. In vitro, IL-33 stimulation of human subepithelial myofibroblasts induced the expression of extracellular matrix components and growth factors associated with intestinal tumor progression. IL-33 deficiency reduced mast cell accumulation in Apc(Min/+) polyps and suppressed the expression of mast cell-derived proteases and cytokines known to promote polyposis. Based on these findings, we propose that IL-33 derived from the tumor epithelium promotes polyposis through the coordinated activation of stromal cells and the formation of a protumorigenic microenvironment.

  18. Gastrointestinal bleeding

    ... Sigmoidoscopy Alternative Names Lower GI bleeding; GI bleeding; Upper GI bleeding; Hematochezia Images GI bleeding - series Fecal occult blood test References Kovacs TO, Jensen DM. Gastrointestinal hemorrhage. In: Goldman L, Schafer AI, eds. Goldman- ...

  19. Adenomas of the common bile duct in familial adenomatous polyposis

    Yan, Mao-Lin; Pan, Jun-Yong; Bai, Yan-Nan; Lai, Zhi-De; Chen, Zhong; Wang, Yao-Dong

    2015-01-01

    Familial adenomatous polyposis (FAP) or Gardner’s syndrome is often accompanied by adenomas of the stomach and duodenum. We experienced a case of adenomas of the common bile duct in a 40-year-old woman with FAP presenting with acute cholangitis. Only 8 cases of adenomas or adenocarcinoma of the common bile duct have been reported in the literature in patients with FAP or Gardner’s syndrome. Those patients presented with acute cholangitis or pancreatitis. Local excision or Whipple procedure may be the reasonable surgical option. PMID:25780319

  20. Progression of desmoid tumors in familial polyposis: a case report

    Lee, Yong Il; Lee, Hae Kyung; Hong, Hyung Sook; Kwon, Kui Hyang; Choi, Deuk Lin; Kim, Jae Joon

    2001-01-01

    Multiple large bowel polyps are the hallmark of familial adenomatous polyposis (FAP), and many progress to colorectal cancer. Desmoid tumors are more common in patients with FAP than in other people, occurring, particulary, in those who have previously undergone prophylatic total colectomy. In such patients, desmoid tumors are a common cause of death. In an FAP patient without extracolic menifestation, who has undergone prophylatic surgery, multifocal desmoid tumors occur periodically. We report the serial radiologic findings of progressive desmoid tumors in FAP, drawing attention to the related findings of previous research

  1. Progression of desmoid tumors in familial polyposis: a case report

    Lee, Yong Il; Lee, Hae Kyung; Hong, Hyung Sook; Kwon, Kui Hyang; Choi, Deuk Lin; Kim, Jae Joon [Soonchunhyang Univ. College of Medicine, A-san (Korea, Republic of)

    2001-01-01

    Multiple large bowel polyps are the hallmark of familial adenomatous polyposis (FAP), and many progress to colorectal cancer. Desmoid tumors are more common in patients with FAP than in other people, occurring, particulary, in those who have previously undergone prophylatic total colectomy. In such patients, desmoid tumors are a common cause of death. In an FAP patient without extracolic menifestation, who has undergone prophylatic surgery, multifocal desmoid tumors occur periodically. We report the serial radiologic findings of progressive desmoid tumors in FAP, drawing attention to the related findings of previous research.

  2. Lynch syndrome and Lynch syndrome mimics: The growing complex landscape of hereditary colon cancer

    Carethers, John M; Stoffel, Elena M

    2015-01-01

    Hereditary non-polyposis colorectal cancer (HNPCC) was previously synonymous with Lynch syndrome; however, identification of the role of germline mutations in the DNA mismatch repair (MMR) genes has made it possible to differentiate Lynch syndrome from other conditions associated with familial colorectal cancer (CRC). Broadly, HNPCC may be dichotomized into conditions that demonstrate defective DNA MMR and microsatellite instability (MSI) vs those conditions that demonstrate intact DNA MMR. Conditions characterized by MMR deficient CRCs include Lynch syndrome (germline MMR mutation), Lynch-like syndrome (biallelic somatic MMR mutations), constitutional MMR deficiency syndrome (biallelic germline MMR mutations), and sporadic MSI CRC (somatic biallelic methylation of MLH1). HNPCC conditions with intact DNA MMR associated with familial CRC include polymerase proofreading associated polyposis and familial colorectal cancer type X. Although next generation sequencing technologies have elucidated the genetic cause for some HNPCC conditions, others remain genetically undefined. Differentiating between Lynch syndrome and the other HNPCC disorders has profound implications for cancer risk assessment and surveillance of affected patients and their at-risk relatives. Clinical suspicion coupled with molecular tumor analysis and testing for germline mutations can help differentiate the clinical mimicry within HNPCC and facilitate diagnosis and management. PMID:26309352

  3. Lynch syndrome and Lynch syndrome mimics: The growing complex landscape of hereditary colon cancer.

    Carethers, John M; Stoffel, Elena M

    2015-08-21

    Hereditary non-polyposis colorectal cancer (HNPCC) was previously synonymous with Lynch syndrome; however, identification of the role of germline mutations in the DNA mismatch repair (MMR) genes has made it possible to differentiate Lynch syndrome from other conditions associated with familial colorectal cancer (CRC). Broadly, HNPCC may be dichotomized into conditions that demonstrate defective DNA MMR and microsatellite instability (MSI) vs those conditions that demonstrate intact DNA MMR. Conditions characterized by MMR deficient CRCs include Lynch syndrome (germline MMR mutation), Lynch-like syndrome (biallelic somatic MMR mutations), constitutional MMR deficiency syndrome (biallelic germline MMR mutations), and sporadic MSI CRC (somatic biallelic methylation of MLH1). HNPCC conditions with intact DNA MMR associated with familial CRC include polymerase proofreading associated polyposis and familial colorectal cancer type X. Although next generation sequencing technologies have elucidated the genetic cause for some HNPCC conditions, others remain genetically undefined. Differentiating between Lynch syndrome and the other HNPCC disorders has profound implications for cancer risk assessment and surveillance of affected patients and their at-risk relatives. Clinical suspicion coupled with molecular tumor analysis and testing for germline mutations can help differentiate the clinical mimicry within HNPCC and facilitate diagnosis and management.

  4. Identity, community and care in online accounts of hereditary colorectal cancer syndrome.

    Ross, Emily; Broer, Tineke; Kerr, Anne; Cunningham-Burley, Sarah

    2018-01-01

    Sociological literature has explored how shifts in the point at which individuals may be designated as diseased impact upon experiences of ill health. Research has shown that experiences of being genetically "at risk" are shaped by and shape familial relations, coping strategies, and new forms of biosociality. Less is known about how living with genetic risk is negotiated in the everyday and over time, and the wider forms of identity, communities and care this involves. This article explores these arrangements drawing on online bloggers' accounts of Familial Adenomatous Polyposis (FAP). We show how accounts of genetic risk co-exist with more palpable experiences of FAP in everyday life, notably the consequences of prophylactic surgeries. We consider how the act of blogging represents but also constitutes everyday experiences of hereditary cancer syndrome as simultaneously ordinary and exceptional, and reflect on the implications of our analysis for understanding experiences of genetic cancer risk.

  5. Kindler syndrome - a rare type of hereditary epidermolysis bullosa

    V. I. Albanova

    2015-01-01

    Full Text Available The Kindler syndrome is one of the types of hereditary epidermolysis bullosa with its onset related to mutations of the KIND1 gene. The authors describe a case of a family with three members suffering from this rare disease. All of these patients have typical clinical manifestations of the Kindler syndrome such as the formation of blisters on the skin and mucous membranes right after the birth, scarring with the formation of contractures, pseudosyndactyly, microstomia and ankyloglossia, progressive poikiloderma, photosensibility, affections of the gastrointestinal tract - dysphagia, esophagostenosis, stool disorders, dental pathology, phimosis vaginalis in women.

  6. Hereditary pancreatitis: current perspectives

    Raphael KL

    2016-07-01

    Full Text Available Kara L Raphael, Field F Willingham Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA Abstract: Hereditary pancreatitis (HP is a rare cause of acute, recurrent acute, and chronic pancreatitis. It may present similarly to other causes of acute and chronic pancreatitis, and often there has been a protracted evaluation prior to the diagnosis of HP. Since it was first described in 1952, multiple genetic defects that affect the action of digestive enzymes in the pancreas have been implicated. The most common mutations involve the PRSS1, CFTR, SPINK1, and CTRC genes. New mutations in these genes and previously unrecognized mutations in other genes are being discovered due to the increasing use of next-generation genomic sequencing. While the inheritance pathways of these genetic mutations may be variable and complex, sometimes involving coinheritance of other mutations, the clinical presentation of patients tends to be similar. Interactions with environmental triggers often play a role. Patients tend to present at an early age (prior to the second decade of life and have a significantly increased risk for the development of pancreatic adenocarcinoma. Patients with HP may develop sequelae of chronic pancreatitis such as strictures and fluid collections as well as exocrine and endocrine insufficiency. Management of patients with HP involves avoidance of environmental triggers, surveillance for pancreatic adenocarcinoma, medical therapy for endocrine and exocrine insufficiency, pain management, and endoscopic or surgical treatment for complications. Care for affected patients should be individualized, with an emphasis on early diagnosis and multidisciplinary involvement to develop a comprehensive treatment strategy. Keywords: pancreatic cancer, chronic pancreatitis, idiopathic pancreatitis, pancreatitis, familial pancreatitis, genetic mutations

  7. Genetics Home Reference: hereditary diffuse gastric cancer

    ... Health Conditions Hereditary diffuse gastric cancer Hereditary diffuse gastric cancer Printable PDF Open All Close All Enable Javascript ... Diffuse Gastric Cancer MedlinePlus Encyclopedia: Gastric Cancer National Cancer ... Option Overview General Information from MedlinePlus ( ...

  8. Gastrointestinal System

    Jepson, Mark A.; Bouwmeester, Hans

    2017-01-01

    The epithelial lining of the gastrointestinal tract (GIT) acts as a barrier to uptake of potentially dangerous material while allowing absorption of processed food. The gut may be exposed to a diverse range of engineered nanomaterials due to their deliberate addition to food and consumer products

  9. Cellular characteristics of hereditary diseases of man

    Sasaki, Masao

    1978-01-01

    Hereditary diseases of which abnormal characters could be detected at cultured cell level were introduced, and tissue cultures of them were described. Characteristics such as reproduction, disorder, elimination, and repair of DNA in hereditary diseases with high cancer risk such as Bloom syndrome, etc. were investigated. Radiosensitivity of these hereditary diseases was also described, and factors of carcinogenesis were investigated. (Serizawa, K.)

  10. Infection and HLA-G Molecules in Nasal Polyposis

    Roberta Rizzo

    2014-01-01

    Full Text Available Sinonasal polyposis (SNP is a chronic inflammatory pathology with an unclear aetiopathogenesis. Human papillomavirus (HPV infection is one candidate for the development of SNP for its epithelial cell trophism, hyperproliferative effect, and the induction of immune-modulatory molecules as HLA-G. We enrolled 10 patients with SNP without concomitant allergic diseases (SNP-WoAD, 10 patients with SNP and suffering from allergic diseases (SNP-WAD, and 10 control subjects who underwent rhinoplasty. We analyzed the presence of high- and low-risk HPV DNA and the expression of membrane HLA-G (mHLA-G and IL-10 receptor (IL-10R and of soluble HLA-G (sHLA-G and IL-10 by polyp epithelial cells. The results showed the presence of HPV-11 in 50% of SNP-WoAD patients (OR:5.5, all characterized by a relapsing disease. HPV-11 infection was absent in nonrelapsing SNP-WoAD patients, in SNP-WAD patients and in controls, supporting the hypothesis that HPV-11 increases risk of relapsing disease. HPV-11 positive SNP-WoAD patients presented with mHLA-G and IL-10R on epithelial cells from nasal polyps and showed secretion of sHLA-G and IL-10 in culture supernatants. No HLA-G expression was observed in HPV negative polyps. These data highlight new aspects of polyposis aetiopathogenesis and suggest HPV-11 and HLA-G/IL-10 presence as prognostic markers in the follow-up of SNP-WoAD.

  11. Presence of c.3956delC mutation in familial adenomatous polyposis patients from Brazil.

    Moreira-Nunes, Caroline Aquino; Alcântara, Diego di Felipe Ávila; Lima-Júnior, Sérgio Figueiredo; Cavalléro, Sandro Roberto de Araújo; Rey, Juan Antonio; Pinto, Giovanny Rebouças; de Assumpção, Paulo Pimentel; Burbano, Rommel Rodriguez

    2015-08-21

    To characterize APC gene mutations and correlate them with patient phenotypes in individuals diagnosed with familial adenomatous polyposis (FAP) in northern Brazil. A total of 15 individuals diagnosed with FAP from 5 different families from the north of Brazil were analyzed in this study. In addition to patients with histopathological diagnosis of FAP, family members who had not developed the disease were also tested in order to identify mutations and for possible genetic counseling. All analyzed patients or their guardians signed a consent form approved by the Research Ethics Committee of the João de Barros Barreto University Hospital (Belem, Brazil). DNA extracted from the peripheral blood of a member of each of the affected families was subjected to direct sequencing. The proband of each family was sequenced to identify germline mutations using the Ion Torrent platform. To validate the detected mutations, Sanger sequencing was also performed. The samples from all patients were also tested for the identification of mutations by real-time quantitative polymerase chain reaction using the amplification refractory mutation system. Through interviews with relatives and a search of medical records, it was possible to construct genograms for three of the five families included in the study. All 15 patients from the five families with FAP exhibited mutations in the APC gene, and all mutations were detected in exon 15 of the APC gene. In addition to the patients with a histological diagnosis of FAP, family members without disease symptoms showed the mutation in the APC gene. In the present study, we detected two of the three most frequent germline mutations in the literature: the mutation at codon 1309 and the mutation at codon 1061. The presence of c.3956delC mutation was found in all families from this study, and suggests that this mutation was introduced in the population of the State of Pará through ancestor immigration (i.e., a de novo mutation that arose in one

  12. Immunophenotyping of hereditary breast cancer

    van der Groep, P.

    2009-01-01

    Hereditary breast cancer runs in families where several family members in different generations are affected. Most of these breast cancers are caused by mutations in the high penetrance genes BRCA1 and BRCA2 which account for about 5% of all breast cancers. However, mutations in BRCA1 and BRCA2 may

  13. Genetics Home Reference: hereditary hemochromatosis

    ... Type 1 hemochromatosis results from mutations in the HFE gene, and type 2 hemochromatosis results from mutations in ... about the genes associated with hereditary hemochromatosis HAMP HFE HJV PNPLA3 SLC40A1 TFR2 Related Information What is a gene? What is a gene mutation and how do ...

  14. Patient accuracy of reporting on hereditary non-polyposis colorectal cancer-related malignancy in family members

    Katballe, Niels; Juul, Svend; Christensen, M.

    2001-01-01

    was rejected in three of 14 cases (false-positive rate 21 per cent). Furthermore, seven of 18 probands whose families met the Amsterdam criteria I or II after verification were identified by further exploration in families who, according to the probands, met weaker criteria (false-negative rate 39 per cent......). CONCLUSION: The present study suggests that family studies on HNPCC are not reliable unless the diagnoses of family members are verified from official sources. If endoscopic screening is offered entirely on the basis of unverified information from patients with colorectal cancer, there is a risk that a large...

  15. Cost-effectiveness of surveillance programs for families at high and moderate risk of hereditary non-polyposis colorectal cancer

    Olsen, Kim R.; Bojesen, Stig E.; Gerdes, Anne-Marie M.

    2007-01-01

    for the group at high risk. The aim of the present study is to determine cost-effectiveness of surveillance programs where families at both high and moderate risk of HNPCC participate. METHODS: A decision analytic model (Markov model) is developed to assess surveillance programs where families at high......OBJECTIVES: Surveillance programs are recommended to both families at high risk (Amsterdam-positive families with known- and unknown mutation) and moderate risk (families not fulfilling all Amsterdam criteria) of colorectal cancer (CRC). Cost-effectiveness has so far only been estimated...

  16. gastrointestinal tract

    Rolandas Vaicekauskas

    2016-07-01

    Full Text Available Introduction : Accurate diagnosis of subepithelial lesions (SELs in the gastrointestinal tract depends on a variety of methods: endoscopy, endoscopic ultrasound and different types of biopsy. Making an error-free diagnosis is vital for the subsequent application of an appropriate treatment. Aim: To evaluate the efficacy of deep biopsy via the endoscopic submucosal dissection (ESD technique for SELs in the upper gastrointestinal tract. Material and methods: It was a case series study. Deep biopsy via the ESD technique was completed in 38 patients between November 2012 and October 2014. Thirty-eight SELs in the upper gastrointestinal tract of varying size (very small ≤ 1 cm, small 1–2 cm and large ≥ 2 cm by means of the ESD technique after an incision with an electrosurgical knife of the overlying layers and revealing a small part of the lesion were biopsied under direct endoscopic view. Results: Deep biopsy via the ESD technique was diagnostic in 28 of 38 patients (73.3%; 95% CI: 59.7–89.7%. The diagnostic yield for SELs with a clear endophytic shape increased to 91.3%. An evident endophytic appearance of a subepithelial lesion, the mean number of biopsied samples (6.65 ±1.36 and the total size in length of all samples per case (19.88 ±8.07 mm were the main criteria influencing the positiveness of deep biopsy in the diagnostic group compared to the nondiagnostic one (p = 0.001; p = 0.025; p = 0.008. Conclusions : Deep biopsy via the ESD technique is an effective and safe method for the diagnosis of SELs especially with a clear endophytic appearance in a large number of biopsied samples.

  17. NTHL1 and MUTYH polyposis syndromes: two sides of the same coin?

    Weren, Robbert DA; Ligtenberg, Marjolijn Jl; Geurts van Kessel, Ad; De Voer, Richarda M; Hoogerbrugge, Nicoline; Kuiper, Roland P

    2018-02-01

    It is now well established that germline genomic aberrations can underlie high-penetrant familial polyposis and colorectal cancer syndromes, but a genetic cause has not yet been found for the major proportion of patients with polyposis. Since next-generation sequencing has become widely accessible, several novel, but rare, high-penetrant risk factors for adenomatous polyposis have been identified, all operating in pathways responsible for genomic maintenance and DNA repair. One of these is the base excision repair pathway. In addition to the well-established role of the DNA glycosylase gene MUTYH, biallelic mutations in which predispose to MUTYH-associated polyposis, a second DNA glycosylase gene, NTHL1, has recently been associated with adenomatous polyposis and a high colorectal cancer risk. Both recessive polyposis syndromes are associated with increased risks for several other cancer types as well, but the spectrum of benign and malignant tumours in individuals with biallelic NTHL1 mutations was shown to be broader; hence the name NTHL1-associated tumour syndrome. Colorectal tumours encountered in patients with these syndromes show unique, clearly distinct mutational signatures that may facilitate the identification of these syndromes. On the basis of the prevalence of pathogenic MUTYH and NTHL1 variants in the normal population, we estimate that the frequency of the novel NTHL1-associated tumour syndrome is five times lower than that of MUTYH-associated polyposis. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  18. Somatic APC mosaicism and oligogenic inheritance in genetically unsolved colorectal adenomatous polyposis patients.

    Ciavarella, Michele; Miccoli, Sara; Prossomariti, Anna; Pippucci, Tommaso; Bonora, Elena; Buscherini, Francesco; Palombo, Flavia; Zuntini, Roberta; Balbi, Tiziana; Ceccarelli, Claudio; Bazzoli, Franco; Ricciardiello, Luigi; Turchetti, Daniela; Piazzi, Giulia

    2018-03-01

    Germline variants in the APC gene cause familial adenomatous polyposis. Inherited variants in MutYH, POLE, POLD1, NTHL1, and MSH3 genes and somatic APC mosaicism have been reported as alternative causes of polyposis. However, ~30-50% of cases of polyposis remain genetically unsolved. Thus, the aim of this study was to investigate the genetic causes of unexplained adenomatous polyposis. Eight sporadic cases with >20 adenomatous polyps by 35 years of age or >50 adenomatous polyps by 55 years of age, and no causative germline variants in APC and/or MutYH, were enrolled from a cohort of 56 subjects with adenomatous colorectal polyposis. APC gene mosaicism was investigated on DNA from colonic adenomas by Sanger sequencing or Whole Exome Sequencing (WES). Mosaicism extension to other tissues (peripheral blood, saliva, hair follicles) was evaluated using Sanger sequencing and/or digital PCR. APC second hit was investigated in adenomas from mosaic patients. WES was performed on DNA from peripheral blood to identify additional polyposis candidate variants. We identified APC mosaicism in 50% of patients. In three cases mosaicism was restricted to the colon, while in one it also extended to the duodenum and saliva. One patient without APC mosaicism, carrying an APC in-frame deletion of uncertain significance, was found to harbor rare germline variants in OGG1, POLQ, and EXO1 genes. In conclusion, our restrictive selection criteria improved the detection of mosaic APC patients. In addition, we showed for the first time that an oligogenic inheritance of rare variants might have a cooperative role in sporadic colorectal polyposis onset.

  19. Clinical symptoms according to genotype amongst patients with hereditary haemorrhagic telangiectasia

    Kjeldsen, A D; Møller, T R; Brusgaard, K

    2005-01-01

    BACKGROUND: Hereditary haemorrhagic telangiectasia (HHT) is a dominantly inherited disease, characterized by a wide variety of clinical manifestations, including epistaxis, gastrointestinal (GI) bleeding, pulmonary arteriovenous malformations (PAVMs) and neurological symptoms. HHT is a genetically...... patients had experienced more severe GI bleeding than HHT2 patients. There was no significant difference in severity of epistaxis or age at debut. Finally the mortality over a 90-month observation period was not significantly increased....

  20. Neurologic Manifestation as Initial Presentation in a Case of Hereditary Haemorrhagic Telangiectasia

    Yeow Kwan Teo

    2010-01-01

    Full Text Available Hereditary Haemorrhagic Telangiectasia (HHT, or Osler-Weber-Rendu syndrome is an uncommon autosomal dominant multi-organ condition of vascular dysplasias. We describe a 19 year old Indian female who presented with cerebral abscess secondary to paradoxical emboli from pulmonary arteriovenous malformations (PAVMs associated with HHT. Cerebral, pulmonary, hepatic and gastrointestinal involvement can be life-threatening and it is important to have lifelong follow-ups on these patients.

  1. New treatments of hereditary blindness

    Bertelsen, Mette; Rosenberg, Thomas; Larsen, Michael

    2013-01-01

    Ongoing clinical trials are targeting several previously intractable hereditary causes of blindness of congenital, childhood or early adulthood onset, mainly in the optic nerve and retina. The intended stage of initiation of the new therapeutic approaches ranges from neonatal life and a structura......Ongoing clinical trials are targeting several previously intractable hereditary causes of blindness of congenital, childhood or early adulthood onset, mainly in the optic nerve and retina. The intended stage of initiation of the new therapeutic approaches ranges from neonatal life...... and a structurally intact retinal tissue to adult life with a complete loss of photoreceptors. It must be assumed that some of the trials will succeed in producing new therapies and action must be taken to refine and accelerate diagnostics and to preserve therapeutic potential in blind people....

  2. Hereditary breast and ovarian cancer

    Nielsen, Finn Cilius; Hansen, Thomas van Overeem; Sørensen, Claus Storgaard

    2016-01-01

    Genetic abnormalities in the DNA repair genes BRCA1 and BRCA2 predispose to hereditary breast and ovarian cancer (HBOC). However, only approximately 25% of cases of HBOC can be ascribed to BRCA1 and BRCA2 mutations. Recently, exome sequencing has uncovered substantial locus heterogeneity among...... of putative causal variants and the clinical application of new HBOC genes in cancer risk management and treatment decision-making....

  3. Gastrointestinal Traumatic Injuries: Gastrointestinal Perforation.

    Revell, Maria A; Pugh, Marcia A; McGhee, Melanie

    2018-03-01

    The abdomen is a big place even in a small person. Gastrointestinal trauma can result in injury to the stomach, small bowel, colon, or rectum. Traumatic causes include blunt or penetrating trauma, such as gunshot wounds, stabbings, motor vehicle collisions, and crush injuries. Nontraumatic causes include appendicitis, Crohn disease, cancer, diverticulitis, ulcerative colitis, blockage of the bowel, and chemotherapy. The mechanism of injury will affect both the nature and severity of any resulting injuries. Treatment must address the critical and emergent nature of these injuries as well as issues that affect all trauma situations, which include management of hemodynamic instability. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Family history, surgery, and APC mutation are risk factors for desmoid tumors in familial adenomatous polyposis: an international cohort study

    Nieuwenhuis, Marry H; Lefevre, Jérémie H; Bülow, Steffen

    2011-01-01

    Ability to identify patients with familial adenomatous polyposis who have a high risk of developing desmoid tumors may affect decisions in clinical practice.......Ability to identify patients with familial adenomatous polyposis who have a high risk of developing desmoid tumors may affect decisions in clinical practice....

  5. Familial adenomatous polyposis patients without an identified APC germline mutation have a severe phenotype

    Bisgaard, M L; Ripa, R; Knudsen, Anne Louise

    2004-01-01

    BACKGROUND: Development of more than 100 colorectal adenomas is diagnostic of the dominantly inherited autosomal disease familial adenomatous polyposis (FAP). Germline mutations can be identified in the adenomatous polyposis coli (APC) gene in approximately 80% of patients. The APC protein...... comprises several regions and domains for interaction with other proteins, and specific clinical manifestations are associated with the mutation assignment to one of these regions or domains. AIMS: The phenotype in patients without an identified causative APC mutation was compared with the phenotype...... in patients with a known APC mutation and with the phenotypes characteristic of patients with mutations in specific APC regions and domains. PATIENTS: Data on 121 FAP probands and 149 call up patients from 70 different families were extracted from the Danish Polyposis register. METHODS: Differences in 16...

  6. Multiple desmoid tumors in a patient with familial adenomatous polyposis caused by the novel W421X mutation Tumor desmoide múltiple en un paciente con poliposis adenomatosa familiar originada por la nueva mutación W421X

    Orestis Ioannidis

    2012-03-01

    Full Text Available Familial adenomatous polyposis (FAP is a rare syndrome characterized by the presence of hundreds to thousands of colorectal adenomas and is responsible for less than 1% of all colorectal cancers. The syndrome is also characterized by extra-colorectal features including amongst others upper gastrointestinal tract polyps and desmoid tumors. The syndrome is inherited by an autosomal dominant gene, the adenomatous polyposis coli (APC gene. We present the physical history, clinical presentation, diagnosis and treatment of a patient with a novel germline APC mutation, the W421X mutation, which resulted in FAP presenting with about a hundred colorectal polyps, gastric hyperplastic polyps and multiple aggressive intra-abdominal and extra-abdominal desmoid tumors.

  7. POSSIBILITY OF PHARMACOMODULATION OF THE HYPERSENSITIVE RHINITIS JOINED WITH THE NASAL POLYPOSIS

    Dejan Ursulović

    2001-11-01

    Full Text Available The research goai is to examine the effects of the local corticosteroidapplication to the number of eosinophils in the nasal secretion of the patients withhypersensitive rhinitis joined with the nasal polyposis. The study comprises 13patients with hypersensitive rhinitis joined with the nasal polyposis; 9 of them madeup the experimental group. The local corticosteroid (bechomethasone dipropionatein water spray was given at 12 hours in individual doses of 200 micrograms to theexperimental group patients in six weeks. During the treatment it was confirmed thatthere was a highly important reduction of the number of eosinophils of the nasalsecretion in the experimental group patients.

  8. Frequency of fungal infection in the nasal polyposis patients undergoing polypectomy in a tertiary care unit

    Jawad, A.; Nisar, Y.B.

    2015-01-01

    Objective: To determine the frequency of fungal infection in nasal polyposis patients undergoing polypectomy in a tertiary care ENT unit. Methodology: This cross sectional study was conducted in the department of ENT, Pakistan Institute of Medical Sciences, Islamabad. A total of 60 patients with nasal polyposis were enrolled. Patients who did not give consent, with sinonasal malignancy, diabetes, and pregnant or lactating women were excluded from study. All the patients were operated and specimens of polypectomies were sent to the Department of Pathology for fungal culture, direct microscopy and histopathology. Data was entered and analysed using SPSS version 20. (author)

  9. Hereditary iron and copper deposition

    Aaseth, Jan; Flaten, Trond Peder; Andersen, Ole

    2007-01-01

    Hereditary deposition of iron (primary haemochromatosis) or copper (Wilson's disease) are autosomal recessive metabolic disease characterized by progressive liver pathology and subsequent involvement of various other organs. The prevalence of primary haemochromatosis is approximately 0.5%, about......, they may be inadequate in patients diagnosed so late that extensive body deposits of metal have been developed. The main research needs in this field are to further clarify molecular mechanisms of disease progression and to develop new chelators that are more effective and less toxic than those presently...

  10. Local IgE production in nonatopic nasal polyposis.

    Sheahan, Patrick

    2012-02-01

    INTRODUCTION: Chronic rhinosinusitis with nasal polyposis (CRSwNP) represents an eosinophilic T-helper 2 inflammatory response. Local production of IgE within nasal polyps (NPs) has been demonstrated, suggesting a role for local IgE in the pathogenesis of NP in atopic CRS patients. We hypothesized that local IgE specific to inhalant allergens may also play a role in the genesis of NP in nonatopic CRS patients. METHODS: Sinus and inferior turbinate tissue was obtained from nonatopic CRSwNP patients (n = 7), chronic rhinosinusitis without nasal polyps (CRSsNP) patients (n = 15), and healthy controls (n = 9) at the time of surgery. ImmunoCAP analysis (Phadia AB, Portage, MI) for 14 common inhalant antigens was performed on tissue homogenates to determine the antigen-specific response. RESULTS: Total IgE levels did not differ in sinus or turbinate tissue between CRSwNP, CRSsNP, or control patients. CRSwNP sinus tissue had higher levels of specific IgE for cockroach and plantain (p = .03) than other groups and elevated Alternaria IgE levels when compared with CRSsNP sinus tissue (p < .05). No significant differences were found for any of the other antigen-specific IgE levels. Fifty-seven percent of CRSwNP polyps demonstrated a polyclonal IgE response, whereas the other 43% had no demonstrable antigen-specific IgE. In contrast, only 17% of CRSsNP patients demonstrated a polyclonal response within sinus tissue, whereas 67% had no detectable antigen-specific IgE. There was no significant difference in levels of IgE in inferior turbinate tissue between the groups (p > .05). CONCLUSIONS: Localized mucosal IgE specific to common inhalant allergens appears to play a role in a subset of CRSwNP patients without evidence of systemic atopy.

  11. Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema.

    Cicardi, Marco; Banerji, Aleena; Bracho, Francisco; Malbrán, Alejandro; Rosenkranz, Bernd; Riedl, Marc; Bork, Konrad; Lumry, William; Aberer, Werner; Bier, Henning; Bas, Murat; Greve, Jens; Hoffmann, Thomas K; Farkas, Henriette; Reshef, Avner; Ritchie, Bruce; Yang, William; Grabbe, Jürgen; Kivity, Shmuel; Kreuz, Wolfhart; Levy, Robyn J; Luger, Thomas; Obtulowicz, Krystyna; Schmid-Grendelmeier, Peter; Bull, Christian; Sitkauskiene, Brigita; Smith, William B; Toubi, Elias; Werner, Sonja; Anné, Suresh; Björkander, Janne; Bouillet, Laurence; Cillari, Enrico; Hurewitz, David; Jacobson, Kraig W; Katelaris, Constance H; Maurer, Marcus; Merk, Hans; Bernstein, Jonathan A; Feighery, Conleth; Floccard, Bernard; Gleich, Gerald; Hébert, Jacques; Kaatz, Martin; Keith, Paul; Kirkpatrick, Charles H; Langton, David; Martin, Ludovic; Pichler, Christiane; Resnick, David; Wombolt, Duane; Fernández Romero, Diego S; Zanichelli, Andrea; Arcoleo, Francesco; Knolle, Jochen; Kravec, Irina; Dong, Liying; Zimmermann, Jens; Rosen, Kimberly; Fan, Wing-Tze

    2010-08-05

    Hereditary angioedema is characterized by recurrent attacks of angioedema of the skin, larynx, and gastrointestinal tract. Bradykinin is the key mediator of symptoms. Icatibant is a selective bradykinin B2 receptor antagonist. In two double-blind, randomized, multicenter trials, we evaluated the effect of icatibant in patients with hereditary angioedema presenting with cutaneous or abdominal attacks. In the For Angioedema Subcutaneous Treatment (FAST) 1 trial, patients received either icatibant or placebo; in FAST-2, patients received either icatibant or oral tranexamic acid, at a dose of 3 g daily for 2 days. Icatibant was given once, subcutaneously, at a dose of 30 mg. The primary end point was the median time to clinically significant relief of symptoms. A total of 56 and 74 patients underwent randomization in the FAST-1 and FAST-2 trials, respectively. The primary end point was reached in 2.5 hours with icatibant versus 4.6 hours with placebo in the FAST-1 trial (P=0.14) and in 2.0 hours with icatibant versus 12.0 hours with tranexamic acid in the FAST-2 trial (P<0.001). In the FAST-1 study, 3 recipients of icatibant and 13 recipients of placebo needed treatment with rescue medication. The median time to first improvement of symptoms, as assessed by patients and by investigators, was significantly shorter with icatibant in both trials. No icatibant-related serious adverse events were reported. In patients with hereditary angioedema having acute attacks, we found a significant benefit of icatibant as compared with tranexamic acid in one trial and a nonsignificant benefit of icatibant as compared with placebo in the other trial with regard to the primary end point. The early use of rescue medication may have obscured the benefit of icatibant in the placebo trial. (Funded by Jerini; ClinicalTrials.gov numbers, NCT00097695 and NCT00500656.)

  12. Hereditary & familial colorectal cancer : Identification, characteristics, surveillance

    Kallenberg, F.G.J.

    2017-01-01

    Of all colorectal cancer (CRC) cases, 15-20% is related to familial or hereditary factors. Diagnosing familial and hereditary CRC syndromes is important for several reasons. One of these is that surveillance colonoscopies can reduce CRC incidence and mortality importantly. A complete family history

  13. The molecular classification of hereditary endocrine diseases.

    Ye, Lei; Ning, Guang

    2015-12-01

    Hereditary endocrine diseases are an important group of diseases with great heterogeneity. The current classification for hereditary endocrine disease is mostly based upon anatomy, which is helpful for pathophysiological interpretation, but does not address the pathogenic variability associated with different underlying genetic causes. Identification of an endocrinopathy-associated genetic alteration provides evidence for differential diagnosis, discovery of non-classical disease, and the potential for earlier diagnosis and targeted therapy. Molecular diagnosis should be routinely applied when managing patients with suspicion of hereditary disease. To enhance the accurate diagnosis and treatment of patients with hereditary endocrine diseases, we propose categorization of endocrine diseases into three groups based upon the function of the mutant gene: cell differentiation, hormone synthesis and action, and tumorigenesis. Each category was further grouped according to the specific gene function. We believe that this format would facilitate practice of precision medicine in the field of hereditary endocrine diseases.

  14. Novel mutations and phenotypic associations identified through APC, MUTYH, NTHL1, POLD1, POLE gene analysis in Indian Familial Adenomatous Polyposis cohort.

    Khan, Nikhat; Lipsa, Anuja; Arunachal, Gautham; Ramadwar, Mukta; Sarin, Rajiv

    2017-05-22

    Colo-Rectal Cancer is a common cancer worldwide with 5-10% cases being hereditary. Familial Adenomatous Polyposis (FAP) syndrome is due to germline mutations in the APC or rarely MUTYH gene. NTHL1, POLD1, POLE have been recently reported in previously unexplained FAP cases. Unlike the Caucasian population, FAP phenotype and its genotypic associations have not been widely studied in several geoethnic groups. We report the first FAP cohort from South Asia and the only non-Caucasian cohort with comprehensive analysis of APC, MUTYH, NTHL1, POLD1, POLE genes. In this cohort of 112 individuals from 53 FAP families, we detected germline APC mutations in 60 individuals (45 families) and biallelic MUTYH mutations in 4 individuals (2 families). No NTHL1, POLD1, POLE mutations were identified. Fifteen novel APC mutations and a new Indian APC mutational hotspot at codon 935 were identified. Eight very rare FAP phenotype or phenotypes rarely associated with mutations outside specific APC regions were observed. APC genotype-phenotype association studies in different geo-ethnic groups can enrich the existing knowledge about phenotypic consequences of distinct APC mutations and guide counseling and risk management in different populations. A stepwise cost-effective mutation screening approach is proposed for genetic testing of south Asian FAP patients.

  15. Gastrointestinal tract

    James, R.D.; Pointon, R.C.S.

    1985-01-01

    At the time of writing, radiotherapy is of only minor use in the management of adenocarcinoma of the gastrointestinal tract, for a number of reasons. First, an exploratory laparotomy is generally needed for diagnosis, and if possible the tumour is resected or by-passed. Second, radiotherapy planning in the upper abdomen is complicated by the proximity of small bowel, kidneys, and spinal cord. Third, it has been assumed that these tumours cause death largely as a result of distant metastases, so that local radiotherapy, even if effective, would contribute little to survival. The continued interest in radiotherapy for this group of tumours arises out of the poor survival rates following surgery, which have not changed for many years, and the morbidity associated with their resection. It was hoped that the addition of cytotoxic agents to radical surgery would improve survival rates in carcinoma of the stomach and intraperitoneal colon. Despite a large number of well-organised prospective trials, using a variety of cytotoxic drugs, there is so far no evidence that the addition of chemotherapy to radical surgery improves survival for either tumour site. The authors are therefore faced with a group of tumours which are not only common, but commonly fatal and many surgeons would accept that a new approach using modern radiotherapy techniques may well be justified. There is evidence that this movement is already taking place for carcinoma of the rectum, and the indications for radiotherapy in this condition will be dealt with below. Before considering these it is worth dwelling briefly on recent changes in surgical and radiological practices which, if they fulfil expectations, might allow radiotherapy to be used for carcinoma of the colon, stomach, and pancreas as it is now used for rectal cancer

  16. Paediatric intestinal cancer and polyposis due to bi-allelic PMS2 mutations: case series, review and follow-up guidelines.

    Herkert, Johanna C; Niessen, Renée C; Olderode-Berends, Maria J W; Veenstra-Knol, Hermine E; Vos, Yvonne J; van der Klift, Heleen M; Scheenstra, Rene; Tops, Carli M J; Karrenbeld, Arend; Peters, Frans T M; Hofstra, Robert M W; Kleibeuker, Jan H; Sijmons, Rolf H

    2011-05-01

    Bi-allelic germline mutations of one of the DNA mismatch repair genes, so far predominantly found in PMS2, cause constitutional MMR-deficiency syndrome. This rare disorder is characterised by paediatric intestinal cancer and other malignancies. We report the clinical, immunohistochemical and genetic characterisation of four families with bi-allelic germline PMS2 mutations. We present an overview of the published gastrointestinal manifestations of CMMR-D syndrome and propose recommendations for gastro-intestinal screening. The first proband developed a cerebral angiosarcoma at age 2 and two colorectal adenomas at age 7. Genetic testing identified a complete PMS2 gene deletion and a frameshift c.736_741delinsTGTGTGTGAAG (p.Pro246CysfsX3) mutation. In the second family, both the proband and her brother had multiple intestinal adenomas, initially wrongly diagnosed as familial adenomatous polyposis. A splice site c.2174+1G>A, and a missense c.137G>T (p.Ser46Ile) mutation in PMS2 were identified. The third patient was diagnosed with multiple colorectal adenomas at age 11; he developed a high-grade dysplastic colorectal adenocarcinoma at age 21. Two intragenic PMS2 deletions were found. The fourth proband developed a cerebral anaplastic ganglioma at age 9 and a high-grade colerectal dysplastic adenoma at age 10 and carries a homozygous c.2174+1G>A mutation. Tumours of all patients showed microsatellite instability and/or loss of PMS2 expression. Our findings show the association between bi-allelic germline PMS2 mutations and severe childhood-onset gastrointestinal manifestations, and support the notion that patients with early-onset gastrointestinal adenomas and cancer should be investigated for CMMR-D syndrome. We recommend yearly follow-up with colonoscopy from age 6 and simultaneous video-capsule small bowel enteroscopy from age 8. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Colectomy and ileorectal anastomosis is still an option for selected patients with familial adenomatous polyposis

    Bülow, Steffen; Bulow, C.; Vasen, H.

    2008-01-01

    PURPOSE: The risk of rectal cancer after colectomy and ileorectal anastomosis may be reduced in the last decades, as patients with severe polyposis now have an ileoanal pouch. We have reevaluated the risk of rectal cancer and proctectomy for all causes according to the year of operation. METHODS:...

  18. Increased colorectal cancer risk in first-degree relatives of patients with hyperplastic polyposis syndrome

    Boparai, K. S.; Reitsma, J. B.; Lemmens, V.; van Os, T. A. M.; Mathus-Vliegen, E. M. H.; Koornstra, J. J.; Nagengast, F. M.; van Hest, L. P.; Keller, J. J.; Dekker, E.

    2010-01-01

    Introduction Hyperplastic polyposis syndrome (HPS) is characterised by the presence of multiple colorectal hyperplastic polyps and is associated with an increased colorectal cancer (CRC) risk. For first-degree relatives of HPS patients (FDRs) this has not been adequately quantified. Reliable

  19. Attitudes toward genetic testing in childhood and reproductive decision-making for familial adenomatous polyposis

    Douma, K.F.L.; Aaronson, N.K.; Vasen, H.F.A.; Verhoef, S.; Gundy, C.M.; Bleiker, E.M.A.

    2010-01-01

    Childhood DNA testing, prenatal diagnosis (PND) and preimplantation genetic diagnosis (PGD) are available for familial adenomatous polyposis (FAP). However, the use of PND and PGD is controversial. The purpose of this study was to investigate attitudes toward, and experiences with, childhood DNA

  20. Desmoid tumors in a dutch cohort of patients with familial adenomatous polyposis

    Nieuwenhuis, Marry H.; de Vos Tot Nederveen Cappel, Wouter; Botma, Akke; Nagengast, Fokko M.; Kleibeuker, Jan H.; Mathus-Vliegen, Elisabeth M. H.; Dekker, Evelien; Dees, Jan; Wijnen, Juul; Vasen, Hans F. A.

    2008-01-01

    BACKGROUND & AIMS: Desmoid tumors are a severe extracolonic manifestation in familial adenomatous polyposis (FAP). Identification of risk factors might be helpful in the management of FAP patients with such tumors. The aim of this study was to assess potential risk factors for the development of

  1. A proposed staging system and stage-specific interventions for familial adenomatous polyposis

    Lynch, Patrick M; Morris, Jeffrey S; Wen, Sijin

    2016-01-01

    BACKGROUND: It is not possible to accurately count adenomas in many patients with familial adenomatous polyposis (FAP). Nevertheless, polyp counts are critical in evaluating each patient's response to interventions. However, the U.S. Food and Drug Administration no longer recognizes the decrease ...

  2. Increased colorectal cancer risk in first-degree relatives of patients with hyperplastic polyposis syndrome.

    Boparai, K.S.; Reitsma, J.B.; Lemmens, V.; Os, T.A. van; Mathus-Vliegen, E.M.H.; Koornstra, J.J.; Nagengast, F.M.; Hest, L.P. van; Keller, J.J.; Dekker, E. den

    2010-01-01

    INTRODUCTION: Hyperplastic polyposis syndrome (HPS) is characterised by the presence of multiple colorectal hyperplastic polyps and is associated with an increased colorectal cancer (CRC) risk. For first-degree relatives of HPS patients (FDRs) this has not been adequately quantified. Reliable

  3. Increased colorectal cancer risk in first-degree relatives of patients with hyperplastic polyposis syndrome

    Boparai, K. S.; Lemmens, V.; van Os, T. A. M.; Mathus-Vliegen, E. M. H.; Koornstra, J. J.; Nagengast, F. M.; van Hest, L. P.; Keller, J. J.; Dekker, E.; Reitsma, J.

    Introduction Hyperplastic polyposis syndrome (HPS) is characterised by the presence of multiple colorectal hyperplastic polyps and is associated with an increased colorectal cancer (CRC) risk. For first-degree relatives of HPS patients (FDRs) this has not been adequately quantified. Reliable

  4. Colorectal adenomatous polyposis syndromes: Genetic determinism, clinical presentation and recommendations for care.

    Buecher, Bruno

    2016-02-01

    Colorectal adenomatous polyposis constitutes a diverse group of disorders with different modes of inheritance. Molecular diagnosis of this condition has become more complex. In fact, somatic mosaicism for APC mutations now appears to be more frequent than previously thought and rare germline alterations of this gene may be implicated in patients tested negative for "classical" APC mutations (point mutations and large genomic rearrangements). Moreover, the knowledge concerning several aspects of the MUTYH-associated polyposis has improved since its first description in 2002 and germline mutations in new genes have recently been implicated in some cases of unexplained adenomatous polyposis. Genetic testing in probands and their relatives should be conducted in the context of pre- and post-test genetic counseling. The recent advent of New Generation Sequencing (NGS) techniques affords the opportunity to rapidly screen patients for a comprehensive panel of colorectal cancer susceptibility genes in a cost-effective fashion. This type of approach will probably replace the classical sequential approach based on clinical presumptive diagnoses in the near future. The risk of colorectal cancer is very high in affected patients in the absence of appropriate care. Clinical management is complex and should be provided in centers with special expertise in these diseases. This review focuses on the various colorectal adenomatous polyposis syndromes with special attention to more innovative and important aspects. Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  5. Genotype predicting phenotype in familial adenomatous polyposis: a practical application to the choice of surgery

    Nieuwenhuis, Marry H; Bülow, Steffen; Björk, Jan

    2009-01-01

    PURPOSE: Genetic information may help preoperatively select patients with familial adenomatous polyposis for either colectomy with ileorectal anastomosis or proctocolectomy with ileal pouch-anal anastomosis. Although complicated, the latter procedure has a low long-term risk of rectal cancer. MET...

  6. Tumour Suppressor Adenomatous Polyposis Coli (APC) localisation is regulated by both Kinesin-1 and Kinesin-2

    Ruane, Peter T; Gumy, Laura F; Bola, Becky; Anderson, Beverley; Wozniak, Marcin J; Hoogenraad, Casper C; Allan, Victoria J

    2016-01-01

    Microtubules and their associated proteins (MAPs) underpin the polarity of specialised cells. Adenomatous polyposis coli (APC) is one such MAP with a multifunctional agenda that requires precise intracellular localisations. Although APC has been found to associate with kinesin-2 subfamily members,

  7. Culture of primary epithelial adenoma cells from familial adenomatous polyposis patients

    Fostira, F.; Apessos, A.; Oikonomou, E.; Kouklis, P.; Baratsis, S.; Manifikos, G.; Anděra, Ladislav; Yannoukakos, D.; Pintzas, A.; Nasioulas, G.

    2008-01-01

    Roč. 28, 2A (2008), s. 843-846 ISSN 0250-7005 Institutional research plan: CEZ:AV0Z50520514 Keywords : colorectal neoplasia * adenomatous polyposis coli * epithelial cells Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.390, year: 2008

  8. Decision analysis in the management of duodenal adenomatosis in familial adenomatous polyposis

    Vasen, H. F.; Bülow, S.; Myrhøj, T.; Mathus-Vliegen, L.; Griffioen, G.; Buskens, E.; Taal, B. G.; Nagengast, F.; Slors, J. F.; de Ruiter, P.

    1997-01-01

    Patients with familial adenomatous polyposis are not only at high risk of developing adenomas in the colorectum but a substantial number of patients also develop polyps in the duodenum. Because treatment of duodenal polyps is extremely difficult and it is unknown how many patients ultimately develop

  9. Evaluation of 28 years of surgical treatment of children and young adults with familial adenomatous polyposis

    Booij, Klaske A. C.; Mathus-Vliegen, Elisabeth M. H.; Taminiau, Jan A. J. M.; ten Kate, Fibo J. W.; Slors, J. Frederick M.; Tabbers, Merit M.; Aronson, Daniel C.

    2010-01-01

    Background: In this retrospective study, 28 years of surgical treatment of children and young adults with familial adenomatous polyposis (FAP) was analyzed. Methods: Forty-three patients were operated on before the age of 26 years. Endoscopic aspects, operative data, and complications were analyzed,

  10. Evaluation of 28 years of surgical treatment of children and young adults with familial adenomatous polyposis.

    Booij, K.A.; Mathus-Vliegen, E.M.H.; Taminiau, J.A.; Kate, F.J. ten; Slors, J.F.M.; Tabbers, M.M.; Aronson, D.C.

    2010-01-01

    BACKGROUND: In this retrospective study, 28 years of surgical treatment of children and young adults with familial adenomatous polyposis (FAP) was analyzed. METHODS: Forty-three patients were operated on before the age of 26 years. Endoscopic aspects, operative data, and complications were analyzed,

  11. Desmoid tumors in a dutch cohort of patients with familial adenomatous polyposis

    Nieuwenhuis, M.H.; Vos to Nederveen Cappel, de W.; Botma, A.; Nagengast, F.M.; Kleibeuker, J.H.; Mathus-Vliegen, E.M.; Dekker, E.; Dees, J.; Wijnen, J.; Vasen, H.F.

    2008-01-01

    Background & Aims: Desmoid tumors are a severe extracolonic manifestation in familial adenomatous polyposis (FAP). Identification of risk factors might be helpful in the management of FAP patients with such tumors. The aim of this study was to assess potential risk factors for the development of

  12. Prophylactic Therapy for Hereditary Angioedema.

    Longhurst, Hilary; Zinser, Emily

    2017-08-01

    Long-term prophylaxis is needed in many patients with hereditary angioedema and poses many challenges. Attenuated androgens are effective in many but are limited by side effect profiles. There is less evidence for efficacy of tranexamic acid and progestagens; however, the small side effect profile makes tranexamic acid an option for prophylaxis in children and progestagens an option for women. C1 inhibitor is beneficial, but at present requires intravenous delivery and may need dose titration for maximum efficacy. Short-term prophylaxis should be considered for all procedures. New therapies are promising in overcoming many problems encountered with current options for long-term prophylaxis. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Imaging of Hereditary Hemorrhagic Telangiectasia

    Carette, Marie-France; Nedelcu, Cosmina; Tassart, Marc; Grange, Jean-Didier; Wislez, Marie; Khalil, Antoine

    2009-01-01

    This pictorial review is based on our experience of the follow-up of 120 patients at our multidisciplinary center for hereditary hemorrhagic telangiectasia (HHT). Rendu-Osler-Weber disease or HHT is a multiorgan autosomal dominant disorder with high penetrance, characterized by epistaxis, mucocutaneous telangiectasis, and visceral arteriovenous malformations (AVMs). The research on gene mutations is fundamental and family screening by clinical examination, chest X-ray, research of pulmonary shunting, and abdominal color Doppler sonography is absolutely necessary. The angioarchitecture of pulmonary AVMs can be studied by unenhanced multidetector computed tomography; however, all other explorations of liver, digestive bowels, or brain require administration of contrast media. Magnetic resonance angiography is helpful for central nervous system screening, in particular for the spinal cord, but also for pulmonary, hepatic, and pelvic AVMs. Knowledge of the multiorgan involvement of HHT, mechanism of complications, and radiologic findings is fundamental for the correct management of these patients.

  14. Hereditary syndromes with enhanced radiosensitivity

    Lohmann, D.

    2000-01-01

    Sensitivity to ionizing radiation is modified by heritable genetic factors. This is exemplified by heritable disorders that are characterized by predisposition to the development of neoplasms. Cells derived from patients with ataxia telangiectasia, Nijmegen breakage syndrome and ataxia telangiektasia-like disorder show a markedly changed reaction to exposure to ionizing radiation. Correspondingly, at least in patients with ataxia telangiectasia, an enhanced radiosensitivity that is of clinical importance has been observed. In addition to these recessive disorders, some autosomal dominant cancer predisposition syndromes are associated with increased radiosensitivity. As cells from these patients still have a normal allele (that is dominant over the mutant allele), the cellular phenotype is most often normal. Specifically, there is no overtly altered reaction in response to ionizing radiation. Nevertheless, two dominant cancer predisposition syndromes, namely hereditary retinoblastoma and naevoid basal cell carcinoma syndrome, are associated with a enhanced radiosensitivity as indicated by increased development of tumors following radiation therapy. (orig.) [de

  15. Elucidating the clinical significance of two PMS2 missense variants coexisting in a family fulfilling hereditary cancer criteria.

    González-Acosta, Maribel; Del Valle, Jesús; Navarro, Matilde; Thompson, Bryony A; Iglesias, Sílvia; Sanjuan, Xavier; Paúles, María José; Padilla, Natàlia; Fernández, Anna; Cuesta, Raquel; Teulé, Àlex; Plotz, Guido; Cadiñanos, Juan; de la Cruz, Xavier; Balaguer, Francesc; Lázaro, Conxi; Pineda, Marta; Capellá, Gabriel

    2017-10-01

    The clinical spectrum of germline mismatch repair (MMR) gene variants continues increasing, encompassing Lynch syndrome, Constitutional MMR Deficiency (CMMRD), and the recently reported MSH3-associated polyposis. Genetic diagnosis of these hereditary cancer syndromes is often hampered by the presence of variants of unknown significance (VUS) and overlapping phenotypes. Two PMS2 VUS, c.2149G>A (p.V717M) and c.2444C>T (p.S815L), were identified in trans in one individual diagnosed with early-onset colorectal cancer (CRC) who belonged to a family fulfilling clinical criteria for hereditary cancer. Clinico-pathological data, multifactorial likelihood calculations and functional analyses were used to refine their clinical significance. Likelihood analysis based on cosegregation and tumor data classified the c.2444C>T variant as pathogenic, which was supported by impaired MMR activity associated with diminished protein expression in functional assays. Conversely, the c.2149G>A variant displayed MMR proficiency and protein stability. These results, in addition to the conserved PMS2 expression in normal tissues and the absence of germline microsatellite instability (gMSI) in the biallelic carrier ruled out a CMMRD diagnosis. The use of comprehensive strategies, including functional and clinico-pathological information, is mandatory to improve the clinical interpretation of naturally occurring MMR variants. This is critical for appropriate clinical management of cancer syndromes associated to MMR gene mutations.

  16. Genetics 101 --The Hereditary Material of Life

    ... of this page please turn Javascript on. Feature: Genetics 101 Genetics 101 — The Hereditary Material of Life Past Issues / Summer 2013 Table of Contents Genetics is the study of heredity, the process in ...

  17. Hereditary History Preserving Bisimilarity Is Undecidable

    Jurdzinski, Marcin; Nielsen, Mogens

    2000-01-01

    History preserving bisimilarity (hp-bisimilarity) and hereditary history preserving bisimilarity (hhp-bisimilarity) are behavioural equivalences taking into account causal relationships between events of concurrent systems. Their prominent feature is being preserved under action refinement...

  18. Genetics Home Reference: hereditary hypophosphatemic rickets

    ... A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. ... families, hereditary hypophosphatemic rickets has had an autosomal dominant inheritance pattern, which means one copy of an ...

  19. Clinical features of Hereditary Haemorrhagic Telangiectasia

    Hosman, A.E.

    2017-01-01

    Hereditary Haemorrhagic Telangiectasia (HHT), also known as Rendu-Osler-Weber disease (ROW), is an autosomal dominant disease with multi-systemic vascular dysplasia characterized by mucocutaneous telangiectasia, arteriovenous malformations and recurrent spontaneous epistaxis (nosebleeds). Most cases

  20. Splenic Involvement in Hereditary Hemorrhagic Telangiectasia

    Susumu Takamatsu

    2016-01-01

    Full Text Available A 33-year-old man who presented with prolonged epigastric pain was referred to our hospital. He had experienced recurrent epistaxis and had a family history of hereditary hemorrhagic telangiectasia. Computed tomography and magnetic resonance imaging revealed splenomegaly and a 9 cm hypervascular mass in his spleen. Computed tomography also showed a pulmonary arteriovenous malformation and heterogeneous enhancement of the liver parenchyma, suggesting the presence of arteriosystemic shunts and telangiectases. Based on these findings, the patient was definitely diagnosed with hereditary hemorrhagic telangiectasia according to Curaçao criteria. He underwent splenectomy, and his symptoms disappeared after surgery. Pathological examination of the resected specimen revealed that the hypervascular lesion of the spleen was not a tumor but was composed of abnormal vessels associated with hereditary hemorrhagic telangiectasia. Symptomatic splenic involvement may be a rare manifestation of hereditary hemorrhagic telangiectasia but can be revealed by imaging modalities.

  1. A Review of Hereditary Fructose Intolerance

    Mogoş Tiberius

    2016-03-01

    Full Text Available Fructose intolerance is a metabolic disorder with hereditary determinism, clinically manifested on terms of fructose intake. Untreated, hereditary fructose intolerance may result in renal and hepatic failure. Unfortunately, there are no formal diagnostic and surveillance guidelines for this disease. If identified and treated before the occurrence of permanent organ damage, patients can improve their symptoms and self-rated health. Implementation and adherence to a strict fructose free diet is often difficult, but not impossible.

  2. Zinc and gastrointestinal disease

    Sonja; Skrovanek; Katherine; DiGuilio; Robert; Bailey; William; Huntington; Ryan; Urbas; Barani; Mayilvaganan; Giancarlo; Mercogliano; James; M; Mullin

    2014-01-01

    This review is a current summary of the role that both zinc deficiency and zinc supplementation can play in the etiology and therapy of a wide range of gastrointestinal diseases. The recent literature describing zinc action on gastrointestinal epithelial tight junctions and epithelial barrier function is described. Zinc enhancement of gastrointestinal epithelial barrier function may figure prominently in its potential therapeutic action in several gastrointestinal diseases.

  3. Hereditary sensory neuropathy type I

    Auer-Grumbach Michaela

    2008-03-01

    Full Text Available Abstract Hereditary sensory neuropathy type I (HSN I is a slowly progressive neurological disorder characterised by prominent predominantly distal sensory loss, autonomic disturbances, autosomal dominant inheritance, and juvenile or adulthood disease onset. The exact prevalence is unknown, but is estimated as very low. Disease onset varies between the 2nd and 5th decade of life. The main clinical feature of HSN I is the reduction of sensation sense mainly distributed to the distal parts of the upper and lower limbs. Variable distal muscle weakness and wasting, and chronic skin ulcers are characteristic. Autonomic features (usually sweating disturbances are invariably observed. Serious and common complications are spontaneous fractures, osteomyelitis and necrosis, as well as neuropathic arthropathy which may even necessitate amputations. Some patients suffer from severe pain attacks. Hypacusis or deafness, or cough and gastrooesophageal reflux have been observed in rare cases. HSN I is a genetically heterogenous condition with three loci and mutations in two genes (SPTLC1 and RAB7 identified so far. Diagnosis is based on the clinical observation and is supported by a family history. Nerve conduction studies confirm a sensory and motor neuropathy predominantly affecting the lower limbs. Radiological studies, including magnetic resonance imaging, are useful when bone infections or necrosis are suspected. Definitive diagnosis is based on the detection of mutations by direct sequencing of the SPTLC1 and RAB7 genes. Correct clinical assessment and genetic confirmation of the diagnosis are important for appropriate genetic counselling and prognosis. Differential diagnosis includes the other hereditary sensory and autonomic neuropathies (HSAN, especially HSAN II, as well as diabetic foot syndrome, alcoholic neuropathy, neuropathies caused by other neurotoxins/drugs, immune mediated neuropathy, amyloidosis, spinal cord diseases, tabes dorsalis, lepra

  4. Hereditary sensory neuropathy type I.

    Auer-Grumbach, Michaela

    2008-03-18

    Hereditary sensory neuropathy type I (HSN I) is a slowly progressive neurological disorder characterised by prominent predominantly distal sensory loss, autonomic disturbances, autosomal dominant inheritance, and juvenile or adulthood disease onset. The exact prevalence is unknown, but is estimated as very low. Disease onset varies between the 2nd and 5th decade of life. The main clinical feature of HSN I is the reduction of sensation sense mainly distributed to the distal parts of the upper and lower limbs. Variable distal muscle weakness and wasting, and chronic skin ulcers are characteristic. Autonomic features (usually sweating disturbances) are invariably observed. Serious and common complications are spontaneous fractures, osteomyelitis and necrosis, as well as neuropathic arthropathy which may even necessitate amputations. Some patients suffer from severe pain attacks. Hypacusis or deafness, or cough and gastrooesophageal reflux have been observed in rare cases. HSN I is a genetically heterogenous condition with three loci and mutations in two genes (SPTLC1 and RAB7) identified so far. Diagnosis is based on the clinical observation and is supported by a family history. Nerve conduction studies confirm a sensory and motor neuropathy predominantly affecting the lower limbs. Radiological studies, including magnetic resonance imaging, are useful when bone infections or necrosis are suspected. Definitive diagnosis is based on the detection of mutations by direct sequencing of the SPTLC1 and RAB7 genes. Correct clinical assessment and genetic confirmation of the diagnosis are important for appropriate genetic counselling and prognosis. Differential diagnosis includes the other hereditary sensory and autonomic neuropathies (HSAN), especially HSAN II, as well as diabetic foot syndrome, alcoholic neuropathy, neuropathies caused by other neurotoxins/drugs, immune mediated neuropathy, amyloidosis, spinal cord diseases, tabes dorsalis, lepra neuropathy, or decaying skin

  5. Broad phenotypic spectrum in familial adenomatous polyposis; from early onset and severe phenotypes to late onset of attenuated polyposis with the first manifestation at age 72

    Nilbert, Mef; Kristoffersson, Ulf; Ericsson, Mats

    2008-01-01

    ABSTRACT: Background Familial adenomatous polyposis (FAP) is typically characterized by multiple colonic polyps and frequent extracolonic features. Whereas the number of colonic polyps has been linked to the APC gene mutation, possible genotype-phenotype correlations largely remain to be defined...... cancer at age 72 as the first manifestation of attenuated FAP. Conclusion With an increasing number of FAP families diagnosed, a broad and variable tumor spectrum and a high frequency of extracolonic manifestations are gradually recognized. We report novel APC mutations and present two FAP cases...

  6. The technical hereditary of CWD

    Smulders, P.T.

    1990-01-01

    An overview is given of the activities of the Dutch foundation CWD since 1975. The financing of the foundation stopped July 1st 1990. From 1975 the CWD stimulated the use of small scale wind energy to pump up water in developing countries. The hereditary of the CWD consists of knowledge of the design and performance of components of wind mills, knowledge to design integral systems based on these components and preconditions, and knowledge how to manufacture, install and maintain the wind mills locally. The CWD designed three wind mill pumps of which 250 have been brought into operation in developing countries. A CWD-type pump was developed in Sri-Lanka of which 150 pumps were installed. Also attention is paid to the external situation which effected the CWD activities: the lack of interest from the Dutch industry to cooperate in developing CWD pumps; the actual market far away in developing countries; and too little competition in the research and development. The nature of the CWD-participants caused some internal friction which did not contribute to the effectivity of the CWD organisation. It is recommended to continue the development and testing of small wind energy systems and to preserve the knowledge gained by the CWD. 3 figs., 2 tabs., 3 refs

  7. Movement disorders in hereditary ataxias.

    Garcia Ruiz, Pedro J; Mayo, David; Hernandez, Jaime; Cantarero, Susana; Ayuso, Carmen

    2002-10-15

    Movement disorders are well known features of some dominant hereditary ataxias (HA), specially SCA3/Machado-Joseph disease and dentatorubropallidolusyan atrophy. However, little is known about the existence and classification of movement disorders in other dominant and recessive ataxias. We prospectively studied the presence of movement disorders in patients referred for HA over the last 3 years. Only those patients with a confirmed family history of ataxia were included. We studied 84 cases of HA, including 46 cases of recessive and 38 cases of dominant HA. Thirty out of 46 cases of recessive HA could be classified as: Friedreich ataxia (FA), 29 cases; vitamin E deficiency, 1 case. Twenty-three out of 38 cases of dominant HA could be classified as: SCA 2, 4 cases; SCA 3, 8 cases; SCA 6, 4 cases; SCA 7, 6 cases and SCA 8, 1 case. We observed movement disorders in 20/38 (52%) patients with dominant HA and 25/46 (54%) cases with recessive HA, including 16 patients (16/29) with FA. In general, postural tremor was the most frequent observed movement disorder (27 cases), followed by dystonia (22 cases). Five patients had akinetic rigid syndrome, and in 13 cases, several movement disorders coexisted. Movement disorders are frequent findings in HA, not only in dominant HA but also in recessive HA. Copyright 2002 Elsevier Science B.V.

  8. Filiform serrated adenomatous polyposis arising in a diverted rectum of an inflammatory bowel disease patient

    Klarskov, Louise; Mogensen, Anne Mellon; Jespersen, Niels

    2011-01-01

    Klarskov L, Mogensen AM, Jespersen N, Ingeholm P, Holck S. Filiform serrated adenomatous polyposis arising in a diverted rectum of an inflammatory bowel disease patient. APMIS 2011; 119: 393-8. A 54-year-old man, previously colectomized for inflammatory bowel disease, developed carcinoma in the i......Klarskov L, Mogensen AM, Jespersen N, Ingeholm P, Holck S. Filiform serrated adenomatous polyposis arising in a diverted rectum of an inflammatory bowel disease patient. APMIS 2011; 119: 393-8. A 54-year-old man, previously colectomized for inflammatory bowel disease, developed carcinoma...... during the adenoma carcinoma sequence included the acquisition of CK7 expression in the malignant portion. Gastric mucin may play a role in the initial step of the neoplastic evolution and CK7 may denote neoplastic progression. This case confirms the notion of a widely variegated morphology of precursor...

  9. Colorectal Adenomatous Polyposis: Heterogeneity of Susceptibility Gene Mutations and Phenotypes in a Cohort of Italian Patients.

    Marabelli, Monica; Molinaro, Valeria; Abou Khouzam, Raefa; Berrino, Enrico; Panero, Mara; Balsamo, Antonella; Venesio, Tiziana; Ranzani, Guglielmina Nadia

    2016-12-01

    Colorectal adenomatous polyposis entailing cancer predisposition is caused by constitutional mutations in different genes. APC is associated with the familial adenomatous polyposis (FAP/AFAP) and MUTYH with the MUTYH-associated polyposis (MAP), while POLE and POLD1 mutations cause the polymerase proofreading-associated polyposis (PPAP). We screened for mutations in patients with multiple adenomas/FAP: 121 patients were analyzed for APC and MUTYH mutations, and 36 patients were also evaluated for POLE and POLD1 gene mutations. We found 20 FAP/AFAP, 15 MAP, and no PPAP subjects: pathogenic mutations proved to be heterogeneous, and included 5 APC and 1 MUTYH novel mutations. The mutation detection rate was significantly different between patients with 5-100 polyps and those with >100 polyps (p = 8.154 × 10 -7 ), with APC mutations being associated with an aggressive phenotype (p = 1.279 × 10 -9 ). Mean age at diagnosis was lower in FAP/AFAP compared to MAP (p = 3.055 × 10 -4 ). Mutation-negative probands showed a mean age at diagnosis that was significantly higher than FAP/AFAP (p = 3.46986 × 10 -7 ) and included 45.3% of patients with <30 polyps and 70.9% of patients with no family history. This study enlarges the APC and MUTYH mutational spectra, and also evaluated variants of uncertain significance, including the MUTYH p.Gln338His mutation. Moreover this study underscores the phenotypic heterogeneity and genotype-phenotype correlations in a cohort of Italian patients.

  10. Sulfate-reducing bacteria colonize pouches formed for ulcerative colitis but not for familial adenomatous polyposis.

    Duffy, M

    2012-02-03

    PURPOSE: Ileal pouch-anal anastomosis remains the "gold standard" in surgical treatment of ulcerative colitis and familial adenomatous polyposis. Pouchitis occurs mainly in patients with a background of ulcerative colitis, although the reasons for this are unknown. The aim of this study was to characterize differences in pouch bacterial populations between ulcerative colitis and familial adenomatous pouches. METHODS: After ethical approval was obtained, fresh stool samples were collected from patients with ulcerative colitis pouches (n = 10), familial adenomatous polyposis (n = 7) pouches, and ulcerative colitis ileostomies (n = 8). Quantitative measurements of aerobic and anaerobic bacteria were performed. RESULTS: Sulfate-reducing bacteria were isolated from 80 percent (n = 8) of ulcerative colitis pouches. Sulfate-reducing bacteria were absent from familial adenomatous polyposis pouches and also from ulcerative colitis ileostomy effluent. Pouch Lactobacilli, Bifidobacterium, Bacteroides sp, and Clostridium perfringens counts were increased relative to ileostomy counts in patients with ulcerative colitis. Total pouch enterococci and coliform counts were also increased relative to ileostomy levels. There were no significant quantitative or qualitative differences between pouch types when these bacteria were evaluated. CONCLUSIONS: Sulfate-reducing bacteria are exclusive to patients with a background of ulcerative colitis. Not all ulcerative colitis pouches harbor sulfate-reducing bacteria because two ulcerative colitis pouches in this study were free of the latter. They are not present in familial adenomatous polyposis pouches or in ileostomy effluent collected from patients with ulcerative colitis. Total bacterial counts increase in ulcerative colitis pouches after stoma closure. Levels of Lactobacilli, Bifidobacterium, Bacteroides sp, Clostridium perfringens, enterococci, and coliforms were similar in both pouch groups. Because sulfate-reducing bacteria are

  11. Benign colonic metaplasia at a previous stoma site in a patient without adenomatous polyposis.

    Prouty, Megan; Patrawala, Samit; Vogt, Adam; Kelleher, Michael; Lee, Michael; Parker, Douglas C

    2016-03-01

    There are few reported cases of cutaneous intestinal metaplasia or primary adenocarcinoma arising at the ileostomy site following panproctocolectomy. These complications have been seen almost exclusively in patients with familial adenomatous polyposis and inflammatory bowel disease (IBD). However, benign intraepidermal colonic mucosa at a reversed ileostomy site in a patient without familial adenomatous polyposis or IBD has not been documented. We report a case of a 51-year-old female with a history of colonic adenocarcinoma who presented with pruritic, erythematous, scaly plaques on the right lower abdomen, present since reversal of her ileostomy in 2007. Skin biopsy revealed benign foci of colonic epithelium with no evidence of adenomatous change. Benign intraepidermal colonic mucosa was diagnosed based on histopathologic findings and immunohistochemistry. To our knowledge, this is the first case of intraepidermal benign colonic metaplasia forming in a patient following ostomy reversal. The case emphasizes the importance of patient education and physical examination of the stoma or stoma remnants for detection of unusual or changing lesions due to the risk for malignant transformation. It also demonstrates that benign colonic mucosa should be considered in the differential diagnosis when evaluating lesions near ileostomy sites, regardless of whether the patient has a history of familial adenomatous polyposis or IBD. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Repurposing the FDA-approved pinworm drug pyrvinium as a novel chemotherapeutic agent for intestinal polyposis.

    Bin Li

    Full Text Available Mutations in the WNT-pathway regulator ADENOMATOUS POLYPOSIS COLI (APC promote aberrant activation of the WNT pathway that is responsible for APC-associated diseases such as Familial Adenomatous Polyposis (FAP and 85% of spontaneous colorectal cancers (CRC. FAP is characterized by multiple intestinal adenomas, which inexorably result in CRC. Surprisingly, given their common occurrence, there are few effective chemotherapeutic drugs for FAP. Here we show that the FDA-approved, anti-helminthic drug Pyrvinium attenuates the growth of WNT-dependent CRC cells and does so via activation of CK1α. Furthermore, we show that Pyrvinium can function as an in vivo inhibitor of WNT-signaling and polyposis in a mouse model of FAP: APCmin mice. Oral administration of Pyrvinium, a CK1α agonist, attenuated the levels of WNT-driven biomarkers and inhibited adenoma formation in APCmin mice. Considering its well-documented safe use for treating enterobiasis in humans, our findings suggest that Pyrvinium could be repurposed for the clinical treatment of APC-associated polyposes.

  13. Sulphomucin expression in ileal pouches: emerging differences between ulcerative colitis and familial adenomatous polyposis pouches.

    Bambury, Niamh

    2012-02-03

    PURPOSE: We characterized the expression of sialomucin and sulphomucin in pouches fashioned for familial adenomatous polyposis and ulcerative colitis. We correlated sulphomucin expression with bacterial colonization and mucosal inflammation. METHODS: Ethical approval and informed consent were obtained. Mucosal biopsies from 9 patients with familial adenomatous polyposis and 12 with ulcerative colitis were obtained. Sulphomucin levels were assessed by using the high iron-diamine stain. Mucous gel layer composition was correlated with villous height, crypt depth, and total mucosal thickness. Mucous gel layer composition was correlated with acute and chronic inflammatory infiltrates. Colonization by a panel of seven bacterial species (including sulphate reducing bacteria) was established and correlated with sulphomucin levels. RESULTS: High-iron-diamine positivity (i.e., sulphomucin expression) was greater in ulcerative colitis pouch mucous gel (2.083 +\\/- 0.5 vs. 0.556 +\\/- 0.4, P = 0.003). Sulphomucin expression correlated with reduced crypt depth, villous height, and total mucosal thickness. In the ulcerative colitis group, chronic inflammatory infiltrate scores were significantly greater for high-iron-diamine-positive patients. Colonization by sulphate reducing bacteria was increased in high-iron-diamine-positive patients. CONCLUSIONS: Sulphomucin expression is increased in the mucous gel layer of the ulcerative colitis pouch compared with that of the familial adenomatous polyposis pouch. Sulphomucin expression is associated with colonization by sulphate-reducing bacteria and increased chronic inflammation.

  14. Contribution of APC and MUTYH mutations to familial adenomatous polyposis susceptibility in Hungary.

    Papp, Janos; Kovacs, Marietta Eva; Matrai, Zoltan; Orosz, Enikő; Kásler, Miklós; Børresen-Dale, Anne-Lise; Olah, Edith

    2016-01-01

    Familial adenomatous polyposis (FAP) is a colorectal cancer predisposition syndrome with considerable genetic and phenotypic heterogeneity, defined by the development of multiple adenomas throughout the colorectum. FAP is caused either by monoallelic mutations in the adenomatous polyposis coli gene APC, or by biallelic germline mutations of MUTYH, this latter usually presenting with milder phenotype. The aim of the present study was to characterize the genotype and phenotype of Hungarian FAP patients. Mutation screening of 87 unrelated probands from FAP families (21 of them presented as the attenuated variant of the disease, showing APC were identified in 65 patients (75 %), including nine cases (37.5 %) with large genomic alterations. Twelve of the point mutations were novel. In addition, APC-negative samples were also tested for MUTYH mutations and we were able to identify biallelic pathogenic mutations in 23 % of these cases (5/22). Correlations between the localization of APC mutations and the clinical manifestations of the disease were observed, cases with a mutation in the codon 1200-1400 region showing earlier age of disease onset (p APC- and MUTYH-associated FAP in our cohort: the age at onset of polyposis was significantly delayed for biallelic MUTYH mutation carriers as compared to patients with an APC mutation. Our data represent the first comprehensive study delineating the mutation spectra of both APC and MUTYH in Hungarian FAP families, and underscore the overlap between the clinical characteristics of APC- and MUTYH-associated phenotypes, necessitating a more appropriate clinical characterization of FAP families.

  15. Nasal polyposis in cystic fibrosis: follow-up of children and adolescents for a 3-year period.

    Weber, Silke Anna Theresa; Iyomasa, Renata Mizusaki; Corrêa, Camila de Castro; Florentino, Wellington Novais Mafra; Ferrari, Giesela Fleischer

    Nasal polyposis is often found in patients with cystic fibrosis. To assess the incidence of nasal polyposis, the response to medical treatment, recurrence and the need for surgical intervention in children and adolescents with cystic fibrosis during a three-year follow-up. Clinical symptoms (pulmonary, pancreatic insufficiency, malnutrition, nasal obstruction), two positive sweat chloride tests, and genotype findings in 23 patients with cystic fibrosis were analyzed. All patients underwent nasal endoscopy every 12 months from January 2005 to December 2007, to assess the presence and grade of Nasal Polyps. Nasal polyposis, when present, were treated with topical corticosteroids for 6-12 months, with progress being evaluated within the 3 years of follow-up. In the first evaluation, nasal polyposis was diagnosed in 30.43% of patients (3 bilateral and 4 unilateral), recurrent pneumonia in 82.6%, pancreatic insufficiency in 87%, and malnutrition in 74%. The presence of nasal polyposis was not associated with chloride values in the sweat, genotype, clinical signs of severity of cystic fibrosis, or nasal symptoms. In the three-year period of follow up, 13 patients (56.52%) had at least one event of polyposis, with the youngest being diagnosed at 32 months of age. Only one patient underwent surgery (polypectomy), and there was one diagnosis of nasopharyngeal carcinoma. The study showed a high incidence of nasal polyposis. Monitoring through routine endoscopy in patients with cystic fibrosis, even in the absence of nasal symptoms, is highly recommended. The therapy with topical corticosteroids achieved good results. Thus, an interaction between pediatricians and otolaryngologists is necessary. Copyright © 2016 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  16. Genetics Home Reference: hereditary sensory neuropathy type IA

    ... sensory neuropathy type IA Hereditary sensory neuropathy type IA Printable PDF Open All Close All Enable Javascript ... expand/collapse boxes. Description Hereditary sensory neuropathy type IA is a condition characterized by nerve abnormalities in ...

  17. Genetics Home Reference: hereditary leiomyomatosis and renal cell cancer

    ... Home Health Conditions HLRCC Hereditary leiomyomatosis and renal cell cancer Printable PDF Open All Close All Enable Javascript ... expand/collapse boxes. Description Hereditary leiomyomatosis and renal cell cancer ( HLRCC ) is a disorder in which affected individuals ...

  18. [Paediatric retinal detachment and hereditary vitreoretinal disorders].

    Meier, P

    2013-09-01

    The number of retinal detachments in children is very low in comparison to the number in adults. One predisposing factor for development of paediatric retinal detachment is suffering from hereditary vitreoretinal degeneration (e.g., Stickler syndrome, Wagner syndrome, Kniest dysplasia, familial exudative vitreoretinopathy, congenital X-linked retinoschisis, Knobloch syndrome, incontinentia pigmenti, Norrie disease). Hereditary vitreoretinopathies are characterised by an abnormal-appearing vitreous gel with associated retinal changes. In most of these eyes further ocular abnormalities can be diagnosed. A group of hereditary disorders is associated with characteristic systemic abnormalities. Allied conditions should be considered in the clinical diagnosis. Vitreoretinopathies are the most common cause of inherited retinal detachment. In most eyes primary vitrectomy is necessary, and disease-specific surgical treatment is discussed. Georg Thieme Verlag KG Stuttgart · New York.

  19. Pancreatic cancer risk in hereditary pancreatitis

    Frank Ulrich Weiss

    2014-02-01

    Full Text Available Inflammation is part of the body’s immune response in order to remove harmful stimuli – like pathogens, irritants or damaged cells - and start the healing process. Recurrent or chronic inflammation on the other side seems a predisposing factor for carcinogenesis and has been found associated with cancer development. In chronic pancreatitis mutations of the cationic trypsinogen (PRSS1 gene have been identified as risk factors of the disease. Hereditary pancreatitis is a rare cause of chronic pancreatic inflammation with an early onset, mostly during childhood. Hereditary pancreatitis often starts with recurrent episodes of acute pancreatitis and the clinical phenotype is not very much different from other etiologies of the disease. The long-lasting inflammation however generates a tumor promoting environment and represents a major risk factor for tumor development This review will reflect our knowledge concerning the specific risk of hereditary pancreatitis patients to develop pancreatic cancer.

  20. Nonvariceal upper gastrointestinal bleeding

    Burke, Stephen J.; Weldon, Derik; Sun, Shiliang; Golzarian, Jafar

    2007-01-01

    Nonvariceal upper gastrointestinal bleeding (NUGB) remains a major medical problem even after advances in medical therapy with gastric acid suppression and cyclooxygenase (COX-2) inhibitors. Although the incidence of upper gastrointestinal bleeding presenting to the emergency room has slightly decreased, similar decreases in overall mortality and rebleeding rate have not been experienced over the last few decades. Many causes of upper gastrointestinal bleeding have been identified and will be reviewed. Endoscopic, radiographic and angiographic modalities continue to form the basis of the diagnosis of upper gastrointestinal bleeding with new research in the field of CT angiography to diagnose gastrointestinal bleeding. Endoscopic and angiographic treatment modalities will be highlighted, emphasizing a multi-modality treatment plan for upper gastrointestinal bleeding. (orig.)

  1. Nonvariceal upper gastrointestinal bleeding

    Burke, Stephen J.; Weldon, Derik; Sun, Shiliang [University of Iowa, Department of Radiology, Iowa, IA (United States); Golzarian, Jafar [University of Iowa, Department of Radiology, Iowa, IA (United States); University of Iowa, Department of Radiology, Carver College of Medicine, Iowa, IA (United States)

    2007-07-15

    Nonvariceal upper gastrointestinal bleeding (NUGB) remains a major medical problem even after advances in medical therapy with gastric acid suppression and cyclooxygenase (COX-2) inhibitors. Although the incidence of upper gastrointestinal bleeding presenting to the emergency room has slightly decreased, similar decreases in overall mortality and rebleeding rate have not been experienced over the last few decades. Many causes of upper gastrointestinal bleeding have been identified and will be reviewed. Endoscopic, radiographic and angiographic modalities continue to form the basis of the diagnosis of upper gastrointestinal bleeding with new research in the field of CT angiography to diagnose gastrointestinal bleeding. Endoscopic and angiographic treatment modalities will be highlighted, emphasizing a multi-modality treatment plan for upper gastrointestinal bleeding. (orig.)

  2. Considerations concerning a tailored, individualized therapeutic management of patients with (neuro)endocrine tumours of the gastrointestinal tract and pancreas

    W.W. de Herder (Wouter); E.P. Krenning (Eric); C.H.J. van Eijck (Casper); S.W.J. Lamberts (Steven)

    2004-01-01

    textabstractEndocrine tumours of the gastrointestinal tract and pancreas may present at different disease stages with either hormonal or hormone-related symptoms/syndromes, or without hormonal symptoms. They may occur either sporadically or as part of hereditary syndromes. In the

  3. Therapeutic Strategies for Hereditary Kidney Cancer.

    Sidana, Abhinav; Srinivasan, Ramaprasad

    2016-08-01

    The study of hereditary forms of kidney cancer has vastly increased our understanding of metabolic and genetic pathways involved in the development of both inherited and sporadic kidney cancers. The recognition that diverse molecular events drive different forms of kidney cancers has led to the preclinical and clinical development of specific pathway-directed strategies tailored to treat distinct subgroups of kidney cancer. Here, we describe the molecular mechanisms underlying the pathogenesis of several different types of hereditary renal cancers, review their clinical characteristics, and summarize the treatment strategies for the management of these cancers.

  4. Diagnosis and management of hereditary hemochromatosis.

    Salgia, Reena J; Brown, Kimberly

    2015-02-01

    Hereditary hemochromatosis is a rare genetic disorder that can have significant clinical consequences. Hemochromatosis is associated with iron overload, and can initially be recognized through laboratory testing for serum ferritin and transferrin saturation. Genetic testing for the HFE mutation can be performed in patients with elevated iron indices and a suspicion for hemochromatosis or liver disease. The main pathway resulting in iron overload is through altered hepcidin levels. Treatment of patients with the clinical phenotype of hereditary hemochromatosis is commonly through phlebotomy for removal of excess iron stores. This article highlights the current information and data regarding the diagnosis and management of hemochromatosis. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Gastrointestinal nuclear imaging

    Anon.

    1988-01-01

    This book contains paper grouped under the headings of: salivary scintigraphy, abscess detection with radionuclides; pediatric gastroenterology; liver spleen, and miscellaneous GI studies: gastrointestinal

  6. Localized Giant Inflammatory Polyposis of the Ileocecum Associated with Crohn’s Disease: Report of a Case

    Yuichi Fumimoto

    2008-04-01

    Full Text Available Although inflammatory polyposis is one of the common complications in patients with inflammatory bowel disease, it is rare that each poly grows up to more than 1.5 cm. We describe a case of localized giant inflammatory polyposis of the ileocecum associated with Crohn’s disease. A 40-year-old man who had been followed for 28 years because of Crohn’s disease was hospitalized for right lower abdominal pain after meals. Barium enema and colonoscopy showed numerous worm-like polyps in the ascending colon which grew up to the hepatic flexure of the colon from the ileocecum, causing an obstruction of the ileocecal orifice. Since histology of a biopsy specimen taken from the giant polyps showed no dysplasia, he was diagnosed with ileus due to the localized giant inflammatory polyposis. A laparoscopically assisted ileocecal resection was performed. The resected specimen showed that the giant polyps grew up into the ileocecum. Histological examination revealed inflammatory polyposis without neoplasm. Generally, conservative treatment is indicated for localized giant inflammatory polyposis because this lesion is regarded as benign. However, occasionally serious complications arise, requiring surgical treatment.

  7. WNT Inhibitory Activity of Malus Pumila miller cv Annurca and Malus domestica cv Limoncella Apple Extracts on Human Colon-Rectal Cells Carrying Familial Adenomatous Polyposis Mutations.

    Riccio, Gennaro; Maisto, Maria; Bottone, Sara; Badolati, Nadia; Rossi, Giovanni Battista; Tenore, Gian Carlo; Stornaiuolo, Mariano; Novellino, Ettore

    2017-11-18

    Inhibitors of the Wingless-related Integration site (WNT)/β-catenin pathway have recently been under consideration as potential chemopreventive agents against Familial Adenomatous Polyposis (FAP). This autosomal-dominant syndrome is caused by germline mutations in the gene coding for the protein APC and leads to hyperactivation of the WNT/β-catenin signaling pathway, uncontrolled intestinal cell proliferation and formation of adenocarcinomas. The aim of the present work was to: (i) test, on in vitro cultures of cells carrying FAP mutations and on ex vivo biopsies of FAP patients, the WNT inhibitory activity of extracts from two common southern Italian apples, Malus pumila Miller cv. 'Annurca' and Malus domestica cv 'Limoncella'; (ii) identify the mechanisms underpinning their activities and; (iii) evaluate their potency upon gastrointestinal digestion. We here show that both Annurca and Limoncella apple extracts act as WNT inhibitors, mostly thanks to their polyphenolic contents. They inhibit the pathway in colon cells carrying FAP mutations with active dilutions falling in ranges close to consumer-relevant concentrations. Food-grade manufacturing of apple extracts increases their WNT inhibitory activity as result of the conversion of quercetin glycosides into the aglycone quercetin, a potent WNT inhibitor absent in the fresh fruit extract. However, in vitro simulated gastrointestinal digestion severely affected WNT inhibitory activity of apple extracts, as result of a loss of polyphenols. In conclusion, our results show that apple extracts inhibit the WNT pathway in colon cells carrying FAP mutations and represent a potential nutraceutical alternative for the treatment of this pathology. Enteric coating is advisable to preserve the activity of the extracts in the colon-rectal section of the digestive tract.

  8. WNT Inhibitory Activity of Malus Pumila miller cv Annurca and Malus domestica cv Limoncella Apple Extracts on Human Colon-Rectal Cells Carrying Familial Adenomatous Polyposis Mutations

    Gennaro Riccio

    2017-11-01

    Full Text Available Inhibitors of the Wingless-related Integration site (WNT/β-catenin pathway have recently been under consideration as potential chemopreventive agents against Familial Adenomatous Polyposis (FAP. This autosomal-dominant syndrome is caused by germline mutations in the gene coding for the protein APC and leads to hyperactivation of the WNT/β-catenin signaling pathway, uncontrolled intestinal cell proliferation and formation of adenocarcinomas. The aim of the present work was to: (i test, on in vitro cultures of cells carrying FAP mutations and on ex vivo biopsies of FAP patients, the WNT inhibitory activity of extracts from two common southern Italian apples, Malus pumila Miller cv. ‘Annurca’ and Malus domestica cv ‘Limoncella’; (ii identify the mechanisms underpinning their activities and; (iii evaluate their potency upon gastrointestinal digestion. We here show that both Annurca and Limoncella apple extracts act as WNT inhibitors, mostly thanks to their polyphenolic contents. They inhibit the pathway in colon cells carrying FAP mutations with active dilutions falling in ranges close to consumer-relevant concentrations. Food-grade manufacturing of apple extracts increases their WNT inhibitory activity as result of the conversion of quercetin glycosides into the aglycone quercetin, a potent WNT inhibitor absent in the fresh fruit extract. However, in vitro simulated gastrointestinal digestion severely affected WNT inhibitory activity of apple extracts, as result of a loss of polyphenols. In conclusion, our results show that apple extracts inhibit the WNT pathway in colon cells carrying FAP mutations and represent a potential nutraceutical alternative for the treatment of this pathology. Enteric coating is advisable to preserve the activity of the extracts in the colon-rectal section of the digestive tract.

  9. Idiopathic Thrombocytopenic Purpura Misdiagnosed as Hereditary Angioedema

    Andersen, Michelle Fog; Bygum, Anette

    2015-01-01

    however not always have to be caused by angioedema but can relate to other concomitant disorders. In this report we are focusing on misdiagnosis in a patient with known hereditary angioedema, whose bleeding episode caused by idiopathic thrombocytopenic purpura was mistaken for an acute attack...

  10. Hereditary spherocytosis: Consequences of delayed diagnosis

    Sarah C Steward

    2014-08-01

    Full Text Available Objective: To determine whether patients with undiagnosed hereditary spherocytosis hospitalized for transfusions might have avoided hospitalization via earlier diagnosis. Study design: Charts of all (N = 30 patients with hereditary spherocytosis seen in pediatric hematology at West Virginia University-Charleston were reviewed. Family and transfusion history and presence of neonatal jaundice were recorded. Complete blood count and reticulocyte values during infancy were available for 20 of 30 patients, while baseline steady-state values were available for all 30. Results: Transfusions were given to 22 patients; 12 of 14 with an aplastic crisis were undiagnosed. In 10 of 12, the severity of anemia led to hospitalization (3 to intensive care. All 10 had prior mean corpuscular hemoglobin concentration and/or red cell distribution width elevations and a history of neonatal jaundice; 7 of 10 had a positive family history. Conclusions: Undiagnosed hereditary spherocytosis may lead to inpatient transfusions for severe anemia. Earlier detection of hereditary spherocytosis is easily achievable and may reduce hospitalizations via closer monitoring.

  11. Major and minor form of hereditary hyperekplexia

    Tijssen, MAJ; Vergouwe, MN; van Dijk, JG; Rees, M; Frants, RR; Brown, P

    Hyperekplexia is a hereditary neurological disorder characterized by excessive startle responses. Within the disorder two clinical forms can be distinguished. The major form is characterized by continuous generalized stiffness in the first year of life and an exaggerated startle reflex, accompanied

  12. MRI in Leber's hereditary optic neuropathy

    Matthews, Lucy; Enzinger, Christian; Fazekas, Franz

    2015-01-01

    BACKGROUND: Leber's hereditary optic neuropathy (LHON) and a multiple sclerosis (MS)-like illness appear to coexist 50 times more frequently than would be expected by chance. This association of LHON and MS (LMS) raises an important question about whether there could be a common pathophysiological...

  13. Autosomal dominant hereditary ataxia in Sri Lanka

    Sumathipala, Dulika S; Abeysekera, Gayan S; Jayasekara, Rohan W; Tallaksen, Chantal ME; Dissanayake, Vajira HW

    2013-01-01

    Background Spinocerebellar ataxias (SCA) are a group of hereditary neurodegenerative disorders. Prevalence of SCA subtypes differ worldwide. Autosomal dominant ataxias are the commonest types of inherited ataxias seen in Sri Lanka. The aim of the study is to determine the genetic etiology of patients with autosomal dominant ataxia in Sri Lanka and to describe the clinical features of each genetic subtype. Methods ...

  14. Hereditary hemochromatosis: An opportunity for gene therapy

    FERNANDO EZQUER

    2006-01-01

    Full Text Available Levels of body iron should be tightly controlled to prevent the formation of oxygen radicals, lipoperoxidation, genotoxicity, and the production of cytotoxic cytokines, which result in damage to a number of organs. Enterocytes in the intestinal villae are involved in the apical uptake of iron from the intestinal lumen; iron is further exported from the cells into the circulation. The apical divalent metal transporter-1 (DMT1 transports ferrous iron from the lumen into the cells, while the basolateral transporter ferroportin extrudes iron from the enterocytes into the circulation. Patients with hereditary hemochromatosis display an accelerated transepithelial uptake of iron, which leads to body iron accumulation that results in cirrhosis, hepatocellular carcinoma, pancreatitis, and cardiomyopathy. Hereditary hemochromatosis, a recessive genetic condition, is the most prevalent genetic disease in Caucasians, with a prevalence of one in 300 subjects. The majority of patients with hereditary hemochromatosis display mutations in the gene coding for HFE, a protein that normally acts as an inhibitor of transepithelial iron transport. We discuss the different control points in the homeostasis of iron and the different mutations that exist in patients with hereditary hemochromatosis. These control sites may be influenced by gene therapeutic approaches; one general therapy for hemochromatosis of different etiologies is the inhibition of DMT1 synthesis by antisense-generating genes, which has been shown to markedly inhibit apical iron uptake by intestinal epithelial cells. We further discuss the most promising strategies to develop gene vectors and deliver them into enterocytes

  15. Epidemiology of Non-hereditary Angioedema

    Madsen, Flemming; Attermann, Jorn; Linneberg, Allan

    2012-01-01

    The prevalence of non-hereditary angioedema was investigated in a general population sample (n = 7,931) and in a sample of Danish patients (n = 7,433) tested for deficiency of functional complement C1 esterase inhibitor protein (functional C1 INH). The general population sample (44% response rate...

  16. Epidemiology of Non-hereditary Angioedema

    Madsen, Flemming; Attermann, Jørn; Linneberg, Allan

    2012-01-01

    The prevalence of non-hereditary angioedema was investigated in a general population sample (n¿=¿7,931) and in a sample of Danish patients (n¿=¿7,433) tested for deficiency of functional complement C1 esterase inhibitor protein (functional C1 INH). The general population sample (44% response rate...

  17. Revisited diagnostics of hereditary epidermolysis bullosa

    V. I. Albanova

    2014-01-01

    Full Text Available Hereditary epidermolysis bullosa is a big group of hereditary diseases with the main manifestations in the form of blisters on the skin and mucous coat after slight mechanical injuries. It is not always possible to diagnose this disease based on the clinical picture. The article discusses current laboratory diagnostics methods for hereditary epidermolysis bullosa including immunofluorescence antigen mapping (IFM, transmission electron microscopy (TEM and genetic analysis (molecular or DNA diagnostics as well as their advantages and disadvantages. TEM determines the micro splitting level and nature of ultrafine changes in the area of the dermoepidermal junction; at the same time, such tests need special expensive equipment. Substantial experience is also needed to analyze the resulting submicroscopic images. IFM determines whether expression of the affected protein related to the disease development is reduced or absent; however, invalid (false positive or false negative results can be obtained in patients with the reduced expression of the affected protein. Genetic analysis plays a key role for prenatal diagnostics. Therefore, to make an exact diagnosis of hereditary epidermolysis bullosa, it is expedient to apply IFM, TEM and genetic analysis. The need to set an exact diagnosis of the disease is related to the fact that the promising treatment methods being currently developed are aimed at treating patients with certain forms of the disease.

  18. Hereditary hemorrhagic telangiectasia clinical and molecular genetics

    Letteboer, T.G.W.

    2010-01-01

    Hereditary hemorrhagic telangiectasia (HHT) or Rendu-Osler-Weber (ROW) syndrome is an autosomal dominant disease characterized by vascular malformations in multiple organ systems. HHT has an age-related penetrance and variable clinical expression. The clinical symptoms are caused by direct

  19. Fruit-induced FPIES masquerading as hereditary fructose intolerance.

    Fiocchi, Alessandro; Dionisi-Vici, Carlo; Cotugno, Giovanna; Koch, Pierluigi; Dahdah, Lamia

    2014-08-01

    Hereditary fructose intolerance (HFI) symptoms develop at first introduction of fruit during weaning. We report on an infant with suspected HFI who presented with repeated episodes of vomiting and hypotension after ingestion of fruit-containing meals. The first episode occurred at age 4 months. Despite negative genetic testing for HFI, strict avoidance of fruit ingestion resulted in lack of recurrence of symptoms. Oral-fructose-tolerance testing conducted with an apple mousse did not determine hypoglycemia or fructosuria but caused severe hypotension. Allergy evaluations were negative, and the history was diagnostic for fruit-induced food protein-induced enterocolitis syndrome. Because this non-immunoglobulin E-mediated gastrointestinal food hypersensitivity manifests as profuse, repetitive vomiting, often with diarrhea, leading to acute dehydration and lethargy, it may be misinterpreted as HFI. We advise pediatricians to consider food protein-induced enterocolitis syndrome in the differential diagnosis when there is a suspicion of HFI. Copyright © 2014 by the American Academy of Pediatrics.

  20. Abnormal sensitivity of skin fibroblasts from familial polyposis patients to DNA alkylating agents

    Barfknecht, T.R.; Little, J.B.

    1982-01-01

    Fibroblast cell strains derived from different patients all afflicted with genetic predisposing to the development of intestinal polyposis and cancer were tested for their sensitivity to the lethal effects of the DNA alkylating agents methylmethanesulfonate (MMS), ethyl methanesulfonate, N-methyl-N'-nitro-N-nitrosoguanidine, and 4-nitroquinoline 1-oxide. The genetic syndromes studied were: (a) adenomatosis of the colon and rectum only, an autosomal dominant trait; (b) Turcot's syndrome, a rare autosomal recessive polyposis syndrome also characterized by central nervous system tumors; and (c) Gardner's syndrome, an autosomal dominant syndrome which, in addition to intestinal polyposis, is also clinically characterized by osteomas and soft tissue tumors. Fibroblasts from a patient with Turcot's syndrome were hypersensitive to MMS, having a D0 value of 0.24 mM (p less than 0.01) versus the normal average D0 of 0.36 mM and a D10 value of 0.95 mM (p less than 0.01) compared with the normal average value of 1.3 mM. Fibroblasts from the Gardner's syndrome proband were moderately sensitive to MMS, ethyl methanesulfonate, and N-methyl-N'-nitro-N-nitrosoguanidine due to significant differences of D10 values of 0.60 mM (p less than 0.01), 15 mM (p less than 0.01), and 4.8 microM (p less than 0.025), respectively, versus the normal average values of 1.3 mM, 28 mM, and 9.4 microM. Fibroblasts from the clinically affected Gardner's syndrome daughter of the proband were significantly more sensitive to MMS treatment, D0 of 0.22 mM (p less than 0.01) versus the normal average D0 of 0.36 mM and a D10 of 0.97 mM (p less than 0.01) versus the normal average. This differential sensitivity to the several DNA alkylating agents suggests that different mechanisms of hypersensitivity to these chemicals may be associated with fibroblasts from the various forms of familial polyposis

  1. Is epidermal growth factor involved in development of duodenal polyps in familial polyposis coli?

    Poulsen, Steen Seier

    1988-01-01

    Duodenal adenomas are a frequent extracolonic manifestation in patients with familial polyposis coli (FPC). Epidermal growth factor (EGF), a polypeptide that stimulates cellular growth and differentiation, is localized in Paneth cells in the small intestine. In two patients with FPC, we found EGF...... immunoreactivity in duodenal adenomas. Numerous EGF immunoreactive Paneth cells were localized, not as usually, in the bottom of the crypts, but scattered along the crypts alone or in clusters. We do not know whether EGF is involved in the development of duodenal polyps in FPC patients, or whether the present...

  2. Phosphorylation near nuclear localization signal regulates nuclear import of adenomatous polyposis coli protein

    Zhang, Fang; White, Raymond L.; Neufeld, Kristi L.

    2000-01-01

    Mutation of the adenomatous polyposis coli (APC) gene is an early step in the development of colorectal carcinomas. APC protein is located in both the cytoplasm and the nucleus. The objective of this study was to define the nuclear localization signals (NLSs) in APC protein. APC contains two potential NLSs comprising amino acids 1767–1772 (NLS1APC) and 2048–2053 (NLS2APC). Both APC NLSs are well conserved among human, mouse, rat, and fly. NLS1APC and NLS2APC each w...

  3. Mantle cell lymphoma of the gastrointestinal tract presenting with multiple intussusceptions – case report and review of literature

    Abo Stephen M

    2009-07-01

    Full Text Available Abstract Background Mantle cell lymphoma (MCL is an aggressive type of B-cell non-Hodgkin's lymphoma that originates from small to medium sized lymphocytes located in the mantle zone of the lymph node. Extra nodal involvement is present in the majority of cases, with a peculiar tendency to invade the gastro-intestinal tract in the form of multiple lymphomatous polyposis. MCL can be accurately diagnosed with the use of the highly specific marker Cyclin D1. Few cases of mantle cell lymphoma presenting with intussuception have been reported. Here we present a rare case of multiple intussusceptions caused by mantle cell lymphoma and review the literature of this disease. Case presentation A 68-year-old male presented with pain, tenderness in the right lower abdomen, associated with nausea and non-bilious vomiting. CT scan of abdomen revealed ileo-colic intussusception. Laparoscopy confirmed multiple intussusceptions involving ileo-colic and ileo-ileal segments of gastrointestinal tract. A laparoscopically assisted right hemicolectomy and extended ileal resection was performed. Postoperative recovery was uneventful. The histology and immuno-histochemistry of the excised small and large bowel revealed mantle cell lymphoma with multiple lymphomatous polyposis and positivity to Cyclin D1 marker. The patient was successfully treated with Rituximab-CHOP chemotherapy and remains in complete remission at one-year follow-up. Conclusion This is a rare case of intestinal lymphomatous polyposis due to mantle cell lymphoma presenting with multiple small bowel intussusceptions. Our case highlights laparoscopic-assisted bowel resection as a potential and feasible option in the multi-disciplinary treatment of mantle cell lymphoma.

  4. Hereditary noetherian prime rings and idealizers

    Levy, Lawrence S

    2011-01-01

    The direct sum behaviour of its projective modules is a fundamental property of any ring. Hereditary Noetherian prime rings are perhaps the only noncommutative Noetherian rings for which this direct sum behaviour (for both finitely and infinitely generated projective modules) is well-understood, yet highly nontrivial. This book surveys material previously available only in the research literature. It provides a re-worked and simplified account, with improved clarity, fresh insights and many original results about finite length modules, injective modules and projective modules. It culminates in the authors' surprisingly complete structure theorem for projective modules which involves two independent additive invariants: genus and Steinitz class. Several applications demonstrate its utility. The theory, extending the well-known module theory of commutative Dedekind domains and of hereditary orders, develops via a detailed study of simple modules. This relies upon the substantial account of idealizer subrings wh...

  5. Hereditary spastic paraplegia with cerebellar ataxia

    Nielsen, J E; Johnsen, B; Koefoed, P

    2004-01-01

    Complex forms of hereditary spastic paraplegia (HSP) are rare and usually transmitted in an autosomal recessive pattern. A family of four generations with autosomal dominant hereditary spastic paraplegia (AD-HSP) and a complex phenotype with variably expressed co-existing ataxia, dysarthria......, unipolar depression, epilepsy, migraine, and cognitive impairment was investigated. Genetic linkage analysis and sequencing of the SPG4 gene was performed and electrophysiologic investigations were carried out in six individuals and positron emission tomography (PET) in one patient. The disease was linked...... in those individuals who were clinically affected by a complex phenotype consisting of HSP and cerebellar ataxia. Other features noted in this kindred including epilepsy, cognitive impairment, depression, and migraine did not segregate with the HSP phenotype or mutation, and therefore the significance...

  6. Rare mutations predisposing to familial adenomatous polyposis in Greek FAP patients

    Mihalatos, Markos; Fountzilas, George; Agnantis, Niki J; Nasioulas, Georgios; Apessos, Angela; Dauwerse, Hans; Velissariou, Voula; Psychias, Aristidis; Koliopanos, Alexander; Petropoulos, Konstantinos; Triantafillidis, John K; Danielidis, Ioannis

    2005-01-01

    Familial Adenomatous Polyposis (FAP) is caused by germline mutations in the APC (Adenomatous Polyposis Coli) gene. The vast majority of APC mutations are point mutations or small insertions / deletions which lead to truncated protein products. Splicing mutations or gross genomic rearrangements are less common inactivating events of the APC gene. In the current study genomic DNA or RNA from ten unrelated FAP suspected patients was examined for germline mutations in the APC gene. Family history and phenotype were used in order to select the patients. Methods used for testing were dHPLC (denaturing High Performance Liquid Chromatography), sequencing, MLPA (Multiplex Ligation – dependent Probe Amplification), Karyotyping, FISH (Fluorescence In Situ Hybridization) and RT-PCR (Reverse Transcription – Polymerase Chain Reaction). A 250 Kbp deletion in the APC gene starting from intron 5 and extending beyond exon 15 was identified in one patient. A substitution of the +5 conserved nucleotide at the splice donor site of intron 9 in the APC gene was shown to produce frameshift and inefficient exon skipping in a second patient. Four frameshift mutations (1577insT, 1973delAG, 3180delAAAA, 3212delA) and a nonsense mutation (C1690T) were identified in the rest of the patients. Screening for APC mutations in FAP patients should include testing for splicing defects and gross genomic alterations

  7. The role of human papilloma virus and herpes viruses in the etiology of nasal polyposis.

    Koçoğlu, Mücahide Esra; Mengeloğlu, Fırat Zafer; Apuhan, Tayfun; Özsoy, Şeyda; Yilmaz, Beyhan

    2016-02-17

    The aim of this study was to investigate the etiological role of human papilloma virus (HPV), herpes simplex virus (HSV), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpes virus-6 (HHV-6) and -7 (HHV-7) in the occurrence of nasal polyposis. Nasal polyp samples from 30 patients with nasal polyposis and normal nasal mucosa from 10 patients without nasal polyps were obtained. DNA was extracted from tissues. Real-time polymerase chain reaction was performed for all runs. No HSV-1, HSV-2, or VZV was detected in the samples. Among the patient samples, EBV and HHV-7 DNA were detected in 18 (60%), HHV-6 was detected in 20 (66.7%), and HPV was detected in 4 (13.3%) samples. Among the controls, CMV DNA was positive in one (10%). EBV was positive in 5 (50%), HHV-6 and HHV-7 were positive in 7 (70%), and HPV was positive in 2 (20%) samples. No significant difference was found among the groups with any test in terms of positivity. The association of Herpesviridae and HPV with the pathogenesis of nasal polyps was investigated in this study and no relationship was found. Thus, these viruses do not play a significant role in the formation of nasal polyps.

  8. Assessing barriers to a rational chemoprevention trial design in young patients with familial adenomatous polyposis.

    Wood, Joanna P; Howells, Lynne M; Brown, Karen; Thomas, Anne L

    2017-07-01

    Familial adenomatous polyposis coli (FAP) is an autosomal dominant condition caused by a germline mutation in the adenomatous polyposis coli gene. Colonic adenomas form and almost all patients will develop colorectal cancer if they are not managed at an early stage. The safest preventive strategy is surgical resection of the colon, most commonly performed in late teenage years. There is a paucity of trials investigating the use of primary chemoprevention to delay polyp formation in paediatric FAP. There are extensive preclinical and early clinical data demonstrating that curcumin may be a safe and effective chemotherapeutic agent in reducing the polyp burden in this disease. We ultimately proposed to design and conduct a clinical study to assess whether curcumin treatment delays the need for surgery and/or prevents cancer in young patients with FAP. Research into clinical trial protocols has demonstrated that assessing patients' perceptions at the initial stage leads to better outcomes. We therefore conducted a questionnaire study of patients and parents of children affected by FAP to gain information to aid the protocol design. Results demonstrated that there are some FAP patients for whom this study is relevant and desirable. Those with a personal history of curcumin use reported that it was well tolerated. However, the response rate was poor (25%), indicating that there are potential difficulties ensuring adequate recruitment to the proposed trial. This report draws on lessons learnt from prior trials and the findings from the questionnaire to outline the challenges faced in designing such a study.

  9. Evidence-based management of nasal polyposis by intranasal corticosteroids: from the cause to the clinic.

    Bachert, Claus

    2011-01-01

    Nasal polyposis is an inflammatory disorder involving the mucosa of the nose and paranasal sinuses and affecting approximately 2-4% of the general population. A literature search of Medline and Embase was conducted to obtain an overview of the epidemiology, pathophysiology, and current treatment of nasal polyposis, focusing on evidence-based efficacy of intranasal corticosteroids (INSs) as primary and postoperative therapy. Recent research on INSs in nasal polyp treatment, along with notable historic findings, was reviewed. Nasal polyps are mostly characterized by eosinophil infiltration, a complex inflammation of nasal mucosa, and possibly production of polyclonal IgE. Current treatment modalities include INSs, oral corticosteroids, and surgery; surgery is generally limited to those with an insufficient response to medical treatment. Because of their effects on eosinophil-dominated inflammation, INSs and oral corticosteroids are the primary medical treatment strategies. The very low (≤1%) systemic bioavailability of newer INSs minimizes the systemic adverse effects seen with oral corticosteroids. Based on randomized, controlled trials, guidelines recommend INSs as first-line therapy for nasal polyps and for care after polypectomy. Clinical data suggest INSs are effective in reducing polyp size and relieving nasal symptoms. INS treatment has also reduced nasal polyp recurrence in patients undergoing functional endoscopic sinus surgery. Treatment with these mainstay options has been found to improve quality of life, which, along with symptom improvement, is a key factor in disease treatment. Copyright © 2011 S. Karger AG, Basel.

  10. APC promoter 1B deletion in seven American families with familial adenomatous polyposis.

    Snow, A K; Tuohy, T M F; Sargent, N R; Smith, L J; Burt, R W; Neklason, D W

    2015-10-01

    Familial adenomatous polyposis (FAP) is a colorectal cancer predisposition syndrome caused by mutations in the adenomatous polyposis coli (APC) gene. Clinical genetic testing fails to identify disease causing mutations in up to 20% of clinically apparent FAP cases. Following the inclusion of multiplex ligation-dependent probe amplification (MLPA) probes specific for APC promoter 1B, seven probands were identified with a deletion of promoter 1B. Using haplotype analysis spanning the APC locus, the seven families appear to be identical by descent from a common founder. The clinical phenotype of 19 mutation carriers is classical FAP with colectomy at an average age of 24. The majority of cases had a large number of duodenal and gastric polyps. Measurements of allele-specific expression of APC mRNA using TaqMan assay confirmed that relative expression in the allele containing the promoter 1B deletion was reduced 42-98%, depending on tissue type. This study confirms the importance of APC promoter deletions as a cause of FAP and identifies a founder mutation in FAP patients from the United States. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Hereditary Nonpolyposis Colorectal Cancer and Cancer Syndromes: Recent Basic and Clinical Discoveries

    Erbao Chen

    2018-01-01

    Full Text Available Approximately one-third of individuals diagnosed with colorectal cancer have a family history of cancer, suggesting that CRCs may result from a heritable component. Despite the availability of current gene-identification techniques, only 5% of all CRCs emerge from well-identifiable inherited causes for predisposition, including polyposis and nonpolyposis syndromes. Hereditary nonpolyposis colorectal cancer represents a large proportion of cases, and robustly affected patients are at increased risk for early onset, synchronous, and metachronous colorectal malignancies and extracolonic malignancies. HNPCC encompasses several cancer syndromes, such as Lynch syndrome, Lynch-like syndrome, and familial colorectal cancer type X, which have remarkable clinical presentations and overlapping genetic profiles that make clinical diagnosis a challenging task. Therefore, distinguishing between the HNPCC disorders is crucial for physicians as an approach to tailor different recommendations for patients and their at-risk family members according to the risks for colonic and extracolonic cancer associated with each syndrome. Identification of these potential patients through epidemiological characteristics and new genetic testing can estimate the individual risk, which informs appropriate cancer screening, surveillance, and/or treatment strategies. In the past three years, many appealing and important advances have been made in our understanding of the relationship between HNPCC and CRC-associated syndromes. The knowledge from the genetic profile of cancer syndromes and unique genotype-phenotype profiles in the different syndromes has changed our cognition. Therefore, this review presents and discusses HNPCC and several common nonpolyposis syndromes with respect to molecular phenotype, histopathologic features, and clinical presentation.

  12. Hereditary Transthyretin Amyloidosis in Eight Chinese Families

    Ling-Chao Meng

    2015-01-01

    Full Text Available Background: Mutations of transthyretin (TTR cause the most common type of autosomal-dominant hereditary systemic amyloidosis, which occurs worldwide. To date, more and more mutations in the TTR gene have been reported. Some variations in the clinical presentation are often observed in patients with the same mutation or the patients in the same family. The purpose of this study was to find out the clinicopathologic and genetic features of Chinese patients with hereditary TTR amyloidosis. Methods: Clinical and necessary examination materials were collected from nine patients of eight families with hereditary TTR amyloidosis at Peking University First Hospital from January 2007 to November 2014. Sural nerve biopsies were taken for eight patients and skin biopsies were taken in the calf/upper arm for two patients, for light and electron microscopy examination. The TTR genes from the nine patients were analyzed. Results: The onset age varied from 23 to 68 years. The main manifestations were paresthesia, proximal and/or distal weakness, autonomic dysfunction, cardiomyopathy, vitreous opacity, hearing loss, and glossohypertrophia. Nerve biopsy demonstrated severe loss of myelinated fibers in seven cases and amyloid deposits in three. One patient had skin amyloid deposits which were revealed from electron microscopic examination. Genetic analysis showed six kinds of mutations of TTR gene, including Val30Met, Phe33Leu, Ala36Pro, Val30Ala, Phe33Val, and Glu42Gly in exon 2. Conclusions: Since the pathological examinations of sural nerve were negative for amyloid deposition in most patients, the screening for TTR mutations should be performed in all the adult patients, who are clinically suspected with hereditary TTR amyloidosis.

  13. Multiple Hereditary Osteochondromatosis: A Case Report

    K???kesmen, ?i?dem; ?zen, Bu?ra; Ak?am, Mustafa

    2007-01-01

    Objectives Common carious lesions owing to vomiting are not widespread in children. In this case, we aimed to report an 11-years-old male patient with common carious lesions due to repeated vomitings, chewing and eating difficulty and retarded growth with Multiple Hereditary Osteochondromatosis (MHO). Case Report An 11-years-old boy was referred to Department of Pediatric Dentistry in Faculty of Dentistry because of eating difficulty owing to common carious lesions. It was seen that the patie...

  14. Mania associated with complicated hereditary spastic paraparesis

    Raghavendra B Nayak; Govind S Bhogale; Nanasaheb M Patil; Aditya A Pandurangi

    2011-01-01

    Hereditary spastic paraparesis (HSP) is an inherited group of neurological disorders with progressive lower limb spasticity. HSP can be clinically grouped into pure and complicated forms. Pure HSP is one without any associated neurological/psychiatric comorbidity. Depression is the most common psychiatric comorbidity. Presence of mania or bipolar affective illness with HSP is a rare phenomenon. We report a case of a 17-year-old boy who presented with classical features of HSP with complaints ...

  15. Cellular Pathways of Hereditary Spastic Paraplegia*

    Blackstone, Craig

    2012-01-01

    Human voluntary movement is controlled by the pyramidal motor system, a long CNS pathway comprising corticospinal and lower motor neurons. Hereditary spastic paraplegias (HSPs) are a large, genetically diverse group of inherited neurologic disorders characterized by a length-dependent distal axonopathy of the corticospinal tracts, resulting in lower limb spasticity and weakness. A range of studies are converging on alterations in the shaping of organelles, particularly the endoplasmic reticul...

  16. Current problems in haematology. 2: Hereditary spherocytosis.

    Smedley, J C; Bellingham, A J

    1991-01-01

    Hereditary spherocytosis is a relatively common haematological disorder and will be encountered by all haematologists. The abundance of new information, dealing principally with molecular and genetic aspects of pathophysiology, is beginning to have implications for its investigation and management. While these advances have not yet exerted a large influence at therapeutic level, the promise of such advents as prenatal diagnosis make this an exciting field to watch.

  17. Multimodality imaging features of hereditary multiple exostoses

    Kok, H K; Fitzgerald, L; Campbell, N; Lyburn, I D; Munk, P L; Buckley, O; Torreggiani, W C

    2013-01-01

    Hereditary multiple exostoses (HME) or diaphyseal aclasis is an inherited disorder characterised by the formation of multiple osteochondromas, which are cartilage-capped osseous outgrowths, and the development of associated osseous deformities. Individuals with HME may be asymptomatic or develop clinical symptoms, which prompt imaging studies. Different modalities ranging from plain radiographs to cross-sectional and nuclear medicine imaging studies can be helpful in the diagnosis and detecti...

  18. Pancreatic cancer risk in hereditary pancreatitis

    Weiss, Frank U.

    2014-01-01

    Inflammation is part of the body’s immune response in order to remove harmful stimuli – like pathogens, irritants or damaged cells - and start the healing process. Recurrent or chronic inflammation on the other side seems a predisposing factor for carcinogenesis and has been found associated with cancer development. In chronic pancreatitis mutations of the cationic trypsinogen (PRSS1) gene have been identified as risk factors of the disease. Hereditary pancreatitis is a rare cause of chronic...

  19. Disease expression in women with hereditary angioedema

    Bouillet, Laurence; Longhurst, Hilary; Boccon-Gibod, Isabelle

    2008-01-01

    OBJECTIVE: Fluctuations in sex hormones can trigger angioedema attacks in women with hereditary angioedema. Combined oral contraceptive therapies, as well as pregnancy, can induce severe attacks. The course of angioedema may be very variable in different women. STUDY DESIGN: Within the PREHAEAT p......-sensitive phenotype for some patients. CONCLUSION: The course of angioedema in women with C1 inhibitor deficiency is affected by physiologic hormonal changes; consequently, physicians should take these into account when advising on management.......OBJECTIVE: Fluctuations in sex hormones can trigger angioedema attacks in women with hereditary angioedema. Combined oral contraceptive therapies, as well as pregnancy, can induce severe attacks. The course of angioedema may be very variable in different women. STUDY DESIGN: Within the PREHAEAT...... project launched by the European Union, data on 150 postpubertal women with hereditary angioedema were collected in 8 countries, using a patient-based questionnaire. RESULTS: Puberty worsened the disease for 62%. Combined oral contraceptives worsened the disease for 79%, whereas progestogen-only pills...

  20. Hereditary pituitary hyperplasia with infantile gigantism.

    Gläsker, Sven; Vortmeyer, Alexander O; Lafferty, Antony R A; Hofman, Paul L; Li, Jie; Weil, Robert J; Zhuang, Zhengping; Oldfield, Edward H

    2011-12-01

    We report hereditary pituitary hyperplasia. The objective of the study was to describe the results of the clinical and laboratory analysis of this rare instance of hereditary pituitary hyperplasia. The study is a retrospective analysis of three cases from one family. The study was conducted at the National Institutes of Health, a tertiary referral center. A mother and both her sons had very early-onset gigantism associated with high levels of serum GH and prolactin. The condition was treated by total hypophysectomy. We performed clinical, pathological, and molecular evaluations, including evaluation basal and provocative endocrine testing, neuroradiological assessment, and assessment of the pituitary tissue by microscopic evaluation, immunohistochemistry, and electron microscopy. All three family members had very early onset of gigantism associated with abnormally high serum levels of GH and prolactin. Serum GHRH levels were not elevated in either of the boys. The clinical, radiographic, surgical, and histological findings indicated mammosomatotroph hyperplasia. The pituitary gland of both boys revealed diffuse mammosomatotroph hyperplasia of the entire pituitary gland without evidence of adenoma. Prolactin and GH were secreted by the same cells within the same secretory granules. Western blot and immunohistochemistry demonstrated expression of GHRH in clusters of cells distributed throughout the hyperplastic pituitary of both boys. This hereditary condition seems to be a result of embryonic pituitary maldevelopment with retention and expansion of the mammosomatotrophs. The findings suggest that it is caused by paracrine or autocrine pituitary GHRH secretion during pituitary development.

  1. Advances and challenges in hereditary cancer pharmacogenetics.

    Cascorbi, Ingolf; Werk, Anneke Nina

    2017-01-01

    Cancer pharmacogenetics usually considers tumor-specific targets. However, hereditary genetic variants may interfere with the pharmacokinetics of antimetabolites and other anti-cancer drugs, which may lead to severe adverse events. Areas covered: Here, the impact of hereditary genes considered in drug labels such as thiopurine S-methyltransferase (TPMT), UDP-glucuronosyltransferase 1A1 (UTG1A1) and dihydropyrimidine dehydrogenase (DPYD) are discussed with respect to guidelines of the Clinical Pharmacogenetics Implementation Consortium (CPIC). Moreover, the association between genetic variants of drug transporters with the clinical outcome is comprehensively discussed. Expert opinion: Precision therapy in the field of oncology is developing tremendously. There are a number of somatic tumor genetic markers that are indicative for treatment with anti-cancer drugs. By contrast, for some hereditary variants, recommendations have been developed. Although we have vast knowledge on the association between drug transporter variants and clinical outcome, the overall data is inconsistent and the predictability of the related phenotype is low. Further developments in research may lead to the discovery of rare, but functionally relevant single nucleotide polymorphisms and a better understanding of multiple genomic, epigenomic as well as phenotypic factors, contributing to drug response in malignancies.

  2. Psychological distress in women at risk of hereditary breast/ovarian or HNPCC cancers in the absence of demonstrated mutations.

    Geirdal, Amy Østertun; Reichelt, Jon G; Dahl, Alv A; Heimdal, Ketil; Maehle, Lovise; Stormorken, Astrid; Møller, Pål

    2005-01-01

    To examine psychological distress in women at risk of familial breast-ovarian cancer (FBOC) or hereditary non-polyposis colorectal cancer (HNPCC) with absence of demonstrated mutations in the family (unknown mutation). Two-hundred and fifty three consecutive women at risk of FBOC and 77 at risk of HNPCC and with no present or past history of cancer. They were aware of their risk and had received genetic counseling. Comparisons were made between these two groups, normal controls, and women who were identified to be BRCA1 mutation carriers. The questionnaires Beck Hopelessness Scale (BHS), General Health Questionnaire (GHQ-28), Hospital Anxiety and Depression Scale (HADS) and Impact of Event Scale (IES) were employed to assess psychological distress. No significant differences concerning psychological distress were observed between women with FBOC and women with HNPCC. Compared to mutation carriers for BRCA1, the level of anxiety and depression was significantly higher in the FBOC group with absence of demonstrated mutation. Compared to normal controls, the level of anxiety was higher, while the level of depression was lower in the groups with unknown mutation. Women in the absence of demonstrated mutations have higher anxiety and depression levels than women with known mutation-carrier status. Access to genetic testing may be of psychologically benefit to women at risk for FBOC or HNPCC.

  3. Outcome of 24 years national surveillance in different hereditary colorectal cancer subgroups leading to more individualised surveillance

    Lindberg, Lars Joachim; Ladelund, Steen; Frederiksen, Birgitte Lidegaard

    2017-01-01

    BACKGROUND: Individuals with hereditary non-polyposis colorectal cancer (HNPCC) have a high risk of colorectal cancer (CRC). The benefits of colonic surveillance in Lynch syndrome and Amsterdam-positive (familial CRC type X familial colorectal cancer type X (FCCTX)) families are clear; only...... in the Lynch subgroup (2.0%) than in any other subgroup (0.0-0.4%, pLynch (3.6%) and non-Lynch (2.3-3.9%, p=0.28) subgroups. Non-Lynch Amsterdam-positive and Amsterdam-negative families were similar in their CRC (0.1-0.4%, p=0.......072), advanced adenoma (2.3-3.3%, p=0.32) and simple adenoma (8.4-9.9%, p=0.43) incidence. In moderate-risk families, no CRC and only one advanced adenoma was found. CONCLUSIONS: The risk of CRC in Lynch families is considerable, despite biannual surveillance. We suggest less frequent and more individualised...

  4. High proportion of large genomic deletions and a genotype phenotype update in 80 unrelated families with juvenile polyposis syndrome

    Aretz, S; Stienen, D; Uhlhaas, S

    2007-01-01

    BACKGROUND: In patients with juvenile polyposis syndrome (JPS) the frequency of large genomic deletions in the SMAD4 and BMPR1A genes was unknown. METHODS: Mutation and phenotype analysis was used in 80 unrelated patients of whom 65 met the clinical criteria for JPS (typical JPS) and 15 were susp...

  5. Increased polyp detection using narrow band imaging compared with high resolution endoscopy in patients with hyperplastic polyposis syndrome

    Boparai, K. S.; van den Broek, F. J. C.; van Eeden, S.; Fockens, P.; Dekker, E.

    2011-01-01

    Hyperplastic polyposis syndrome (HPS) is associated with colorectal cancer and is characterized by multiple hyperplastic polyps, sessile serrated adenomas (SSAs) and adenomas. Narrow band imaging (NBI) may improve the detection of polyps in HPS. We aimed to compare polyp miss rates with NBI with

  6. Angiography and the gastrointestinal bleeder

    Baum, S.

    1982-01-01

    The role of angiography in the diagnosis and treatment of gastrointestinal hemorrhage is discussed. Three categories of gastrointestinal bleeding are considered: upper gastrointestinal bleeding due to gastroesophageal varices, upper gastrointestinal bleeding of arterial or capillary origin, and lower gastrointestinal bleeding. The advantages and disadvantages of angiography are compared with those of radionuclide scanning and endoscopy or colonoscopy. It is anticipated that, as radionuclide scans are more widely employed, angiography will eventually be performed only in those patients with positive scans

  7. Genetics of Colorectal Cancer (PDQ®)—Health Professional Version

    Hereditary colorectal cancer syndromes include Lynch syndrome and several polyposis syndromes (familial adenomatous polyposis, MUTYH-associated polyposis, juvenile polyposis syndrome, Peutz-Jeghers syndrome, and serrated polyposis syndrome). Learn about the genetics, clinical manifestations, management, and psychosocial aspects of these and other hereditary colon cancer syndromes in this expert-reviewed summary.

  8. Do mtDNA Deletions Play a Role in the Development of Nasal Polyposis?

    Arzu Tatar

    2014-04-01

    Full Text Available Objective:Nasal polyposis (NP is an inflammatory disease of the nasal mucosa and paranasal sinuses. Mitochondria are the cellular organelles which produce cellular energy by Oxidative Phosphorylation (OXPHOS, and they have own inheritance material, mtDNA. mtDNA is affected by reactive oxygen samples (ROS which are produced by both OXPHOS and the inflammatory process. The aim of this study was to investigate the 4977 bp and 7400 bp deletions of mtDNA in nasal polyposis tissue, and to indicate the possible association of mtDNA deletions with NP. Methods:Thirty-three patients, aged 15 to 65 years, with nasal polyposis were selected to be assessed for mitochondrial DNA deletions. The patients with possible mtDNA mutations due to mitochondrial disease, being treated with radiotherapy, of advanced age, with a familiar history, aspirin hypersensitivity, or a history of asthma, were excluded. Polyp excision surgery was applied to the treatment of the NP, and after histopathological diagnosis 1x1 cm of polyp tissue samples were used to isolate mtDNA. The 4977 bp and 7400 bp deletion regions, and two control regions of mtDNA were assessed by using four pairs of primers. DNA extractions from the NP tissues and peripheral blood samples of the patients were made, and then Polymerase Chain Reactions (PCR were made. PCR products were separated in 2% agarose gel.Results:No patient had either the 4977 bp deletion or the 7400 bp deletion in their NP tissue, and neither were these deletions evident in their peripheral blood. Two control sequences, one of them from a non-deleted region, and the other from a possible deletion region, were detected in the NP tissues and peripheral blood of all the patients.Conclusions:We had anticipated that some mtDNA deletion might have occurred in NP tissue due to the increased ROS levels caused by chronic inflammation, but we did not detect any deletion. Probably, the duration of inflammation in NP is insufficient to form mt

  9. Syndromic Gastric Polyps : At the Crossroads of Genetic and Environmental Cancer Predisposition

    Brosens, Lodewijk A A; Giardiello, Francis M; Offerhaus, G Johan; Montgomery, Elizabeth A

    2016-01-01

    Gastric polyps occur in 1-4 % of patients undergoing gastroscopy. Although most are sporadic, some gastric polyps are part of an underlying hereditary syndrome. Gastric polyps can be seen in each of the well-known gastrointestinal polyposis syndromes, but also in Lynch syndrome and in several rare

  10. Hereditary Colorectal Cancer (CRC Program in Latvia

    Irmejs Arvids

    2003-12-01

    Full Text Available Abstract Introduction The aim of the study is to evaluate the incidence and phenotype - genotype characteristics of hereditary colorectal cancer syndromes in Latvia in order to develop the basis of clinical management for patients and their relatives affected by these syndromes. Materials and methods From 02/1999-09/2002 in several hospitals in Latvia cancer family histories were collected from 865 patients with CRC. In families suspected of having a history consistent with a hereditary colorectal cancer syndrome, DNA testing for MLH1, MSH2 and MSH6 genes was performed. In addition immunohistochemical (IH examination of the normal and cancer tissue from large bowel tumors for MSH2 and MSH6 protein expression was performed prior to DNA analysis. Results From the 865 CRC cases only 3 (0.35% pedigrees fulfilled the Amsterdam II criteria of Hereditary Nonpolyposis Colorectal Cancer (HNPCC and 15 cases (1.73% were suspected of HNPCC. In 69 cases (8% with a cancer family aggregation (CFA were identified. Thus far 27 IH analyses have been performed and in 3 cancers homogenous lack of MSH2 or MSH6 protein expression was found. In one of these cases a mutation in MSH6 was identified. In 18 patients suspected of HNPCC or of matching the Amsterdam II criteria, denaturing high performance liquid chromatography (DHPLC followed by DNA sequencing of any heteroduplexes of the 35 exons comprising both MLH1 and MSH2 was performed revealing 3 mutations. For all of kindreds diagnosed definitively or with a high probability of being an HNPCC family appropriate recommendations concerning prophylactic measures, surveillance and treatment were provided in written form. Conclusions Existing pedigree/clinical data suggest that in Latvia the frequency of HNPCC is around 2% of consecutive colorectal cancer patients. It is crucial that genetic counseling is an integral part of cancer family syndrome management.

  11. Dento-osseous anomalies associated to familial adenomatous polyposis mimicking florid cemento-osseous dysplasia.

    Almeida, Fabiana Tolentino; Leite, André Ferreira; de Souza Figueiredo, Paulo Tadeu; Melo, Nilce Santos; Sousa, João Batista; Almeida, Rômulo; Acevedo, Ana Carolina; Silva Guerra, Eliete Neves

    2012-12-01

    Familial adenomatous polyposis (FAP) is a colorectal cancer syndrome characterized by the development of multiple polyps of the colon and rectum with high risk of malignant transformation. The extraintestinal manifestations such as dento-osseous changes are associated with FAP. This is a case report of a 36-year-old female patient who was referred for dental treatment with the initial diagnosis of florid cemento-osseous dysplasia (FCOD). However, the association of the imaging dento-osseous findings with the medical history confirmed the diagnosis of FAP. The paper illustrates the clinical characteristics and imaging findings associated with FAP, and also discusses misdiagnosis based exclusively on imaging features. Copyright © 2012 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  12. A metabolic switch controls intestinal differentiation downstream of Adenomatous polyposis coli (APC).

    Sandoval, Imelda T; Delacruz, Richard Glenn C; Miller, Braden N; Hill, Shauna; Olson, Kristofor A; Gabriel, Ana E; Boyd, Kevin; Satterfield, Christeena; Remmen, Holly Van; Rutter, Jared; Jones, David A

    2017-04-11

    Elucidating signaling pathways that regulate cellular metabolism is essential for a better understanding of normal development and tumorigenesis. Recent studies have shown that mitochondrial pyruvate carrier 1 (MPC1) , a crucial player in pyruvate metabolism, is downregulated in colon adenocarcinomas. Utilizing zebrafish to examine the genetic relationship between MPC1 and Adenomatous polyposis coli (APC), a key tumor suppressor in colorectal cancer, we found that apc controls the levels of mpc1 and that knock down of mpc1 recapitulates phenotypes of impaired apc function including failed intestinal differentiation. Exogenous human MPC1 RNA rescued failed intestinal differentiation in zebrafish models of apc deficiency. Our data demonstrate a novel role for apc in pyruvate metabolism and that pyruvate metabolism dictates intestinal cell fate and differentiation decisions downstream of apc .

  13. Brain abscesses and hereditary hemorrhagic telangiectasia

    Vives, Daniel A.; Bauni, Carlos E.; Mendoza, Monica E.

    2003-01-01

    Rendu-Osler-Weber disease or Hereditary Hemorrhagic Telangiectasia (HHT) is a generalized familial angiodysplastic disorder. The neurological manifestations of this entity are due to Central Nervous System vascular lesions or to complications of other visceral lesions such as pulmonary arteriovenous fistulae. This report describes two patients (males, 40 and 61 years old), with brain abscesses associated with HHT. The CT, MRI and Angiographic findings as well as the therapeutic approach are analyzed. Patients with brain abscess of unknown origin must be evaluated for the presence of lung vascular malformation in association with HHT. (author)

  14. Bone scintigraphy in hereditary multiple exostoses

    Epstein, D.A.; Levin, E.J.

    1978-01-01

    Two adult patients with multiple hereditary exostoses, a skeletal disorder with recognized malignant potential, each demonstrated increased /sup 99m/Tc diphosphonate uptake in an exostosis in which renewed growth had begun. None of the other multiple exostoses in either patient showed abnormal uptake. Histologic study of the lesions demonstrated chondrosarcoma in one case and benign osteochondroma in the second. Although bone scintigraphy nonspecifically identifies bone growth rather than malignant degeneration, it is more useful than radiographic bone survey in the periodic surveillance of adult patients with this disorder

  15. Skin deposits in hereditary cystatin C amyloidosis

    Benedikz, Eirikur; Blöndal, H; Gudmundsson, G

    1990-01-01

    Clinically normal skin from 47 individuals aged 9-70 years was investigated. Cystatin C amyloid deposits were found in various locations of the skin by light and/or electron microscopy, in all 12 patients with a clinical history of hereditary cystatin C amyloidosis (HCCA). Six asymptomatic...... individuals, who had the Alu 1 restriction fragment length polymorphism (RFLP) marker reported to cosegregate with the disease, also had cystatin C amyloid deposits in the skin. Three asymptomatic individuals (age 17-46) belonging to the HCCA families were without amyloid in the skin but had Alu 1 RFLP marker...

  16. Colorectal carcinomas in MUTYH-associated polyposis display histopathological similarities to microsatellite unstable carcinomas

    Nielsen, Maartje; Hes, Frederik J; Morreau, Hans; Miranda, Noel FCC de; Puijenbroek, Marjo van; Jordanova, Ekaterina S; Middeldorp, Anneke; Wezel, Tom van; Eijk, Ronald van; Tops, Carli MJ; Vasen, Hans FA

    2009-01-01

    MUTYH-associated polyposis (MAP) is a recessively inherited disorder which predisposes biallelic carriers for a high risk of polyposis and colorectal carcinoma (CRC). Since about one third of the biallelic MAP patients in population based CRC series has no adenomas, this study aimed to identify specific clinicopathological characteristics of MAP CRCs and compare these with reported data on sporadic and Lynch CRCs. From 44 MAP patients who developed ≥ 1 CRCs, 42 of 58 tumours were analyzed histologically and 35 immunohistochemically for p53 and beta-catenin. Cell densities of CD3, CD8, CD57, and granzyme B positive lymphocytes were determined. KRAS2, the mutation cluster region (MCR) of APC, p53, and SMAD4 were analyzed for somatic mutations. MAP CRCs frequently localized to the proximal colon (69%, 40/58), were mucinous in 21% (9/42), and had a conspicuous Crohn's like infiltrate reaction in 33% (13/40); all of these parameters occurred at a higher rate than reported for sporadic CRCs. Tumour infiltrating lymphocytes (TILs) were also highly prevalent in MAP CRCs. Somatic APC MCR mutations occurred in 14% (5/36) while 64% (23/36) had KRAS2 mutations (22/23 c.34G>T). G>T tranversions were found in p53 and SMAD4, although the relative frequency compared to other mutations was low. MAP CRCs show some similarities to micro-satellite unstable cancers, with a preferential proximal location, a high rate of mucinous histotype and increased presence of TILs. These features should direct the practicing pathologist towards a MAP aetiology of CRC as an alternative for a mismatch repair deficient cause. High frequent G>T transversions in APC and KRAS2 (mutated in early tumour development) but not in P53 and SMAD4 (implicated in tumour progression) might indicate a predominant MUTYH effect in early carcinogenesis

  17. Knowledge regarding basic concepts of hereditary cancers, and the ...

    Background. In families with hereditary cancer, at-risk individuals can benefit from genetic counselling and testing. General practitioners (GPs) are ideally placed to identify such families and refer them appropriately. Objective. To assess the practices, knowledge and attitudes of GPs regarding common hereditary cancers.

  18. Attitude towards pre-implantation genetic diagnosis for hereditary cancer

    Lammens, Chantal; Bleiker, Eveline; Aaronson, Neil; Vriends, Annette; Ausems, Margreet; Jansweijer, Maaike; Wagner, Anja; Sijmons, Rolf; van den Ouweland, Ans; van der Luijt, Rob; Spruijt, Liesbeth; Gómez García, Encarna; Ruijs, Mariëlle; Verhoef, Senno

    2009-01-01

    The use of pre-implantation genetic diagnosis (PGD) for hereditary cancer is subject to on-going debate, particularly among professionals. This study evaluates the attitude towards PGD and attitude-associated characteristics of those concerned: family members with a hereditary cancer predisposition.

  19. Hereditary lymphedema of the leg – A Case Report

    Heinig, Birgit; Lotti, T.; Tchernev, Georgi; Wollina, Uwe

    2017-01-01

    Primary of hereditary lymphedema is a rare but progressive disease. It is yet not curable. We present a 48-year-old male patient with hereditary lymphedema of his left leg, that was realised by minor trauma (able twist) when he was seven years old. He had never been treated for lymphedema but

  20. Hereditary motor and autonomic neuronopathy 1 maps to chromosome 20q13.2-13.3

    W. Marques Jr.

    2004-11-01

    Full Text Available The spinal muscular atrophies (SMA or hereditary motor neuronopathies result from the continuous degeneration and death of spinal cord lower motor neurons, leading to progressive muscular weakness and atrophy. We describe a large Brazilian family exhibiting an extremely rare, late-onset, dominant, proximal, and progressive SMA accompanied by very unusual manifestations, such as an abnormal sweating pattern, and gastrointestinal and sexual dysfunctions, suggesting concomitant involvement of the autonomic nervous system. We propose a new disease category for this disorder, `hereditary motor and autonomic neuronopathy', and attribute the term, `survival of motor and autonomic neurons 1' (SMAN1 to the respective locus that was mapped to a 14.5 cM region on chromosome 20q13.2-13.3 by genetic linkage analysis and haplotype studies using microsatellite polymorphic markers. This locus lies between markers D20S120 and D20S173 showing a maximum LOD score of 4.6 at D20S171, defining a region with 33 known genes, including several potential candidates. Identifying the SMAN1 gene should not only improve our understanding of the molecular mechanisms underlying lower motor neuron diseases but also help to clarify the relationship between motor and autonomic neurons.

  1. BRCA1/2 associated hereditary breast cancer

    Li-song TENG; Yi ZHENG; Hao-hao WANG

    2008-01-01

    Breast cancer is one of the leading causes of death in women today. Some of the patients are hereditary, with a large proportion characterized by mutation in BRCA1 and/or BRCA2 genes. In this review, we provide an overview of these two genes,focusing on their relationship with hereditary breast cancers. BRCA1/2 associated hereditary breast cancers have unique features that differ from the general breast cancers, including alterations in cellular molecules, pathological bases, biological behavior, and a different prevention strategy. But the outcome of BRCA1/2 associated hereditary breast cancers still remains controversial;further studies are needed to elucidate the nature of BRCA1/2 associated hereditary breast cancers.

  2. Management of gastrointestinal hemorrhage.

    Hilsden, R. J.; Shaffer, E. A.

    1995-01-01

    Acute gastrointestinal hemorrhage is a common problem that requires prompt recognition and management to prevent serious morbidity and mortality. Management goals are stabilization of the patient with vigorous fluid resuscitation followed by investigation and definitive treatment of the bleeding source. Endoscopy is often the initial diagnostic test and allows therapeutic measures to be performed at the same time.

  3. Pavlodar city children's some hereditary diseases

    Shajmardanova, B. Kh.; Gorbach, S.V.

    1997-01-01

    Territory of the Pavlodar region directly adjoining to the Semipalatinsk test site is unique object for study of many year tests consequences on population health. Health worsening caused by small doses of radiation on artificial pollution background is defined. Purpose of the work is Pavlodar city children's some hereditary diseases (Downs syndrome, crack of upper lip and/or palate, hemophilia) under study of frequency dynamic of statistical data within period from 1980 by 1995. It is defined: a) tendency to growth Downs syndrome frequency has been distinctly observed beginning of the 1982; b) it is noted Downs syndrome frequency growth stabilization within period from 1988 by 1991; c) among children with Downs syndrome is distinguished low viability; d) there is rather higher correlation rate of Downs syndrome and congenial heart threshold against average statistical index; e) character of frequencies changes of crack of upper lip and/or palate has tendency to growth; f) it is defined that boys predominate among children with this disease; g) congenial crack of soft palate have being revealed as solitary thresholds of development; h) genealogy analysis of hemophilia sick reveals, that it has only hereditary character. 8 refs

  4. Genetics of Hereditary Ataxia in Scottish Terriers.

    Urkasemsin, G; Nielsen, D M; Singleton, A; Arepalli, S; Hernandez, D; Agler, C; Olby, N J

    2017-07-01

    Scottish Terriers have a high incidence of juvenile onset hereditary ataxia primarily affecting the Purkinje neuron of the cerebellar cortex and causing slowly progressive cerebellar dysfunction. To identify chromosomal regions associated with hereditary ataxia in Scottish Terriers. One hundred and fifty-three Scottish Terriers were recruited through the Scottish Terrier Club of America. Prospective study. Dogs were classified as affected if they had slowly progressive cerebellar signs. When possible, magnetic resonance imaging and histopathological evaluation of the brain were completed as diagnostic aids. To identify genomic regions connected with the disease, genome-wide mapping was performed using both linkage- and association-based approaches. Pedigree evaluation and homozygosity mapping were also performed to examine mode of inheritance and to investigate the region of interest, respectively. Linkage and genome-wide association studies in a cohort of Scottish Terriers both identified a region on CFA X strongly associated with the disease trait. Homozygosity mapping revealed a 4 Mb region of interest. Pedigree evaluation failed to identify the possible mode of inheritance due to the lack of complete litter information. This finding suggests that further genetic investigation of the potential region of interest on CFA X should be considered in order to identify the causal mutation as well as develop a genetic test to eliminate the disease from this breed. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  5. Surgical treatment of hereditary lens subluxations.

    Ozdek, Sengul; Sari, Ayca; Bilgihan, Kamil; Akata, Fikret; Hasanreisoglu, Berati

    2002-01-01

    To evaluate the effectiveness and results of pars plana vitreolensectomy approach with transscleral fixation of intraocular lens in hereditary lens subluxations. Fifteen eyes of 9 consecutive patients with a mean age of 12.8+/-6.2 years (6-26 years) with hereditary lens subluxation were operated on and the results were evaluated in a prospective study. Surgery was considered if best spectacle corrected visual acuity (BSCVA) was less than 20/70. All eyes underwent a 2-port pars plana vitreolensectomy and transscleral fixation of an intraocular lens (IOL). The mean follow-up period was 12.6+/-7.5 months (6-22 months). There was no major intraoperative complication. Preoperatively, 8 eyes (53.3%) had a BSCVA of counting fingers (CF) and 7 eyes (46.6%) had a BSCVA of 20/200 to 20/70. Postoperatively, 14 eyes (93.3%) had a BSCVA of 20/50 or better. None of the patients had IOL decentration or intraocular pressure (IOP) increase during the follow-up period. There was a macular hole formation in 1 eye postoperatively. The early results of pars plana vitreolensectomy with IOL implantation using scleral fixation technique had shown that it not only promises a rapid visual rehabilitation but it is also a relatively safe method. More serious complications, however, may occur in the long term.

  6. Recommendations regarding splenectomy in hereditary hemolytic anemias

    Iolascon, Achille; Andolfo, Immacolata; Barcellini, Wilma; Corcione, Francesco; Garçon, Loïc; De Franceschi, Lucia; Pignata, Claudio; Graziadei, Giovanna; Pospisilova, Dagmar; Rees, David C.; de Montalembert, Mariane; Rivella, Stefano; Gambale, Antonella; Russo, Roberta; Ribeiro, Leticia; Vives-Corrons, Jules; Martinez, Patricia Aguilar; Kattamis, Antonis; Gulbis, Beatrice; Cappellini, Maria Domenica; Roberts, Irene; Tamary, Hannah

    2017-01-01

    Hereditary hemolytic anemias are a group of disorders with a variety of causes, including red cell membrane defects, red blood cell enzyme disorders, congenital dyserythropoietic anemias, thalassemia syndromes and hemoglobinopathies. As damaged red blood cells passing through the red pulp of the spleen are removed by splenic macrophages, splenectomy is one possible therapeutic approach to the management of severely affected patients. However, except for hereditary spherocytosis for which the effectiveness of splenectomy has been well documented, the efficacy of splenectomy in other anemias within this group has yet to be determined and there are concerns regarding short- and long-term infectious and thrombotic complications. In light of the priorities identified by the European Hematology Association Roadmap we generated specific recommendations for each disorder, except thalassemia syndromes for which there are other, recent guidelines. Our recommendations are intended to enable clinicians to achieve better informed decisions on disease management by splenectomy, on the type of splenectomy and the possible consequences. As no randomized clinical trials, case control or cohort studies regarding splenectomy in these disorders were found in the literature, recommendations for each disease were based on expert opinion and were subsequently critically revised and modified by the Splenectomy in Rare Anemias Study Group, which includes hematologists caring for both adults and children. PMID:28550188

  7. Molecular biology of hereditary diabetes insipidus.

    Fujiwara, T Mary; Bichet, Daniel G

    2005-10-01

    The identification, characterization, and mutational analysis of three different genes-the arginine vasopressin gene (AVP), the arginine vasopressin receptor 2 gene (AVPR2), and the vasopressin-sensitive water channel gene (aquaporin 2 [AQP2])-provide the basis for understanding of three different hereditary forms of "pure" diabetes insipidus: Neurohypophyseal diabetes insipidus, X-linked nephrogenic diabetes insipidus (NDI), and non-X-linked NDI, respectively. It is clinically useful to distinguish two types of hereditary NDI: A "pure" type characterized by loss of water only and a complex type characterized by loss of water and ions. Patients who have congenital NDI and bear mutations in the AVPR2 or AQP2 genes have a "pure" NDI phenotype with loss of water but normal conservation of sodium, potassium, chloride, and calcium. Patients who bear inactivating mutations in genes (SLC12A1, KCNJ1, CLCNKB, CLCNKA and CLCNKB in combination, or BSND) that encode the membrane proteins of the thick ascending limb of the loop of Henle have a complex polyuro-polydipsic syndrome with loss of water, sodium, chloride, calcium, magnesium, and potassium. These advances provide diagnostic and clinical tools for physicians who care for these patients.

  8. ["Screening" in special situations. Assessing predictive genetic screening for hereditary breast and colorectal cancer].

    Jonas, Susanna; Wild, Claudia; Schamberger, Chantal

    2003-02-01

    The aim of this health technology assessment was to analyse the current scientific and genetic counselling on predictive genetic testing for hereditary breast and colorectal cancer. Predictive genetic testing will be available for several common diseases in the future and questions related to financial issues and quality standards will be raised. This report is based on a systematic/nonsystematic literature search in several databases (e.g. EmBase, Medline, Cochrane Library) and on a specific health technology assessment report (CCOHTA) and review (American Gastroenterological Ass.), respectively. Laboratory test methods, early detection methods and the benefit from prophylactic interventions were analysed and social consequences interpreted. Breast and colorectal cancer are counted among the most frequently cancer diseases. Most of them are based on random accumulation of risk factors, 5-10% show a familial determination. A hereditary modified gene is responsible for the increased cancer risk. In these families, high tumour frequency, young age at diagnosis and multiple primary tumours are remarkable. GENETIC DIAGNOSIS: Sequence analysis is the gold standard. Denaturing high performance liquid chromatography is a quick alternative method. The identification of the responsible gene defect in an affected family member is important. If the test result is positive there is an uncertainty whether the disease will develop or not, when and in which degree, which is founded in the geno-/phenotype correlation. The individual risk estimation is based upon empirical evidence. The test results affect the whole family. Currently, primary prevention is possible for familial adenomatous polyposis (celecoxib, prophylactic colectomy) and for hereditary mamma carcinoma (prophylactic mastectomy). The so-called preventive medical check-ups are early detection examinations. The evidence about early detection methods for colorectal cancer is better than for breast cancer. Prophylactic

  9. The differentiation and prognostic implication of the solitary colonic polyp and the polyposis syndromes: A radiologic, histologic, and pathologic approach

    Olmsted, W.W.; Lichtenstein, J.E.

    1987-01-01

    The differential diagnosis of the solitary colonic polyp and the implications and prognostic significance of the solitary colonic polyp and the polyposis syndromes are frequently confusing because of imprecise and overlapping terminology. Such confusion may lead to misdiagnosis or overdiagnosis and improper patient treatment and surveillance. In the first part of this course, basic terms are defined to acquaint all participants with current common ground. The most frequently occurring solitary polyps (e.g., the colonic adenoma, hyperplastic polyp, Peutz-Jeghers hamartoma, juvenile hamartoma, and inflammatory polyp) are illustrated in detail with radiologic-histologic-pathologic correlation. The prognostic significance of each type of lesion and a scheme for proper colonic surveillance is discussed. In the second part of the session, there is a thorough discussion of multiple colonic polyps and the polyposis syndromes. Radiologic-pathologic correlation are used to illustrate these entities, and therapeutic and diagnostic implications are thoroughly covered. The differential diagnosis of the polyposis syndromes, including lymphoid abnormalities, pneumatosis intestinalis, and colitis cystica profunda, are mentioned. The participant should expect to gain a full understanding of the solitary and multiple colonic polyp states and algorithms for prognosis and treatment

  10. Zileuton, 5-lipoxygenase inhibitor, acts as a chemopreventive agent in intestinal polyposis, by modulating polyp and systemic inflammation.

    Elias Gounaris

    Full Text Available Leukotrienes and prostaglandins, products of arachidonic acid metabolism, sustain both systemic and lesion-localized inflammation. Tumor-associated Inflammation can also contribute to the pathogenesis of colon cancer. Patients with inflammatory bowel disease (IBD have increased risk of developing colon cancer. The levels of 5-lipoxygenase (5-LO, the key enzyme for leukotrienes production, are increased in colon cancer specimens and colonic dysplastic lesions. Here we report that Zileuton, a specific 5-LO inhibitor, can prevent polyp formation by efficiently reducing the tumor-associated and systemic inflammation in APCΔ468 mice.In the current study, we inhibited 5-LO by dietary administration of Zileuton in the APCΔ468 mouse model of polyposis and analyzed the effect of in vivo 5-LO inhibition on tumor-associated and systemic inflammation.Zileuton-fed mice developed fewer polyps and displayed marked reduction in systemic and polyp-associated inflammation. Pro-inflammatory cytokines and pro-inflammatory innate and adaptive immunity cells were reduced both in the lesions and systemically. As part of tumor-associated inflammation Leukotriene B4 (LTB4, product of 5-LO activity, is increased focally in human dysplastic lesions. The 5-LO enzymatic activity was reduced in the serum of Zileuton treated polyposis mice.This study demonstrates that dietary administration of 5-LO specific inhibitor in the polyposis mouse model decreases polyp burden, and suggests that Zileuton may be a potential chemo-preventive agent in patients that are high-risk of developing colon cancer.

  11. GASTROINTESTINAL STROMAL TUMOR (GIST

    Luigi eTornillo

    2014-11-01

    Full Text Available Gastrointestinal stromal tumors are the most frequent mesenchymal tumors of the gastrointestinal tract. The discovery that these tumors, formerly thought of smooth muscle origin, are indeed better characterized by specific activating mutation in genes coding for the receptor tyrosine kinases CKIT and PDGFRA and that these mutations are strongly predictive for the response to targeted therapy with receptor tyrosine kinase inhibitors has made GISTs the typical example of the integration of basic molecular knowledge in the daily clinical activity. The information on the mutational status of these tumors is essential to predict (and subsequently to plan the therapy. As resistant cases are frequently wild-type, other possible oncogenic events, defining other entities, have been discovered (e.g. succinil dehydrogenase mutation/dysregulation, insuline growth factor expression, mutations in the RAS-RAF-MAPK pathway. The classification of disease must nowadays rely on the integration of the clinico-morphological characteristics with the molecular data.

  12. Radiology illustrated. Gastrointestinal tract

    Choi, Byung Ihn

    2015-01-01

    Radiology Illustrated: Gastrointestinal Tract is the second of two volumes designed to provide clear and practical guidance on the diagnostic imaging of abdominal diseases. The book presents approximately 300 cases with 1500 carefully selected and categorized illustrations of gastrointestinal tract diseases, along with key text messages and tables that will help the reader easily to recall the relevant images as an aid to differential diagnosis., Essential points are summarized at the end of each text message to facilitate rapid review and learning. Additionally, brief descriptions of each clinical problem are provided, followed by case studies of both common and uncommon pathologies that illustrate the roles of the different imaging modalities, including ultrasound, radiography, computed tomography, and magnetic resonance imaging.

  13. Radiology illustrated. Gastrointestinal tract

    Choi, Byung Ihn (ed.) [Seoul National University Hospital (Korea, Republic of). Dept. of Radiology

    2015-02-01

    Radiology Illustrated: Gastrointestinal Tract is the second of two volumes designed to provide clear and practical guidance on the diagnostic imaging of abdominal diseases. The book presents approximately 300 cases with 1500 carefully selected and categorized illustrations of gastrointestinal tract diseases, along with key text messages and tables that will help the reader easily to recall the relevant images as an aid to differential diagnosis., Essential points are summarized at the end of each text message to facilitate rapid review and learning. Additionally, brief descriptions of each clinical problem are provided, followed by case studies of both common and uncommon pathologies that illustrate the roles of the different imaging modalities, including ultrasound, radiography, computed tomography, and magnetic resonance imaging.

  14. Gastrointestinal Complications of Obesity

    Camilleri, Michael; Malhi, Harmeet; Acosta, Andres

    2017-01-01

    Obesity usually is associated with morbidity related to diabetes mellitus and cardiovascular diseases. However, there are many gastrointestinal and hepatic diseases for which obesity is the direct cause (eg, nonalcoholic fatty liver disease) or is a significant risk factor, such as reflux esophagitis and gallstones. When obesity is a risk factor, it may interact with other mechanisms and result in earlier presentation or complicated diseases. There are increased odds ratios or relative risks of several gastrointestinal complications of obesity: gastroesophageal reflux disease, erosive esophagitis, Barrett’s esophagus, esophageal adenocarcinoma, erosive gastritis, gastric cancer, diarrhea, colonic diverticular disease, polyps, cancer, liver disease including nonalcoholic fatty liver disease, cirrhosis, hepatocellular carcinoma, gallstones, acute pancreatitis, and pancreatic cancer. Gastroenterologists are uniquely poised to participate in the multidisciplinary management of obesity as physicians caring for people with obesity-related diseases, in addition to their expertise in nutrition and endoscopic interventions. PMID:28192107

  15. Gastrointestinal food allergies.

    Heine, Ralf G

    2015-01-01

    Gastrointestinal food allergies present during early childhood with a diverse range of symptoms. Cow's milk, soy and wheat are the three most common gastrointestinal food allergens. Several clinical syndromes have been described, including food protein-induced enteropathy, proctocolitis and enterocolitis. In contrast with immediate, IgE-mediated food allergies, the onset of gastrointestinal symptoms is delayed for at least 1-2 hours after ingestion in non-IgE-mediated allergic disorders. The pathophysiology of these non-IgE-mediated allergic disorders is poorly understood, and useful in vitro markers are lacking. The results of the skin prick test or measurement of the food-specific serum IgE level is generally negative, although low-positive results may occur. Diagnosis therefore relies on the recognition of a particular clinical phenotype as well as the demonstration of clear clinical improvement after food allergen elimination and the re-emergence of symptoms upon challenge. There is a significant clinical overlap between non-IgE-mediated food allergy and several common paediatric gastroenterological conditions, which may lead to diagnostic confusion. The treatment of gastrointestinal food allergies requires the strict elimination of offending food allergens until tolerance has developed. In breast-fed infants, a maternal elimination diet is often sufficient to control symptoms. In formula-fed infants, treatment usually involves the use an extensively hydrolysed or amino acid-based formula. Apart from the use of hypoallergenic formulae, the solid diets of these children also need to be kept free of specific food allergens, as clinically indicated. The nutritional progress of infants and young children should be carefully monitored, and they should undergo ongoing, regular food protein elimination reassessments by cautious food challenges to monitor for possible tolerance development. © 2015 S. Karger AG, Basel.

  16. Upper gastrointestinal bleeding.

    Feinman, Marcie; Haut, Elliott R

    2014-02-01

    Upper gastrointestinal (GI) bleeding remains a commonly encountered diagnosis for acute care surgeons. Initial stabilization and resuscitation of patients is imperative. Stable patients can have initiation of medical therapy and localization of the bleeding, whereas persistently unstable patients require emergent endoscopic or operative intervention. Minimally invasive techniques have surpassed surgery as the treatment of choice for most upper GI bleeding. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Orexins and gastrointestinal functions.

    Baccari, M C

    2010-03-01

    Orexin A (OXA) and orexin B (OXB) are recently discovered neuropeptides that appear to play a role in various distinct functions such as arousal and the sleep-wake cycle as well as on appetite and regulation of feeding and energy homeostasis. Orexins were first described as neuropeptides expressed by a specific population of neurons in the lateral hypothalamic area, a region classically implicated in feeding behaviour. Orexin neurons project to numerous brain regions, where orexin receptors have been shown to be widely distributed: both OXA and OXB act through two subtypes of receptors (OX1R and OX2R) that belong to the G protein-coupled superfamily of receptors. Growing evidence indicates that orexins act in the central nervous system also to regulate gastrointestinal functions: animal studies have indeed demonstrated that centrally-injected orexins or endogenously released orexins in the brain stimulates gastric secretion and influence gastrointestinal motility. The subsequent identification of orexins and their receptors in the enteric nervous system (including the myenteric and the submucosal plexuses) as well as in mucosa and smooth muscles has suggested that these neuropeptides may also play a local action. In this view, emerging studies indicate that orexins also exert region-specific contractile or relaxant effects on isolated gut preparations. The aim of the proposed review is to summarize both centrally- and peripherally-mediated actions of orexins on gastrointestinal functions and to discuss the related physiological role on the basis of the most recent findings.

  18. Dementia in hereditary cystatin C amyloidosis

    Blöndal, H; Guomundsson, G; Benedikz, Eirikur

    1989-01-01

    in seventeen cases of whom two presented with dementia. At the last examination the majority had severe dementia and severely abnormal EEG. Anti-cystatin C positive amyloid vascular and perivascular infiltrates were found. The resulting damage to the microvasculature of the brain and secondary hemorrhages......Nineteen cases with verified Hereditary Cystatin C Amyloid Angiopathy are presented. All of the cases had one or more cerebrovascular insults starting at the age of 20-41 years and survived from 10 days to 23 years after the first insult. Progressive dementia was a prominent clinical feature...... and infarctions were considered to be an adequate explanation for the dementia in these cases. Skin biopsies can now probably be used to demonstrate cystatin C positive amyloid deposits conclusively in the tissues of these patients....

  19. Leber's Hereditary Optic Neuropathy: A Case Report

    Chi-Wu Chang

    2003-10-01

    Full Text Available Leber's hereditary optic neuropathy (LHON is a maternally inherited mitochondrial disease that primarily affects the optic nerve, causing bilateral vision loss in juveniles and young adults. A 12-year-old boy had complained of blurred vision in both eyes for more than 1 year. His best-corrected visual acuity was 0.08 in the right eye and 0.1 in the left. Ophthalmologic examination showed bilateral optic disc hyperemia and margin blurring, peripapillary telangiectasis, and a relative afferent pupil defect in his right eye. Fluorescein angiography showed no stain or leakage around the optic disc in the late phase. Visual field analysis showed central scotoma in the left eye and a near-total defect in the right. Upon examination of the patient's mitochondrial DNA, a point mutation at nucleotide position 11778 was found, and the diagnosis of LHON was confirmed. Coenzyme Q10 was used to treat the patient.

  20. Mania associated with complicated hereditary spastic paraparesis

    Raghavendra B Nayak

    2011-01-01

    Full Text Available Hereditary spastic paraparesis (HSP is an inherited group of neurological disorders with progressive lower limb spasticity. HSP can be clinically grouped into pure and complicated forms. Pure HSP is one without any associated neurological/psychiatric comorbidity. Depression is the most common psychiatric comorbidity. Presence of mania or bipolar affective illness with HSP is a rare phenomenon. We report a case of a 17-year-old boy who presented with classical features of HSP with complaints of excessive happiness, irritability, increased self-esteem and decreased sleep since 1 month. The patient also had complex partial seizure ever since he had features of HSP. The patient′s father and younger sister suffer from pure HSP. The patient was diagnosed to have first episode mania with complicated HSP. The details of treatment and possible neurobiology are discussed in this case report.

  1. Mania associated with complicated hereditary spastic paraparesis.

    Nayak, Raghavendra B; Bhogale, Govind S; Patil, Nanasaheb M; Pandurangi, Aditya A

    2011-07-01

    Hereditary spastic paraparesis (HSP) is an inherited group of neurological disorders with progressive lower limb spasticity. HSP can be clinically grouped into pure and complicated forms. Pure HSP is one without any associated neurological/psychiatric comorbidity. Depression is the most common psychiatric comorbidity. Presence of mania or bipolar affective illness with HSP is a rare phenomenon. We report a case of a 17-year-old boy who presented with classical features of HSP with complaints of excessive happiness, irritability, increased self-esteem and decreased sleep since 1 month. The patient also had complex partial seizure ever since he had features of HSP. The patient's father and younger sister suffer from pure HSP. The patient was diagnosed to have first episode mania with complicated HSP. The details of treatment and possible neurobiology are discussed in this case report.

  2. Deprivation amblyopia and congenital hereditary cataract.

    Mansouri, Behzad; Stacy, Rebecca C; Kruger, Joshua; Cestari, Dean M

    2013-01-01

    Amblyopia is a neurodevelopmental disorder of vision associated with decreased visual acuity, poor or absent stereopsis, and suppression of information from one eye.(1,2) Amblyopia may be caused by strabismus (strabismic amblyopia), refractive error (anisometropic amblyopia), or deprivation from obstructed vision (deprivation amblyopia). 1 In the developed world, amblyopia is the most common cause of childhood visual impairment, 3 which reduces quality of life 4 and also almost doubles the lifetime risk of legal blindness.(5, 6) Successful treatment of amblyopia greatly depends on early detection and treatment of predisposing disorders such as congenital cataract, which is the most common cause of deprivational amblyopia. Understanding the genetic causes of congenital cataract leads to more effective screening tests, early detection and treatment of infants and children who are at high risk for hereditary congenital cataract.

  3. Recurrent IVF failure and hereditary thrombophilia.

    Safdarian, Leila; Najmi, Zahra; Aleyasin, Ashraf; Aghahosseini, Marzieh; Rashidi, Mandana; Asadollah, Sara

    2014-07-01

    The largest percentage of failed invitro fertilization (IVF (cycles, are due to lack of implantation. As hereditary thrombophilia can cause in placentation failure, it may have a role in recurrent IVF failure. Aim of this case-control study was to determine whether hereditary thrombophilia is more prevalent in women with recurrent IVF failures. Case group comprised 96 infertile women, with a history of recurrent IVF failure. Control group was comprised of 95 healthy women with proven fertility who had conceived spontaneously. All participants were assessed for the presence of inherited thrombophilias including: factor V Leiden, methilen tetrahydrofolate reductase (MTHFR) mutation, prothrombin mutation, homocystein level, protein S and C deficiency, antithrombin III (AT-III) deficiency and plasminogen activator inhibitor-1 (PAI-1) mutation. Presence of thrombophilia was compared between groups. Having at least one thrombophilia known as a risk factor for recurrent IVF failure (95% CI=1.74-5.70, OR=3.15, p=0.00). Mutation of factor V Leiden (95% CI=1.26-10.27, OR=3.06, P=0.01) and homozygote form of MTHFR mutation (95% CI=1.55-97.86, OR=12.33, p=0.05) were also risk factors for recurrent IVF failure. However, we could not find significant difference in other inherited thrombophilia's. Inherited thrombophilia is more prevalent in women with recurrent IVF failure compared with healthy women. Having at least one thrombophilia, mutation of factor V Leiden and homozygote form of MTHFR mutation were risk factors for recurrent IVF failure.

  4. Chaperonopathies: spotlight on hereditary motor neuropathies

    Vincenzo Lupo

    2016-12-01

    Full Text Available Distal hereditary motor neuropathies (dHMN comprise a group of rare hereditary neuromuscular disorders characterized by a peroneal muscular atrophy without sensory symptoms. To date twenty-three genes for dHMN have been reported and four of them encode for chaperones: DNAJB2, which encodes a member of the HSP40/DNAJ co-chaperone family, and HSPB1, HSPB3 and HSPB8, which encode three members of the family of small heat shock proteins. Except for HSPB1, with around thirty different mutations, the remaining three genes comprise a much low number of cases. Thus, only one case has been described caused by an HSPB3 mutation, whereas few DNAJB2 and HSPB8 cases are known, most of them caused by a founder c.352+1G>A mutation in DNAJB2 and by mutations affecting the hot spot K141 residue of the HSPB8 chaperone. This low number of cases makes it difficult to understand the pathomechanism underlying the neuropathy. Chaperones can assemble in multi-chaperone complexes forming an integrative chaperone network in the cell, which plays relevant cellular roles in a variety of processes such as the correct folding of newly synthesized proteins, their escort to their precise cellular locations to form functional proteins and complexes and the response to protein misfolding, including the degradation of proteins that fail to refold properly. Despite of this variety of functions, mutations in some of them lead to diseases with a similar clinical picture, suggesting common pathways. This review gives an overview of the genetics of dHMNs caused by mutations in four genes, DNAJB2, HSPB1, HSPB3 and HSPB8, which encode chaperones and show a common disease mechanism.

  5. Gender specific issues in hereditary ocular disorders.

    Iragavarapu, Saradha; Gorin, Michael B

    2015-02-01

    This review is intended to summarize the current knowledge from basic science and clinical medical literature cited within PubMed that pertain to gender-related factors and affect those individuals with hereditary ocular disorders. We consider gender-related biological factors that (a) affect disease onset and progression, (b) gender differences for major X-linked ocular disorders, (c) gender-specific conditions, (d) medications that may influence genetic eye disorders, and finally, (e) gender-related issues that influence the management and quality of life of these patients. Several studies have demonstrated the manner in which sex-related hormones in animal models are capable of influencing cell pathway and survival that are likely to affect hereditary eye disorders. There are very few clinical studies that provide compelling evidence for gender differences in human ocular conditions, other than for a number of X-linked disorders. Disease expression for X-linked disorders may be impacted by genetic mechanisms such as lyonization or uniparental disomy. Clinical evidence regarding the impact of gender-related medical conditions and therapies on eye conditions is extremely limited and primarily based on anecdotal evidence. Gender-specific factors may play a major role in the underlying biological pathways that influence the onset, rate of progression, and clinical findings associated with ocular genetic conditions. Clinicians need to be aware of the variable phenotypes observed in female carriers of X-linked disorders of gender specific issues, many of which are inadequately addressed in the current literature. Clinicians need to be sensitive to gender differences in social, cultural, and religious systems and they should also be aware of how their own gender biases may influence how they counsel patients. Finally, it is clear that the lack of effective clinical studies in this area creates an opportunity for future research that will have real benefits for these

  6. Hombre de 75 años con edemas y sangrado digestivo inferior A 75 years old man with edema and inferior gastrointestinal bleeding

    Alberto Carlos Reino Buelvas

    2004-02-01

    Full Text Available Se presenta el caso de un hombre de 75 años, quien consultó por edemas generalizados originados en un síndrome nefrótico, secundario a una glomerulopatía clasificada como de cambios mínimos. Se le iniciaron esteroides con mejoría de su proteinuria, pero al disminuir las dosis de éstos, recayó, por lo que requirió nueva hospitalización en la que se le documentaron trombosis venosa profunda y sangrado por tracto gastrointestinal inferior. Se le implantó un filtro de vena cava inferior y se le practicó una colonoscopia, en la que se encontró poliposis coli. Al estudio histológico se reportó un linfoma no Hodgkin compatible con un linfoma del manto (poliposis linfomatoide versus linfoma marginal tipo MALT de bajo grado. The case of a 75 year old man is presented. He consulted because of generalized edema and the diagnosis of nephrotic syndrome was done. Histologic study of a renal biopsy reported a glomerulopathy of minimal changes. Treatment with steroids improved of proteinuria, but on reducing the doses, proteinuria returned. In a second hospitalization deep venous thrombosis and gastrointestinal bleeding were diagnosed. A cava vein filter was implanted, colonoscopy was performed and Polyposis Coli was found. A non Hodgkin lymphoma compatible with MANTLE CELL lymphoma (lymphomatous polyposis vs MALT lymphoma was reported in the colonic biopsy.

  7. Aspirin augments the expression of Adenomatous Polyposis Coli protein by suppression of IKKβ

    Ashida, Noboru; Kishihata, Masako; Tien, Dat Nguyen; Kamei, Kaeko; Kimura, Takeshi; Yokode, Masayuki

    2014-01-01

    Highlights: • Clinical studies revealed aspirin inhibits cancer, but the mechanism is not known. • Adenomatous Polyposis Coli (APC) is a well-known tumor-suppressing gene. • We found aspirin up-regulates the protein of APC. • Aspirin suppressed the expression of IKKβ, an essential kinase in NFκB activation. • The deletion of IKKβ significantly increases the expression of APC protein. - Abstract: Aspirin has been widely used as analgesic, antipyretic and anti-inflammatory medicine for long. In addition to these traditional effects, clinical studies suggest that aspirin can protect against cancer, but its mechanism has not been explored. To unveil it, we identified the proteins up- or down-regulated after incubation with aspirin by using proteomics analysis with Nano-flow LC/MALDI-TOF system. Interestingly, the analysis identified the protein of Adenomatous Polyposis Coli (APC) as one of the most up-regulated protein. APC regulates cell proliferation or angiogenesis, and is widely known as a tumor-suppressing gene which can cause colorectal cancer when it is mutated. Western blots confirmed this result, and real-time PCR indicated it is transcriptionally regulated. We further tried to elucidate the molecular mechanism with focusing on IKKβ. IKKβ is the essential kinase in activation of nuclear factor-kappa B (NF-κB), major transcriptional factors that regulate genes responsible for inflammation or immune response. Previous reports indicated that aspirin specifically inhibits IKKβ activity, and constitutively active form of IKKβ accelerates APC loss. We found that aspirin suppressed the expression of IKKβ, and the deletion of IKKβ by siRNA increases the expression of APC in HEK294 cells. Finally, we observed similar effects of aspirin in human umbilical vein endothelial cells. Taken together, these results reveal that aspirin up-regulates the expression of APC via the suppression of IKKβ. This can be a mechanism how aspirin prevents cancer at

  8. Aspirin augments the expression of Adenomatous Polyposis Coli protein by suppression of IKKβ

    Ashida, Noboru, E-mail: nashida@kuhp.kyoto-u.ac.jp [Department of Clinical Innovative Medicine, Institute for Advancement of Clinical and Translational Science, Faculty of Medicine, Kyoto University, Kyoto (Japan); Kishihata, Masako [Department of Clinical Innovative Medicine, Institute for Advancement of Clinical and Translational Science, Faculty of Medicine, Kyoto University, Kyoto (Japan); Tien, Dat Nguyen [Department of Clinical Innovative Medicine, Institute for Advancement of Clinical and Translational Science, Faculty of Medicine, Kyoto University, Kyoto (Japan); Department of Biomolecular Engineering, Kyoto Institute of Technology, Kyoto (Japan); Kamei, Kaeko [Department of Biomolecular Engineering, Kyoto Institute of Technology, Kyoto (Japan); Kimura, Takeshi [Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Yokode, Masayuki [Department of Clinical Innovative Medicine, Institute for Advancement of Clinical and Translational Science, Faculty of Medicine, Kyoto University, Kyoto (Japan)

    2014-04-04

    Highlights: • Clinical studies revealed aspirin inhibits cancer, but the mechanism is not known. • Adenomatous Polyposis Coli (APC) is a well-known tumor-suppressing gene. • We found aspirin up-regulates the protein of APC. • Aspirin suppressed the expression of IKKβ, an essential kinase in NFκB activation. • The deletion of IKKβ significantly increases the expression of APC protein. - Abstract: Aspirin has been widely used as analgesic, antipyretic and anti-inflammatory medicine for long. In addition to these traditional effects, clinical studies suggest that aspirin can protect against cancer, but its mechanism has not been explored. To unveil it, we identified the proteins up- or down-regulated after incubation with aspirin by using proteomics analysis with Nano-flow LC/MALDI-TOF system. Interestingly, the analysis identified the protein of Adenomatous Polyposis Coli (APC) as one of the most up-regulated protein. APC regulates cell proliferation or angiogenesis, and is widely known as a tumor-suppressing gene which can cause colorectal cancer when it is mutated. Western blots confirmed this result, and real-time PCR indicated it is transcriptionally regulated. We further tried to elucidate the molecular mechanism with focusing on IKKβ. IKKβ is the essential kinase in activation of nuclear factor-kappa B (NF-κB), major transcriptional factors that regulate genes responsible for inflammation or immune response. Previous reports indicated that aspirin specifically inhibits IKKβ activity, and constitutively active form of IKKβ accelerates APC loss. We found that aspirin suppressed the expression of IKKβ, and the deletion of IKKβ by siRNA increases the expression of APC in HEK294 cells. Finally, we observed similar effects of aspirin in human umbilical vein endothelial cells. Taken together, these results reveal that aspirin up-regulates the expression of APC via the suppression of IKKβ. This can be a mechanism how aspirin prevents cancer at

  9. Squamous cell carcinoma complicating an hereditary epidermo-lysis bullosa

    Mseddi, M.; Turki, H.; Marrekchi, S.; Abdelmaksoud, W.; Masmoudi, A.; Bouassida, S.; Zahaf, A.

    2004-01-01

    The dystrophic form of hereditary epidermo-lysis bullosa is associated with an increased frequency of squamous cell carcinoma. We report a new case. An 18-year-old patient, carrying a Hallopeau Siemens hereditary epidermo-lysis bullosa, presented a subcutaneous nodular lesion, for 1 year that ulcerated and budded with inguinal lymphadenopathy. The histological study ted to the conclusion of a well differentiated squamous cell carcinoma. The patient was treated surgically. Tumor and metastatic lymph nodes were excised. A radiotherapy was decided but the postoperative course was fatal due to an infection and to a deterioration of her general condition. Squamous cell carcinoma frequently occurs on the cicatricial lesion of hereditary epidermo-lysis bullosa and usually affects males with recessive hereditary epidermo-lysis bullosa. Metastases are frequent, precocious and multiple. The treatment may be surgical. The particularities of our observation are the young age of patient and the localization. (author)

  10. Hereditary Lymphedema of the Leg – A Case Report

    Birgit Heinig

    2017-07-01

    Full Text Available Primary of hereditary lymphedema is a rare but progressive disease. It is yet not curable. We present a 48-year-old male patient with hereditary lymphedema of his left leg, that was realised by minor trauma (able twist when he was seven years old. He had never been treated for lymphedema but experienced multiple erysipelas during his life. After diagnostic procedures to exclude other causes of leg swelling, the diagnosis of hereditary lymphedema of the leg, stage III was confirmed. We initialized complex decongestive therapy. During two weeks of intensive treatment, the circumference of the left leg could be reduced by 10 cm. This case illustrates the "natural course" hereditary lymphedema. But it raises the hope that even after decades of ignorance, the patients benefits from complex decongestive treatment. Therapeutic nihilism is unnecessary and poses lymphedema patients to risks of infection and secondary malignancies like Stewart-Trewes syndrome.

  11. EPHB2 germline variants in patients with colorectal cancer or hyperplastic polyposis

    Kokko, Antti; Tomlinson, Ian PM; Vahteristo, Pia; Aaltonen, Lauri A; Laiho, Päivi; Lehtonen, Rainer; Korja, Sanna; Carvajal-Carmona, Luis G; Järvinen, Heikki; Mecklin, Jukka-Pekka; Eng, Charis; Schleutker, Johanna

    2006-01-01

    Ephrin receptor B2 (EPHB2) has recently been proposed as a novel tumor suppressor gene in colorectal cancer (CRC). Inactivation of the gene has been shown to correlate with progression of colorectal tumorigenesis, and somatic mutations have been reported in both colorectal and prostate tumors. Here we have analyzed the EPHB2 gene for germline alterations in 101 individuals either with 1) CRC and a personal or family history of prostate cancer (PC), or 2) intestinal hyperplastic polyposis (HPP), a condition associated with malignant degeneration such as serrated adenoma and CRC. Four previously unknown missense alterations were observed, which may be associated with the disease phenotype. Two of the changes, I361V and R568W, were identified in Finnish CRC patients, but not in over 300 Finnish familial CRC or PC patients or more than 200 population-matched healthy controls. The third change, D861N, was observed in a UK HPP patient, but not in additional 40 UK HPP patients or in 200 UK healthy controls. The fourth change R80H, originally identified in a Finnish CRC patient, was also found in 1/106 familial CRC patients and in 9/281 healthy controls and is likely to be a neutral polymorphism. We detected novel germline EPHB2 alterations in patients with colorectal tumors. The results suggest a limited role for these EPHB2 variants in colon tumor predisposition. Further studies including functional analyses are needed to confirm this

  12. Two Metachronous Neoplasms in the Radiotherapy Fields of a Young Man With Familial Adenomatous Polyposis

    Patrick A. Williams BS

    2013-04-01

    Full Text Available Background: It is recognized that various radiation-induced malignancies often follow childhood radiotherapy. Radiation-induced neoplasms have been shown to occur with increased frequency in syndromes due to mutated tumor suppressor genes. There exist no recommendations for the management of cancer patients with germline APC gene mutations. Preclinical data suggest that APC gene mutations cause enhanced radiosensitivity, but no clinical observations exist that show that patients with this mutation are at higher risk for radiation-induced malignancies. Results: We report the case of a 32-year-old man with a genetic diagnosis of familial adenomatous polyposis (FAP who initially presented at age 10 with a medulloblastoma treated with radiotherapy and surgery. Radiation-induced papillary thyroid carcinoma followed 13 years later. Finally, radiation-induced soft tissue osteosarcoma occurred with widespread metastasis 20 years thereafter. Conclusions: This is the first report of 2 malignancies in the prior radiotherapy fields of a patient with a genetic diagnosis of FAP. More important, this suggests that APC-defective cells are at an enhanced sensitivity to the carcinogenic effects of radiotherapy compared with APC-proficient cells. This could argue for genetic screening in affected members of these families and for creation of treatment recommendations to more seriously consider the risks of radiation therapy.

  13. Current status of prophylactic surgical treatment for familial adenomatous polyposis in Japan.

    Yamadera, Masato; Ueno, Hideki; Kobayashi, Hirotoshi; Konishi, Tsuyoshi; Ishida, Fumio; Yamaguchi, Tatsuro; Hinoi, Takao; Inoue, Yasuhiro; Kanemitsu, Yukihide; Tomita, Naohiro; Ishida, Hideyuki; Sugihara, Kenichi

    2017-06-01

    We conducted this study to clarify the current clinical practice of prophylactic colectomy for patients with familial adenomatous polyposis (FAP) in Japan. This retrospective multi-center cohort study involved 23 specialized institutions for colorectal disease in Japan. We analyzed the records of 147 patients who underwent prophylactic surgical treatment between 2000 and 2012. Patients were divided into Group 1 (2000-2006) and Group 2 (2007-2012) based on their date of surgery. Age at the time of prophylactic surgery was 27 and 31 years in Groups 1 and 2, respectively. The proportion of attenuated FAP was significantly lower in Group 2 than in Group 1 (1.0 vs. 13 %, respectively). Pathological examination revealed an increased incidence of malignant polyps in the resected specimens from Group 2 patients (10 vs. 23 %, respectively; P = 0.034). Laparoscopic surgery was more frequent in Group 2 than in Group 1 (61 vs. 40 %, respectively). There was no surgical mortality in either group. Prophylactic surgery for FAP results in good short-term surgical outcomes in Japan. The current surgical approach is characterized by limited surgical indications for patients with attenuated FAP, delayed timing of colectomy, and the increasing standardization of laparoscopic surgery.

  14. Clinical and genetic characterization of classical forms of familial adenomatous polyposis: a Spanish population study.

    Rivera, B; González, S; Sánchez-Tomé, E; Blanco, I; Mercadillo, F; Letón, R; Benítez, J; Robledo, M; Capellá, G; Urioste, M

    2011-04-01

    Classical familial adenomatous polyposis (FAP) is characterized by the appearance of >100 colorectal adenomas. We screened the APC and MUTYH genes for mutations and evaluated the genotype-phenotype correlation in 136 Spanish classical FAP families. APC/MUTYH mutations were detected in 107 families. Sixty-four distinct APC point mutations were detected in 95 families of which all were truncating mutations. A significant proportion (39.6%) had not been previously reported. Mutations were spread over the entire coding region and great rearrangements were identified in six families. Another six families exhibited biallelic MUTYH mutations. No APC or MUTYH mutations were detected in 29 families. These APC/MUTYH-negative families showed clinical differences with the APC-positive families. A poor correlation between phenotype and mutation site was observed. Our results highlight that a broad approach in the genetic study must be considered for classical FAP due to involvement of both APC and MUTYH and the heterogeneous spectrum of APC mutations observed in this Spanish population. The scarcely consistent genotype-phenotype correlation does not allow making specific recommendations regarding screening and management. Differences observed in APC/MUTYH-negative families may reflect a genetic basis other than mutations in APC and MUTYH genes for FAP predisposition. © The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

  15. New forms of -compactness with respect to hereditary classes

    Abdo Mohammed Qahis

    2019-01-01

    Full Text Available A hereditary class on a set X is a nonempty collection of subsets closed under heredity. The aim of this paper is to introduce and study strong forms of u-compactness in generalized topological spaces with respect to a hereditary class, called  SuH-compactness and S- SuH-compactness. Also several of their properties are presented. Finally some eects of various kinds of functions on them are studied.

  16. DNA mismatch repair deficiency and hereditary syndromes in Latino patients with colorectal cancer.

    Ricker, Charité N; Hanna, Diana L; Peng, Cheng; Nguyen, Nathalie T; Stern, Mariana C; Schmit, Stephanie L; Idos, Greg E; Patel, Ravi; Tsai, Steven; Ramirez, Veronica; Lin, Sonia; Shamasunadara, Vinay; Barzi, Afsaneh; Lenz, Heinz-Josef; Figueiredo, Jane C

    2017-10-01

    The landscape of hereditary syndromes and clinicopathologic characteristics among US Latino/Hispanic individuals with colorectal cancer (CRC) remains poorly understood. A total of 265 patients with CRC who were enrolled in the Hispanic Colorectal Cancer Study were included in the current study. Information regarding CRC risk factors was elicited through interviews, and treatment and survival data were abstracted from clinical charts. Tumor studies and germline genetic testing results were collected from medical records or performed using standard molecular methods. The mean age of the patients at the time of diagnosis was 53.7 years (standard deviation, 10.3 years), and 48.3% were female. Overall, 21.2% of patients reported a first-degree or second-degree relative with CRC; 3.4% met Amsterdam I/II criteria. With respect to Bethesda guidelines, 38.5% of patients met at least 1 criterion. Of the 161 individuals who had immunohistochemistry and/or microsatellite instability testing performed, 21 (13.0%) had mismatch repair (MMR)-deficient (dMMR) tumors. dMMR tumors were associated with female sex (61.9%), earlier age at the time of diagnosis (50.4 ± 12.4 years), proximal location (61.9%), and first-degree (23.8%) or second-degree (9.5%) family history of CRC. Among individuals with dMMR tumors, 13 (61.9%) had a germline MMR mutation (MutL homolog 1 [MLH1] in 6 patients; MutS homolog 2 [MSH2] in 4 patients; MutS homolog 6 [MHS6] in 2 patients; and PMS1 homolog 2, mismatch repair system component [PMS2] in 1 patient). The authors identified 2 additional MLH1 mutation carriers by genetic testing who had not received immunohistochemistry/microsatellite instability testing. In total, 5.7% of the entire cohort were confirmed to have Lynch syndrome. In addition, 6 individuals (2.3%) had a polyposis phenotype. The percentage of dMMR tumors noted among Latino individuals (13%) is similar to estimates in non-Hispanic white individuals. In the current study, the majority of

  17. Embolization for gastrointestinal hemorrhages

    Kraemer, S.C.; Goerich, J.; Rilinger, N.; Aschoff, A.J.; Vogel, J.; Brambs, H.J.; Siech, M.

    2000-01-01

    Retrospective evaluation of interventional embolization therapy in the treatment of gastrointestinal hemorrhage over a long-term observation period from 1989 to 1997. Included in the study were 35 patients (age range 18-89 years) with gastrointestinal bleeding (GI) referred for radiological intervention either primarily or following unsuccessful endoscopy or surgery. Sources of GI bleeding included gastric and duodenal ulcers (n = 7), diverticula (n = 3), erosion of the intestinal wall secondary to malignancy (n = 6), vascular malformations (n = 4), and hemorrhoids (n = 2), as well as from postoperative (n = 6), posttraumatic (n = 2), postinflammatory (n = 4) or unknown (n = 1) causes. Ethibloc (12 cases) or metal coils (14 cases) were predominantly used as embolisates. In addition, combinations of tissue adhesive and gelfoam particles and of coils and Ethibloc were used (six cases). Finally, polyvinyl alcohol particles, a coated stent, and an arterial wire dissection were utilized in one case each. Bleeding was stopped completely in 29 of 35 cases (83 %). In one case (3 %) the source of bleeding was recognized but the corresponding vessel could not be catheterized. In five other cases (14 %) there was partial success with reduced, though still persistent, bleeding. The rate of complications was 14 %, including four instances of intestinal ischemia with fatal outcome in the first years, and, later, one partial infarction of the spleen without serious consequences. Gastrointestinal hemorrhage can be controlled in a high percentage of patients, including the seriously ill and those who had previously undergone surgery, with the use of minimally invasive interventional techniques. The availability of minicoils instead of fluid embolization agents has reduced the risk of serious complications. (orig.)

  18. Embolization for gastrointestinal hemorrhages

    Kraemer, S.C.; Goerich, J.; Rilinger, N.; Aschoff, A.J.; Vogel, J.; Brambs, H.J. [Dept. of Diagnostic Radiology, University of Ulm (Germany); Siech, M. [Dept. of Abdominal Surgery, University of Ulm (Germany)

    2000-05-01

    Retrospective evaluation of interventional embolization therapy in the treatment of gastrointestinal hemorrhage over a long-term observation period from 1989 to 1997. Included in the study were 35 patients (age range 18-89 years) with gastrointestinal bleeding (GI) referred for radiological intervention either primarily or following unsuccessful endoscopy or surgery. Sources of GI bleeding included gastric and duodenal ulcers (n = 7), diverticula (n = 3), erosion of the intestinal wall secondary to malignancy (n = 6), vascular malformations (n = 4), and hemorrhoids (n = 2), as well as from postoperative (n = 6), posttraumatic (n = 2), postinflammatory (n = 4) or unknown (n = 1) causes. Ethibloc (12 cases) or metal coils (14 cases) were predominantly used as embolisates. In addition, combinations of tissue adhesive and gelfoam particles and of coils and Ethibloc were used (six cases). Finally, polyvinyl alcohol particles, a coated stent, and an arterial wire dissection were utilized in one case each. Bleeding was stopped completely in 29 of 35 cases (83 %). In one case (3 %) the source of bleeding was recognized but the corresponding vessel could not be catheterized. In five other cases (14 %) there was partial success with reduced, though still persistent, bleeding. The rate of complications was 14 %, including four instances of intestinal ischemia with fatal outcome in the first years, and, later, one partial infarction of the spleen without serious consequences. Gastrointestinal hemorrhage can be controlled in a high percentage of patients, including the seriously ill and those who had previously undergone surgery, with the use of minimally invasive interventional techniques. The availability of minicoils instead of fluid embolization agents has reduced the risk of serious complications. (orig.)

  19. in upper gastrointestinal endoscopy

    Sinan Uzman

    2016-07-01

    Full Text Available Introduction : There is increasing interest in sedation for upper gastrointestinal endoscopy (UGE. Prospective randomized studies comparing sedation properties and complications of propofol and midazolam/meperidine in upper gastrointestinal endoscopy (UGE are few. Aim: To compare propofol and midazolam/meperidine sedation for UGE in terms of cardiopulmonary side effects, patient and endoscopist satisfaction and procedure-related times. Material and methods: This was a prospective, randomized, double-blind study of propofol versus midazolam and meperidine in 100 patients scheduled for diagnostic upper gastrointestinal endoscopy. The patients were divided into propofol and midazolam/meperidine groups. Randomization was generated by a computer. Cardiopulmonary side effects (hypotension, bradycardia, hypoxemia, procedure-related times (endoscopy time, awake time, time to hospital discharge, and patient and endoscopist satisfaction were compared between groups. Results: There was no significant difference between the groups with respect to the cost, endoscopy time, or demographic and clinical characteristics of the patients. Awake time and time to hospital discharge were significantly shorter in the propofol group (6.58 ±4.72 vs. 9.32 ±4.26 min, p = 0.030 and 27.60 ±7.88 vs. 32.00 ±10.54 min, p = 0.019. Hypotension incidence was significantly higher in the propofol group (12% vs. 0%, p = 0.027. The patient and endoscopist satisfaction was better with propofol. Conclusions : Propofol may be preferred to midazolam/meperidine sedation, with a shorter awake and hospital discharge time and better patient and endoscopist satisfaction. However, hypotension risk should be considered with propofol, and careful evaluation is needed, particularly in cardiopulmonary disorders.

  20. Gastrointestinal Headache; a Narrative Review

    Majid T Noghani; Hossein Rezaeizadeh; Sayed Mohammad Baqer Fazljoo; Mahmoud Yousefifard; Mansoor Keshavarz

    2016-01-01

    There are studies reporting primary headaches to be associated with gastrointestinal disorders, and some report resolution of headache following the treatment of the associated gastrointestinal disorder. Headache disorders are classified by The International Headache Society as primary or secondary; however, among the secondary headaches, those attributed to gastrointestinal disorders are not appreciated. Therefore, we aimed to review the literature to provide evidence for headaches, which or...

  1. Gastrointestinal and hepatobiliary radiology

    Graham, R.N.J.; Perriss, R.W.; Scarsbrook, A.F.

    2006-01-01

    This is the fifth in the series of short reviews of internet-based radiological learning resources and will focus on gastrointestinal (GI) and hepatobiliary radiology. Below are details of a few of the higher quality resources currently available. Most of the sites cater for medical students and trainee or non-specialist radiologists, but may be also be of interest to specialists, especially for use in teaching. Hyperlinks are available in the electronic version of this article and were all active at the time of going to press (May 2006)

  2. Gastrointestinal stromal tumors

    Sufliarsky, J.

    2011-01-01

    Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the digestive tract. Better understanding of the molecular characteristics of GISTs led to the clinical development of imatinib for treating patients with this disease. New immuno markers and mechanisms of primary and secondary resistance were discovered. Adjuvant imatinib in intermediate or high risk GIST has improved the recurrence-free survival. Sunitinib in patients with intolerance or progression on imatinib demonstrated significant improvements in progression-free and overall survival versus placebo. Second-generation tyrosine kinase inhibitors, such as sorafenib, dasatinib, and nilotinib, have shown activity in patients with imatinib- and sunitinib-resistant GIST. (author)

  3. Evidence-based management of epistaxis in hereditary haemorrhagic telangiectasia.

    Syed, I; Sunkaraneni, V S

    2015-05-01

    There are currently no guidelines in the UK for the specific management of hereditary haemorrhagic telangiectasia related epistaxis. The authors aimed to review the literature and provide an algorithm for the management of hereditary haemorrhagic telangiectasia related epistaxis. The Medline and Embase databases were interrogated on 15 November 2013 using the search items 'hereditary haemorrhagic telangiectasia' (title), 'epistaxis' (title) and 'treatment' (title and abstract), and limiting the search to articles published in English. A total of 46 publications were identified, comprising 1 systematic review, 2 randomised, controlled trials, 27 case series, 9 case reports, 4 questionnaire studies and 3 in vitro studies. There is a lack of high-level evidence for the use of many of the available treatments for the specific management of epistaxis in hereditary haemorrhagic telangiectasia. Current management should be based on a multidisciplinary team approach involving both a hereditary haemorrhagic telangiectasia physician and an ENT surgeon, especially when systemic therapy is being considered. The suggested treatment algorithm considers that the severity of epistaxis merits intervention at different levels of the treatment ladder. The patient should be assessed using a reproducible validated assessment tool, for example an epistaxis severity score, to guide treatment. More research is required, particularly in the investigation of topical agents targeting the development and fragility of telangiectasiae in hereditary haemorrhagic telangiectasia.

  4. Gastrointestinal Manifestations of Cystic Fibrosis

    2016-01-01

    Cystic fibrosis has historically been considered a pulmonary disease, but with the increasing life expectancy of these patients, gastrointestinal manifestations are becoming more important. Furthermore, nutritional status is closely linked to pulmonary function and, thus, overall mortality. This article discusses gastrointestinal manifestations (which involve nutritional, pancreatic, hepatobiliary, and, in particular, gastrointestinal tract issues) of cystic fibrosis as well as management of the disease. In addition, the article discusses studies that have been critical to our understanding of gastrointestinal manifestations of cystic fibrosis. PMID:27330503

  5. Hereditary neuropathies: systematization and diagnostics (clinical case of hereditary motor and sensor neuropathy of the IA type

    Kolokolova A.M.

    2016-09-01

    Full Text Available Aim: to study the value of routine methods (clinical symptoms, electrophysiological findings and results of DNA analysis in diagnostics of hereditary motor sensory neuropathy type IA in outpatient clinics. Material and Methods. The review of foreign literature is represented. The phenotypic polymorphism, genetic heterogeneity and the difficulties of diagnostics are identified. A family with hereditary motor sensory neuropathy of lAtype is presented, which was diagnosed on the base of available methods in outpatient practice (clinical symptoms, genealogical method, electro-physiological findings and DNA analysis results. Results. Routine algorithm (consistent valuation of clinical symptoms, neurophysiologic findings and the results of DNA analysis helped to verify the diagnosis of hereditary motor sensory neuropathy of lAtype in outpatient practice after more than 20 years of the onset of the disease. Conclusion. The neurologists of outpatient clinics and other specialists must be informed about the availability of diagnostics of hereditary diseases of nervous system.

  6. Hereditary and non-hereditary microangiopathies in the young. An up-date.

    Ringelstein, E Bernd; Kleffner, Ilka; Dittrich, Ralf; Kuhlenbäumer, Gregor; Ritter, Martin A

    2010-12-15

    In recent years, a considerable number of new sporadic or hereditary small artery diseases of the brain have been detected which preferably occur in younger age, below 45 years. Cerebral microangiopathies constitute an appreciable portion of all strokes. In middle aged patients, hereditary cerebral small vessel diseases have to be separated from sporadic degenerative cerebral microangiopathy which is mainly due to a high vascular risk load. Features of the following disorders and details how to differentiate them, are reviewed here, namely CADASIL, MELAS, AD-RVLC, HEMID, CARASIL, PADMAL, FABRY, COL4A1-related cerebral small vessel diseases and a Portuguese type of autosomal dominant cerebral small vessel disease (SVDB). The symptomatic overlap of the cerebral microangiopathies include also other distinctive non-hereditary diseases like posterior (reversible) encephalopathy and Susac's syndrome which are also described. Some of the microangiopathies described here are not only seen in the young but also in the elderly. The precise diagnosis has direct therapeutic implications in several of these entities. Cerebral microangiopathies cause recurring strokes and diffuse white matter lesions leading to a broad spectrum of gait disturbances and in most of these disorders cognitive impairment or even vascular dementia in the long term. Often, they also involve the eye, the inner ear or the kidney. Several typical imaging findings from illustrative cases are presented. The order in which these diseases are presented here is not dictated by an inner logic principle, because a genetically or pathophysiologically based classification system of all these entities does not exist yet. Some entities are well established and not unusual, whereas others have only been described in a few cases in total. Copyright © 2010 Elsevier B.V. All rights reserved.

  7. Gastrointestinal Eosinofilic Disorders

    Rodriguez Maria, Roberto; Bohorquez, Maria Amalia; Gonzalez, Irene; Torregroza, Gustavo

    2007-01-01

    The gastrointestinal eosinofilic disorders are little frequent diseases, of etiopatogenia little clear, that are characterized by the presence of an infiltrated eosinofilo that can affect the different layers of the wall of the alimentary canal in absence of known causes of eosinofilia. The clinical manifestations are variable and the symptoms are conditioned by the degree of eosinofilia of the wall, the number of layers affected and the segment of the gastrointestinal tract implied. The presentations symptoms vary from diarrhea, vomits, abdominal pain and loss of weigh until the acute intestinal obstruction. They are characterized to present peripherical eosinofilia, although it is not a forced criterion. Its definite diagnosis is anatomopatologic. The steroid use is considered as the angular stone of the treatment. We present two cases, with different clinical presentation forms, with initial answer to steroids and later relapse after the suspension of these, remaining without symptoms actually with dependency of low doses of steroids. Next we will do the revision of the available literature emphasizing the pathophysiologic data, the clinical evaluation and the therapeutic aspects

  8. Gastrointestinal medications and breastfeeding.

    Hagemann, T M

    1998-09-01

    Medications used to treat gastrointestinal symptoms are increasingly being used as more have been gained nonprescription status. Most of the gastrointestinal medications, such as laxatives, antacids, and antidiarrheal agents, are used short term. Women who breastfeed should be aware of the risks of taking any medications, whether prescription or nonprescription. There is little information describing transfer into breast milk for many of these products. Cimetidine, atropine, cascara, cisapride, loperamide, magnesium sulfate, and senna are the only products identified by the AAP as compatible with breast feeding. Metoclopramide is listed by the AAP as a drug whose effect on nursing infants is unknown but may be of potential concern, although studies published to date have not reported any adverse effects. The safest laxatives and antidiarrheals are those that are not absorbed and should be considered first-line therapy for conditions of constipation or loose stools. Famotidine and nizatidine are excreted into breast milk to a lesser extent than cimetidine or ranitidine and may be the preferred histamine antagonists. Despite the limited data on the use of cisapride in nursing women, it is considered safe by the AAP and may be preferred over metoclopramide for first-line prescription treatment of heartburn. Although most of these agents appear safe in the nursing infant, caretakers should be aware of the potential adverse reactions that may occur in infants whose mothers require these products.

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

    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. Inactivation of promoter 1B of APC causes partial gene silencing: evidence for a significant role of the promoter in regulation and causative of familial adenomatous polyposis

    Rohlin, A; Engwall, Y; Fritzell, K

    2011-01-01

    inactivation of promoter 1B is disease causing in FAP; (ii) expression of transcripts from promoter 1B is generated at considerable higher levels compared with 1A, demonstrating a hitherto unknown importance of 1B; (iii) adenoma formation in FAP, caused by impaired function of promoter 1B, does not require......Familial adenomatous polyposis (FAP) is caused by germline mutations in the adenomatous polyposis coli (APC) gene. Two promoters, 1A and 1B, have been recognized in APC, and 1B is thought to have a minor role in the regulation of the gene. We have identified a novel deletion encompassing half...... of this promoter in the largest family (Family 1) of the Swedish Polyposis Registry. The mutation leads to an imbalance in allele-specific expression of APC, and transcription from promoter 1B was highly impaired in both normal colorectal mucosa and blood from mutation carriers. To establish the significance...

  11. Leber hereditary optic neuropathy: current perspectives

    Meyerson, Cherise; Van Stavern, Greg; McClelland, Collin

    2015-01-01

    Leber hereditary optic neuropathy (LHON) is one of the most common inherited optic neuropathies causing bilateral central vision loss. The disorder results from point mutations in mitochondrial DNA and subsequent mitochondrial dysfunction. The primary cell type that is lost in LHON is the retinal ganglion cell, which is highly susceptible to disrupted ATP production and oxidative stress. Inheritance of LHON follows that of mitochondrial genetics, and it has a highly variable clinical phenotype, as other genetic and environmental factors also play a role. Although LHON usually presents with isolated vision loss, some patients suffer other neurological sequelae. For ill-defined reasons, male LHON mutation carriers are more affected than females. Most LHON patients remain legally blind, but a small proportion can experience spontaneous partial recovery, often within the first year of symptom onset. Unfortunately, at this time there are no established curative interventions and treatment is largely supportive. Patients should be offered low vision services and counseled on mitigating risk factors for additional vision loss, such as smoking and consuming alcohol. Encouraging treatments currently undergoing investigation includes ubiquinone analogs, such as idebenone, as well as gene therapy and stem cells to restore ATP synthesis and provide neuroprotection to surviving retinal ganglion cells. PMID:26170609

  12. Molecular Diagnostic and Pathogenesis of Hereditary Hemochromatosis

    Paulo C. J. L. Santos

    2012-02-01

    Full Text Available 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.

  13. Genetics of hereditary neurological disorders in children.

    Huang, Yue; Yu, Sui; Wu, Zhanhe; Tang, Beisha

    2014-04-01

    Hereditary neurological disorders (HNDs) are relatively common in children compared to those occurring in adulthood. Recognising clinical manifestations of HNDs is important for the selection of genetic testing, genetic testing results interpretation, and genetic consultation. Meanwhile, advances in next generation sequencing (NGS) technologies have significantly enabled the discovery of genetic causes of HNDs and also challenge paediatricians on applying genetic investigation. Combination of both clinical information and advanced technologies will enhance the genetic test yields in clinical setting. This review summarises the clinical presentations as well as genetic causes of paediatric neurological disorders in four major areas including movement disorders, neuropsychiatric disorders, neuron peripheral disorders and epilepsy. The aim of this review is to help paediatric neurologists not only to see the clinical features but also the complex genetic aspect of HNDs in order to utilise genetic investigation confidently in their clinical practice. A smooth transition from research based to clinical use of comprehensive genetic testing in HNDs in children could be foreseen in the near future while genetic testing, genetic counselling and genetic data interpretation are in place appropriately.

  14. Eviendep® reduces number and size of duodenal polyps in familial adenomatous polyposis patients with ileal pouch-anal anastomosis.

    Calabrese, Carlo; Praticò, Chiara; Calafiore, Andrea; Coscia, Maurizio; Gentilini, Lorenzo; Poggioli, Gilberto; Gionchetti, Paolo; Campieri, Massimo; Rizzello, Fernando

    2013-09-14

    To evaluate if 3 mo oral supplementation with Eviendep® was able to reduce the number of duodenal polyps in familial adenomatous polyposis (FAP) patients with ileal pouch-anal anastomosis (IPAA). Eleven FAP patients with IPAA and duodenal polyps were enrolled. They underwent upper gastrointestinal (GI) endoscopy at the baseline and after 3 mo of treatment. Each patient received 5 mg Eviendep twice a day, at breakfast and dinner time, for 3 mo. Two endoscopists evaluated in a blinded manner the number and size of duodenal polyps. Upper GI endoscopies with biopsies were performed at the baseline (T0) with the assessment of the Spigelman score. Polyps > 10 mm were removed during endoscopy and at the end of the procedure a new Spigelman score was determined (T1). The procedure was repeated 3 mo after the baseline (T2). Four photograms were examined for each patient, at T1 and T2. The examined area was divided into 3 segments: duodenal bulb, second and third portion duodenum. Biopsy specimens were taken from all polyps > 10 mm and from all suspicious ones, defined by the presence of a central depression, irregular surface, or irregular vascular pattern. Histology was classified according to the updated Vienna criteria. At baseline the mean number of duodenal detected polyps was 27.7 and mean sizes were 15.8 mm; the mean Spigelman score was 7.1. After polypectomy the mean number of duodenal detected polyps was 25.7 and mean sizes were 7.6 mm; the mean Spigelman score was 6.4. After 3 mo of Eviendep bid, all patients showed a reduction of number and size of duodenal polyps. The mean number of duodenal polyps was 8 (P = 0.021) and mean size was 4.4 mm; the mean Spigelman score was 6.6. Interrater agreement was measured. Lesions > 1 cm found a very good degree of concordance (kappa 0.851) and a good concordance was as well encountered for smaller lesions (kappa 0.641). Our study demonstrated that short-term (90 d) supplementation with Eviendep® in FAP patients with IPAA

  15. Gastrointestinal Headache; a Narrative Review

    Majid T Noghani

    2016-08-01

    Full Text Available There are studies reporting primary headaches to be associated with gastrointestinal disorders, and some report resolution of headache following the treatment of the associated gastrointestinal disorder. Headache disorders are classified by The International Headache Society as primary or secondary; however, among the secondary headaches, those attributed to gastrointestinal disorders are not appreciated. Therefore, we aimed to review the literature to provide evidence for headaches, which originate from the gastrointestinal system. Gastrointestinal disorders that are reported to be associated with primary headaches include dyspepsia, gastro esophageal reflux disease (GERD, constipation, functional abdominal pain, inflammatory bowel syndrome (IBS, inflammatory bowel disorders (IBD, celiac disease, and helicobacter pylori (H. Pylori infection. Some studies have demonstrated remission or improvement of headache following the treatment of the accompanying gastrointestinal disorders. Hypotheses explaining this association are considered to be central sensitization and parasympathetic referred pain, serotonin pathways, autonomic nervous system dysfunction, systemic vasculopathy, and food allergy. Traditional Persian physicians, namely Ebn-e-Sina (Avicenna and Râzi (Rhazes believed in a type of headache originating from disorders of the stomach and named it as an individual entity, the "Participatory Headache of Gastric Origin". We suggest providing a unique diagnostic entity for headaches coexisting with any gastrointestinal abnormality that are improved or cured along with the treatment of the gastrointestinal disorder.

  16. Comorbidities in severe asthma: frequency of rhinitis, nasal polyposis, gastroesophageal reflux disease, vocal cord dysfunction and bronchiectasis

    Carla Bisaccioni

    2009-01-01

    Full Text Available OBJECTIVES: Severe asthma is found in approximately 10% of patients with asthma. Some factors associated with worse asthma control include rhinitis, gastroesophageal reflux disease, vocal cord dysfunction (VCD, nasal polyposis and bronchiectasis. Therefore, we evaluated the prevalence of these illnesses in patients with severe asthma. METHODS: We conducted a retrospective analysis of data obtained from electronic medical records of patients with severe asthma between January 2006 and June 2008. Symptoms of rhinitis and gastroesophageal reflux disease were evaluated as well as intolerance to nonsteroidal anti-inflammatory drugs. We evaluated the results of esophagogastroduodenoscopy, videolaryngoscopy and CT scans of the chest in order to confirm gastroesophageal reflux disease, nasal polyposis, vocal cord dysfunction and bronchiectasis. RESULTS: We evaluated 245 patients. Rhinitis symptoms were present in 224 patients (91.4%; 18 (7.3% had intolerance to nonsteroidal anti-inflammatory drugs, and 8 (3.3% had nasal polyposis. Symptoms of gastroesophageal reflux disease were reported for 173 (70.6% patients, although the diagnosis of gastroesophageal reflux disease was confirmed based on esophagogastroduodenoscopy or laryngoscopy findings in just 58 (33.6% patients. Vocal cord dysfunction was suspected in 16 (6.5% and confirmed through laryngoscopy in 4 (1.6%. The patient records provided CT scans of the chest for 105 patients, and 26 (24.8% showed bronchiectasis. DISCUSSION: Rhinitis and gastroesophageal reflux disease were the most common comorbidities observed, in addition to bronchiectasis. Therefore, in patients with severe asthma, associated diseases should be investigated as the cause of respiratory symptoms and uncontrolled asthma.

  17. Surgical management of hereditary colorectal cancer: surgery based on molecular analysis and family history Manejo quirúrgico del cáncer colorrectal hereditario: cirugía basadas en el análisis molecular y los antecedentes familiares

    J. Perea

    2009-08-01

    Full Text Available The importance of colorectal cancer (CRC is increasing. A proportion show a hereditary component, as in Lynch syndrome and Familial Adenomatous Polyposis, and a recently defined entity as well, namely, Familial Colorectal Cancer type X. The high probability to develop CRC in these groups may, at the time of recognition, change surgical management, including its timing or even the surgical technique. In some cases prophylactic surgery can play an important role. The possibility of using tools that allow recognition of the aforementioned syndromes, including microsatellite instability, immunohistochemistry for DNA mismatch repair system proteins, and especially their mutations, is on the basis of therapeutic strategies that differ from those employed in sporadic CRC cases.

  18. Scintigraphic assessment of gastrointestinal motility

    Madsen, Jan Lysgård

    2014-01-01

    intestinal and colonic transit. This article reviews current imaging techniques, methods for data processing and principles for evaluating results when scintigraphy is used to assess gastrointestinal motility. Furthermore, clinical indications for performing scintigraphy are reviewed.......Gastrointestinal transit reflects overall gastrointestinal motor activity and is regulated by a complex interplay between neural and hormonal stimuli. Thus, transit measurements provide a measure of the combined effects of gastrointestinal muscular activity and feedback from the gut and brain....... Dysmotility in the different major segments of the gastrointestinal tract may give rise to similar symptoms; hence, localizing transit abnormalities to a specific segment is a valuable element of diagnostic evaluation. Scintigraphy is an effective noninvasive tool to assess gastric emptying as well as small...

  19. Hereditary hemorrhagic telangiectasia and pregnancy: potential adverse events and pregnancy outcomes

    Bari O

    2017-05-01

    Full Text Available Omar Bari,1 Philip R Cohen2 1School of Medicine, University of California San Diego, La Jolla, CA, USA; 2Department of Dermatology, University of California San Diego, La Jolla, CA, USA Abstract: Hereditary hemorrhagic telangiectasia (HHT is an autosomal dominant condition with a prevalence of ~1 in 5,000 individuals. The pathophysiology of this condition centers on the lack of capillary beds between arterioles and venules, leading to direct contact between these vessels. This results in telangiectases on characteristic locations such as the face, fingers, mouth, and nasal mucosa. Visceral arteriovenous malformations (AVMs are also observed in many patients, and these are most commonly seen in the brain, gastrointestinal tract, and lungs. Liver AVMs are present in many patients with HHT, though these individuals are usually asymptomatic; however, liver AVMs may lead to serious complications, such as high output cardiac failure. Diagnosis of HHT hinges upon fulfilling three out of four criteria: family history of the condition, mucocutaneous telangiectases, spontaneous and recurrent episodes of epistaxis, and visceral AVMs. Management is guided by international consensus guidelines and targets patients’ specific AVMs. Prognosis is good, though severe complications including hemorrhage and paradoxical emboli are possible. Novel therapeutics are being explored in clinical trials; bevacizumab and pazopanib inhibit angiogenesis, while thalidomide bolsters blood vessel maturation. Pregnancy in patients with HHT is considered high risk. While the majority of pregnancies proceed normally, severe complications have been reported in some women with HHT; these include heart failure, intracranial hemorrhage, pulmonary hemorrhage, and stroke. Such complications occur most often in the second and third trimesters when maternal changes such as peripheral vasodilation and increased cardiac output are at their maximum. Awareness of the diagnosis of HHT has

  20. The gastrointestinal tract

    Bartels, Else M.; Harrison, Adrian Paul

    2009-01-01

    The gastrointestinal tract (GIT) has always been and remains a major source of interest in terms of both its function, and its malfunction. Our current knowledge of age-related changes in this system, as well as drug-food interactions, however, remains relatively limited. Paradoxically, the GIT......-related GIT damage and dysfunction. New and novel aspects of drug delivery and drug-dietary supplement interactions are discusses and much needed areas of focus in terms of drug GIT testing are identified....... is not one of the core battery of tests that pharmaceutical companies are obliged to investigate as part of drug development. This review aims to cover the basics of GIT function before highlighting aspects of relevance for safety pharmacology in terms of age, cancerogenesis, and noth drug and diet...

  1. Gastrointestinal infections in children.

    Mönkemüller, K E; Wilcox, C M

    2001-01-01

    Gastrointestinal infections in children are a major cause of morbidity and mortality worldwide. Children living in developing countries are particularly susceptible to infectious diarrhea because of poor standards of hygiene and sanitation. Although the magnitude of diarrheal illnesses in developed countries is less, costly hospital admissions are still frequent. The causal agent of infectious diarrhea is most frequently related to age, geographical location, lifestyle habits, use of antibiotics, associated medical conditions, social circumstances, and degree of immune competence. In this article we present some of the most important articles published in the field during the last year. The role of Helicobacter pylori in the pathogenesis of gastritis and peptic ulcer disease has been shown in adults and children. Information about the natural history of H. pylori, symptomatology, and diagnostic therapeutic approaches for children are being generated constantly; we discuss some of the most relevant information in this review.

  2. Estrogen and gastrointestinal malignancy.

    Hogan, A M

    2012-02-01

    The concept that E2 exerts an effect on the gastrointestinal tract is not new and its actions on intestinal mucosa have been investigated for at least three decades. An attempt to consolidate results of these investigations generates more questions than answers, thus suggesting that many unexplored avenues remain and that the full capabilities of this steroid hormone are far from understood. Evidence of its role in esophageal, gastric and gallbladder cancers is confusing and often equivocal. The most compelling evidence regards the protective role conferred by estrogen (or perhaps ERbeta) against the development and proliferation of colon cancer. Not only has the effect been described but also many mechanisms of action have been explored. It is likely that, along with surgery, chemotherapy and radiotherapy, hormonal manipulation will play an integral role in colon cancer management in the very near future.

  3. Attitudes toward genetic testing in childhood and reproductive decision-making for familial adenomatous polyposis.

    Douma, Kirsten F L; Aaronson, Neil K; Vasen, Hans F A; Verhoef, Senno; Gundy, Chad M; Bleiker, Eveline M A

    2010-02-01

    Childhood DNA testing, prenatal diagnosis (PND) and preimplantation genetic diagnosis (PGD) are available for familial adenomatous polyposis (FAP). However, the use of PND and PGD is controversial. The purpose of this study was to investigate attitudes toward, and experiences with, childhood DNA testing, PND and PGD among members of families at high risk for FAP. In this nationwide, cross-sectional study, questionnaires were sent to individuals from families at high risk for FAP assessing attitudes toward and experiences with childhood testing, PND and PGD, as well as several sociodemographic, clinical and psychosocial variables. Of the individuals from FAP families invited to participate in the study, 525 members participated (response rate=64%). Most parents who had children who were minors (n=93) (82%) were satisfied with the DNA testing procedure. One-third of all individuals wanted DNA testing for their children before age 12. Forty percent of FAP patients indicated that the disease influenced their desire to have children. Only 15% considered termination of pregnancy for FAP acceptable. Approximately 30% of individuals with a FAP diagnosis and their partners considered PND and PGD as acceptable for themselves. A positive attitude was associated with higher levels of guilt and a positive attitude toward termination of pregnancy. Importantly, of those with FAP at childbearing age, 84% had had no previous information at all about either PND or PGD. Future efforts should be aimed at educating FAP family members about reproductive options, allowing them to make an informed choice about family planning. Routine discussion of all reproductive options with a medical specialist should be encouraged.

  4. Clinical characteristics of patients with serrated polyposis syndrome in Korea: comparison with Western patients

    Eun Ran Kim

    2017-07-01

    Full Text Available Background/Aims: Serrated polyposis syndrome (SPS has been shown to increase the risk of colorectal cancer (CRC. However, little is known about the characteristics of Asian patients with SPS. This study aimed to identify the clinicopathological features and risk of CRC in Korean patients with SPS as well as the differences between Korean and Western patients based on a literature review.Methods: This retrospective study included 30 patients with SPS as defined by World Health Organization classification treated at Samsung Medical Center, Korea, between March 1999 and May 2011.Results: Twenty patients (67% were male. The median patient age at diagnosis was 56 years (range, 39–76 years. A total of 702 polyps were identified during a median follow-up of 43 months (range, 0–149 months. Serrated polyps were noted more frequently in the distal colon (298/702, 55%. However, large serrated polyps and serrated adenomas were mainly distributed throughout the proximal colon (75% vs. 25% and 81% vs. 19%, respectively; 73.3% had synchronous adenomatous polyps. The incidence of CRC was 10% (3/30 patients, but no interval CRC was detected. A total of 87% of the patients underwent esophagogastroduodenoscopy and 19.2% had significant lesions.Conclusions: The phenotype of SPS in Korean patients is different from that of Western patients. In Korean patients, SPS is more common in men, there were fewer total numbers of serrated adenoma/polyps, and the incidence of CRC was lower than that in Western patients. Korean patients tend to more frequently have abnormal gastric lesions. However, the prevalence of synchronous adenomatous polyps is high in both Western and Korean patients.

  5. Lower gastrointestinal malignancies

    Minsky, Bruce D.

    1995-01-01

    Objective: This refresher course will review the current knowledge as well as ongoing and future research strategies in lower gastrointestinal malignancies. Radiation therapy has a significant role in the adjuvant treatment of lower gastrointestinal malignancies. Furthermore, there are data to suggest that radiation therapy is an integral component of the conservative management (organ preservation) of rectal and anal cancers. 1. Colon cancer. The standard adjuvant treatment for node positive or high risk transmural colon cancer is postoperative 5-FU and Levamisole. There are retrospective data to suggest that certain subsets of high risk patients may benefit from postoperative radiation therapy. 2. Rectal cancer. Randomized trials have revealed an advantage of postoperative radiation therapy plus chemotherapy in transmural and/or node positive rectal cancer. In the adjuvant setting the use of continuous infusion 5-FU may be more beneficial compared with bolus 5-FU. Despite the improvement in survival, postoperative therapies are associated with an approximately 35% incidence of grade 3+ toxicity. Recent data suggest that the use of preoperative combined modality therapy may be associated with less toxicity as well as increase the chance of sphincter preservation. New Intergroup trials addressing these issues will be presented. In patients with locally advanced unresectable rectal cancer, the addition of intraoperative radiation therapy may further improve local control. 3. Anal cancer. The use of combined 5-FU/Mitomycin-C and pelvic radiation therapy is effective in the treatment of anal carcinoma. The RTOG has recently completed a randomized trial addressing the question of the effectiveness and toxicity of Mitomycin-C. The replacement Intergroup Phase III trial will be presented

  6. Stromal gastrointestinal tumors (GIST)

    Balev, B.; Boykova, K.

    2015-01-01

    Full text: GIST are a heterogeneous group of mesenchymal tumors of the gastrointestinal tract with varying tumor grade and frequency of 1: 100 000 per year. Mazur and Clark introduced the term for the first time in 1983. GIST constitute approximately 2% of the tumors in the gastrointestinal tract. The average age is 60 years. The most common locations are the stomach (60%), small intestine (30%), esophagus (1%), and rectum (5%). Learning objective: to demonstrate the imaging characteristics of the disease according to the current ESMO guidelines and to present the diagnostic accuracy of different imaging modalitiesnbased on review of literature and on own observations. GIST originate from interstitial cells (of Cajal) in the GIT wall, belonging to the autonomic nervous system, which is responsible for motility. 90% of GIST show overexpression of the KIT receptor, also known as CD117 or stem cell factor receptor. those that do not express c-KIT mutations, activate mutations in PDGFRA gene. Tumor’s macromorphology determines the imaging features on different modalities. Most of these tumors are exophytic, subepithelial, reach large size and enhance inhomogeneous due to necrosis. They usually do not cause obstruction. Ultrasound as the initiation method shows low sensitivity and specificity in GIST detection, CT with intravenous contrast is the gold standard. MRI contributes with assessing the vascularisation, cellularity and pH. FDG-PET/CT registers the metabolism of intratumoral acidosis. CT is the method of choice in the early diagnosis and determination of resectability of GIST. MRI is an additional method. PET FDG-CT is useful for the monitoring of patients treated with Imatinib

  7. Lower gastrointestinal malignancies

    Minsky, Bruce D.

    1996-01-01

    Objective: This refresher course will review the current knowledge as well as ongoing and future research strategies in lower gastrointestinal malignancies. Radiation therapy has a significant role in the adjuvant treatment of lower gastrointestinal malignancies. Furthermore, there are data to suggest that radiation therapy is an integral component of the conservative management (organ preservation) of rectal and anal cancers. 1. Colon cancer. The standard adjuvant treatment for node positive or high risk transmural colon cancer is postoperative 5-FU and Levamisole. There are retrospective data to suggest that certain subsets of high risk patients may benefit from postoperative radiation therapy. 2. Rectal cancer. Randomized trials have revealed an advantage of postoperative radiation therapy plus chemotherapy in transmural and/or node positive rectal cancer. In the adjuvant setting the use of continuous infusion 5-FU may be more beneficial compared with bolus 5-FU. Despite the improvement in survival, postoperative therapies are associated with an approximately 35% incidence of grade 3+ toxicity. Recent data suggest that the use of preoperative combined modality therapy may be associated with less toxicity as well as increase the chance of sphincter preservation. New Intergroup trials addressing these issues will be presented. In patients with locally advanced unresectable rectal cancer, the addition of intraoperative radiation therapy may further improve local control. 3. Anal cancer. The use of combined 5-FU/Mitomycin-C and pelvic radiation therapy is effective in the treatment of anal carcinoma. The RTOG has recently completed a randomized trial addressing the question of the effectiveness and toxicity of Mitomycin-C. The replacement Intergroup Phase III trial will be presented

  8. Treatment for speech disorder in Friedreich ataxia and other hereditary ataxia syndromes.

    Vogel, Adam P; Folker, Joanne; Poole, Matthew L

    2014-10-28

    specific data on speech performance; all were comparisons with placebo. Improvements in overall disease severity were observed with α-tocopheryl quinone; however, no significant changes were found on the speech subscale in a group of individuals with Friedreich ataxia. A statistically significant improvement in speech according to a speech disorders subscale was observed with betamethasone. Riluzole was found to have a statistically significant effect on speech in a group of participants with mixed hereditary, sporadic and unknown origin ataxias. No significant differences were observed between treatment and placebo in any other pharmaceutical study. A statistically significant improvement in functional independence occurred at the end of the treatment period in the rehabilitation study compared to the delayed treatment group but these effects were not present 12 to 24 weeks after treatment. Of the four studies that assessed quality of life, none found a significant effect. A variety of minor adverse events were reported for the 13 pharmaceutical therapies, including gastrointestinal side effects and nausea. Serious adverse effects were reported in two participants in one of the L-5HT trials (participants discontinued due to gastrointestinal effects), and in four participants (three taking idebenone, one taking placebo) in the idebenone studies. Serious adverse events with idebenone were gastrointestinal side effects and, in people with a previous history of these events, chest pain and idiopathic thrombocytopenic purpura. The rehabilitation study did not report any adverse events.We considered six studies to be at high risk of bias in some respect. We suspected inadequate blinding of participants or assessors in four studies and poor randomisation in a further two studies. There was a high risk of reporting bias in two studies and attrition bias in four studies. Only one study had a low risk of bias across all criteria. Taken together with other limitations of the

  9. The prevalence of depression in hereditary spastic paraplegia.

    Vahter, L; Braschinsky, M; Haldre, S; Gross-Paju, K

    2009-09-01

    To evaluate the prevalence of depression and sensitivity and specificity of the single-item interview 'Are you depressed?' for people with hereditary spastic paraplegia in Estonia. Single-item interview 'Are you depressed?' was used as a screening question for depression; all participants then completed the Beck Depression Inventory. People with hereditary spastic paraplegia identified from the epidemiological database who agreed to participate in the study. Beck Depression Inventory, clinical interview. The epidemiological database consisted of 59 patients with clinically confirmed diagnosis of hereditary spastic paraplegia. Forty-eight of these consented to participate in the study. The Beck Depression Inventory score was higher than cut-off point in 58% (28/48) and lower in 42% (20/48). Of the study group, 44% (21/48) had mild, 13% (6/48) moderate and one person revealed severe depression. There was a statistically significant correlation between Beck Depression Inventory score and level of mobility; no other significant correlations with other measures were detected. Of the participants, 54% (26/48) had subjective complaints about depression and answered 'Yes' to the single-item interview 'Are you depressed?'. The sensitivity of the one-item interview in the hereditary spastic paraplegia group was 75% and specificity 75%. Our results show that mild depression is prevalent among people with hereditary spastic paraplegia. Although the single question may be helpful, it cannot be relied upon entirely when assessing a person for depression.

  10. Musculoskeletal disease burden of hereditary hemochromatosis.

    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.

  11. Outcomes of Lensectomy in Hereditary Lens Subluxation

    Mohammad-Hossein Dehghan

    2008-12-01

    Full Text Available

    PURPOSE: To evaluate the results of pars plana lensectomy in patients with hereditary lens subluxation. METHOD: Hospital records of patients with hereditary lens subluxation who had undergone pars plana lensectomy at Labbafinejad Medical Center, Tehran-Iran from 1996 to 2003 were reviewed. Patients with more than 6 months of follow up were included. Underlying disorders, best corrected visual acuity (BCVA before and after surgery, intraocular pressure (IOP, postoperative refraction and complications were evaluated. RESULTS: Overall, records of 87 eyes of 49 patients including 27 male and 22 female subjects were reviewed. Mean follow up duration was 20±18 months. Underlying disorders leading to lens subluxation included Marfan syndrome (79.5%, Weill-Marchesani syndrome (8.2%, simple ectopia lentis (8.2%, and homocystinuria (4.1%. The most common indication for surgery was non-correctable refractive error (92.1%. Mean BCVA was 1.13 LogMAR (20/250 preoperatively, which improved to 0.26 LogMAR (20/30-20/40 postoperatively (P < 0.001. BCVA better than 20/40 was achieved in 82.8% of cases after surgery. Angle-supported anterior chamber intraocular lens (ACIOL was implanted in

  12. Bevacizumab for Refractory Gastrointestinal Bleeding in Rendu-Osler-Weber Disease

    Bernardes, Carlos; Santos, Sara; Loureiro, Rafaela; Borges, Verónica; Ramos, Gonçalo

    2018-01-01

    Rendu-Osler-Weber disease, also known as hereditary hemorrhagic telangiectasia, is a rare autosomal dominant disorder which is often characterized by recurrent epistaxis, mucocutaneous and gastrointestinal telangiectasias, and visceral arteriovenous malformations. Patients with gastrointestinal involvement can present with a wide spectrum of severity, which may vary from uncomplicated iron deficiency anemia to continuous and refractory bleeding. We present the case of a 62-year-old female, who was admitted with anemia following several episodes of melena, and whose endoscopic examination revealed multiple angiodysplasias in the stomach and small bowel. Despite endoscopic and medical treatment attempts with hormonal agents and octreotide, she developed persistent hemorrhage and severe anemia, requiring frequent red blood cell transfusions. Immediately after initiating bevacizumab (7.5 mg/kg, every 3 weeks), complete cessation of bleeding episodes was observed. Currently, after 1 year of follow-up, she maintained sustained remission without the occurrence of adverse events. PMID:29662934

  13. Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis

    Vasen, H. F.; Wijnen, J. T.; Menko, F. H.; Kleibeuker, J. H.; Taal, B. G.; Griffioen, G.; Nagengast, F. M.; Meijers-Heijboer, E. H.; Bertario, L.; Varesco, L.; Bisgaard, M. L.; Mohr, J.; Fodde, R.; Khan, P. M.

    1996-01-01

    Hereditary nonpolyposis colorectal cancer is characterized by early-onset colorectal cancer and the occurrence of various other cancers. The recent isolation of four mismatch repair genes responsible for hereditary nonpolyposis colorectal cancer allows for the identification of carriers within

  14. Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis

    Vasen, HFA; Wijnen, JT; Menko, FH; Kleibeuker, JH; Taal, BG; Griffioen, G; Nagengast, FM; MeijersHeijboer, EH; Bertario, L; Varesco, L; Bisgaard, ML; Mohr, J; Fodde, R; Khan, PM

    Background & Aims: Hereditary nonpolyposis colorectal cancer is characterized by early-onset colorectal cancer and the occurrence of various other cancers, The recent isolation of four mismatch repair genes responsible for hereditary nonpolyposis colorectal cancer allows for the identification of

  15. Neuromyelitis optica antibody in Leber hereditary optic neuropathy: case report

    Luciano Mesquita Simão

    2012-08-01

    Full Text Available Neuromyelitis optica antibody (or aquaporin-4 antibody is a well stablished serum marker associated to high-risk neuromyelitis optica syndrome that presents as an inflammatory demyelinating disease characterized by the occurrence of bilateral and simultaneous optic neuritis without complete visual recovery or it occurs as an isolated episode of transverse myelitis accompanied by longitudinally extensive spinal cord lesions. On the other hand, Leber hereditary optic neuropathy is a primarily hereditary disorder that affects all tissues of the body and its clinical presentation is tissue-specific for the optic nerve and, eventually, it might reach the spinal cord. Overlapping clinical features of neuromyelitis optica and Leber hereditary optic neuropathy may suggest common target organ diseases. The case report described herein emphasizes the coexistence of serum markers of both diseases, and suggests that further investigation of this challenging clinical presentation is warranted to confirm or rule out this association.

  16. Intragenic Duplication A Novel Mutational Mechanism in Hereditary Pancreatitis

    Joergensen, M. T.; Geisz, A.; Brusgaard, K.

    2011-01-01

    OBJECTIVES: In a hereditary pancreatitis family from Denmark, we identified a novel intragenic duplication of 9 nucleotides in exon-2 of the human cationic trypsinogen (PRSS1) gene (c.63_71dup) which at the amino-acid level resulted in the insertion of 3 amino acids within the activation peptide...... pancreatitis. The accelerated activation of p.K23_I24insIDK by cathepsin B is a unique biochemical property not found in any other pancreatitis-associated trypsinogen mutant. In contrast, the robust autoactivation of the novel mutant confirms the notion that increased autoactivation is a disease......-relevant mechanism in hereditary pancreatitis....

  17. Fetal MRI of hereditary multiple intestinal atresia with postnatal correlation

    Githu, Tangayi; Merrow, Arnold C.; Lee, Jason K.; Garrison, Aaron P.; Brown, Rebeccah L.

    2014-01-01

    Hereditary multiple intestinal atresia (HMIA) is an extremely uncommon cause of congenital bowel obstruction. The morbidity and mortality of this disease differ significantly from those of isolated intestinal atresias and non-hereditary forms of multiple intestinal atresia. Most notably, despite successful operative repairs of the atresias found in this disease, HMIA maintains a 100% lethality rate from continued post-operative intestinal failure and an associated severe immunodeficiency. We present a case of HMIA evaluated with fetal MRI and subsequently diagnosed by a combination of corroborative postnatal imaging with surgical exploration and pathological examination. (orig.)

  18. Hereditary Gigantism-the biblical giant Goliath and his brothers.

    Donnelly, Deirdre E; Morrison, Patrick J

    2014-05-01

    The biblical giant Goliath has an identifiable family tree suggestive of autosomal dominant inheritance. We suggest that he had a hereditary pituitary disorder possibly due to the AIP gene, causing early onset and familial acromegaly or gigantism. We comment on the evidence within the scriptures for his other relatives including a relative with six digits and speculate on possible causes of the six digits. Recognition of a hereditary pituitary disorder in the biblical Goliath and his family sheds additional information on his and other family members' battles with David and his relatives.

  19. Dysphonia and vocal fold telangiectasia in hereditary hemorrhagic telangiectasia.

    Chang, Joseph; Yung, Katherine C

    2014-11-01

    This case report is the first documentation of dysphonia and vocal fold telangiectasia as a complication of hereditary hemorrhagic telangiectasia (HHT). Case report of a 40-year-old man with HHT presenting with 2 years of worsening hoarseness. Hoarseness corresponded with a period of anticoagulation. Endoscopy revealed vocal fold scarring, vocal fold telangiectasias, and plica ventricular is suggestive of previous submucosal vocal fold hemorrhage and subsequent counterproductive compensation with ventricular phonation. Hereditary hemorrhagic telangiectasia may present as dysphonia with vocal fold telangiectasias and place patients at risk of vocal fold hemorrhage. © The Author(s) 2014.

  20. Fetal MRI of hereditary multiple intestinal atresia with postnatal correlation

    Githu, Tangayi [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Radiology of Huntsville, P.C., Huntsville, AL (United States); Merrow, Arnold C.; Lee, Jason K. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Garrison, Aaron P. [Cincinnati Children' s Hospital Medical Center, Department of Surgical Services, Division of Pediatric General and Thoracic Surgery, Cincinnati, OH (United States); Akron Children' s Hospital, Pediatric Surgery, Akron, OH (United States); Brown, Rebeccah L. [Cincinnati Children' s Hospital Medical Center, Department of Surgical Services, Division of Pediatric General and Thoracic Surgery, Cincinnati, OH (United States)

    2014-03-15

    Hereditary multiple intestinal atresia (HMIA) is an extremely uncommon cause of congenital bowel obstruction. The morbidity and mortality of this disease differ significantly from those of isolated intestinal atresias and non-hereditary forms of multiple intestinal atresia. Most notably, despite successful operative repairs of the atresias found in this disease, HMIA maintains a 100% lethality rate from continued post-operative intestinal failure and an associated severe immunodeficiency. We present a case of HMIA evaluated with fetal MRI and subsequently diagnosed by a combination of corroborative postnatal imaging with surgical exploration and pathological examination. (orig.)

  1. Gastrointestinal nuclear medicine

    Koblik, P.D.; Hornof, W.J.

    1985-01-01

    General localization of gastrointestinal bleeding through the use of labeled red blood cells may be performed in children, or (99m)Tc-pertechnetate may be used if a Meckel's diverticulum is suspected. As in adults, cholecystitis and biliary leak may be assessed in children via (99m)Tc-IDA derivatives. Gastroesophageal reflux can be evaluated by oral consumption of the child's usual diet labeled with (99m)Tc sulfur colloid. For the scintigraphic determination of pulmonary aspiration, a relatively high concentration of tracer within a drop of liquid is placed beneath the child's tongue followed by dynamic imaging of the respiratory tract. Colonic transit scintigraphy can aid in the identification and therapeutic decision-making in patients with functional fecal retention, the most common cause of chronic constipation in children. (18)F-DOPA positron emission tomography is useful for classifying pancreatic involvement in infantile hyperinsulinism as focal or diffuse, thereby differentiating between patients who should receive curative focal pancreatic resection versus those who should receive medical management. Assessment of protein-losing enteropathy can be conducted scintigraphically and, compared with fecal alpha-1 antitrypsin collection, the scintigraphic method can detect esophageal and gastric protein loss. Also, scintigraphic quantification of protein loss can be performed without the requirement for fecal collection. Intestinal inflammation in children with inflammatory bowel disease can be evaluated using (99m)Tc white blood cells. The scintigraphic method is safe, accurate, well-tolerated by children and complementary to endoscopy in most patients

  2. Gastrointestinal scanning agent

    Francis, M.D.

    1980-01-01

    An easily prepared radiolabeled gastrointestinal scanning agent is described. Technetium-99m has ideal characteristics for imaging the upper and lower GI tract and determining stomach emptying and intestinal transit time when used with an insoluble particulate material. For example, crystalline and amorphous calcium phosphate particles can be effectively labeled in a one-step process using sup(99m)TcO 4 and SnCl 2 . These labeled particles have insignificant mass and when administered orally pass through the GI tract unchanged, without affecting the handling and density of the intestinal contents. Visualization of the esophageal entry into the stomach, the greater and lesser curvatures of the stomach, ejection into the duodenum, and rates of passage through the upper and lower GI tract are obtained. The slurry of sup(99m)TC particulate can be given rectally by enema. Good images of the cecum and the ascending, transverse, and descending colon are obtained. Mucosal folds and the splenic and hepatic flexures are visualized. The resilience of the large intestine is also readily visualized by pneumocolonographic techniques. (author)

  3. Quality of life after total colectomy with ileorectal anastomosis or proctocolectomy and ileal pouch-anal anastomosis for familial adenomatous polyposis

    van Duijvendijk, P.; Slors, J. F.; Taat, C. W.; Oosterveld, P.; Sprangers, M. A.; Obertop, H.; Vasen, H. F.

    2000-01-01

    BACKGROUND: Knowledge of postoperative health status is important in decision-making about the type of operation necessary in patients with familial adenomatous polyposis (FAP). This study compared the quality of life (QoL) between patients with an ileorectal anastomosis (group 1) and those with an

  4. Expression of IGF-1R and iNOS in nasal polyps; epithelial cell homeostasis and innate immune mechanisms in pathogenesis of nasal polyposis

    Fundová, P.; Filipovský, T.; Funda, David P.; Hovorka, Ondřej; Holý, R.; Navara, M.; Tlaskalová, Helena

    2008-01-01

    Roč. 53, č. 6 (2008), s. 558-562 ISSN 0015-5632 R&D Projects: GA MZd NR8517 Institutional research plan: CEZ:AV0Z50200510 Keywords : nasal polyposis * igf -1r * inos Subject RIV: EC - Immunology Impact factor: 1.172, year: 2008

  5. Clinical characteristics and outcomes in familial adenomatous polyposis patients with a long-term treatment of celecoxib: a matched cohort study

    Huang, Kui; Gutierrez, Lia P; Bülow, Steffen

    2011-01-01

    Familial adenomatous polyposis (FAP) is a rare genetic disease. Without treatment, FAP patients have a 100% lifetime risk of developing colorectal cancer. This study was conducted to evaluate the effect of celecoxib treatment in prolonging the time to FAP-related events and to document the safety...

  6. The role of high-resolution endoscopy and narrow-band imaging in the evaluation of upper GI neoplasia in familial adenomatous polyposis

    Lopez-Ceron, Maria; van den Broek, Frank J. C.; Mathus-Vliegen, Elisabeth M.; Boparai, Karam S.; van Eeden, Susanne; Fockens, Paul; Dekker, Evelien

    2013-01-01

    The Spigelman classification stratifies cancer risk in familial adenomatous polyposis (FAP) patients with duodenal adenomatosis. High-resolution endoscopy (HRE) and narrow-band imaging (NBI) may identify lesions at high risk. To compare HRE and NBI for the detection of duodenal and gastric polyps

  7. Adenocarcinoma in the anal canal after ileal pouch-anal anastomosis for familial adenomatous polyposis using a double-stapled technique: report of two cases

    Vrouenraets, Bart C.; van Duijvendijk, Peter; Bemelman, Willem A.; Offerhaus, G. Johan A.; Slors, J. Frederik M.

    2004-01-01

    Restorative proctocolectomy with an ileal pouch-anal anastomosis is thought to abolish the risk of colorectal adenoma development in patients suffering from familial adenomatous polyposis. Both after mucosectomy with a handsewn anastomosis and after a double-stapled anastomosis, rectal mucosa is

  8. Scintigraphic evaluation of gastrointestinal bleeding

    Park, Yong Tai; Lee, Choon Keun; Lee, Sun Wha; Choi, Woo Suk; Yoon, Yup; Lim, Jae Hoon

    1988-01-01

    Gastrointestinal bleeding remains a major diagnostic problem. Although advances have been made in the medical and surgical methods of managing gastrointestinal bleeding, the commonly employed techniques of barium radiography, endoscopy, and angiography may not successfully localize the site and define the cause of gastrointestinal bleeding. Two widely available technetium-99m-labeled radiopharmaceuticals, sulfur colloid and red blood cells are currently used in the evaluation of patients who are bleeding from the gastrointestinal tract. Surgically confirmed 19 patients with use of 99m Tc-sulfur colloid (7 cases) and 99m Tc-RBC (12 cases) were retrospectively evaluated. The overall sensitivity of scintigraphy in detection of bleeding and localization of bleeding site was 68% and 84%, respectively. The authors conclude that bleeding scintigraphy is a safe, sensitive, and non-invasive method as an effective screening test before performing angiography or surgery.

  9. Sleep Dysfunction and Gastrointestinal Diseases.

    Khanijow, Vikesh; Prakash, Pia; Emsellem, Helene A; Borum, Marie L; Doman, David B

    2015-12-01

    Sleep deprivation and impaired sleep quality have been associated with poor health outcomes. Many patients experience sleep disturbances, which can increase the risk of medical conditions such as hypertension, obesity, stroke, and heart disease as well as increase overall mortality. Recent studies have suggested that there is a strong association between sleep disturbances and gastrointestinal diseases. Proinflammatory cytokines, such as tumor necrosis factor, interleukin-1, and interleukin-6, have been associated with sleep dysfunction. Alterations in these cytokines have been seen in certain gastrointestinal diseases, such as gastroesophageal reflux disease, inflammatory bowel disease, liver disorders, and colorectal cancer. It is important for gastroenterologists to be aware of the relationship between sleep disorders and gastrointestinal illnesses to ensure good care for patients. This article reviews the current research on the interplay between sleep disorders, immune function, and gastrointestinal diseases.

  10. Radiological Atlas of Gastrointestinal Disease

    Nolan, D.J.

    1983-01-01

    This book is a reference to gastrointestinal disease and radiographic methods. It provides complete information for diagnosis and management and includes coverage of plain radiography, barium studies, water-soluble contrast studies, and more

  11. GASTROINTESTINAL INJURIES FROM BLUNT ABDOMINAL ...

    hi-tech

    2004-04-04

    Apr 4, 2004 ... Subjects: Twenty one children managed for gastrointestinal injuries from blunt trauma ... ileus, urinary tract infection and chest infection, respectively postoperatively. .... predictive value with CT scan, (9) the positive predictive.

  12. CT of acute gastrointestinal disease

    Wittenberg, J.

    1991-01-01

    The application of computerized tomography in gastrointestinal tract diseases are presented, including advantages in surgical belly that are: anatomic clarity, wide survey and rapid performance. (C.G.C.)

  13. Drug therapy for gastrointestinal and liver diseases

    Ballinger, Anne; Farthing, M. J. G. (Michael J. G.)

    2001-01-01

    ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 Gastrointestinal bleeding Matthew R Banks, Peter D Fairclough . . . . . . . . . . . . . . . . . . . . 63 Inflammatory bowel...

  14. Antioxidant supplements for preventing gastrointestinal cancers

    Bjelakovic, G; Nikolova, D; Simonetti, R G

    2004-01-01

    Oxidative stress may cause gastrointestinal cancers. The evidence on whether antioxidant supplements are effective in preventing gastrointestinal cancers is contradictory.......Oxidative stress may cause gastrointestinal cancers. The evidence on whether antioxidant supplements are effective in preventing gastrointestinal cancers is contradictory....

  15. Foreign bodies in gastrointestinal tract

    Ayşe Kefeli

    2014-03-01

    Full Text Available Objective: Ingested foreign bodies in gastrointestinal tract are a common event which can cause serious morbidity and mortality in the children and adult population. For this reason, early diagnosis and treatment are crucial for preventing these life threatening complications. In this study, we aimed to analyze the characteristics of the patients with upper gastrointestinal foreign bodies that were treated in our department. Methods: Patients diagnosed with upper gastrointestinal foreign bodies who were admitted to our hospital between February 2010 and August2013 were evaluated retrospectively. The data regarding their age, gender, clinical profile, type and localization of the esophageal foreign body, performed endoscopic procedure and initial symptoms of the patients were noted and analyzed statistically. Results: Thirty-eight patients with a diagnosis of gastrointestinal foreign body were included in this study. Of these patients, 21 were male and 17 were female. The youngest patient was 17 years old and the oldest patient was 79 years old. Most of the foreign bodies (%55.3 detected in the stomach. Food waste and metallic objects in 21 and 16 patients respectively. The most common complaint was dysphagia (%50. After endoscopic intervention three of the patients were directed to surgery. Conclusion: Early recognition and treatment of gastrointestinal foreign bodies is important as their complications are life threatening. The best method of removal of foreign bodies is controversial. Early management with upper gastrointestinal endoscopy is the most efficient and safe treatment method in current conditions.

  16. [Treatment of ASS-Associated Polyposis (ASSAP) with a cysteinyl leukotriene receptor antagonist - a prospective drug study on its antiinflammatory effects].

    Grundmann, T; Töpfner, M

    2001-10-01

    In a high rate of cases with recurrent polyposis an association with ASS-intolerance is detectable despite missing pulmonary symptoms. New examinations of a disturbed arachidonic acid metabolism lead to the development of new therapeutical options. Treatment with leukotriene-receptor antogonists (LTA) showed primarily good results in therapy of ASS-associated asthma. 18 patients with ASS-intolerance trias - diagnosed by oral provocation - were treated with the LTA Montelukast, after undergoing sinus surgery. Patients underwent a diagnostic pathway of provocation including four groups: recurrent chronic sinusitis, excessive polyposis, polyposis associated with asthma and anaphylactic symptoms after oral ASS-intake. Clinically we examined the following parameters periodically after sinus surgery: nasal and pulmonal symptoms by scoring levels, recurrency of polypoid hyperplasia by endoscopic follow-ups and serum ECP-levels. To evaluate antiinflammatory tissue effects of LTA EG1/EG2 labelled cells and cytokine levels of Interleukin 5 in mucosa samples of the lower turbinate were analysed under LTA-therapy. Under therapy with LTA we saw a beneficial effect on nasal and pulmonary symptoms and a significant reduction of recurrent polyposis in endoscopic examinations in relation to the untreated group. Results were proven by a permanent reduction of serum ECP-level. A reduction of the rate of EG2-positive cells according to decreased Interleukin 5 levels in the nasal mucosa unter LTA-treatment assumed antiinflammatory effects on ASS-associated polyposis. We could demonstrate antiinflammatory effects of Leukotriene-Receptor-Antagonists primarily during postoperative treatment of patients with ASS-associated nasal polyps.

  17. Hereditary angioedema type I: a case report

    Francisca Muñoz Peralta

    2016-03-01

    Full Text Available El angioedema hereditario es una enfermedad rara, de gran heterogeneidad en los síntomas, manifestándose con edema a nivel cutáneo, mucosa gastrointestinal y de laringe/faringe. Aunque existen tres variedades, el tipo I es el más frecuente y es provocado por una deficiencia en la síntesis del complemento C1 inhibidor. La gravedad de la clínica, junto a la baja prevalencia de la enfermedad y la necesidad de un tratamiento específico, hacen que el diagnóstico y tratamiento de dicha patología sea aún una asignatura pendiente para el médico de familia en atención primaria. Presentamos el caso de un adolescente varón con déficit de α-1 antitripsina desde los seis meses de edad, con aparición de angioedemas en piernas y brazos a los 11 años, diagnosticado de angioedema hereditario tipo I un año después. El diagnóstico definitivo de la enfermedad permitió instaurar un tratamiento adecuado a su patología, que consiste en la prevención de brotes que puedan comprometer la vida del paciente y, en el caso de que aparezcan, en la administración del complemento C1 inhibidor.

  18. A role for MLH3 in hereditary nonpolyposis colorectal cancer

    Wu, Y; Berends, MJW; Sijmons, RH; Mensink, RGJ; Verlind, E; Kooi, KA; van der Sluis, T; Kempinga, C; van der Zee, AGJ; Hollema, H; Buys, CHCM; Kleibeuker, JH; Hofstra, RMW

    2001-01-01

    We investigated a possible role of the mismatch-repair gene MLH3 in hereditary nonpolyposis colorectal cancer by scanning for mutations in 39 HNPCC families and in 288 patients suspected of having HNPCC. We identified ten different germline MLH3 variants, one frameshift and nine missense mutations,

  19. Hereditary hemochromatosis: genetic complexity and new diagnostic approaches.

    Swinkels, D.W.; Janssen, M.C.H.; Bergmans, J.; Marx, J.J.M.

    2006-01-01

    Since the discovery of the hemochromatosis gene (HFE) in 1996, several novel gene defects have been detected, explaining the mechanism and diversity of iron-overload diseases. At least 4 main types of hereditary hemochromatosis (HH) have been identified. Surprisingly, genes involved in HH encode for

  20. Alterations of red blood cell metabolome in overhydrated hereditary stomatocytosis.

    Darghouth, D.; Koehl, B.; Heilier, J.F.; Madalinski, G.; Bovee, P.H.; Bosman, G.J.C.G.M.; Delaunay, J.; Junot, C.; Romeo, P.H.

    2011-01-01

    Overhydrated hereditary stomatocytosis, clinically characterized by hemolytic anemia, is a rare disorder of the erythrocyte membrane permeability to monovalent cations, associated with mutations in the Rh-associated glycoprotein gene. We assessed the red blood cell metabolome of 4 patients with this

  1. Intragenic duplication: a novel mutational mechanism in hereditary pancreatitis

    Joergensen, Maiken T; Geisz, Andrea; Brusgaard, Klaus

    2011-01-01

    In a hereditary pancreatitis family from Denmark, we identified a novel intragenic duplication of 9 nucleotides in exon-2 of the human cationic trypsinogen (PRSS1) gene (c.63_71dup) which at the amino-acid level resulted in the insertion of 3 amino acids within the activation peptide of cationic...

  2. Hereditary Angioedema - Consequences of a New Treatment Paradigm in Denmark

    Bygum, Anette

    2014-01-01

    stopped long-term prophylaxis with danazol or tranexamic acid and changed treatment regimen to on-demand treatment with C1 inhibitor concentrate or icatibant. At least 10% of the attacks remained un-treated. More than half of the patients felt that hereditary angioedema had a significant psychological...

  3. On the many faces of Leber hereditary optic neuropathy

    Oostra, RJ; Tijmes, NT; Cobben, JM; Bolhuis, PA; vanNesselrooij, BPM; Houtman, WA; deKokNazaruk, MM; BleekerWagemakers, EM

    Leber hereditary optic neuropathy (LHON) is a maternally inherited disorder, associated with mutations in the mitochondrial DNA, which is notorious for its aspecific presentations. Two pedigrees are described with cases that are atypical for LHON with respect to sex, age of onset, interval between

  4. On the many faces of Leber hereditary optic neuropathy

    Oostra, R. J.; Tijmes, N. T.; Cobben, J. M.; Bolhuis, P. A.; van Nesselrooij, B. P.; Houtman, W. A.; de Kok-Nazaruk, M. M.; Bleeker-Wagemakers, E. M.

    1997-01-01

    Leber hereditary optic neuropathy (LHON) is a maternally inherited disorder, associated with mutations in the mitochondrial DNA, which is notorious for its aspecific presentations. Two pedigrees are described with cases that are atypical for LHON with respect to sex, age of onset, interval between

  5. RB1 mutations and second primary malignancies after hereditary retinoblastoma

    Dommering, Charlotte J.; Marees, Tamara; van der Hout, Annemarie H.; Imhof, Saskia M.; Meijers-Heijboer, Hanne; Ringens, Peter J.; van Leeuwen, Flora E.; Moll, Annette C.

    2012-01-01

    Survivors of hereditary retinoblastoma have a high risk of second primary malignancies, but it has not been investigated whether specific RB1 germline mutations are associated with greater risk of second primary malignancies in a large cohort. We conducted a retrospective cohort study of 199

  6. RB1 mutations and second primary malignancies after hereditary retinoblastoma

    Dommering, Charlotte J.; Marees, Tamara; van der Hout, Annemarie H.; Imhof, Saskia M.; Meijers-Heijboer, Hanne; Ringens, Peter J.; van Leeuwen, Flora E.; Moll, Annette C.

    Survivors of hereditary retinoblastoma have a high risk of second primary malignancies, but it has not been investigated whether specific RB1 germline mutations are associated with greater risk of second primary malignancies in a large cohort. We conducted a retrospective cohort study of 199

  7. Leber's hereditary optic neuropathy and vitamin B12 deficiency

    Pott, Jan Willem R.; Wong, Kwok H.

    2006-01-01

    Background: Leber's hereditary optic neuropathy (LHON) is a maternally inherited optic neuropathy caused by mutations in mitochondrial DNA (mtDNA). It is also believed that several epigenetic factors have an influence on the development of LHON. Methods: A case series was observed. Results: Three

  8. Visual Rehabilitation of Persons with Leber's Hereditary Optic Neuropathy.

    Rudanko, S.-L.

    1995-01-01

    This article presents results of a noncontrolled clinical study of 20 persons with Leber's hereditary optic neuropathy who were treated from 1976 to 1990 at the Low Vision Centre of the Finnish Federation of the Visually Handicapped. The importance of early functional visual rehabilitation is emphasized, as is the use of low vision aids to help…

  9. Motor activation in SPG4-linked hereditary spastic paraplegia

    Scheuer, KH; Nielsen, JE; Krabbe, Katja

    2006-01-01

    OBJECTIVE: The aim of this study was to investigate the extent of motor cortical functional reorganisation in patients with SPG4-linked hereditary spastic paraplegia by exploring cortical motor activation related to movements of clinically affected (lower) and unaffected (upper) limbs. METHODS: T...

  10. Hereditary breast cancer: from molecular pathology to tailored therapies.

    Tan, D S P; Marchiò, C; Reis-Filho, J S

    2008-10-01

    Hereditary breast cancer accounts for up to 5-10% of all breast carcinomas. Recent studies have demonstrated that mutations in two high-penetrance genes, namely BRCA1 and BRCA2, are responsible for about 16% of the familial risk of breast cancer. Even though subsequent studies have failed to find another high-penetrance breast cancer susceptibility gene, several genes that confer a moderate to low risk of breast cancer development have been identified; moreover, hereditary breast cancer can be part of multiple cancer syndromes. In this review we will focus on the hereditary breast carcinomas caused by mutations in BRCA1, BRCA2, Fanconi anaemia (FANC) genes, CHK2 and ATM tumour suppressor genes. We describe the hallmark histological features of these carcinomas compared with non-hereditary breast cancers and show how an accurate histopathological diagnosis may help improve the identification of patients to be screened for mutations. Finally, novel therapeutic approaches to treat patients with BRCA1 and BRCA2 germ line mutations, including cross-linking agents and PARP inhibitors, are discussed.

  11. Study of glycolytic intermediates in hereditary elliptocytosis with thalassemia

    Pavri Roshan

    1977-01-01

    Full Text Available Glycolytic intermediates like ATP, DPG and GSH have been studied in a family with. hereditary elliptocytosis and thalassemia. Results indicate a fall in ATP with a concomitant rise in DPG in the Patient. Findings are discussed in relation to other data.

  12. RECRUITMENT OF PATIENTS WITH HEREDITARY HAEMOCHROMATOSIS AS BLOOD DONORS

    Marko Cukjati

    2004-12-01

    Full Text Available Background. Hereditary haemochromatosis is the most common inherited disorder in white persons with prevalence of about 1 in 200. Therapeutic phlebotomy is an effective treatment for the disease and prevents its sequele. In addition to their altruism, patients with hereditary haemochromatosis have also medical and monetary incentives for blood donation. Current guidelines do not allow haemochromatosis patients to donate blood. About two thirds of patients are eligible as blood donors and about two thirds of therapeutically drawn blood is suitable for transfusion. Therapeutically drawn blood could increase the blood supply by 1.5 to 30%.Conclusions. The number of states that already accept patients with hereditary haemochromatosis as blood donors is increasing. To avoid monetary incentives they offer free phlebotomies for all patients with hereditary haemochromatosis. There have been no reports about higher incidence of transfusion reactions. In Slovenia the number of therapeutic phlebotomy is increasing. We should evaluate the possibilities for recruitment of haemochromatosis patients as blood donors also in our country. It is necessary to modify regulatory restrictions and to ensure that there is no other incentives than altruism for blood donation.

  13. An ABC of the Warning Signs of Hereditary Angioedema

    Grumach, Anete Sevciovic; Ferraroni, Natasha; Olivares, Maria Margarita

    2017-01-01

    Hereditary angioedema (HAE) with C1 inhibitor deficiency is a genetic disorder that clinically manifests with attacks of angioedema in the subcutaneous and submucosal tissues, mainly in the extremities, abdomen, and upper airway. During attacks, vascular permeability is increased due to increased...

  14. Genetics and ionizing radiations. 1. Genetics and hereditary diseases

    Dutrillaux, B.

    1980-01-01

    The desoxyribonucleic acid (DNA) is the chemical vehicle of heredity. Each hereditary character is determined by a short segment of the DNA molecule called gene. Gene operations are governed by regulating systems. The DNA is located in the chromosomes, easily analysed by light microscopy. The chromosome number and form are fairly characteristic of a species. Ours has 46 chromosomes, i.e. 23 pairs. Anomalies of the hereditary stock can be qualitative: affecting one gene they are expressed by diversely serious diseases. They can be quantitative and bear on the lack or excess of a chromosome or a segment of chromosome; most often, resulting diseases are very serious; Downs's syndrome is a well-known example. The various modes of transmission of these hereditary characters are analysed. The change of a chromosome or a gene from a normal to an abnormal form is called a mutation. It occurs scarcely, but the effects of mutations accumulate. At birth, nearly 10% of children should have one abnormal hereditary character at least, however most of these characters do not induce a true disease. Anomalies are more frequent at conception, many abnormal embryos or foetuses being aliminated by miscarriages [fr

  15. Hereditary Ovarian Cancer: Not Only BRCA 1 and 2 Genes

    Angela Toss

    2015-01-01

    Full Text Available More than one-fifth of ovarian tumors have hereditary susceptibility and, in about 65–85% of these cases, the genetic abnormality is a germline mutation in BRCA genes. Nevertheless, several other suppressor genes and oncogenes have been associated with hereditary ovarian cancers, including the mismatch repair (MMR genes in Lynch syndrome, the tumor suppressor gene, TP53, in the Li-Fraumeni syndrome, and several other genes involved in the double-strand breaks repair system, such as CHEK2, RAD51, BRIP1, and PALB2. The study of genetic discriminators and deregulated pathways involved in hereditary ovarian syndromes is relevant for the future development of molecular diagnostic strategies and targeted therapeutic approaches. The recent development and implementation of next-generation sequencing technologies have provided the opportunity to simultaneously analyze multiple cancer susceptibility genes, reduce the delay and costs, and optimize the molecular diagnosis of hereditary tumors. Particularly, the identification of mutations in ovarian cancer susceptibility genes in healthy women may result in a more personalized cancer risk management with tailored clinical and radiological surveillance, chemopreventive approaches, and/or prophylactic surgeries. On the other hand, for ovarian cancer patients, the identification of mutations may provide potential targets for biologic agents and guide treatment decision-making.

  16. The neuropathology of hereditary congenital facial palsy vs Mobius syndrome.

    Verzijl, H.T.F.M.; Zwaag, B. van der; Lammens, M.M.Y.; Donkelaar, H.J. ten; Padberg, G.W.A.M.

    2005-01-01

    OBJECTIVE: To characterize the neuropathology of hereditary congenital facial palsy. METHODS: The authors compared brainstem pathology of three members of one family with autosomal dominant congenital facial palsy to that in three age-matched controls. The neuropathologic findings of the familial

  17. Hereditary hemochromatosis and risk of ischemic heart disease

    Ellervik, Christina; Tybjaerg-Hansen, Anne; Grande, Peer

    2005-01-01

    BACKGROUND: We tested the hypothesis that the hereditary hemochromatosis genotypes C282Y/C282Y, C282Y/H63D, or C282Y/wild-type are risk factors for ischemic heart disease (IHD) and myocardial infarction (MI). METHODS AND RESULTS: We performed a prospective study of 9178 individuals from the Danish...

  18. Friedreich's ataxia mimicking hereditary motor and sensory neuropathy.

    Panas, Marios; Kalfakis, Nikolaos; Karadima, Georgia; Davaki, Panagiota; Vassilopoulos, Demetris

    2002-11-01

    Four patients from three unrelated families, with clinical and electrophysiological findings compatible with the diagnosis of hereditary motor and sensory neuropathy, are presented. The molecular analysis showed that the affected individuals were homozygous for the mutation in the X25 gene, characteristic of Friedreich's ataxia. These patients seem to represent a form of Friedreich's ataxia mimicking Charcot-Marie-Tooth disease.

  19. Organization and Running of the First Comprehensive Hereditary Cancer Clinic in India

    Rajkumar T

    2005-11-01

    Full Text Available Abstract Hereditary cancers are thought to account for around 5% of cancers, particularly breast/ovarian and colorectal cancers. In India there is a paucity of data on hereditary cancers and the mutations in some of the common genes linked to hereditary cancers, such as BRCA1, BRCA2, hMSH2 and hMLH1. The country's first comprehensive hereditary cancer clinic was established in February 2002. The article describes the organization and running of the Clinic. It also discusses some of the social issues relevant to the given population in running the Hereditary Cancer Clinic.

  20. Overview of hereditary angioedema caused by C1-inhibitor deficiency: assessment and clinical management.

    Bork, K; Davis-Lorton, M

    2013-02-01

    Hereditary angioedema due to C1-inhibitor deficiency (HAE-C1-INH) is a rare, autosomal-dominant disease. HAE-C1-INH is characterized by recurrent attacks of marked, diffuse, nonpitting and nonpruritic skin swellings, painful abdominal attacks, and laryngeal edema. The extremities and the gastrointestinal tract are most commonly affected. Swelling of the upper respiratory mucosa poses the greatest risk because death from asphyxiation can result from laryngealedema. HAE-C1-INH attacks are variable, unpredictable, and may be induced by a variety of stimuli, including stress or physical trauma. Because the clinical presentation of HAE-C1-INH is similar to other types of angioedema, the condition may be a challenge to diagnose. Accurate identification of HAE-C1-INH is critical in order to avoid asphyxiation by laryngeal edema and to improve the burden of disease. Based on an understanding of the underlying pathophysiology of IHAE-C1-INH, drugs targeted specifically to the disease, such as C1-inhibitor therapy, bradykinin B2-receptor antagonists, and kallikrein-inhibitors, have become available for both treatment and prevention of angioedema attacks. This article reviews the clinical features, differential diagnosis, and current approaches to management of HAE-C1-INH.

  1. Hereditary hemorrhagic telangiectasia with bilateral pulmonary vascular malformations: A case report

    Lončarević Olivera

    2016-01-01

    Full Text Available Introduction. Hereditary hemorrhagic telangiectasia (HHT also known as Osler-Weber-Rendu syndrome is an autosomal dominant disease that occurs due to vascular dysplasia associated with the disorder in the signaling pathway of transforming growth factor β (TGF-β. The clinical consequence is a disorder of blood vessels in multiple organ systems with the existence of telangiectasia which causes dilation of capillaries and veins, are present from birth and are localized on the skin and mucosa of the mouth, respiratory, gastrointestinal and urinary tract. They can make a rupture with consequent serious bleeding that can end up with fatal outcome. Since there is a disruption of blood vessels of more than one organic system, the diagnosis is very complex and requires a multidisciplinary approach. Case report. We reported a 40-year-old female patient with a long-time evolution of problems, who was diagnosed and treated at the Clinic for Lung Diseases of the Military Medical Academy in Belgrade, Serbia, because of bilaterally pulmonary arteriovenous malformations associated with HHT. Embolization was performed in two acts, followed with normalization of clinical, radiological and functional findings with the cessation of hemoptysis, effort intolerance with a significant improvement of the quality of life. Conclusion. HHT is a rare dominant inherited multisystem disease that requires multidisciplinary approach to diagnosis and treatment. Embolization is the method of choice in the treatment of arteriovenous malformations with minor adverse effects and very satisfying therapeutic effect.

  2. PI3 kinase inhibition improves vascular malformations in mouse models of hereditary haemorrhagic telangiectasia.

    Ola, Roxana; Dubrac, Alexandre; Han, Jinah; Zhang, Feng; Fang, Jennifer S; Larrivée, Bruno; Lee, Monica; Urarte, Ana A; Kraehling, Jan R; Genet, Gael; Hirschi, Karen K; Sessa, William C; Canals, Francesc V; Graupera, Mariona; Yan, Minhong; Young, Lawrence H; Oh, Paul S; Eichmann, Anne

    2016-11-29

    Activin receptor-like kinase 1 (ALK1) is an endothelial serine-threonine kinase receptor for bone morphogenetic proteins (BMPs) 9 and 10. Inactivating mutations in the ALK1 gene cause hereditary haemorrhagic telangiectasia type 2 (HHT2), a disabling disease characterized by excessive angiogenesis with arteriovenous malformations (AVMs). Here we show that inducible, endothelial-specific homozygous Alk1 inactivation and BMP9/10 ligand blockade both lead to AVM formation in postnatal retinal vessels and internal organs including the gastrointestinal (GI) tract in mice. VEGF and PI3K/AKT signalling are increased on Alk1 deletion and BMP9/10 ligand blockade. Genetic deletion of the signal-transducing Vegfr2 receptor prevents excessive angiogenesis but does not fully revert AVM formation. In contrast, pharmacological PI3K inhibition efficiently prevents AVM formation and reverts established AVMs. Thus, Alk1 deletion leads to increased endothelial PI3K pathway activation that may be a novel target for the treatment of vascular lesions in HHT2.

  3. Inherited focal, episodic neuropathies: hereditary neuropathy with liability to pressure palsies and hereditary neuralgic amyotrophy.

    Chance, Phillip F

    2006-01-01

    Hereditary neuropathy with liability to pressure palsies (HNPP; also called tomaculous neuropathy) is an autosomal-dominant disorder that produces a painless episodic, recurrent, focal demyelinating neuropathy. HNPP generally develops during adolescence, and may cause attacks of numbness, muscular weakness, and atrophy. Peroneal palsies, carpal tunnel syndrome, and other entrapment neuropathies may be frequent manifestations of HNPP. Motor and sensory nerve conduction velocities may be reduced in clinically affected patients, as well as in asymptomatic gene carriers. The histopathological changes observed in peripheral nerves of HNPP patients include segmental demyelination and tomaculous or "sausage-like" formations. Mild overlap of clinical features with Charcot-Marie-Tooth (CMT) disease type 1 (CMT1) may lead patients with HNPP to be misdiagnosed as having CMT1. HNPP and CMT1 are both demyelinating neuropathies, however, their clinical, pathological, and electrophysiological features are quite distinct. HNPP is most frequently associated with a 1.4-Mb pair deletion on chromosome 17p12. A duplication of the identical region leads to CMT1A. Both HNPP and CMT1A result from a dosage effect of the PMP22 gene, which is contained within the deleted/duplicated region. This is reflected in reduced mRNA and protein levels in sural nerve biopsy samples from HNPP patients. Treatment for HNPP consists of preventative and symptom-easing measures. Hereditary neuralgic amyotrophy (HNA; also called familial brachial plexus neuropathy) is an autosomal-dominant disorder causing episodes of paralysis and muscle weakness initiated by severe pain. Individuals with HNA may suffer repeated episodes of intense pain, paralysis, and sensory disturbances in an affected limb. The onset of HNA is at birth or later in childhood with prognosis for recovery usually favorable; however, persons with HNA may have permanent residual neurological dysfunction following attack(s). Episodes are often

  4. Classification and risk assessment of individuals with familial polyposis, Gardner's syndrome, and familial non-polyposis colon cancer from [3H]thymidine labeling patterns in colonic epithelial cells

    Lipkin, M.; Blattner, W.A.; Gardner, E.J.; Burt, R.W.; Lynch, H.; Deschner, E.; Winawer, S.; Fraumeni, J.F. Jr.

    1984-01-01

    A probabilistic analysis has been developed to assist the binary classification and risk assessment of members of familial colon cancer kindreds. The analysis is based on the microautoradiographic observation of [ 3 H]thymidine-labeled epithelial cells in colonic mucosa of the kindred members. From biopsies of colonic mucosa which are labeled with [ 3 H]thymidine in vitro, the degree of similarity of each subject's cell-labeling pattern measured over entire crypts was automatically compared to the labeling patterns of high-risk and low-risk reference populations. Each individual was then presumptively classified and assigned to one of the reference populations, and a degree of risk for the classification was provided. In carrying out the analysis, a linear score was calculated for each individual relative to each of the reference populations, and the classification was based on the polarity of the score difference; the degree of risk was then quantitated from the magnitude of the score difference. When the method was applied to kindreds having either familial polyposis or familial non-polyposis colon cancer, it effectively segregated individuals affected with disease from others at low risk, with sensitivity and specificity ranging from 71 to 92%. Further application of the method to asymptomatic family members believed to be at 50% risk on the basis of pedigree evaluation revealed a biomodal distribution to nearly zero or full risk. The accuracy and simplicity of this approach and its capability of revealing early stages of abnormal colonic epithelial cell development indicate potential for preclinical screening of subjects at risk in cancer-prone kindreds and for assisting the analysis of modes of inheritance

  5. Oestrogen receptor beta isoform expression in sporadic colorectal cancer, familial adenomatous polyposis and progressive stages of colorectal cancer

    Stevanato Filho, Paulo Roberto; Aguiar Júnior, Samuel; Begnami, Maria Dirlei

    2017-01-01

    BACKGROUND: Among the sex hormones, oestrogen may play a role in colorectal cancer, particularly in conjunction with oestrogen receptor-β (ERβ). The expression of ERβ isoform variants and their correlations with familial adenomatous polyposis (FAP) syndrome and sporadic colorectal carcinomas...... was identified in sporadic polyps and in sporadic colorectal cancer as well as in polyps from FAP syndrome patients compared with normal tissues (p expression in polyps (p ..., no differences were observed when sporadic colorectal carcinomas were compared to normal mucosa tissues. These findings suggest an association of the ERβ isoform variants in individuals affected by germline mutations of the APC gene. Progressively decreased expression of ERβ was found in polyps at early stages...

  6. Pesquisa de fungos em 20 pacientes com polipose nasossinusal Fungal research in 20 patientes with nasal polyposis

    Carla R. Monteiro

    2002-10-01

    Full Text Available Introdução: Polipose nasossinusal é uma doença freqüente na prática clínica otorrinolaringológica. Sua associação com fungos, porém, tem recebido mais atenção apenas nos últimos 20 anos, principalmente após o reconhecimento da sinusite fúngica alérgica. Objetivo: Identificar a presença de fungos nos seios paranasais de pacientes portadores de polipose nasossinusal e analisar a reatividade destes pacientes para aeroalérgenos. Forma de Estudo: Clínico prospectivo. Material e Método: Avaliamos de forma prospectiva 20 pacientes com diagnóstico de polipose nasossinusal, que se apresentaram ao ambulatório de Otorrinolaringologia do Hospital Universitário Clementino Fraga Filho. Durante o tratamento cirúrgico, a secreção removida dos seios paranasais foi colocada em Sabouraud com cloranfenicol e submetida à análise histopatológica. Foram dosados níveis séricos de IgE total, IgE específica para Aspergillus fumigatus e contagem de eosinófilos do sangue periférico. Testes cutâneos com antígenos de Dermatophagoides pteronyssinus, Dermatophagoides farinae, Blomia tropicalis, Blattella germânica, Blattella americana e Aspergillus fumigatus foram realizados .Resultados: Seis pacientes (30% apresentaram crescimento fúngico, sendo quatro Aspergillus sp, um Candida tropicalis e outro Cladophialophora carrionii. Treze (68,42% apresentaram teste de puntura positivo para os aeroalérgenos acima citados. Em dez pacientes (50% foi encontrada eosinofilia. Níveis séricos elevados de IgE total foram encontrados em oito (44,4%. Nível sérico elevado de IgE específica para Aspergillus fumigatus foi encontrado em apenas um. Conclusão: Salientamos a importância da pesquisa de fungos e de uma investigação do sistema imune nos pacientes com polipose nasossinusal para ser feito um diagnóstico preciso e tratamento adequado.Introduction: Nasal polyposis is a frequent disease in the otolaryngology clinical practice. The association

  7. Socioeconomic burden of hereditary angioedema: results from the hereditary angioedema burden of illness study in Europe.

    Aygören-Pürsün, Emel; Bygum, Anette; Beusterien, Kathleen; Hautamaki, Emily; Sisic, Zlatko; Wait, Suzanne; Boysen, Henrik B; Caballero, Teresa

    2014-07-04

    Hereditary angioedema (HAE) due to C1 inhibitor deficiency is a rare but serious and potentially life-threatening disease marked by spontaneous, recurrent attacks of swelling. The study objective was to characterize direct and indirect resource utilization associated with HAE from the patient perspective in Europe. The study was conducted in Spain, Germany, and Denmark to assess the real-world experience of HAE via a cross-sectional survey of HAE patients, including direct and indirect resource utilization during and between attacks for patients and their caregivers over the past 6 months. A regression model examined predictors of medical resource utilization. Overall, 164 patients had an attack in the past 6 months and were included in the analysis. The most significant predictor of medical resource utilization was the severity of the last attack (OR 2.6; p career/educational advancement. HAE poses a considerable burden on patients and their families in terms of direct medical costs and indirect costs related to lost productivity. This burden is substantial at the time of attacks and in between attacks.

  8. Prevalence of human papilloma virus and human herpes virus types 1-7 in human nasal polyposis.

    Zaravinos, Apostolos; Bizakis, John; Spandidos, Demetrios A

    2009-09-01

    This study aimed to investigate the prevalence of human papilloma virus (HPV), herpes simplex virus-1/-2 (HSV-1/-2), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpes virus-6/-7 (HHV-6/-7) in 23 human nasal polyps by applying PCR. Two types of control tissues were used: adjacent inferior/middle turbinates from the patients and inferior/middle turbinates from 13 patients undergoing nasal corrective surgery. EBV was the virus most frequently detected (35%), followed by HPV (13%), HSV-1 (9%), and CMV (4%). The CMV-positive polyp was simultaneously positive for HSV-1. HPV was also detected in the adjacent turbinates (4%) and the adjacent middle turbinate (4%) of one of the HPV-positive patients. EBV, HSV, and CMV were not detected in the adjacent turbinates of the EBV-, HSV- or CMV-positive patients. All mucosae were negative for the VZV, HHV-6, and HHV-7. This is the first study to deal with the involvement of a comparable group of viruses in human nasal polyposis. The findings support the theory that the presence of viral EBV markedly influences the pathogenesis of these benign nasal tumors. The low incidence of HPV detected confirms the hypothesis that HPV is correlated with infectious mucosal lesions to a lesser extent than it is with proliferative lesions, such as inverted papilloma. The low incidence of HSV-1 and CMV confirms that these two herpes viruses may play a minor role in the development of nasal polyposis. Double infection with HSV-1 and CMV may also play a minor, though causative, role in nasal polyp development. VZV and HHV-6/-7 do not appear to be involved in the pathogenesis of these mucosal lesions.

  9. The TLR3/TICAM-1 signal constitutively controls spontaneous polyposis through suppression of c-Myc in Apc Min/+ mice.

    Ono, Junya; Shime, Hiroaki; Takaki, Hiromi; Takashima, Ken; Funami, Kenji; Yoshida, Sumito; Takeda, Yohei; Matsumoto, Misako; Kasahara, Masanori; Seya, Tsukasa

    2017-10-17

    Intestinal tumorigenesis is promoted by myeloid differentiation primary response gene 88 (MyD88) activation in response to the components of microbiota in Apc Min/+ mice. Microbiota also contains double-stranded RNA (dsRNA), a ligand for TLR3, which activates the toll-like receptor adaptor molecule 1 (TICAM-1, also known as TRIF) pathway. We established Apc Min/+ Ticam1 -/- mice and their survival was compared to survival of Apc Min/+ Myd88 -/- and wild-type (WT) mice. The properties of polyps were investigated using immunofluorescence staining and RT-PCR analysis. We demonstrate that TICAM-1 is essential for suppression of polyp formation in Apc Min/+ mice. TICAM-1 knockout resulted in shorter survival of mice compared to WT mice or mice with knockout of MyD88 in the Apc Min/+ background. Polyps were more frequently formed in the distal intestine of Apc Min/+ Ticam1 -/- mice than in Apc Min/+ mice. Infiltration of immune cells such as CD11b + and CD8α + cells into the polyps was detected histologically. CD11b and CD8α mRNAs were increased in polyps of Apc Min/+ Ticam1 -/- mice compared to Apc Min/+ mice. Gene expression of inducible nitric oxide synthase (iNOS), interferon (IFN)-γ, CXCL9 and IL-12p40 was increased in polyps of Apc Min/+ Ticam1 -/- mice. mRNA and protein expression of c-Myc, a critical transcription factor for inflammation-associated polyposis, were increased in polyps of Apc Min/+ Ticam1 -/- mice. A Lactobacillus strain producing dsRNA was detected in feces of Apc Min/+ mice. These results imply that the TLR3/TICAM-1 pathway inhibits polyposis through suppression of c-Myc expression and supports long survival in Apc Min/+ mice.

  10. Hopefulness predicts resilience after hereditary colorectal cancer genetic testing: a prospective outcome trajectories study

    Chu Annie TW

    2010-06-01

    Full Text Available Abstract Background - Genetic testing for hereditary colorectal cancer (HCRC had significant psychological consequences for test recipients. This prospective longitudinal study investigated the factors that predict psychological resilience in adults undergoing genetic testing for HCRC. Methods - A longitudinal study was carried out from April 2003 to August 2006 on Hong Kong Chinese HCRC family members who were recruited and offered genetic testing by the Hereditary Gastrointestinal Cancer Registry to determine psychological outcomes after genetic testing. Self-completed questionnaires were administered immediately before (pre-disclosure baseline and 2 weeks, 4 months and 1 year after result disclosure. Using validated psychological inventories, the cognitive style of hope was measured at baseline, and the psychological distress of depression and anxiety was measured at all time points. Results - Of the 76 participating subjects, 71 individuals (43 men and 28 women; mean age 38.9 ± 9.2 years from nine FAP and 24 HNPCC families completed the study, including 39 mutated gene carriers. Four patterns of outcome trajectories were created using established norms for the specified outcome measures of depression and anxiety. These included chronic dysfunction (13% and 8.7%, recovery (0% and 4.3%, delayed dysfunction (13% and 15.9% and resilience (76.8% and 66.7%. Two logistic regression analyses were conducted using hope at baseline to predict resilience, with depression and anxiety employed as outcome indicators. Because of the small number of participants, the chronic dysfunction and delayed dysfunction groups were combined into a non-resilient group for comparison with the resilient group in all subsequent analysis. Because of low frequencies, participants exhibiting a recovery trajectory (n = 3 for anxiety and n = 0 for depression were excluded from further analysis. Both regression equations were significant. Baseline hope was a significant

  11. Hopefulness predicts resilience after hereditary colorectal cancer genetic testing: a prospective outcome trajectories study.

    Ho, Samuel M Y; Ho, Judy W C; Bonanno, George A; Chu, Annie T W; Chan, Emily M S

    2010-06-11

    Genetic testing for hereditary colorectal cancer (HCRC) had significant psychological consequences for test recipients. This prospective longitudinal study investigated the factors that predict psychological resilience in adults undergoing genetic testing for HCRC. A longitudinal study was carried out from April 2003 to August 2006 on Hong Kong Chinese HCRC family members who were recruited and offered genetic testing by the Hereditary Gastrointestinal Cancer Registry to determine psychological outcomes after genetic testing. Self-completed questionnaires were administered immediately before (pre-disclosure baseline) and 2 weeks, 4 months and 1 year after result disclosure. Using validated psychological inventories, the cognitive style of hope was measured at baseline, and the psychological distress of depression and anxiety was measured at all time points. Of the 76 participating subjects, 71 individuals (43 men and 28 women; mean age 38.9 +/- 9.2 years) from nine FAP and 24 HNPCC families completed the study, including 39 mutated gene carriers. Four patterns of outcome trajectories were created using established norms for the specified outcome measures of depression and anxiety. These included chronic dysfunction (13% and 8.7%), recovery (0% and 4.3%), delayed dysfunction (13% and 15.9%) and resilience (76.8% and 66.7%). Two logistic regression analyses were conducted using hope at baseline to predict resilience, with depression and anxiety employed as outcome indicators. Because of the small number of participants, the chronic dysfunction and delayed dysfunction groups were combined into a non-resilient group for comparison with the resilient group in all subsequent analysis. Because of low frequencies, participants exhibiting a recovery trajectory (n = 3 for anxiety and n = 0 for depression) were excluded from further analysis. Both regression equations were significant. Baseline hope was a significant predictor of a resilience outcome trajectory for depression

  12. Iron in hereditary retinal degeneration: PIXE microanalysis Preliminary results

    Sergeant, C.; Gouget, B.; Llabador, Y.; Simonoff, M.; Yefimova, M.; Courtois, Y.; Jeanny, J.C.

    1999-01-01

    Several types of hereditary retinal degeneration with progressive alteration of photoreceptors exist in men and animals. Recent immunohistochemical results have shown strong degradation of transferrin, the protein responsible for iron transport, in retinas of rats with hereditary retinal degeneration. Freeze-dried thin sections of rat retinas from different stages of the disease, and respective coeval control sections, have been analyzed using nuclear microprobe. In this first part of the study, the rat retinas at post-natal stages of 35 and 45 days have been analyzed. The sample preparation and the post-irradiation staining to determine precisely the retinal layers involved are described. Preliminary results of element distributions (K, Ca, Fe) in the rat retina layers are discussed. A very high content of calcium in the choriocapillaris of dystrophic rat retinas was observed. Preliminary results on iron distribution in the rat retina layers are presented

  13. Spinal Exostosis in a Boy with Multiple Hereditary Exostoses

    Ali Al Kaissi

    2013-01-01

    Full Text Available We report on a 13-year-old boy who presented with multiple hereditary exostosis and had development of back pain, associated with neurological deficits, and was found to have exostoses in the spinal canal. Spine radiograph showed a cauliflower-like abnormality of multiple exostoses of the posterior arch (pedicle of the thoracic vertebrae (T3–5. Reformatted CT scanning revealed the simultaneous development of intra- and extraspinal osteochondromatosis of T3–5. The spinal cord was compressed by the intraspinal exostosis. Our patient was surgically treated for intraspinal exostoses and showed cessation of neurological deficits. We report what might be a rare association of spinal cord compression in a patient with multiple hereditary exostoses.

  14. Could Ossification of the Achilles Tendon Have a Hereditary Component?

    Chawki Cortbaoui

    2013-01-01

    Full Text Available Ossification of the Achilles tendon (OTA is an unusual clinical condition. It is characterized by the presence of an ossified mass within the fibrocartilaginous substance of the Achilles tendon. The etiology of the ossification of the Achilles tendon is unknown. Review of the literature suggests that its etiology is multifactorial. The major contributing factors are trauma and surgery with other minor causes such as systemic diseases, metabolic conditions, and infections. To our knowledge, no previous reports suggest any genetic/hereditary predisposition in OAT. We report 3 siblings who have OAT with no history of any of the aforementioned predisposing factors. Could OAT have a hereditary component as one of its etiologies?

  15. Hereditary arrhythmias and cardiomyopathies: decision-making about genetic testing.

    Louis, Clauden; Calamaro, Emily; Vinocur, Jeffrey M

    2018-01-01

    The modern field of clinical genetics has advanced beyond the traditional teachings familiar to most practicing cardiologists. Increased understanding of the roles of genetic testing may improve uptake and appropriateness of use. Clinical genetics has become integral to the management of patients with hereditary arrhythmia and cardiomyopathy diagnoses. Depending on the condition, genetic testing may be useful for diagnosis, prognosis, treatment, family screening, and reproductive planning. However, genetic testing is a powerful tool with potential for underuse, overuse, and misuse. In the absence of a substantial body of literature on how these guidelines are applied in clinical practice, we use a case-based approach to highlight key lessons and pitfalls. Importantly, in many scenarios genetic testing has become the standard of care supported by numerous class I recommendations; genetic counselors can improve accessibility to and appropriate use and application of testing. Optimal management of hereditary arrhythmias and cardiomyopathies incorporates genetic testing, applied as per consensus guidelines, with involvement of a multidisciplinary team.

  16. Ethical, social and counselling issues in hereditary cancer susceptibility.

    Garber, J E; Patenaude, A F

    1995-01-01

    Genetic testing for hereditary susceptibility to disease is new. Much has been learned from experience with Huntington's disease and other non-malignant conditions. There are some differences in the case of predisposition testing for cancer: there is often the perception that cancer is preventable and sometimes curable, in contrast to other hereditary conditions. Testing raises many issues new to the medical community and to the public as well. There is great concern that the explosive technology be used responsibly, so that the potential benefits of genetic knowledge are not eclipsed by the risks to autonomy, privacy and justice. Practical concerns about insurability and discrimination may inhibit some at risk individuals from taking advantage of this powerful technology. There has been considerable effort already in the UK, Europe and the USA at the research and social levels to create protection for individuals found to carry genetic susceptibility to disease.

  17. Scintigraphic evaluation of gastrointestinal motility disorders

    Choe, Jae Gol [College of Medicine, Korea Univ., Seoul (Korea, Republic of)

    2001-02-01

    Current scintigraphic tests of gastrointestinal motor function provides relevant pathophysiologic information, but their clinical utility is controversial. Many scintigraphic methods are developed to investigate gastrointestinal motility from oral cavity to colon. These are esophageal transit scintigraphy, oropharyngeal transit study, gastric emptying test, small bowel transit time measurement, colon transit study and gastroesopahgeal reflux scintigraphy. Scintigraphy of gastrointestinal tract is the most physiologic and noninvasive method to evaluate gastrointestinal motility disorders. Stomach emptying test is regarded as a gold standard in motility study. Gastrointestinal transit scintigraphy also has a certain role in assessment of drug effect to GI motility and changes after theraphy of motility disorders. Scintigraphy provides noninvasive and quantitative assessment of physiological transit throughout the gastrointestinal tract, and it is extremely useful for diagnosing gastrointestinal motor dysfunction. This article reviews the current procedures, indications, significance and guidelines for gastrointestinal motility measurements by scintigraphy.

  18. Scintigraphic evaluation of gastrointestinal motility disorders

    Choe, Jae Gol

    2001-01-01

    Current scintigraphic tests of gastrointestinal motor function provides relevant pathophysiologic information, but their clinical utility is controversial. Many scintigraphic methods are developed to investigate gastrointestinal motility from oral cavity to colon. These are esophageal transit scintigraphy, oropharyngeal transit study, gastric emptying test, small bowel transit time measurement, colon transit study and gastroesopahgeal reflux scintigraphy. Scintigraphy of gastrointestinal tract is the most physiologic and noninvasive method to evaluate gastrointestinal motility disorders. Stomach emptying test is regarded as a gold standard in motility study. Gastrointestinal transit scintigraphy also has a certain role in assessment of drug effect to GI motility and changes after theraphy of motility disorders. Scintigraphy provides noninvasive and quantitative assessment of physiological transit throughout the gastrointestinal tract, and it is extremely useful for diagnosing gastrointestinal motor dysfunction. This article reviews the current procedures, indications, significance and guidelines for gastrointestinal motility measurements by scintigraphy

  19. Gastrointestinal Carcinoid Tumors—Health Professional Version

    Gastrointestinal carcinoid tumors are rare, slow-growing tumors that originate in the neuroendocrine cells in the GI tract. Find evidence-based information on gastrointestinal carcinoid tumors treatment and research.

  20. GASTROINTESTINAL FOOD ALLERGY IN CHILDREN

    Svetlana G. Makarova

    2017-01-01

    Full Text Available In recent years, there has been a significant increase in the prevalence  of food allergies. Pathological conditions associated  with a food intolerance are becoming an increasingly urgent problem of pediatrics. According to different researchers, allergic lesions of the gastrointestinal tract occurs in 25–50% of patients with such common pathology as an allergy to cow's milk proteins. The severity of diseases  associated  with food allergies and their prognosis  depend largely on early diagnosis and adequate treatment. Difficulties and errors  in the diagnosis  of gastrointestinal  food allergies  are associated  with both subjective  and objective  reasons,  primarily due to the fact that gastrointestinal  reactions to food are often delayed and non-IgE-mediated. The article describes clinical forms of gastrointestinal food allergy according to the existing classification. Diagnostic algorithms and modern approaches  to differential diagnosis of disease based on evidence-based  medicine and corresponding to international consensus papers are given.

  1. GASTROINTESTINAL TRACT OF CLARIAS GARIEPINUS ...

    DR. AMINU

    one hundred and ninety nine (199) were infested fish samples from gills and gastrointestinal tract .... Body cavity of fish were dissected using a pair of scissors and different portion of the gut (Oesophagus, stomach, intestine and rectum) were isolated and kept in .... Arme, C. and Wakey, M. (1970): The physiology of fishes.

  2. Nutritional management of gastrointestinal malignancies ...

    The evidence connecting food and gastrointestinal cancers from epidemiological studies, case-control studies, and prospective observational studies, indicates that determining the independent effects of specific nutrients is extremely diffi cult, given the many potential environmental factors to consider. The nutritional ...

  3. Approach to upper gastrointestinal bleeding

    Upper gastrointestinal haemorrhage has a variety of causes (Table 1) and is the commonest complication of peptic ulceration and portal hypertension. Peptic ulceration in the duo- denum or stomach and oesophageal varices are the conditions most often responsible for patients who have the potential to present.

  4. Immunity to gastrointestinal nematode infections

    Sorobetea, D.; Svensson Frej, M.; Grencis, R.

    2018-01-01

    Numerous species of nematodes have evolved to inhabit the gastrointestinal tract of animals and humans, with over a billion of the world's population infected with at least one species. These large multicellular pathogens present a considerable and complex challenge to the host immune system give...

  5. Hereditary hypohidrotic ectodermal dysplasia: report of a rare case.

    Paramkusam, Geetha; Meduri, Venkateswarlu; Nadendla, Lakshmi Kavitha; Shetty, Namratha

    2013-09-01

    Hereditary Hypohidrotic Ectodermal Dysplasia (HHED), an X-linked, recessive, Mendelian character, is seen usually in males and it is inherited through female carriers. It is characterised by congenital dysplasia of one or more ectodermal structures and it is manifested by hypohidrosis, hypotrichosis and hypodontia. It results from abnormal morphogenesis of cutaneous and oral embryonic ectoderm. Here, we are presenting a rare case of HHED in a 19 year female with classic features of this condition.

  6. HEREDITARY INTRAVENTRICULAR CONDUCTION DISORDERS IN THE FAMILY FROM KRASNOYARSK

    A. A. Chernova

    2011-01-01

    Full Text Available Pedigree of the family from Krasnoyarsk city with hereditary disorders of intracardiac conduction was studied. The diagnosis of each family member was verified by electrocardiography (ECG, echocardiography , bicycle ergometry , ECG Holter monitoring. The family 10-year follow-up showed familial aggregation of intracardiac conduction disorders in grandson, niece, son of the proband niece, ie, in the III-degree relatives. Family history of III-degree relatives with intracardiac conduction disorders and discordant pathology is identified.

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

    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.

  8. Hereditary spastic paraplegias: membrane traffic and the motor pathway

    Blackstone, Craig; O’Kane, Cahir J.; Reid, Evan

    2011-01-01

    Voluntary movement is a fundamental way in which animals respond to, and interact with, their environment. In mammals, the main CNS pathway controlling voluntary movement is the corticospinal tract, which encompasses connections between the cerebral motor cortex and the spinal cord. Hereditary spastic paraplegias (HSPs) are a group of genetic disorders that lead to a length-dependent, distal axonopathy of fibres of the corticospinal tract, causing lower limb spasticity and weakness. Recent wo...

  9. Increased Mortality and Comorbidity Associated With Leber's Hereditary Optic Neuropathy

    Vestergaard, Nanna; Rosenberg, Thomas; Torp-Pedersen, Christian

    2017-01-01

    Purpose: Leber's hereditary optic neuropathy (LHON) is a mitochondrial genetic disease in which optic neuropathy is considered a key feature. Several other manifestations of LHON have been reported; however, only little is known of their incidence and the life expectancy in LHON patients. Methods...... patients (RR: 4.26, 95% CI: 1.91-9.48; P neuropathy, and alcohol-related disorders. Conclusions: The manifestation of LHON was associated...

  10. The molecular basis of hereditary enamel defects in humans.

    Wright, J T; Carrion, I A; Morris, C

    2015-01-01

    The formation of human enamel is highly regulated at the molecular level and involves thousands of genes. Requisites for development of this highly mineralized tissue include cell differentiation; production of a unique extracellular matrix; processing of the extracellular matrix; altering of cell function during different stages of enamel formation; cell movement and attachment; regulation of ion and protein movement; and regulation of hydration, pH, and other conditions of the microenvironment, to name just a few. Not surprising, there is a plethora of hereditary conditions with an enamel phenotype. The objective of this review was to identify the hereditary conditions listed on Online Mendelian Inheritance in Man (OMIM) that have an associated enamel phenotype and whether a causative gene has been identified. The OMIM database was searched with the terms amelogenesis, enamel, dental, and tooth, and all results were screened by 2 individuals to determine if an enamel phenotype was identified. Gene and gene product function was reviewed on OMIM and from publications identified in PubMed. The search strategy revealed 91 conditions listed in OMIM as having an enamel phenotype, and of those, 71 have a known molecular etiology or linked genetic loci. The purported protein function of those conditions with a known genetic basis included enzymes, regulatory proteins, extracellular matrix proteins, transcription factors, and transmembrane proteins. The most common enamel phenotype was a deficient amount of enamel, or enamel hypoplasia, with hypomineralization defects being reported less frequently. Knowing these molecular defects allows an initial cataloging of molecular pathways that lead to hereditary enamel defects in humans. This knowledge provides insight into the diverse molecular pathways involved in enamel formation and can be useful when searching for the genetic etiology of hereditary conditions that involve enamel. © International & American Associations for

  11. Hereditary Angioedema: The Economics of Treatment of an Orphan Disease.

    Lumry, William Raymond

    2018-01-01

    This review will discuss the cost burden of hereditary angioedema on patients, healthcare systems, and society. The impact of availability of and access to novel and specific therapies on morbidity, mortality, and the overall burden of disease will be explored along with potential changes in treatment paradigms to improve effectiveness and reduce cost of treatment. The prevalence of orphan diseases, legislative incentives to encourage development of orphan disease therapies and the impact of orphan disease treatment on healthcare payment systems will be discussed.

  12. [Hereditary haemorrhagic telangiectasia diagnosed in connection with a traffic accident].

    Sivapalan, Pradeesh; Demény, Ann Kathrin; Almind, Merete; Kjeldsen, Anette Drøhse

    2014-02-17

    Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by vascular dysplasia and haemorrhage. It is manifested by mucocutaneous telangiec-tases and arteriovenous malformations in organs such as lungs, liver and brain. We present a case of HHT. A 16-year-old patient with a history of recurrent epistaxis was admitted to the local hospital with chest pain and desaturation. A CT scan revealed pulmonary arteriovenous malformations.

  13. The Molecular Basis of Hereditary Enamel Defects in Humans

    Carrion, I.A.; Morris, C.

    2015-01-01

    The formation of human enamel is highly regulated at the molecular level and involves thousands of genes. Requisites for development of this highly mineralized tissue include cell differentiation; production of a unique extracellular matrix; processing of the extracellular matrix; altering of cell function during different stages of enamel formation; cell movement and attachment; regulation of ion and protein movement; and regulation of hydration, pH, and other conditions of the microenvironment, to name just a few. Not surprising, there is a plethora of hereditary conditions with an enamel phenotype. The objective of this review was to identify the hereditary conditions listed on Online Mendelian Inheritance in Man (OMIM) that have an associated enamel phenotype and whether a causative gene has been identified. The OMIM database was searched with the terms amelogenesis, enamel, dental, and tooth, and all results were screened by 2 individuals to determine if an enamel phenotype was identified. Gene and gene product function was reviewed on OMIM and from publications identified in PubMed. The search strategy revealed 91 conditions listed in OMIM as having an enamel phenotype, and of those, 71 have a known molecular etiology or linked genetic loci. The purported protein function of those conditions with a known genetic basis included enzymes, regulatory proteins, extracellular matrix proteins, transcription factors, and transmembrane proteins. The most common enamel phenotype was a deficient amount of enamel, or enamel hypoplasia, with hypomineralization defects being reported less frequently. Knowing these molecular defects allows an initial cataloging of molecular pathways that lead to hereditary enamel defects in humans. This knowledge provides insight into the diverse molecular pathways involved in enamel formation and can be useful when searching for the genetic etiology of hereditary conditions that involve enamel. PMID:25389004

  14. Gastrointestinal Stromal Tumors: A Case Report

    Sashidharan, Palankezhe; Matele, Apoorva; Matele, Usha; Al Felahi, Nowfel; Kassem, Khalid F.

    2014-01-01

    Advances in the identification of gastrointestinal stromal tumors, its molecular and immunohiostochemical basis, and its management have been a watershed in the treatment of gastrointestinal tumors. This paradigm shift occurred over the last two decades and gastrointestinal stromal tumors have now come to be understood as rare gastrointestinal tract tumors with predictable behavior and outcome, replacing the older terminologies like leiomyoma, schwannoma or leiomyosarcoma. This report present...

  15. Hereditary myopathies with early respiratory insufficiency in adults.

    Naddaf, Elie; Milone, Margherita

    2017-11-01

    Hereditary myopathies with early respiratory insufficiency as a predominant feature of the clinical phenotype are uncommon and underestimated in adults. We reviewed the clinical and laboratory data of patients with hereditary myopathies who demonstrated early respiratory insufficiency before the need for ambulatory assistance. Only patients with disease-causing mutations or a specific histopathological diagnosis were included. Patients with cardiomyopathy were excluded. We identified 22 patients; half had isolated respiratory symptoms at onset. The diagnosis of the myopathy was often delayed, resulting in delayed ventilatory support. The most common myopathies were adult-onset Pompe disease, myofibrillar myopathy, multi-minicore disease, and myotonic dystrophy type 1. Single cases of laminopathy, MELAS (mitochondrial encephalomyopathy with lactic acidosis and strokelike events), centronuclear myopathy, and cytoplasmic body myopathy were identified. We highlighted the most common hereditary myopathies associated with early respiratory insufficiency as the predominant clinical feature, and underscored the importance of a timely diagnosis for patient care. Muscle Nerve 56: 881-886, 2017. © 2017 Wiley Periodicals, Inc.

  16. Tumor del estroma gastrointestinal Tumor of the gastrointestinal stroma

    Jorge Felipe Montero León

    2012-03-01

    Full Text Available Los tumores del estroma gastrointestinal, conocidos según sus siglas en inglés como GIST (gastrointestinal stromal tumors, son tumores mesenquimales que aparecen en cualquier lugar a lo largo del tracto intestinal. Este trabajo tiene el propósito de presentar una paciente de 60 años de edad que asiste a la consulta de ginecología del Instituto Nacional de Oncología y Radiobiología, por presentar dolor en el epigastrio, que se irradia al flanco derecho, con un aumento de volumen en la fosa iliaca derecha, y por ultrasonografía se plantea un tumor de ovario derecho, que se proyecta hacia el epigastrio y a hipocondrio derecho. Se describe la intervención quirúrgica y los hallazgos encontrados en estudios macro y microscópicos, así como en estudios posteriores por inmunohistoquímica de la lesión. Se concluye con un diagnóstico de tumor del estroma gastrointestinal y los resultados de las intervenciones quirúrgicas y medicamentosas realizadas. Se recomienda valorar la importancia de una estrecha relación entre cirujanos generales y ginecólogos frente a enfermedades inesperadas, por su difícil diagnóstico preoperatorio, que conllevan a un tratamiento quirúrgico adecuado, y que por la complejidad que requieren, necesitan de la competencia de ambas especialidades quirúrgicas.The tumors of the gastrointestinal stroma, known in English language as GIST (gastrointestinal stromal tumors are mesenchymal tumors appearing in any place throughout the intestinal tract. The objective of present paper is to present the case of a female patient aged 60 came to Genecology consultation of the National Institute of Oncology and Radiobiology due pain in epigastrium irradiating to right flank with increase of volume in the right iliac fossa and by ultrasonography it is a tumor of right ovarium projecting to epigastrium and the right hypochondrium. The surgical intervention is described as well as the findings noted in macro- and microscopic studies

  17. Exercise and the gastro-intestinal tract

    on perfonnance and me value of cardiovascular training in improving performance in aerobic sports is well recognised. The role of me gastro-intestinal tracr, bom as a limiting and sustaining facror in aerobic exercises, is less well appreciared. Gastro-intestinal symptoms. The spectrum of gastro-intestinal effecrs of exercise ...

  18. Pharmacological Therapy of Vascular Malformations of the Gastrointestinal Tract

    Andrew Szilagyi

    2006-01-01

    Full Text Available Vascular malformation (AVM in the gastrointestinal tract is an uncommon, but not rare, cause of bleeding and iron deficiency anemia, especially in an aging population. While endoscopic coagulative therapy is the method of choice for controlling bleeding, a substantial number of cases require additional therapy. Adjunctive or even primary phamacotherapy may be indicated in recurrent bleeding. However, there is little evidence-based proof of efficacy for any agent. The bulk of support is derived from anecdotal reports or case series. The present review compares the outcome of AVM after no intervention, coagulative therapy or focus on pharmacological agents. Most of the literature encompasses two common AVMs, angiodysplasia and hereditary hemorrhagic telangiectasia. Similarly, the bulk of information evaluates two therapies, hormones (estrogen and progesterone and the somatostatin analogue octreotide. Of these, the former is the only therapy evaluated in randomized trials, and the results are conflicting without clear guidelines. The latter therapy has been reported only as case reports and case series without prospective trials. In addition, other anecdotally used medications are discussed.

  19. Juvenil polypose-syndrom og hereditær hæmoragisk telangiektasi hos en patient med SMAD4-mutation

    Jelsig, Anne Marie; Tørring, Pernille Mathiesen; Wikman, Friedrik

    2014-01-01

    Germ line mutations in SMAD4 can cause both juvenile polyposis syndrome and hereditary haemorrhagic telangiectasia syndrome. In this case we present a 37-year-old man with a frameshift mutation in SMAD4. The patient had multiple polyps in the gastrointestinal tract and was diagnosed with colon ca...... cancer at the age of 21 and gastro-oesophageal junction cancer at the age of 37. Furthermore the patient had telangiectasias and recurrent epistaxis....

  20. Gastrointestinal Stromal Tumors: A Case Report

    Palankezhe Sashidharan

    2014-03-01

    Full Text Available Advances in the identification of gastrointestinal stromal tumors, its molecular and immunohiostochemical basis, and its management have been a watershed in the treatment of gastrointestinal tumors. This paradigm shift occurred over the last two decades and gastrointestinal stromal tumors have now come to be understood as rare gastrointestinal tract tumors with predictable behavior and outcome, replacing the older terminologies like leiomyoma, schwannoma or leiomyosarcoma. This report presents a case of gastric gastrointestinal stromal tumor operated recently in a 47-year-old female patient and the outcome, as well as literature review of the pathological identification, sites of origin, and factors predicting its behavior, prognosis and treatment.

  1. Radiopharmaceuticals and the gastrointestinal tract

    Frier, M. [Radiopharmacy Unit, Dept. of Medical Physics, Queens Medical Centre, Univ. Hospital Nottingham (United Kingdom); Perkins, A.C. [Radiopharmacy Unit, Dept. of Medical Physics, Queens Medical Centre, Univ. Hospital Nottingham (United Kingdom)

    1994-11-01

    A review is presented of the design of radiolabelled test meals for the evaluation of gastrointestinal function, including oesophageal transit, gastro-oesophageal reflux, gastric emptying, enterogastric reflux and transit through the whole bowel. Descriptions of different systems are presented, together with validations of the procedures used. Published methods for assessment of oesophageal transit show a marked degree of consistency, whereas gastric emptying studies employ a wide range of both liquid and solid test meals. Recommendations are made concerning the optimal system for investigation of each part of the gastrointestinal tract, but whichever system is adopted, it is important to employ some validation procedures, and to establish normal ranges in the population under study. (orig.)

  2. Gastrointestinal hormones and their targets

    Rehfeld, Jens F.

    2014-01-01

    Gastrointestinal hormones are peptides released from endocrine cells and neurons in the digestive tract. More than 30 hormone genes are currently known to be expressed in the gastrointestinal tract, which makes the gut the largest hormone producing organ in the body. Modern biology makes...... it feasible to conceive the hormones under five headings: The structural homology groups a majority of the hormones into nine families, each of which is assumed to originate from one ancestral gene. The individual hormone gene often has multiple phenotypes due to alternative splicing, tandem organization......, or differentiated maturation of the prohormone. By a combination of these mechanisms, more than 100 different hormonally active peptides are released from the gut. Gut hormone genes are also widely expressed in cells outside the gut, some only in extraintestinal endocrine cells and neurons but others also in other...

  3. Precision Medicine in Gastrointestinal Pathology.

    Wang, David H; Park, Jason Y

    2016-05-01

    -Precision medicine is the promise of individualized therapy and management of patients based on their personal biology. There are now multiple global initiatives to perform whole-genome sequencing on millions of individuals. In the United States, an early program was the Million Veteran Program, and a more recent proposal in 2015 by the president of the United States is the Precision Medicine Initiative. To implement precision medicine in routine oncology care, genetic variants present in tumors need to be matched with effective clinical therapeutics. When we focus on the current state of precision medicine for gastrointestinal malignancies, it becomes apparent that there is a mixed history of success and failure. -To present the current state of precision medicine using gastrointestinal oncology as a model. We will present currently available targeted therapeutics, promising new findings in clinical genomic oncology, remaining quality issues in genomic testing, and emerging oncology clinical trial designs. -Review of the literature including clinical genomic studies on gastrointestinal malignancies, clinical oncology trials on therapeutics targeted to molecular alterations, and emerging clinical oncology study designs. -Translating our ability to sequence thousands of genes into meaningful improvements in patient survival will be the challenge for the next decade.

  4. Cost sharing and hereditary cancer risk: predictors of willingness-to-pay for genetic testing.

    Matro, Jennifer M; Ruth, Karen J; Wong, Yu-Ning; McCully, Katen C; Rybak, Christina M; Meropol, Neal J; Hall, Michael J

    2014-12-01

    Increasing use of predictive genetic testing to gauge hereditary cancer risk has been paralleled by rising cost-sharing practices. Little is known about how demographic and psychosocial factors may influence individuals' willingness-to-pay for genetic testing. The Gastrointestinal Tumor Risk Assessment Program Registry includes individuals presenting for genetic risk assessment based on personal/family cancer history. Participants complete a baseline survey assessing cancer history and psychosocial items. Willingness-to-pay items include intention for: genetic testing only if paid by insurance; testing with self-pay; and amount willing-to-pay ($25-$2,000). Multivariable models examined predictors of willingness-to-pay out-of-pocket (versus only if paid by insurance) and willingness-to-pay a smaller versus larger sum (≤$200 vs. ≥$500). All statistical tests are two-sided (α = 0.05). Of 385 evaluable participants, a minority (42%) had a personal cancer history, while 56% had ≥1 first-degree relative with colorectal cancer. Overall, 21.3% were willing to have testing only if paid by insurance, and 78.7% were willing-to-pay. Predictors of willingness-to-pay were: 1) concern for positive result; 2) confidence to control cancer risk; 3) fewer perceived barriers to colorectal cancer screening; 4) benefit of testing to guide screening (all p testing (all p testing, and anticipate benefits to reducing cancer risk. Identifying factors associated with willingness-to-pay for genetic services is increasingly important as testing is integrated into routine cancer care.

  5. [The progress and prospect of application of genetic testing technology-based gene detection technology in the diagnosis and treatment of hereditary cancer].

    He, J X; Jiang, Y F

    2017-08-06

    Hereditary cancer is caused by specific pathogenic gene mutations. Early detection and early intervention are the most effective ways to prevent and control hereditary cancer. High-throughput sequencing based genetic testing technology (NGS) breaks through the restrictions of pedigree analysis, provide a convenient and efficient method to detect and diagnose hereditary cancer. Here, we introduce the mechanism of hereditary cancer, summarize, discuss and prospect the application of NGS and other genetic tests in the diagnosis of hereditary retinoblastoma, hereditary breast and ovarian cancer syndrome, hereditary colorectal cancer and other complex and rare hereditary tumors.

  6. Oestrogen receptor beta isoform expression in sporadic colorectal cancer, familial adenomatous polyposis and progressive stages of colorectal cancer.

    Stevanato Filho, Paulo Roberto; Aguiar Júnior, Samuel; Begnami, Maria Dirlei; Kuasne, Hellen; Spencer, Ranyell Matheus; Nakagawa, Wilson Toshihiko; Bezerra, Tiago Santoro; Kupper, Bruna Catin; Takahashi, Renata Maymi; Barros Filho, Mateus; Rogatto, Silvia Regina; Lopes, Ademar

    2017-11-13

    Among the sex hormones, oestrogen may play a role in colorectal cancer, particularly in conjunction with oestrogen receptor-β (ERβ). The expression of ERβ isoform variants and their correlations with familial adenomatous polyposis (FAP) syndrome and sporadic colorectal carcinomas are poorly described. This study aimed to investigate the expression levels of the ERβ1, ERβ2, ERβ4 and ERβ5 isoform variants using quantitative RT-PCR (921 analyses) in FAP, normal mucosa, adenomatous polyps and sporadic colorectal carcinomas. Decreased expression of ERβ isoforms was identified in sporadic polyps and in sporadic colorectal cancer as well as in polyps from FAP syndrome patients compared with normal tissues (p colorectal carcinomas were compared to normal mucosa tissues. These findings suggest an association of the ERβ isoform variants in individuals affected by germline mutations of the APC gene. Progressively decreased expression of ERβ was found in polyps at early stages of low-grade dysplasia, followed by T1-T2 and T3-T4 tumours (p colorectal cancer, the loss of expression was an independent predictor of recurrence, and ERβ1 and ERβ5 expression levels were associated with better disease-free survival (p = 0.002). These findings may provide a better understanding of oestrogens and their potential preventive and therapeutic effects on sporadic colorectal cancer and cancers associated with FAP syndrome.

  7. Adenomatous polyposis coli (APC) regulates miR17-92 cluster through β-catenin pathway in colorectal cancer.

    Li, Yajuan; Lauriola, Mattia; Kim, Donghwa; Francesconi, Mirko; D'Uva, Gabriele; Shibata, Dave; Malafa, Mokenge P; Yeatman, Timothy J; Coppola, Domenico; Solmi, Rossella; Cheng, Jin Q

    2016-09-01

    Adenomatous polyposis coli (APC) mutation is the most common genetic change in sporadic colorectal cancer (CRC). Although deregulations of miRNAs have been frequently reported in this malignancy, APC-regulated miRNAs have not been extensively documented. Here, by using an APC-inducible cell line and array analysis, we identified a total of 26 deregulated miRNAs. Among them, members of miR-17-92 cluster were dramatically inhibited by APC and induced by enforced expression of β-catenin. Furthermore, we demonstrate that activated β-catenin resulted from APC loss binds to and activates the miR-17-92 promoter. Notably, enforced expression of miR-19a overrides APC tumor suppressor activity, and knockdown of miR-19a in cancer cells with compromised APC function reduced their aggressive features in vitro. Finally, we observed that expression of miR-19a significantly correlates with β-catenin levels in colorectal cancer specimens, and it is associated to the aggressive stage of tumor progression. Thus, our study reveals that miR-17-92 cluster is directly regulated by APC/β-catenin pathway and could be a potential therapeutic target in colon cancers with aberrant APC/β-catenin signaling.

  8. [miR-182 promotes cell proliferation of cervical cancer cells by targeting adenomatous polyposis coli (APC) gene].

    Li, Pei; Hu, Jing; Zhang, Ying; Li, Jianping; Dang, Yunzhi; Zhang, Rui; Wei, Lichun; Shi, Mei

    2018-02-01

    Objective To investigate the role and mechanism of microRNA-182 (miR-182) in the proliferation of cervical cancer cells. Methods With liposome-mediated transient transfection method, the level of miR-182 in HeLa and SiHa cells was increased or decreased. CCK-8 assay and colony formation assay were used to observe the effect of miR-182 on the proliferation of cervical cancer cells. Using bioinformatics predictions, real-time quantitative PCR, and dual luciferase reporter assay, we clarified the role of miR-182 in posttranscriptional regulation of adenomatous polyposis coli (APC) gene and its effect on the downstream molecules (c-Myc and cyclin D1) of Wnt singling pathway. Results Up-regulation of miR-182 significantly promoted the proliferation of cervical cancer cells, while down-regulation of miR-182 significantly inhibited the proliferation of cervical cancer cells. Over-expression of miR-182 inhibited the expression of APC gene in cervical cancer cells and the regulation of miR-182 affected the expression of canonical Wnt signaling pathway downstream molecules in cervical cancer cells. Conclusion The miR-182 stimulates canonical Wnt signaling pathway by targeting APC gene and enhances the proliferation of cervical cancer cells.

  9. Hereditary sensory and autonomic neuropathy type IV and orthopaedic complications.

    Kim, W; Guinot, A; Marleix, S; Chapuis, M; Fraisse, B; Violas, P

    2013-11-01

    Hereditary sensory and autonomic neuropathy type IV (HSAN-IV) is a very rare autosomal recessive disorder characterized by recurrent episodes of unexplained fever, extensive anhidrosis, total insensitivity to pain, hypotonia, and mental retardation. The most frequent complications of this disease are corneal scarring, multiple fractures, joint deformities, osteomyelitis, and disabling self-mutilations. We reported the case of a 12-year-old boy. The goal was to discuss our decision-making and compare this case with cases described in the literature. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  10. [Hereditary motor and sensory neuropathy type 4A].

    Shagina, O A; Dadali, E L; Fedotov, V P; Tiburkova, T B; Poliakov, A V

    2010-01-01

    The first in the Russian Federation clinical cases of patients with autosomal-recessive type of hereditary motor and sensory neuropathy, type 4A, (HMSN 4A) are presented. In all cases, the diagnosis has been verified using molecular-genetic methods (DNA diagnostics). An analysis of features of clinical manifestations was performed in patients, aged from 5 to 34 years, with different disease duration (from 3-to 29 years). Criteria of selection of patients for DNA diagnostics for searching mutations in the GDAP1 gene are specified.

  11. Neuroendocrine Differentiation in Sporadic CRC and Hereditary Nonpolyosis Colorectal Cancer

    M. H. Sun

    2004-01-01

    Full Text Available Extent neuroendocrine differentiation can be encountered in many human neoplasm derived from different organs and systems using immunohistochemistry and ultrastructural techniques. The tumor cells' behaviors resemble those of neurons and neuroendocrine cells. The presence of neuroendocrine differentiation reputedly appears to be associated with a poorer prognosis than the adenocarcinoma counterparts in sporadic human neoplasm. In this review the neuroendocrine carcinoma and the adenocarcinoma with neuroendocrine differentiation of colon and rectum both in sporadic colorectal carcinoma and the hereditary nonpolyposis colorectal cancer, the relationship of neuroendocrine differentiation and some possible molecular pathways in tumorogenesis of colorectal cancer will be discussed. Possible treatment strategy will also be addressed.

  12. Current concepts in the treatment of hereditary ataxias

    Pedro Braga Neto

    2016-03-01

    Full Text Available ABSTRACT Hereditary ataxias (HA represents an extensive group of clinically and genetically heterogeneous neurodegenerative diseases, characterized by progressive ataxia combined with extra-cerebellar and multi-systemic involvements, including peripheral neuropathy, pyramidal signs, movement disorders, seizures, and cognitive dysfunction. There is no effective treatment for HA, and management remains supportive and symptomatic. In this review, we will focus on the symptomatic treatment of the main autosomal recessive ataxias, autosomal dominant ataxias, X-linked cerebellar ataxias and mitochondrial ataxias. We describe management for different clinical symptoms, mechanism-based approaches, rehabilitation therapy, disease modifying therapy, future clinical trials and perspectives, genetic counseling and preimplantation genetic diagnosis.

  13. Hereditary spastic paraplegias: membrane traffic and the motor pathway.

    Blackstone, Craig; O'Kane, Cahir J; Reid, Evan

    2011-01-01

    Voluntary movement is a fundamental way in which animals respond to, and interact with, their environment. In mammals, the main CNS pathway controlling voluntary movement is the corticospinal tract, which encompasses connections between the cerebral motor cortex and the spinal cord. Hereditary spastic paraplegias (HSPs) are a group of genetic disorders that lead to a length-dependent, distal axonopathy of fibres of the corticospinal tract, causing lower limb spasticity and weakness. Recent work aimed at elucidating the molecular cell biology underlying the HSPs has revealed the importance of basic cellular processes — especially membrane trafficking and organelle morphogenesis and distribution— in axonal maintenance and degeneration.

  14. Repetitive Transcranial Magnetic Stimulation in Patients with Hereditary Spastic Paraplegia

    Mehmet Ağırman

    2011-06-01

    Full Text Available Hereditary spastic paraplegia (HSPP is a heterogeneous genetic disease characterized by progressive spasticity of lower extremities. Spasticity is a major cause of long-term disability in HSPP and significantly affects the functional life of patients. Repetitive transcranial magnetic stimulation (rTMS is widely used in diagnosis and treatment of many neurological and psychiatric diseases. Although the positive impacts of rTMS for spasticity have been reported, no study has been found on HSPP. We present two HSPP patients treated with low frequency rTMS (20 minutes at a frequency of 1 Hz (1200 pulses, for a period of 10 treatment sessions.

  15. Repetitive Transcranial Magnetic Stimulation in Patients with Hereditary Spastic Paraplegia

    Mehmet Ağırman

    2011-06-01

    Full Text Available Hereditary spastic paraplegia (HSPP is a heterogeneous genetic disease characterized by progressive spasticity of lower extremities. Spasticity is a major cause of long-term disability in HSPP and significantly affects the functional life of patients. Repetitive transcranial magnetic stimulation (rTMS is widely used in diagnosis and treatment of many neurological and psychiatric diseases. Although the positive impacts of rTMS for spasticity have been reported, no study has been found on HSPP. We present two HSPP patients treated with low frequency rTMS (20 minutes at a frequency of 1 Hz (1200 pulses, for a period of 10 treatment sessions

  16. Mitochondrial DNA Mutation Associated with Leber's Hereditary Optic Neuropathy

    Wallace, Douglas C.; Singh, Gurparkash; Lott, Marie T.; Hodge, Judy A.; Schurr, Theodore G.; Lezza, Angela M. S.; Elsas, Louis J.; Nikoskelainen, Eeva K.

    1988-12-01

    Leber's hereditary optic neuropathy is a maternally inherited disease resulting in optic nerve degeneration and cardiac dysrhythmia. A mitochondrial DNA replacement mutation was identified that correlated with this disease in multiple families. This mutation converted a highly conserved arginine to a histidine at codon 340 in the NADH dehydrogenase subunit 4 gene and eliminated an Sfa NI site, thus providing a simple diagnostic test. This finding demonstrated that a nucleotide change in a mitochondrial DNA energy production gene can result in a neurological disease.

  17. Converging cellular themes for the hereditary spastic paraplegias.

    Blackstone, Craig

    2018-05-10

    Hereditary spastic paraplegias (HSPs) are neurologic disorders characterized by prominent lower-extremity spasticity, resulting from a length-dependent axonopathy of corticospinal upper motor neurons. They are among the most genetically-diverse neurologic disorders, with >80 distinct genetic loci and over 60 identified genes. Studies investigating the molecular pathogenesis underlying HSPs have emphasized the importance of converging cellular pathogenic themes in the most common forms of HSP, providing compelling targets for therapy. Most notably, these include organelle shaping and biogenesis as well as membrane and cargo trafficking. Published by Elsevier Ltd.

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

    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 diagnostics of this severe, but in early recognition curable disease. Early detection and phlebotomy treatment prior to the onset of cirrhosis can reduce morbidity and normalize life expectancy. It is readily

  19. Hereditary properties of Amenability modulo an ideal of Banach algebras

    Hamidreza Rahimi

    2014-10-01

    Full Text Available In this paper we investigate some hereditary properties of amenability modulo an ideal of Banach algebras. We show thatif $(e_{\\alpha}_{\\alpha}$ is a bounded approximate identity modulo $I$ of a Banach algebra $A$ and $X$ is a neo-unital modulo $I$, then $(e_{\\alpha}_{\\alpha}$ is a bounded approximate identity for $X$. Moreover we show that amenability modulo an ideal of a Banach algebra $A$ can be only considered by the neo-unital modulo $I$ Banach algebra over $A$

  20. Automated imaging dark adaptometer for investigating hereditary retinal degenerations

    Azevedo, Dario F. G.; Cideciyan, Artur V.; Regunath, Gopalakrishnan; Jacobson, Samuel G.

    1995-05-01

    We designed and built an automated imaging dark adaptometer (AIDA) to increase accuracy, reliability, versatility and speed of dark adaptation testing in patients with hereditary retinal degenerations. AIDA increases test accuracy by imaging the ocular fundus for precise positioning of bleaching and stimulus lights. It improves test reliability by permitting continuous monitoring of patient fixation. Software control of stimulus presentation provides broad testing versatility without sacrificing speed. AIDA promises to facilitate the measurement of dark adaptation in studies of the pathophysiology of retinal degenerations and in future treatment trials of these diseases.

  1. Treatment of Hereditary Hemorrhagic Telangiectasia-Related Epistaxis.

    Sautter, Nathan B; Smith, Timothy L

    2016-06-01

    Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease with an incidence of 1:5000. Recurrent, spontaneous epistaxis is the most common presenting symptom. Severity of epistaxis varies widely, from mild, self-limited nosebleeds to severe, life-threatening nasal hemorrhage. Treatment of HHT-related epistaxis presents a challenge to the otolaryngologist due to the recurrent, persistent nature of epistaxis often requiring multiple treatments. Treatment modalities range from conservative topical therapies to more aggressive surgical treatments. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Efficiency of laser treatment in patients with hereditary hemorrhagic telangiectasia

    Jørgensen, Gita; Lange, Bibi; Wanscher, Jens Højberg

    2011-01-01

    Earlier studies have shown the effect of laser treatment on epistaxis in patients with hereditary hemorrhagic telangiectasia (HHT). At the present time, only very few prospective trials have been performed, and many studies are based on patients' subjective assessment of the severity of epistaxis....... This prospective study measures the objective effect of laser treatment in HHT patients with mild to moderate epistaxis. We introduce an objective measure to assess the severity of epistaxis: the bleeding time (BT). Before and after treatment, the quality of life, as measured by the patient, was assessed...

  3. Blocking protein quality control to counter hereditary cancers

    Kampmeyer, Caroline; Nielsen, Sofie V.; Clausen, Lene

    2017-01-01

    cancer susceptibility syndromes, such as Lynch syndrome and von Hippel-Lindau disease, are caused by missense mutations in tumor suppressor genes, and in some cases, the resulting amino acid substitutions in the encoded proteins cause the cellular PQC system to target them for degradation, although...... by stabilizing with chemical chaperones, or by targeting molecular chaperones or the ubiquitin-proteasome system, may thus avert or delay the disease onset. Here, we review the potential of targeting the PQC system in hereditary cancer susceptibility syndromes....

  4. [Hereditary hemorrhagic telangiectasia presenting with hematuria and severe anemia].

    Paz, A; Goren, E; Segal, M

    1995-07-01

    A patient with hereditary hemorrhagic telangiectasia was admitted with hematuria and severe anemia after mild recurrent episodes of epistaxis. Telangiectasias were found in the skin and buccal and nasal mucosa. No defect in the coagulation mechanism was found; thrombocyte count and function were normal. On cystoscopy, tortuous engorged vessels, some actively bleeding, were seen in the trigonal mucosa. Biopsy showed enlarged vessels in the lamina propria. Electrocoagulation of the bleeding vessels stopped hematuria, but 6 months later it recurred. This time Nd-YAG laser was used to stop the bleeding after electrocoagulation was ineffective.

  5. Surveillance for hereditary nonpolyposis colorectal cancer: a long-term study on 114 families.

    Vos tot Nederveen Cappel, W.H. de; Nagengast, F.M.; Griffioen, G.; Menko, F.H.; Taal, B.G.; Kleibeuker, J.H.; Vasen, H.F.

    2002-01-01

    PURPOSE: Hereditary nonpolyposis colorectal cancer is caused by germline mutations in DNA mismatch repair genes. Mutation carriers have a 60 to 85 percent risk of developing colorectal cancer. In the Netherlands hereditary nonpolyposis colorectal cancer families are monitored in an intensive

  6. Surveillance for hereditary nonpolyposis colorectal cancer - A long-term study on 114 families

    Cappel, WHDTN; Nagengast, FM; Griffioen, G; Menko, FH; Taal, BG; Kleibeuker, JH; Vasen, HF

    2002-01-01

    PURPOSE: Hereditary nonpolyposis colorectal cancer is caused by germline mutations in DNA mismatch repair genes. Mutation carriers have a 60 to 85 percent risk of developing colorectal cancer. In the Netherlands hereditary nonpolyposis colorectal cancer families are monitored in an intensive

  7. 2010 International consensus algorithm for the diagnosis, therapy and management of hereditary angioedema

    Bowen, Tom; Cicardi, Marco; Farkas, Henriette

    2010-01-01

    ABSTRACT: BACKGROUND: We published the Canadian 2003 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema (HAE; C1 inhibitor [C1-INH] deficiency) and updated this as Hereditary angioedema: a current state-of-the-art review: Canadian Hungarian 2007 ...

  8. Estimation of EuroQol 5-Dimensions health status utility values in hereditary angioedema

    Aygören-Pürsün, Emel; Bygum, Anette; Beusterien, Kathleen

    2016-01-01

    OBJECTIVE: To estimate health status utility (preference) weights for hereditary angioedema (HAE) during an attack and between attacks using data from the Hereditary Angioedema Burden of Illness Study in Europe (HAE-BOIS-Europe) survey. Utility measures quantitatively describe the net impact of a...

  9. Descriptive Epidemiology, Molecular Biology and Genetics of Hereditary Prostate Cancer in Denmark

    Bentzon, Diem Nguyen

    2012-01-01

    A search for markers that can differentiate indolent prostate cancers from more aggressive forms. Assessment of clinical differences between hereditary and sporadicc prostate cancer.......A search for markers that can differentiate indolent prostate cancers from more aggressive forms. Assessment of clinical differences between hereditary and sporadicc prostate cancer....

  10. Clinicoelectrophysiologic and magnetoresonance and tomographic investigation of hereditary and congenital diseases of the brain

    Kamalov, I.I.; Pikuza, O.I.; Idrisova, L.G.; Uryvskij, V.I.

    1996-01-01

    The combined investigation of hereditary and congenital diseases of the brain using magnetoresonance tomography is performed. The hereditary and congenital diseases of the brain accompanied by disorders of liquoroconductive tracts with medullary substance lesion are revealed. The investigation results provide timely development of the treatment tactics and rehabilitation of sick children. Refs. 3

  11. Imaging findings of arteriovenous malformations involving lung and liver in hereditary hemorrhagic telangiectasia(Osler-weber-rendu disease): two cases report

    Yi, Jeong Geun; Lee, Joo Hyuk; Seong, Su Ok

    1999-01-01

    Hereditary hemorrhagic telangiectasia (HHT) or Osler-Weber-Rendu disease is an autosomal dominant disorder characterized by repeated episodes of bleeding. Multiple telangiectases consisting of thin-walled, dilated vascular channels with arteriovenous communication may involve, for example, mucocutaneous tissue, the gastrointestinal tract, and the liver, lung, and brain. We report the imaging findings of two cases of HHT involving arteriovenous malformation of both the lungs and liver, a rare condition. Chest radiography revealed a round mass, while helical CT showed a feeding artery and draining vein with arteriovenous malformation in the lung. Color Doppler sonography revealed an enlarged and tortuous hepatic artery with high systolic velocity. CT demonstrated an enlarged hepatic artery, arteriovenous shunt, and early draining hepatic vein in the liver. Celiac angiography showed arteriovenous malformation

  12. Imaging findings of arteriovenous malformations involving lung and liver in hereditary hemorrhagic telangiectasia(Osler-weber-rendu disease): two cases report

    Yi, Jeong Geun; Lee, Joo Hyuk; Seong, Su Ok [Cheongju St. Mary' s Hospital, Cheongju (Korea, Republic of)

    1999-09-01

    Hereditary hemorrhagic telangiectasia (HHT) or Osler-Weber-Rendu disease is an autosomal dominant disorder characterized by repeated episodes of bleeding. Multiple telangiectases consisting of thin-walled, dilated vascular channels with arteriovenous communication may involve, for example, mucocutaneous tissue, the gastrointestinal tract, and the liver, lung, and brain. We report the imaging findings of two cases of HHT involving arteriovenous malformation of both the lungs and liver, a rare condition. Chest radiography revealed a round mass, while helical CT showed a feeding artery and draining vein with arteriovenous malformation in the lung. Color Doppler sonography revealed an enlarged and tortuous hepatic artery with high systolic velocity. CT demonstrated an enlarged hepatic artery, arteriovenous shunt, and early draining hepatic vein in the liver. Celiac angiography showed arteriovenous malformation.

  13. Upper gastrointestinal bleeding in patients with CKD.

    Liang, Chih-Chia; Wang, Su-Ming; Kuo, Huey-Liang; Chang, Chiz-Tzung; Liu, Jiung-Hsiun; Lin, Hsin-Hung; Wang, I-Kuan; Yang, Ya-Fei; Lu, Yueh-Ju; Chou, Che-Yi; Huang, Chiu-Ching

    2014-08-07

    Patients with CKD receiving maintenance dialysis are at risk for upper gastrointestinal bleeding. However, the risk of upper gastrointestinal bleeding in patients with early CKD who are not receiving dialysis is unknown. The hypothesis was that their risk of upper gastrointestinal bleeding is negatively linked to renal function. To test this hypothesis, the association between eGFR and risk of upper gastrointestinal bleeding in patients with stages 3-5 CKD who were not receiving dialysis was analyzed. Patients with stages 3-5 CKD in the CKD program from 2003 to 2009 were enrolled and prospectively followed until December of 2012 to monitor the development of upper gastrointestinal bleeding. The risk of upper gastrointestinal bleeding was analyzed using competing-risks regression with time-varying covariates. In total, 2968 patients with stages 3-5 CKD who were not receiving dialysis were followed for a median of 1.9 years. The incidence of upper gastrointestinal bleeding per 100 patient-years was 3.7 (95% confidence interval, 3.5 to 3.9) in patients with stage 3 CKD, 5.0 (95% confidence interval, 4.8 to 5.3) in patients with stage 4 CKD, and 13.9 (95% confidence interval, 13.1 to 14.8) in patients with stage 5 CKD. Higher eGFR was associated with a lower risk of upper gastrointestinal bleeding (P=0.03), with a subdistribution hazard ratio of 0.93 (95% confidence interval, 0.87 to 0.99) for every 5 ml/min per 1.73 m(2) higher eGFR. A history of upper gastrointestinal bleeding (Pupper gastrointestinal bleeding risk. In patients with CKD who are not receiving dialysis, lower renal function is associated with higher risk for upper gastrointestinal bleeding. The risk is higher in patients with previous upper gastrointestinal bleeding history and low serum albumin. Copyright © 2014 by the American Society of Nephrology.

  14. Gastrointestinal helminths in migratory Camel

    S G Rewatkar

    Full Text Available Survey of gastrointestinal helminth parasites in camel migrated from U.P., M.P., and Rajasthan at Nagpur region was carried out in early summer, 2008. Total 28 samples (12 males and 16 females were collected from different places of Nagpur region. They revealed parasites as Trichuris sp.(50%, Strongyloides sp.(32.14%, Trichostrongylus sp.(10.71%, Nematodirus sp.(10.71%, Haemonchus sp.(14.28%, Eurytrema sp.(21.42% ,Eimeria sp.(25%, Entamoeba sp.(17.85% and Balantidium sp.(7.14%.All were found positive for mixed helminthic infection. [Vet World 2009; 2(7.000: 258-258

  15. Gastrointestinal obstruction in penguin chicks.

    Perpiñán, David; Curro, Thomas G

    2009-12-01

    A 7-day-old gentoo penguin (Pygoscelis papua) was found dead and postmortem examination revealed impaction of the ventriculus with feathers. A review of mortality in gentoo penguin chicks from 1997 to 2007 at that institution revealed another case of feather impaction of the ventriculus in a 4-week-old chick, a sibling of the previous chick. A third case of gastrointestinal impaction occurred in a 24-day-old king penguin (Aptenodytes patagonicus) with omphallitis and enteritis. In this chick, a fibrin mat produced a complete obstruction of the intestine at the level of Meckel's diverticulum.

  16. Fraccionando la microbiota gastrointestinal humana

    Peris Bondia, Francisco

    2012-01-01

    La microbiota gastrointestinal humana es una de las comunidades microbianas más diversa y compleja que se puede encontrar en la naturaleza. Las nuevas tecnologías de secuenciación permiten obtener una amplia visión de la diversidad microbiana, lo que ha revelado una gran cantidad de bacterias no cultivables. A pesar del potencial de estas tecnologías de alto rendimiento la metagenómica no muestra la imagen completa. La citometría de flujo es una metodología que permite describir y/o separa...

  17. Antimyosin scintigraphy in patients with acquired and hereditary muscular disorders

    Loefberg, M.; Liewendahl, K.; Savolainen, S.; Nikkinen, P.; Lamminen, A.; Tiula, E.; Somer, H.

    1994-01-01

    Scintigraphy with indium-111 labelled antimyosin has an established role in the evaluation of cardiac muscle damage. This antibody has been shown to cross-react with myosin in skeletal muscle. We therefore studied the usefulness of this method for the detection of skeletal muscle lesions in rhabdomyolysis, myositis and hereditary muscular dystrophies. All nine patients with rhabdomyolysis had focal uptake of antimyosin antibody which correlated with the clinical findings of soft tissue damage. However, a number of symptomless lesions were also detected by immunoscintigraphy. In rhabdomyolysis the target to non-target uptake ratios varied from 1.3 to 7.6. Diffuse uptake of antibody in skeletal muscle was observed in all three patients with polymyositis-dermatomyositis and in 12 out of 13 patients with muscular dystrophies. In myositis the intensity of antibody accumulation correlated reasonably well with the magnitude of oedema detected by magnetic resonance imaging (MRI). Most patients with Becker type or non-X-chromosomal muscular dystrophies showed slight or moderate uptake of antibody, mainly in the lower extremities. In these patients more antibody accumulated in the calves than in the thighs, whereas the findings on MRI were more prominent in the thighs than in the calves, presumably because of the better preserved muscle bulk in the calves. We conclude that antimyosin scintigraphy can be used for the detection of muscle lesions not only in acquired muscle diseases but also in hereditary muscular disorders, and that immunoscintigraphy provides information on muscle disease activity not obtainable with MRI. (orig.)

  18. Inflammation and neuropathic attacks in hereditary brachial plexus neuropathy

    Klein, C; Dyck, P; Friedenberg, S; Burns, T; Windebank, A; Dyck, P

    2002-01-01

    Objective: To study the role of mechanical, infectious, and inflammatory factors inducing neuropathic attacks in hereditary brachial plexus neuropathy (HBPN), an autosomal dominant disorder characterised by attacks of pain and weakness, atrophy, and sensory alterations of the shoulder girdle and upper limb muscles. Methods: Four patients from separate kindreds with HBPN were evaluated. Upper extremity nerve biopsies were obtained during attacks from a person of each kindred. In situ hybridisation for common viruses in nerve tissue and genetic testing for a hereditary tendency to pressure palsies (HNPP; tomaculous neuropathy) were undertaken. Two patients treated with intravenous methyl prednisolone had serial clinical and electrophysiological examinations. One patient was followed prospectively through pregnancy and during the development of a stereotypic attack after elective caesarean delivery. Results: Upper extremity nerve biopsies in two patients showed prominent perivascular inflammatory infiltrates with vessel wall disruption. Nerve in situ hybridisation for viruses was negative. There were no tomaculous nerve changes. In two patients intravenous methyl prednisolone ameliorated symptoms (largely pain), but with tapering of steroid dose, signs and symptoms worsened. Elective caesarean delivery did not prevent a typical postpartum attack. Conclusions: Inflammation, probably immune, appears pathogenic for some if not all attacks of HBPN. Immune modulation may be useful in preventing or reducing the neuropathic attacks, although controlled trials are needed to establish efficacy, as correction of the mutant gene is still not possible. The genes involved in immune regulation may be candidates for causing HBPN disorders. PMID:12082044

  19. Hereditary melanoma and predictive genetic testing: why not?

    Riedijk, S R; de Snoo, F A; van Dijk, S; Bergman, W; van Haeringen, A; Silberg, S; van Elderen, T M T; Tibben, A

    2005-09-01

    Since p16-Leiden presymptomatic testing for hereditary melanoma has become available in the Netherlands, the benefits and risks of offering such testing are evaluated. The current paper investigated why the non-participants were reluctant to participate in genetic testing. Sixty six eligible individuals, who were knowledgeable about the test but had not participated in genetic testing by January 2003, completed a self-report questionnaire assessing motivation, anxiety, family dynamics, risk knowledge and causal attributions. Non-participants reported anxiety levels below clinical significance. A principal components analysis on reasons for non-participation distinguished two underlying motives: emotional and rational motivation. Rational motivation for non-participation was associated with more accurate risk knowledge, the inclination to preselect mutation carriers within the family and lower scores on anxiety. Emotional motivation for non-participation was associated with disease misperceptions, hesitation to communicate unfavourable test results within the family and higher scores on anxiety. Rational and emotional motivation for non-participation in the genetic test for hereditary melanoma was found. Emotionally motivated individuals may be reluctant to disseminate genetic risk information. Rationally motivated individuals were better informed than emotionally motivated individuals. It is suggested that a leaflet is added to the invitation letter to enhance informed decision-making about genetic testing.

  20. Hereditary cancer genes are highly susceptible to splicing mutations

    Soemedi, Rachel; Maguire, Samantha; Murray, Michael F.; Monaghan, Sean F.

    2018-01-01

    Substitutions that disrupt pre-mRNA splicing are a common cause of genetic disease. On average, 13.4% of all hereditary disease alleles are classified as splicing mutations mapping to the canonical 5′ and 3′ splice sites. However, splicing mutations present in exons and deeper intronic positions are vastly underreported. A recent re-analysis of coding mutations in exon 10 of the Lynch Syndrome gene, MLH1, revealed an extremely high rate (77%) of mutations that lead to defective splicing. This finding is confirmed by extending the sampling to five other exons in the MLH1 gene. Further analysis suggests a more general phenomenon of defective splicing driving Lynch Syndrome. Of the 36 mutations tested, 11 disrupted splicing. Furthermore, analyzing past reports suggest that MLH1 mutations in canonical splice sites also occupy a much higher fraction (36%) of total mutations than expected. When performing a comprehensive analysis of splicing mutations in human disease genes, we found that three main causal genes of Lynch Syndrome, MLH1, MSH2, and PMS2, belonged to a class of 86 disease genes which are enriched for splicing mutations. Other cancer genes were also enriched in the 86 susceptible genes. The enrichment of splicing mutations in hereditary cancers strongly argues for additional priority in interpreting clinical sequencing data in relation to cancer and splicing. PMID:29505604

  1. Hereditary cancer genes are highly susceptible to splicing mutations.

    Christy L Rhine

    2018-03-01

    Full Text Available Substitutions that disrupt pre-mRNA splicing are a common cause of genetic disease. On average, 13.4% of all hereditary disease alleles are classified as splicing mutations mapping to the canonical 5' and 3' splice sites. However, splicing mutations present in exons and deeper intronic positions are vastly underreported. A recent re-analysis of coding mutations in exon 10 of the Lynch Syndrome gene, MLH1, revealed an extremely high rate (77% of mutations that lead to defective splicing. This finding is confirmed by extending the sampling to five other exons in the MLH1 gene. Further analysis suggests a more general phenomenon of defective splicing driving Lynch Syndrome. Of the 36 mutations tested, 11 disrupted splicing. Furthermore, analyzing past reports suggest that MLH1 mutations in canonical splice sites also occupy a much higher fraction (36% of total mutations than expected. When performing a comprehensive analysis of splicing mutations in human disease genes, we found that three main causal genes of Lynch Syndrome, MLH1, MSH2, and PMS2, belonged to a class of 86 disease genes which are enriched for splicing mutations. Other cancer genes were also enriched in the 86 susceptible genes. The enrichment of splicing mutations in hereditary cancers strongly argues for additional priority in interpreting clinical sequencing data in relation to cancer and splicing.

  2. Ultrastructural evaluation of gingival connective tissue in hereditary gingival fibromatosis.

    Pêgo, Sabina Pena B; de Faria, Paulo Rogério; Santos, Luis Antônio N; Coletta, Ricardo D; de Aquino, Sibele Nascimento; Martelli-Júnior, Hercílio

    2016-07-01

    To describe the ultrastructural features of hereditary gingival fibromatosis (HGF) in affected family members and compare microscopic findings with normal gingival (NG) tissue. Gingival tissue samples from nine patients with HGF from five unrelated families were evaluated by transmission electron microscopy. Nine NG tissue samples were used for comparison. Areas containing collagen fibrils forming loops and folds were observed in both groups, whereas oxytalan fibers were frequently identified in the HGF group. The diameter of collagen fibrils and the interfibrillar space among them were more uniform in the NG group than in the HGF group. Fibroblasts were the most common cells found in both the HGF and NG groups and exhibited enlarged, rough endoplasmic reticulum, mitochondria with well-preserved crests, conspicuous nucleoli, and euchromatic chromatin. Other cells, such as mast cells, plasma cells, and macrophages, were also observed. HGF tissues had ultrastructural characteristics that were very similar to those of NG tissues. Oxytalan fibers were observed more frequently in the HGF samples than in the NG samples. Other studies of HGF in patients from different families should be performed to better understand the pathogenesis of this hereditary condition. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Antimyosin scintigraphy in patients with acquired and hereditary muscular disorders

    Loefberg, M. (Dept. of Neurology, Helsinki Univ. Central Hospital (Finland)); Liewendahl, K. (Dept. of Clinical Chemistry, Helsinki Univ. Central Hospital (Finland)); Savolainen, S. (Dept. of Clinical Chemistry, Helsinki Univ. Central Hospital (Finland)); Nikkinen, P. (Dept. of Clinical Chemistry, Helsinki Univ. Central Hospital (Finland)); Lamminen, A. (Dept. of Radiology, Helsinki Univ. Central Hospital (Finland)); Tiula, E. (First Dept. of Internal Medicine, Helsinki Univ. Central Hospital (Finland)); Somer, H. (Dept. of Neurology, Helsinki Univ. Central Hospital (Finland))

    1994-10-01

    Scintigraphy with indium-111 labelled antimyosin has an established role in the evaluation of cardiac muscle damage. This antibody has been shown to cross-react with myosin in skeletal muscle. We therefore studied the usefulness of this method for the detection of skeletal muscle lesions in rhabdomyolysis, myositis and hereditary muscular dystrophies. All nine patients with rhabdomyolysis had focal uptake of antimyosin antibody which correlated with the clinical findings of soft tissue damage. However, a number of symptomless lesions were also detected by immunoscintigraphy. In rhabdomyolysis the target to non-target uptake ratios varied from 1.3 to 7.6. Diffuse uptake of antibody in skeletal muscle was observed in all three patients with polymyositis-dermatomyositis and in 12 out of 13 patients with muscular dystrophies. In myositis the intensity of antibody accumulation correlated reasonably well with the magnitude of oedema detected by magnetic resonance imaging (MRI). Most patients with Becker type or non-X-chromosomal muscular dystrophies showed slight or moderate uptake of antibody, mainly in the lower extremities. In these patients more antibody accumulated in the calves than in the thighs, whereas the findings on MRI were more prominent in the thighs than in the calves, presumably because of the better preserved muscle bulk in the calves. We conclude that antimyosin scintigraphy can be used for the detection of muscle lesions not only in acquired muscle diseases but also in hereditary muscular disorders, and that immunoscintigraphy provides information on muscle disease activity not obtainable with MRI. (orig.)

  4. Age-dependent cognitive dysfunction in untreated hereditary transthyretin amyloidosis.

    Martins da Silva, Ana; Cavaco, Sara; Fernandes, Joana; Samões, Raquel; Alves, Cristina; Cardoso, Márcio; Kelly, Jeffery W; Monteiro, Cecília; Coelho, Teresa

    2018-02-01

    Central nervous system (CNS) involvement in hereditary transthyretin (TTR) amyloidosis has been described in patients whose disease course was modified by liver transplant. However, cognitive dysfunction has yet to be investigated in those patients. Moreover, CNS involvement in untreated patients or asymptomatic mutation carriers remains to be studied. A series of 340 carriers of the TTRVal30Met mutation (180 symptomatic and 160 asymptomatic) underwent a neuropsychological assessment, which included the Dementia Rating Scale-2 (DRS-2), auditory verbal learning test, semantic fluency, phonemic fluency, and trail making test. Cognitive deficits were identified at the individual level, after adjusting the neuropsychological test scores for demographic characteristics (sex, age, and education), based on large national normative data. The presence of cognitive dysfunction was determined by deficit in DRS-2 and/or multiple cognitive domains. Participants were also screened for depression based on a self-report questionnaire. The frequency of cognitive dysfunction was higher (p = 0.003) in symptomatic (9%) than in asymptomatic (2%) carriers. Among older carriers (≥ 50 years), the frequency of cognitive dysfunction was higher (p hereditary TTR amyloidosis patients with peripheral polyneuropathy, even in the early stages of the disease.

  5. Whole-exome sequencing for diagnosis of hereditary ichthyosis.

    Sitek, J C; Kulseth, M A; Rypdal, K B; Skodje, T; Sheng, Y; Retterstøl, L

    2018-02-14

    Hereditary ichthyosis constitutes a diverse group of cornification disorders. Identification of the molecular cause facilitates optimal patient care. We wanted to estimate the diagnostic yield of applying whole-exome sequencing (WES) in the routine genetic workup of inherited ichthyosis. During a 3-year-period, all ichthyosis patients, except X-linked and mild vulgar ichthyosis, consecutively admitted to a university hospital clinic were offered WES with subsequent analysis of ichthyosis-related genes as a first-line genetic investigation. Clinical and molecular data have been collected retrospectively. Genetic variants causative for the ichthyosis were identified in 27 of 34 investigated patients (79.4%). In all, 31 causative mutations across 13 genes were disclosed, including 12 novel variants. TGM1 was the most frequently mutated gene, accounting for 43.7% of patients suffering from autosomal recessive congenital ichthyosis (ARCI). Whole-exome sequencing appears an effective tool in disclosing the molecular cause of patients with hereditary ichthyosis seen in clinical practice and should be considered a first-tier genetic test in these patients. © 2018 European Academy of Dermatology and Venereology.

  6. Ghrelin and gastrointestinal stromal tumors.

    Zhu, Chang-Zhen; Liu, Dong; Kang, Wei-Ming; Yu, Jian-Chun; Ma, Zhi-Qiang; Ye, Xin; Li, Kang

    2017-03-14

    Ghrelin, as a kind of multifunctional protein polypeptide, is mainly produced in the fundus of the stomach and can promote occurrence and development of many tumors, including gastrointestinal tumors, which has been proved by the relevant researches. Most gastrointestinal stromal tumors (GISTs, about 80%), as the most common mesenchymal tumor, also develop in the fundus. Scientific research has confirmed that ghrelin, its receptors and mRNA respectively can be found in GISTs, which demonstrated the existence of a ghrelin autocrine/paracrine loop in GIST tissues. However, no reports to date have specified the mechanism whether ghrelin can promote the occurrence and development of GISTs. Studies of pulmonary artery endothelial cells in a low-oxygen environment and cardiac muscle cells in an ischemic environment have shown that ghrelin can activate the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway. Moreover, some studies of GISTs have confirmed that activation of the PI3K/AKT/mTOR pathway can indeed promote the growth and progression of GISTs. Whether ghrelin is involved in the development or progression of GISTs through certain pathways remains unknown. Can we find a new target for the treatment of GISTs? This review explores and summaries the relationship among ghrelin, the PI3K/AKT/mTOR pathway and the development of GISTs.

  7. Does Hypothyroidism Affect Gastrointestinal Motility?

    Olga Yaylali

    2009-01-01

    Full Text Available Background. Gastrointestinal motility and serum thyroid hormone levels are closely related. Our aim was to analyze whether there is a disorder in esophagogastric motor functions as a result of hypothyroidism. Materials and Methods. The study group included 30 females (mean age ± SE 45.17 ± 2.07 years with primary hypothyroidism and 10 healthy females (mean age ± SE 39.40 ± 3.95 years. All cases underwent esophagogastric endoscopy and scintigraphy. For esophageal scintigraphy, dynamic imaging of esophagus motility protocol, and for gastric emptying scintigraphy, anterior static gastric images were acquired. Results. The mean esophageal transit time (52.56 ± 4.07 sec for patients; 24.30 ± 5.88 sec for controls; P=.02 and gastric emptying time (49.06 ± 4.29 min for the hypothyroid group; 30.4 ± 4.74 min for the control group; P=.01 were markedly increased in cases of hypothyroidism. Conclusion. Hypothyroidism prominently reduces esophageal and gastric motor activity and can cause gastrointestinal dysfunction.

  8. Radiological diagnosis of gastrointestinal bleeding

    Neufang, K.F.R.; Gross-Fengels, W.; Lorenz, R.

    1990-01-01

    In the diagnosis of acute gastrointestinal bleeding, endoscopy holds the first place today. Radiological investigations are indispensable whenever endoscopy cannot precisely localise the bleeding site, whenever a tumour is present or suspected, in all cases of lower gastrointestinal bleeding, and in haemobilia. A tailored radiological approach is recommended. The radiological basis programme should be at least a complete abdominal ultrasound study and plain abdominal radiograms. CT and ERCP scans may become necessary in selected cases. As a rule, angiographical localisation of the bleeding site will be successful only in the acute stage; selective visceral arteriograms have to be obtained, which may be executed in the digital subtraction technique in patients who are cooperating and clinically stable. Angiodysplasias and aneurysms, however, may be demonstrated angiographically in the interval as well. Upper and/or lower G.I. tract studies with barium or water-soluble contrast media may be indicated in the interval in order to demonstrate tumours, metastatic lesions, diverticula and gut malformations. (orig.) [de

  9. Adenomatous polyposis coli is required for early events in the normal growth and differentiation of the developing cerebral cortex

    Price David J

    2009-01-01

    Full Text Available Abstract Background Adenomatous polyposis coli (Apc is a large multifunctional protein known to be important for Wnt/β-catenin signalling, cytoskeletal dynamics, and cell polarity. In the developing cerebral cortex, Apc is expressed in proliferating cells and its expression increases as cells migrate to the cortical plate. We examined the consequences of loss of Apc function for the early development of the cerebral cortex. Results We used Emx1Cre to inactivate Apc specifically in proliferating cerebral cortical cells and their descendents starting from embryonic day 9.5. We observed reduction in the size of the mutant cerebral cortex, disruption to its organisation, and changes in the molecular identity of its cells. Loss of Apc leads to a decrease in the size of the proliferative pool, disrupted interkinetic nuclear migration, and increased apoptosis. β-Catenin, pericentrin, and N-cadherin proteins no longer adopt their normal high concentration at the apical surface of the cerebral cortical ventricular zone, indicating that cell polarity is disrupted. Consistent with enhanced Wnt/β-catenin signalling resulting from loss of Apc we found increased levels of TCF/LEF-dependent transcription and expression of endogenous Wnt/β-catenin target genes (Axin2 (conductin, Lef1, and c-myc in the mutant cerebral cortex. In the Apc mutant cerebral cortex the expression of transcription factors Foxg1, Pax6, Tbr1, and Tbr2 is drastically reduced compared to normal and many cells ectopically express Pax3, Wnt1, and Wt1 (but not Wnt2b, Wnt8b, Ptc, Gli1, Mash1, Olig2, or Islet1. This indicates that loss of Apc function causes cerebral cortical cells to lose their normal identity and redirect to fates normally found in more posterior-dorsal regions of the central nervous system. Conclusion Apc is required for multiple aspects of early cerebral cortical development, including the regulation of cell number, interkinetic nuclear migration, cell polarity, and

  10. High-resolution Melting Analysis for Gene Scanning of Adenomatous Polyposis Coli (APC) Gene With Oral Squamous Cell Carcinoma Samples.

    Chang, Ya-Sian; Lin, Chien-Yu; Yang, Shu-Fen; Ho, Cheng Mao; Chang, Jan-Gowth

    2016-02-01

    There have been many different mutations reported for the large adenomatous polyposis coli (APC) tumor suppressor gene. APC mutations result in inactivation of APC tumor suppressor action, allowing the progression of tumorigenesis. The present study utilized a highly efficient method to identify APC mutations and investigated the association between the APC genetic variants Y486Y, A545A, T1493T, and D1822V and susceptibility to oral squamous cell carcinoma (OSCC). High-resolution melting (HRM) analysis was used to characterize APC mutations. Genomic DNA was extracted from 83 patient specimens of OSCC and 50 blood samples from healthy control subjects. The 14 exons and mutation cluster region of exon 15 were screened by HRM analysis. All mutations were confirmed by direct DNA sequencing. Three mutations and 4 single nucleotide polymorphisms (SNPs) were found in this study. The mutations were c.573T>C (Y191Y) in exon 5, c.1005A>G (L335L) in exon 9, and c.1488A>T (T496T) in exon 11. Two SNPs, c.4479G>A (T1493T) and c.5465A>T (D1822V), were located in exon 15, whereas c.1458T>C (Y486Y) and c.1635G>A (A545A) were located in exon 11 and 13, respectively. There was no observed association between OSCC risk and genotype for any of the 4 APC SNPs. The mutation of APC is rare in Taiwanese patients with OSCC. HRM analysis is a reliable, accurate, and fast screening method for APC mutations.

  11. Frontal sinus revision rate after nasal polyposis surgery including frontal recess clearance and middle turbinectomy: A long-term analysis.

    Benkhatar, Hakim; Khettab, Idir; Sultanik, Philippe; Laccourreye, Ollivier; Bonfils, Pierre

    2018-08-01

    To determine the frontal sinus revision rate after nasal polyposis (NP) surgery including frontal recess clearance (FRC) and middle turbinectomy (MT), to search for predictive factors and to analyse surgical management. Longitudinal analysis of 153 patients who consecutively underwent bilateral sphenoethmoidectomy with FRC and MT for NP with a minimum follow-up of 7 years. Decision of revision surgery was made in case of medically refractory chronic frontal sinusitis or frontal mucocele. Univariate and multivariate analysis incorporating clinical and radiological variables were performed. The frontal sinus revision rate was 6.5% (10/153). The mean time between the initial procedure and revision surgery was 3 years, 10 months. Osteitis around the frontal sinus outflow tract (FSOT) was associated with a higher risk of frontal sinus revision surgery (p=0.01). Asthma and aspirin intolerance did not increase the risk, as well as frontal sinus ostium diameter or residual frontoethmoid cells. Among revised patients, 60% required multiple procedures and 70% required frontal sinus ostium enlargement. Our long-term study reports that NP surgery including FRC and MT is associated with a low frontal sinus revision rate (6.5%). Patients developing osteitis around the FSOT have a higher risk of frontal sinus revision surgery. As mucosal damage can lead to osteitis, FSOT mucosa should be preserved during initial NP surgery. However, as multiple procedures are common among NP patients requiring frontal sinus revision, frontal sinus ostium enlargement should be considered during first revision in the hope of reducing the need of further revisions. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Computed tomography of the gastrointestinal tract

    Fishman, E.K.; Jones, B.

    1988-01-01

    This book contains 11 chapters and five case studies. Some of the chapter titles are: CT of the Stomach; CT and Other Inflammatory Bowel Disease; Evaluation of Crohn's Disease; Periotoneal Metastasis; CT and MRI Correlation of the Gastrointestinal Tract; CT of Acute Gastrointestinal Abnormlities; and CT of Colorectal Cancer

  13. Possible Waardenburg syndrome with gastrointestinal anomalies.

    Nutman, J; Steinherz, R; Sivan, Y; Goodman, R M

    1986-01-01

    We describe a patient with possible Waardenburg syndrome associated with anal atresia and oesophageal atresia with tracheooesophageal fistula. Three other published cases with atretic gastrointestinal anomalies associated with the Waardenburg syndrome are reviewed. We conclude that the association between atretic lesions of the gastrointestinal tract and the Waardenburg syndrome may be a significant one.

  14. Possible Waardenburg syndrome with gastrointestinal anomalies.

    Nutman, J; Steinherz, R; Sivan, Y; Goodman, R M

    1986-01-01

    We describe a patient with possible Waardenburg syndrome associated with anal atresia and oesophageal atresia with tracheooesophageal fistula. Three other published cases with atretic gastrointestinal anomalies associated with the Waardenburg syndrome are reviewed. We conclude that the association between atretic lesions of the gastrointestinal tract and the Waardenburg syndrome may be a significant one. Images PMID:3712396

  15. Unsedated Flexible Upper Gastrointestinal Endoscopy: Need for ...

    Background: To determine the incidence of oxygen desaturation and whether routine oxygen monitoring is necessary during unsedated diagnostic flexible upper gastrointestinal endoscopy. Methods: A prospective study involving 54 consecutive in and out patients who had diagnostic upper gastrointestinal endoscopy at ...

  16. Peptide Hormones in the Gastrointestinal Tract

    Rehfeld, Jens F.

    2015-01-01

    Gastrointestinal hormones are peptides released from endocrine cells and neurons in the digestive tract. More than 30 hormone genes are currently known to be expressed in the gastrointestinal tract, which makes the gut the largest hormone-producing organ in the body. Modern biology makes it feasi...

  17. Mammalian gastrointestinal parasites in rainforest remnants

    Here, we studied the gastrointestinal parasites of nonhuman mammalian hosts living in 10 rainforest patches of the Anamalai Tiger Reserve, India. We examined 349 faecal samples of 17 mammalian species and successfully identified 24 gastroin-testinal parasite taxa including 1 protozoan, 2 trematode, 3 cestode and 18 ...

  18. Analysis of Genetic Mutations in a Cohort of Hereditary Optic Neuropathy in Shanghai, China.

    Gan, Dekang; Li, Mengwei; Wu, Jihong; Sun, Xinghuai; Tian, Guohong

    2017-01-01

    To evaluate the clinical classification and characteristics of hereditary optic neuropathy patients in a single center in China. Retrospective case study. Patients diagnosed with hereditary optic neuropathy between January 2014 and December 2015 in the neuro-ophthalmology division in Shanghai Eye and ENT Hospital of Fudan University were recruited. Clinical features as well as visual field, brain/orbital MRI, and spectrum domain optical coherence tomography (SD-OCT) were analyzed. Eighty-two patients diagnosed by gene test were evaluated, including 66 males and 16 females. The mean age of the patients was 19.4 years (range, 5-46 years). A total of 158 eyes were analyzed, including 6 unilateral, 61 bilateral, and 15 sequential. The median duration of the disease was 0.5 year (range, 0.1-20 years). Genetic test identified 68 patients with Leber hereditary optic neuropathy, 9 with dominant optic neuropathy, and 2 with a Wolfram gene mutation. There was also one case of hereditary spastic paraplegia, spinocerebellar ataxia, and polymicrogyria with optic nerve atrophy, respectively. Leber hereditary optic neuropathy is the most common detected type of hereditary optic neuropathy in Shanghai, China. The detection of other autosomal mutations in hereditary optic neuropathy is limited by the currently available technique.

  19. Antidepressants and gastrointestinal symptoms in the general Dutch adult population

    Schurink, B.; Tielemans, M.M.; Aaldering, B.R.; Eikendal, T.; Jaspers Focks, J.; Laheij, R.J.F.; Jansen, J.B.M.J.; Rossum, L.G.M. van; Oijen, M.G.H. van

    2014-01-01

    BACKGROUND: Gastrointestinal symptoms are frequently reported adverse effects of antidepressants, but antidepressants are also a treatment modality in functional gastrointestinal disorders. We aimed to assess the association between antidepressant use and gastrointestinal symptoms in the general

  20. HIV-Associated Gastrointestinal Cancer.

    Jensen, Björn E-O; Oette, Mark; Haes, Johannes; Häussinger, Dieter

    2017-01-01

    People living nowadays with HIV and AIDS may be treated effectively regarding virus replication and immunology. However, non-AIDS-defining cancer is of growing relevance due to high incidence and unfavorable outcome. The aim of this review is to summarize current knowledge on gastrointestinal (GI) carcinoma. Although literature on GI cancer is rare, an increased incidence of esophageal, gastric, pancreatic, hepatocellular, and colorectal carcinoma has been demonstrated. However, there are only few reports on therapy strategies and outcome, so that, despite increased occurrence of many GI carcinomas, only little is known about individualized treatment options and outcome in HIV-positive patients. More efforts have to be undertaken to close this gap. © 2017 S. Karger GmbH, Freiburg.