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1.
Ann Intern Med ; 173(12): 989-1001, 2020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-32894695

RESUMO

DESCRIPTION: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease with an estimated prevalence of 1 in 5000 that is characterized by the presence of vascular malformations (VMs). These result in chronic bleeding, acute hemorrhage, and complications from shunting through VMs. The goal of the Second International HHT Guidelines process was to develop evidence-based consensus guidelines for the management and prevention of HHT-related symptoms and complications. METHODS: The guidelines were developed using the AGREE II (Appraisal of Guidelines for Research and Evaluation II) framework and GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. The guidelines expert panel included expert physicians (clinical and genetic) in HHT from 15 countries, guidelines methodologists, health care workers, health care administrators, patient advocacy representatives, and persons with HHT. During the preconference process, the expert panel generated clinically relevant questions in 6 priority topic areas. A systematic literature search was done in June 2019, and articles meeting a priori criteria were included to generate evidence tables, which were used as the basis for recommendation development. The expert panel subsequently convened during a guidelines conference to conduct a structured consensus process, during which recommendations reaching at least 80% consensus were discussed and approved. RECOMMENDATIONS: The expert panel generated and approved 6 new recommendations for each of the following 6 priority topic areas: epistaxis, gastrointestinal bleeding, anemia and iron deficiency, liver VMs, pediatric care, and pregnancy and delivery (36 total). The recommendations highlight new evidence in existing topics from the first International HHT Guidelines and provide guidance in 3 new areas: anemia, pediatrics, and pregnancy and delivery. These recommendations should facilitate implementation of key components of HHT care into clinical practice.


Assuntos
Telangiectasia Hemorrágica Hereditária/diagnóstico , Telangiectasia Hemorrágica Hereditária/terapia , Anemia/etiologia , Anemia/terapia , Malformações Arteriovenosas/etiologia , Malformações Arteriovenosas/terapia , Criança , Epistaxe/etiologia , Epistaxe/terapia , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/terapia , Doenças Genéticas Inatas/etiologia , Doenças Genéticas Inatas/terapia , Humanos , Fígado/irrigação sanguínea , Telangiectasia Hemorrágica Hereditária/complicações
2.
Microvasc Res ; 99: 118-26, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25892364

RESUMO

UNLABELLED: Hereditary hemorrhagic telangiectasia (HHT), the most common inherited vascular disorder, is predominantly caused by mutations in ENG and ACVRL1, which are part of the transforming growth factor beta (TGF-ß) signaling pathway. HHT is characterized by the presence of mucocutaneous telangiectases and arteriovenous malformations in visceral organs, primarily the lungs, brain and liver. The most common symptom in HHT is epistaxis originating from nasal telangiectasia, which can be difficult to prevent and can lead to severe anemia. The clinical manifestations of HHT are extremely variable, even within family members, and the exact mechanism of how endoglin and ALK1 haploinsufficiency leads to HHT manifestations remains to be identified. OBJECTIVES: The purpose of this study was to detect significantly differentially regulated genes in HHT, and try to elucidate the pathways and regulatory mechanisms occurring in the affected tissue of HHT patients, in order to further characterize this disorder and hypothesize on how telangiectases develop. By microarray technology (Agilent G3 Human GE 8x60), we performed global gene expression profiling of mRNA transcripts from HHT nasal telangiectasial (n = 40) and non-telangiectasial (n = 40) tissue using a paired design. Comparing HHT telangiectasial and non-telangiectasial tissue, significantly differentially expressed genes were detected using a paired t-test. Gene set analysis was performed using GSA-SNP. In the group of ENG mutation carriers, we detected 67 differentially expressed mRNAs, of which 62 were down-regulated in the telangiectasial tissue. Gene set analysis identified the gene ontology (GO) terms vasculogenesis, TGF-ß signaling, and Wnt signaling as differentially expressed in HHT1. Altered Wnt signaling might be related to HHT pathogenesis and a greater understanding of this may lead to the discovery of therapeutic targets in HHT.


Assuntos
Receptores de Activinas Tipo II/genética , Antígenos CD/genética , Perfilação da Expressão Gênica , Receptores de Superfície Celular/genética , Telangiectasia Hemorrágica Hereditária/genética , Malformações Arteriovenosas/genética , Biópsia , Análise por Conglomerados , Endoglina , Saúde da Família , Feminino , Genótipo , Humanos , Masculino , Mutação , Mucosa Nasal/patologia , Hibridização de Ácido Nucleico , Análise de Componente Principal , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo
3.
ORL J Otorhinolaryngol Relat Spec ; 76(5): 288-301, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25500788

RESUMO

AIMS: To investigate the presence of surfactant protein (SP) A, B, C and D in nasal airways and to determine whether the proteins exert their main functions in nasal secretions or in the deeper layers of the nasal mucosa. METHODS: Volunteers were recruited from the Department of ENT Head and Neck Surgery, Odense University Hospital, Denmark. The study included 39 subjects. Nasal mucosal biopsies were analyzed by immunohistochemistry, and bronchoalveolar and nasal lavages, nasal brush biopsies and nasal mucus were analyzed for SP-A, -B, -C and -D by SDS-PAGE and Western blotting. The presence of SP-A and SP-D in the first three samplings were also analyzed by enzyme-linked immunosorbent assay. RESULTS: In nasal mucosal biopsies, SP-A, -B, -C and -D were all demonstrated in the serous acini of the submucosal glands and in the surface epithelium. SP-D was detected in nasal brush biopsies, whereas the other SPs were absent. Moreover, SP-A, -B, -C and -D were absent in nasal lavage and mucus. CONCLUSION: SP-A, -B, -C and -D exert their protective effect in the ductal epithelium of the submucosal glands rather than in nasal secretions and mucus. Further studies are required to clarify the functions of these proteins in nasal secretory pathways for understanding upper airway diseases.


Assuntos
Mucosa Nasal/metabolismo , Proteína A Associada a Surfactante Pulmonar/metabolismo , Proteína B Associada a Surfactante Pulmonar/metabolismo , Proteína C Associada a Surfactante Pulmonar/metabolismo , Proteína D Associada a Surfactante Pulmonar/metabolismo , Biópsia , Western Blotting , Lavagem Broncoalveolar , Ensaio de Imunoadsorção Enzimática , Humanos , Técnicas Imunoenzimáticas , Muco/química , Irrigação Terapêutica
4.
Am J Ind Med ; 55(11): 1037-43, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22648974

RESUMO

BACKGROUND: Very little is known about occupational risk factors for chronic rhinosinusitis (CRS). The aim of this study was to evaluate occupational and other potential risk factors for CRS in a Danish population. METHODS: A cross sectional survey study among 4,554 Danes aged 20-75 years evaluated self-reported symptoms of CRS, asthma, and nasal allergy, along with information on smoking habits and occupation. RESULTS: A total of 3,099 returned completed questionnaires (response rate 68.1%). The overall CRS prevalence was 7.8% with no significant differences related to age or gender. Risk ratio estimates revealed an increased risk of CRS among female blue collar workers compared to female white collar workers. Among men the effect of occupation depended on smoking status. Occupational exposure to gasses, fumes, dust, or smoke increased the overall risk of CRS. CRS was reported approximately four times as often in subjects with asthma and in subjects with nasal allergy. Current smoking doubled the CRS prevalence. CONCLUSIONS: CRS prevalence was affected by occupation (blue vs. white collar), but the observed effect depended on gender and smoking status. Exposure to airway irritants (occupational or smoking) increased the CRS prevalence. Studies on larger cohorts are needed to fully assess these tendencies, for example, by more extensive use of Job Exposure Matrix models.


Assuntos
Exposição Ocupacional , Rinite/epidemiologia , Sinusite/epidemiologia , Adulto , Idoso , Doença Crônica , Intervalos de Confiança , Estudos Transversais , Dinamarca/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Risco , Fatores de Risco , Estatística como Assunto , Inquéritos e Questionários , Adulto Jovem
5.
Eur J Med Genet ; 65(10): 104575, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35940549

RESUMO

Hereditary haemorrhagic telangiectasia (HHT) is a rare vascular multisystemic disease that leads to epistaxis, anaemia due to blood loss, and arteriovenous malformations (AVMs) in organs such as the lungs, liver and brain. HHT prevalence is estimated at 1/6000, i.e. around 85,000 European citizens, and is served by the European Reference Network for Rare Multisystemic Vascular Diseases (VASCERN). HHT treatments depend on clinical manifestations, and span multiple different medical, surgical and interventional disciplines. Separate to local treatments in the nose, in severe settings, intravenous bevacizumab has been proposed as treatment option, and the purpose of the current article is to assess the use of intravenous bevacizumab in patients with HHT in 2022 according to available data.


Assuntos
Malformações Arteriovenosas , Telangiectasia Hemorrágica Hereditária , Bevacizumab/uso terapêutico , Epistaxe/tratamento farmacológico , Humanos , Doenças Raras , Telangiectasia Hemorrágica Hereditária/tratamento farmacológico
6.
Orphanet J Rare Dis ; 15(1): 334, 2020 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-33243256

RESUMO

BACKGROUND: This report addresses how patients with hereditary hemorrhagic telangiectasia (HHT) and high output cardiac failure (HOCF) due to hepatic vascular malformations, should be evaluated and could be treated. HHT is a genetic disorder, leading to vascular abnormalities with potentially serious clinical implications. In the liver, arteriovenous malformations occur in more than 70% of patients, but only about 8% present clinical symptoms such as HOCF with pulmonary hypertension and less commonly portal hypertension, biliary ischemia and hepatic encephalopathy. RESULTS: Three female patients with HHT type 2 and HOCF caused by severe arteriovenous malformations in the liver are presented in this case series. The patients were seen at the HHT-Centre at Odense University Hospital. Treatment with either orthotopic liver transplantation (one patient) or bevacizumab (two patients) was initiated. All patients experienced marked symptom relief and objective improvement. New York Heart Association-class were improved, ascites, peripheral edema and hence diuretic treatment was markedly reduced or discontinued in all three patients. Bevacizumab also resulted in notable effects on epistaxis and anemia. CONCLUSION: Our findings substantiate the importance of identification of symptomatic arteriovenous malformations in the liver in patients with HHT. Bevacizumab may possibly, as suggested in this case series and supported by previous case studies, postpone the time to orthotopic liver transplantation or even make it unnecessary. Bevacizumab represents a promising new treatment option, which should be investigated further in clinical trials.


Assuntos
Malformações Arteriovenosas , Insuficiência Cardíaca , Telangiectasia Hemorrágica Hereditária , Bevacizumab , Feminino , Humanos , Fígado , Telangiectasia Hemorrágica Hereditária/complicações , Telangiectasia Hemorrágica Hereditária/tratamento farmacológico
7.
Mol Genet Genomic Med ; 8(11): e1498, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33058509

RESUMO

BACKGROUND: Patients with germline variants in SMAD4 can present symptoms of both juvenile polyposis syndrome (JPS) and Hereditary Hemorrhagic Telangiectasia (HHT): JP-HHT syndrome. Next-Generation Sequencing (NGS) techniques disclose causative sequence variants in around 90% of HHT patients fulfilling the Curaçao criteria. Here we report a translocation event involving SMAD4 resulting in JP-HHT. METHODS: A patient fulfilling the Curaçao criteria was analyzed for variants in ENG, ACVRL1, and SMAD4 using standard techniques. Whole-genome sequencing (WGS) using both short-read NGS technology and long-read Oxford Nanopore technology was performed to define the structural variant and exact breakpoints. RESULTS: No pathogenic variant was detected in ENG, ACVRL1, or SMAD4 in DNA extracted from blood. Due to abortus habitualis, the proband´s daughter was submitted for chromosomal analysis, and a cytogenetically balanced chromosomal reciprocal translocation t(1;18)(p36.1;q21.1) was detected in the daughter and the patient. The balanced translocation segregated with both gastrointestinal cancer and HHT in the family. WGS provided the exact breakpoints of the reciprocal translocation proving disruption of the SMAD4 gene. DISCUSSION: A disease-causing reciprocal translocation between chromosome 1 and 18 with a breakpoint in the SMAD4 locus co-segregated with JP-HHT in an extended family. This observation warrants further analysis for chromosomal rearrangements in individuals with clinical HHT or JP-HHT of unknown cause.


Assuntos
Polipose Intestinal/congênito , Síndromes Neoplásicas Hereditárias/genética , Fenótipo , Proteína Smad4/genética , Telangiectasia Hemorrágica Hereditária/genética , Translocação Genética , Adulto , Pontos de Quebra do Cromossomo , Cromossomos Humanos Par 1/genética , Cromossomos Humanos Par 18/genética , Feminino , Humanos , Polipose Intestinal/genética , Polipose Intestinal/patologia , Masculino , Síndromes Neoplásicas Hereditárias/patologia , Linhagem , Telangiectasia Hemorrágica Hereditária/patologia
8.
Orphanet J Rare Dis ; 15(1): 165, 2020 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-32600364

RESUMO

Hereditary haemorrhagic telangiectasia (HHT) is a multisystemic vascular dysplasia inherited as an autosomal dominant trait. Approximately 10 % of patients have cerebral vascular malformations, a proportion being cerebral arteriovenous malformations (AVMs) and fistulae that may lead to potentially devastating consequences in case of rupture. On the other hand, detection and treatment related-risks are not negligible, and immediate. While successful treatment can be undertaken in individual cases, current data do not support the treatment of unruptured AVMs, which also present a low risk of bleeding in HHT patients. Screening for these AVMs is therefore controversial.Structured discussions, distinctions of different cerebrovascular abnormalities commonly grouped into an "AVM" bracket, and clear guidance by neurosurgical and neurointerventional radiology colleagues enabled the European Reference Network for Rare Vascular Disorders (VASCERN-HHT) to develop the following agreed Position Statement on cerebral screening:1) First, we emphasise that neurological symptoms suggestive of cerebral AVMs in HHT patients should be investigated as in general neurological and emergency care practice. Similarly, if an AVM is found accidentally, management approaches should rely on expert discussions on a case-by-case basis and individual risk-benefit evaluation of all therapeutic possibilities for a specific lesion.2) The current evidence base does not favour the treatment of unruptured cerebral AVMs, and therefore cannot be used to support widespread screening of asymptomatic HHT patients.3) Individual situations encompass a wide range of personal, cultural and clinical states. In order to enable informed patient choice, and avoid conflicting advice, particularly arising from non-neurovascular interpretations of the evidence base, we suggest that all HHT patients should have the opportunity to discuss knowingly brain screening issues with their healthcare provider.4) Any screening discussions in asymptomatic individuals should be preceded by informed pre-test review of the latest evidence regarding preventative and therapeutic efficacies of any interventions. The possibility of harm due to detection of, or intervention on, a vascular malformation that would not have necessarily caused any consequence in later life should be stated explicitly.We consider this nuanced Position Statement provides a helpful, evidence-based framework for informed discussions between healthcare providers and patients in an emotionally charged area.


Assuntos
Malformações Arteriovenosas Intracranianas , Telangiectasia Hemorrágica Hereditária , Adulto , Encéfalo , Criança , Humanos , Malformações Arteriovenosas Intracranianas/diagnóstico , Programas de Rastreamento , Doenças Raras , Telangiectasia Hemorrágica Hereditária/diagnóstico , Telangiectasia Hemorrágica Hereditária/genética
9.
Eur Arch Otorhinolaryngol ; 266(7): 1011-5, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18953553

RESUMO

Post-tonsillectomy hemorrhage (PTH) is a relatively common and potentially life-threatening complication. The objective of this study was to examine the rate of PTH and identify risk factors. A retrospective cohort study was carried out including all tonsillectomies (430 patients) performed at Odense University Hospital (OUH) or Svendborg Hospital (SH), Denmark. PTH occurred in 52 patients (12.1%). Of the 180 patients treated with coblation technique, 41 (22.7%) had PTH. There were no fatal bleeding episodes. Multiple regression analysis resulted in three significant covariates: "Coblation as surgical technique" [relative risk (RR) = 5.3], "peritonsillar abscess as indication for surgery" (RR = 0.3) and "age equal to or above 15 years at the time of surgery" (RR = 5.4). It is concluded that patient age, PTA as indication for surgery and the use of coblation significantly affect the occurrence of PTH when coblation procedures are performed by non-experienced surgeons. We advise that implementation of coblation tonsillectomy is thoroughly planned with sufficient training of surgeons and continuous surveillance of results. If PTH rates comparable to "cold dissections tonsillectomy" cannot be reached intervention (learning or closing down of coblation tonsillectomy) has to be done.


Assuntos
Tonsila Palatina/cirurgia , Hemorragia Pós-Operatória/prevenção & controle , Tonsilectomia/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos de Coortes , Eletrocoagulação/efeitos adversos , Feminino , Hemostasia Cirúrgica , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Hemorragia Pós-Operatória/etiologia , Estudos Retrospectivos , Fatores de Risco , Tonsilectomia/efeitos adversos , Adulto Jovem
10.
Orphanet J Rare Dis ; 14(1): 28, 2019 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-30717761

RESUMO

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is a multisystemic inherited vascular dysplasia that leads to nosebleeds and visceral arteriovenous malformations (AVMs). Anti-angiogenic drugs thalidomide and bevacizumab have been increasingly used off-label with variable results. The HHT working group within the ERN for Rare Multisystemic Vascular Diseases (VASCERN), developed a questionnaire-based retrospective capture of adverse events (AEs) classified using the Common Terminology Criteria for Adverse Events. RESULTS: Sixty-nine HHT patients received bevacizumab, 37 (50.6%) for high output cardiac failure/hepatic AVMs, and 32 (49.4%) for bleeding; the 69 patients received bevacizumab for a mean of 11 months for a total of 63.8 person/years treatment. 67 received thalidomide, all for epistaxis and/or gastrointestinal bleeding; they received thalidomide for a mean of 13.4 months/patient for a total of 75 person/years treatment. AEs were reported in 58 patients, 33 with bevacizumab, 37 with thalidomide. 32 grade 1-3 AEs related to bevacizumab were reported with an average incidence rate of 50 per 100 person-years. 34 grade 1-3 AEs related to thalidomide were reported with an average incidence rate of 45.3 per 100 person-years. Bevacizumab AEs were more common in females (27 AEs in 46 women) than males (6 in 23, p < 0.001). Thalidomide AEs occurred at more similar rates in males (25 AEs in 41 men, 60.9%) and females (12 in 26 (46.2%), but were more common in ENG patients (17 in 17) than in ACVRL1 (14 in 34, p < 0.0001). For bevacizumab, the most common reports were of joint pains (7/69, 10%), headache (3/69, 4.4%) and proteinuria (2/69, 3%), and for thalidomide, peripheral neuropathy (12/67, 18%); drowsiness (8/67, 12%); and dizziness (6/67, 9%). Fatal adverse events were more common in males (p = 0.009), and in patients with ENG pathogenic variants (p = 0.012). One fatal AE was possibly related to bevacizumab (average incidence rate: 1.5 per 100 person-years); 3 fatal AEs were possibly related to thalidomide (average incidence rate: 4 per 100 person-years). CONCLUSIONS: With potential increase in use of Bevacizumab and Thalidomide in HHT patients, data presented support appropriate weighing of the toxicities which can arise in HHT settings and the practice recommendations for their prevention and management.


Assuntos
Bevacizumab/efeitos adversos , Telangiectasia Hemorrágica Hereditária/fisiopatologia , Talidomida/efeitos adversos , Adolescente , Adulto , Bevacizumab/uso terapêutico , Epistaxe/tratamento farmacológico , Epistaxe/metabolismo , Epistaxe/fisiopatologia , Feminino , Hemorragia/tratamento farmacológico , Hemorragia/metabolismo , Hemorragia/fisiopatologia , Humanos , Masculino , Estudos Retrospectivos , Inquéritos e Questionários , Telangiectasia Hemorrágica Hereditária/tratamento farmacológico , Telangiectasia Hemorrágica Hereditária/metabolismo , Talidomida/uso terapêutico , Adulto Jovem
11.
Mol Genet Genomic Med ; 6(1): 121-125, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29243366

RESUMO

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant genetic disorder caused by mutations in ENG, ACVRL1, or SMAD4. Around 90% of HHT patients present with a heterozygous pathogenic genetic variation. Almost all cases of HHT have a family history. Very few cases are de novo or mosaicism. We describe a case with mutational mosaicism that would not be observed in the clinical routine when using Sanger sequencing or a NGS read coverage below app. 100. METHODS: DNA was extracted from peripheral blood leukocytes, and buccal swabs. The coding region, exon-intron boundaries, and the flanking sequences of the genes were sequenced by NGS. RESULTS: The proband had clinical HHT fulfilling the Curaçao criteria and genetic testing identified a frameshift mutation in ENG. The mother of the proband, also with clinical HHT, was found negative when analyzing DNA from blood for the familial mutation using Sanger sequencing. Analyzing her DNA by NGS HHT panel sequencing when extracted from both peripheral blood leukocytes, and cheek swabs, identified the familial ENG mutation at low levels. CONCLUSION: We provide evidence of ENG mutational mosaicism in an individual presenting with clinical HHT. These findings illustrate the importance of considering mutational mosaicism.


Assuntos
Endoglina/genética , Telangiectasia Hemorrágica Hereditária/genética , Receptores de Activinas Tipo II/genética , Adulto , Idoso , Sequência de Bases , Endoglina/fisiologia , Éxons , Feminino , Mutação da Fase de Leitura , Testes Genéticos , Humanos , Mosaicismo , Mutação , Linhagem , Proteína Smad4/genética , Telangiectasia Hemorrágica Hereditária/fisiopatologia
12.
Orphanet J Rare Dis ; 13(1): 136, 2018 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-30111344

RESUMO

Hereditary haemorrhagic telangiectasia (HHT) is a multisystemic vascular dysplasia that leads to nosebleeds, anaemia due to blood loss, and arteriovenous malformations (AVMs) in organs such as the lungs, liver and brain. HHT is estimated to affect 85,000 European citizens, but most health care providers have limited prior HHT exposure or training.Outcome Measures were developed and implemented by the HHT Working Group of the European Reference Network for Rare Vascular Diseases (VASCERN), in order to maximise the number of patients receiving good care. The measures specifically target areas where optimal management reduces morbidity and mortality in HHT patients, and were designed to be robust to emerging new evidence. Thresholds are the percentage of patients in particular settings who have been recommended screening, or provided with written advice. The 5 Outcome Measures cover (1) pulmonary AVM screening; (2) written nosebleed advice, (3) assessment of iron deficiency; (4) antibiotic prophylaxis prior to dental and surgical procedures for patients with pulmonary AVMs, and (5) written advice on pregnancy. They are not a blueprint for detailed HHT management, but are suitable for all clinicians to be aware of and implement.In summary, these 5 Outcome Measures provide metrics to identify healthcare providers of good care, and encourage care improvement by all healthcare providers.


Assuntos
Telangiectasia Hemorrágica Hereditária/diagnóstico , Anemia Ferropriva/diagnóstico , Malformações Arteriovenosas/diagnóstico , Epistaxe/diagnóstico , Feminino , Humanos , Gravidez , Doenças Raras/diagnóstico
13.
Am J Rhinol Allergy ; 29(3): e70-4, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25975241

RESUMO

BACKGROUND: An increased coexistence of gastroesophageal reflux disease (GERD) and chronic rhinosinusitis (CRS) has been reported in epidemiologic and register studies, and reflux has been shown more frequently in patients with CRS in studies using esophagus pH manometry compared to participants without CRS. A discussion is ongoing about whether there might be an association between these two diseases and, if so, whether the association is causal. OBJECTIVE: The purpose of this study was to clinically investigate the prevalence and symptom severity scores of CRS among patients with GERD. The results were compared with those of a randomly assigned control group from the general Danish population. METHOD: In this case-control study, 82 patients with GERD were examined for CRS using the European Position Paper on Rhinosinusitis and Nasal Polyps criteria, which combine patient history and anterior/posterior rhinoscopy results. Sinonasal-related quality of life was assessed by using the Sino-Nasal Outcome Test 22 (SNOT-22). These results were compared with those of a population-based control group examined for CRS in the same way. RESULTS: The prevalence of CRS among patients with GERD was 20.7% (95% confidence interval [CI], 12.0%-29.5%), significantly higher than the CRS prevalence of 8.5% (95% CI, 6.8%-10.2%) in the background population. Patients with GERD and CRS had an average SNOT-22 score of 43.8, whereas patients with CRS from the background population scored, on average, 28.1. Having GERD increased the mean SNOT-22 score in patients with CRS by 15.7 (95% CI, 6.5-24.9). CONCLUSION: The results of this study provide additional evidence of an association between GERD and CRS and indicate that GERD may play a role in the development of CRS. The results also show that sinonasal-related quality of life is decreased in patients with CRS who also suffer from GERD.


Assuntos
Refluxo Gastroesofágico/epidemiologia , Rinite/epidemiologia , Sinusite/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Causalidade , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Qualidade de Vida
14.
Acta Otolaryngol ; 135(7): 706-12, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25813521

RESUMO

CONCLUSION: By consulting an ENT-doctor, patients with chronic rhinosinusitis (CRS), in the general population, receive disease information and adjustment of treatment which can improve disease-specific Quality-of-Life and may improve objective measurements. OBJECTIVES: This study aims to follow persons with clinical diagnosed CRS from the general population, to evaluate their benefit from consultation with an ENT-doctor in terms of severity of symptoms and Quality-of-Life. METHODS: As part of a trans-European study, selected respondents to a survey questionnaire were invited for a clinical visit. Based on the European Position Paper on Rhinosinusitis and Nasal Polyps, persons were diagnosed with CRS and followed for 2 years. Quality-of-Life was measured using the Sino Nasal Outcome Test 22 and European Quality-of-Life - 5 Dimensions. Clinical examination included rhinoscopy, acoustic rhinometry, peak nasal inspiratory flow, smell test, and skin prick test. RESULTS: Out of 91 persons with CRS, only 42% had previously consulted an ENT-doctor, and 51% were in current treatment for CRS. Most patients were advised medical treatment and 20% underwent surgery. Disease-specific Quality-of-Life, peak nasal inspiratory flow, olfactory function, and the nasal volume significantly increased over the 2-year period.


Assuntos
Otolaringologia/estatística & dados numéricos , Rinite/terapia , Sinusite/terapia , Adolescente , Adulto , Doença Crônica , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Inquéritos e Questionários , Adulto Jovem
15.
PLoS One ; 9(3): e90272, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24603890

RESUMO

Hereditary Haemorrhagic Telangiectasia (HHT) is an autosomal dominantly inherited vascular disease characterized by the presence of mucocutaneous telangiectasia and arteriovenous malformations in visceral organs. HHT is predominantly caused by mutations in ENG and ACVRL1, which both belong to the TGF-ß signalling pathway. The exact mechanism of how haploinsufficiency of ENG and ACVRL1 leads to HHT manifestations remains to be identified. As long non-coding RNAs (lncRNAs) are increasingly recognized as key regulators of gene expression and constitute a sizable fraction of the human transcriptome, we wanted to assess whether lncRNAs play a role in the molecular pathogenesis of HHT manifestations. By microarray technology, we profiled lncRNA transcripts from HHT nasal telangiectasial and non-telangiectasial tissue using a paired design. The microarray probes were annotated using the GENCODE v.16 dataset, identifying 4,810 probes mapping to 2,811 lncRNAs. Comparing HHT telangiectasial tissue with HHT non-telangiectasial tissue, we identified 42 lncRNAs that are differentially expressed (q<0.001). Using GREAT, a tool that assumes cis-regulation, we showed that differently expressed lncRNAs are enriched for genomic loci involved in key pathways concerning HHT. Our study identified lncRNAs that are aberrantly expressed in HHT telangiectasia and indicates that lncRNAs may contribute to regulate protein-coding loci in HHT. These results suggest that the lncRNA component of the transcriptome deserves more attention in HHT. A deeper understanding of lncRNAs and their role in telangiectasia formation possesses potential for discovering therapeutic targets in HHT.


Assuntos
Perfilação da Expressão Gênica , Análise de Sequência com Séries de Oligonucleotídeos/métodos , RNA Longo não Codificante/genética , Telangiectasia Hemorrágica Hereditária/genética , Receptores de Activinas Tipo II/genética , Adulto , Antígenos CD/genética , Análise por Conglomerados , Endoglina , Feminino , Ontologia Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Fenótipo , RNA Longo não Codificante/classificação , Receptores de Superfície Celular/genética , Telangiectasia Hemorrágica Hereditária/patologia , Adulto Jovem
16.
Artigo em Inglês | MEDLINE | ID: mdl-23986830

RESUMO

Pulmonary arteriovenous malformations (PAVMs) with feeding arteries of 3 mm or more have been shown to be associated with paradoxical embolization and serious neurologic complications. Therefore it is generally recommended to occlude feeding arteries of this size, while smaller feeding arteries often are left untreated. However, neurologic complications have also been described in patients with small PAVMs, and it has not been possible to stratify risk by size of feeding artery and thus there is no evidence that 3 mm is the critical size of the feeding artery potentially giving complications. Further, it is well-known that with time PAVMs and their feeding arteries may enlarge. Also, embolization of small feeding arteries will minimize the risk of paradoxical emboli and reduce the need for CT follow-up controls in these patients. Two cases demonstrate the possibility to embolize small feeding arteries.

17.
Genet Test Mol Biomarkers ; 16(12): 1419-23, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23046070

RESUMO

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal-dominant vascular disorder with three disease-causing genes identified to date: ENG, ACVRL1, and SMAD4. We report an HHT patient with allelic dropout that on routine sequence analysis for a known mutation in the family (c.817-3T>G in ENG) initially seemed to be homozygous for the mutation. AIM: To explore the possibility of allelic dropout causing a false result in this patient. METHODS: Mutation analysis of additional family members was performed and haplotype analysis carried out. New primers were designed to reveal the presence of a possible sequence variant, which could explain the presumed allelic dropout. RESULTS: Allelic dropout caused by a six-nucleotide duplication close to the standard reverse primer was the assumed cause of a false homozygous diagnosis. CONCLUSION: Sequence variants outside of the primer regions can be the cause of allelic dropout, creating unforeseen errors in genotyping. Our finding emphasizes the need for careful quality control in all molecular genetic studies.


Assuntos
Antígenos CD/genética , Testes Genéticos , Receptores de Superfície Celular/genética , Telangiectasia Hemorrágica Hereditária/genética , Receptores de Activinas Tipo II/genética , Adolescente , Sequência de Bases , Endoglina , Feminino , Genótipo , Humanos , Perda de Heterozigosidade , Masculino , Dados de Sequência Molecular , Proteína Smad4/genética
18.
PLoS One ; 7(11): e47383, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23144819

RESUMO

The complement system is an important part of our immune system, and complement defects lead generally to increased susceptibility to infections and autoimmune diseases. We have studied the role of complement activity in relation with chronic rhinosinusitis (CRS), and more specifically studied whether complement defects collectively predispose individuals for CRS or affect CRS severity. The participants comprised 87 CRS patients randomly selected from the general population, and a control group of 150 healthy blood donors. The CRS patients were diagnosed according to the European Position Paper on Rhinosinusitis and nasal Polyps criteria, and severity was evaluated by the Sino-nasal Outcome Test-22. Serum samples were analysed by ELISA for activity of the respective pathways of complement, and subsequently for serum levels of relevant components. We found that the frequency of complement defects was significantly higher among CRS patients than among healthy control subjects. A majority of Mannan-binding lectin deficient CRS patients was observed. The presence of complement defects had no influence on the severity of subjective symptoms. Our studies show that defects in the complement system collectively may play an immunological role related to the development of CRS. However, an association between severity of symptoms and presence of complement defects could not be demonstrated.


Assuntos
Proteínas do Sistema Complemento/imunologia , Sinusite/sangue , Sinusite/imunologia , Adulto , Idoso , Doença Crônica , Ativação do Complemento , Proteínas do Sistema Complemento/análise , Feminino , Humanos , Masculino , Lectina de Ligação a Manose/sangue , Lectina de Ligação a Manose/imunologia , Pessoa de Meia-Idade , Mucosa Nasal/imunologia , Mucosa Nasal/patologia , Transdução de Sinais , Sinusite/diagnóstico , Adulto Jovem
19.
Cardiovasc Intervent Radiol ; 31(3): 569-74, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18157681

RESUMO

Long-term follow-up results after embolization of 13 pulmonary arteriovenous malformations in 10 patients by use of 14 detachable silicone balloons are given. Patients were followed for a mean of 99 months (range, 63-123 months) with chest x-rays and for a mean of 62 months (range, 3-101 months) with pulmonary angiography. Fifty-four percent of the balloons were deflated at latest radiographic chest film follow-up, but at pulmonary angiographic follow-up all embolized malformations were without flow irrespective of whether or not the balloons were visible. Detachable silicone balloons are not available anymore, but use of these balloons for embolization of pulmonary arteriovenous malformations has been shown to be a safe and precise method, with immediate occlusion of the feeding artery and with long-lasting occlusion, even though many balloons deflate with time, leaving a fibrotic scar replacing the pulmonary arteriovenous malformation. No case of recanalization has been discovered, and these results seem to justify a reduced number of controls of these balloon-embolized malformations.


Assuntos
Fístula Arteriovenosa/terapia , Malformações Arteriovenosas/terapia , Oclusão com Balão/instrumentação , Circulação Pulmonar/fisiologia , Adulto , Idoso , Angiografia , Fístula Arteriovenosa/diagnóstico por imagem , Fístula Arteriovenosa/mortalidade , Malformações Arteriovenosas/diagnóstico por imagem , Malformações Arteriovenosas/mortalidade , Oclusão com Balão/métodos , Desenho de Equipamento , Segurança de Equipamentos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Pulmonar/anormalidades , Veias Pulmonares/anormalidades , Radiologia Intervencionista/métodos , Estudos Retrospectivos , Medição de Risco , Silicones , Estatísticas não Paramétricas , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento
20.
Ugeskr Laeger ; 169(24): 2322-5, 2007 Jun 11.
Artigo em Da | MEDLINE | ID: mdl-17594850

RESUMO

INTRODUCTION: Nose fractures are the most common among facial fractures. A well-approved treatment of isolated nose fractures is closed reposition under local or general anaesthesia. MATERIALS AND METHODS: This study included 150 patients who were treated with closed reposition for simple and isolated nose fracture at the Otorhinolaryngology Department of Odense University Hospital during the period 1 January 2003 until 31 December 2004. The case records were retrospectively examined and the patients were sent a questionnaire and were offered outpatient follow-up. RESULTS: The most frequent cause of damage was violence. The average interval from trauma to treatment was 4.1 days. 60% of the patients filed cosmetic results equal to or better than before fracturing the nose regardless of the anaesthetic procedure, while 69% of the patients experienced the function of the nose as equal to or better than before. CONCLUSION: The majority of nose fractures are treated under local anaesthesia. A follow-up at least 1 year later found no difference between patient satisfaction of cosmetic and functional results of the nose, regardless of whether they had local or general anaesthesia. In general, the patients were satisfied with the anaesthesia, whether it was local or general.


Assuntos
Traumatismos Faciais/cirurgia , Fraturas Ósseas/cirurgia , Osso Nasal/lesões , Satisfação do Paciente , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anestesia Geral , Anestesia Local , Criança , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Estudos Retrospectivos , Inquéritos e Questionários , Resultado do Tratamento
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