RESUMO
BACKGROUND: Local application of fluorouracil (Efudix, 5-FU) induces sclerosis in patients with sinonasal tumors and superficial basocellular skin carcinoma. As a 'back against the wall' treatment, we investigated the local effect of nasally applied 5-FU and whether this could decrease the burden of severe epistaxis in patients with hereditary hemorrhagic telangiectasia (HHT). METHODS: HHT patients with severe and frequent epistaxis, subsequent anemia and a necessity for blood and/or iron infusions were treated with a nasal tampon with 5-FU. This tampon was placed unilaterally in the nasal cavity on the side of the most severe epistaxis and replaced once weekly during 4 weeks. Outcome measures were safety and side effects, the aspect of the nasal mucosa measured with the mucosal HHT score, the epistaxis severity score (ESS), hemoglobin and ferritin plasma levels, and quality of life assessment pre-treatment, one and three months post-treatment. RESULTS: Six HHT patients participated. During treatment and follow-up, the nasal mucosa turned more pale and sclerotic and the number of telangiectases diminished. The mucosal HHT score improved and the ESS declined (p = 0.01). The decline of ESS persisted up to 3 months post-5-FU treatment. Moreover, mean hemoglobin levels increased from 6.0 pre-5-FU to 6.8 after one month post-5-FU. CONCLUSION: Unilateral application of 5-FU on a nasal tampon diminished the severity and frequency of epistaxis in all HHT patients. This effect sustained up to three months post-treatment, despite the fact that the contralateral side remained untreated. Subsequently, hemoglobin levels increased. Intranasal 5-FU is a promising entity for further research on epistaxis treatment in HHT patients.
Assuntos
Epistaxe/tratamento farmacológico , Fluoruracila/administração & dosagem , Telangiectasia Hemorrágica Hereditária/tratamento farmacológico , Administração Intranasal , Adulto , Idoso , Epistaxe/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Índice de Gravidade de Doença , Telangiectasia Hemorrágica Hereditária/metabolismoRESUMO
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 JovemRESUMO
OBJECTIVES/HYPOTHESIS: We aimed to investigate if vascular endothelial growth factor (VEGF) and other angiogenic and inflammatory factors correlated with the clinical presentation in hereditary hemorrhagic telangiectasia (HHT) patients, particularly in regard to the severity of epistaxis. STUDY DESIGN: Prospective, comparative, single-center study. METHODS: One hundred nine samples were collected from 75 HHT patients attending the ear, nose, and throat department at Oslo University Hospital from February 2012 to August 2013. For comparison, samples were collected from 16 healthy controls. Angiogenic and inflammatory factors related to endothelial cell activation were analyzed by enzyme immunoassays. The grade of epistaxis was evaluated using the Epistaxis Severity Score and epistaxis Intensity, Frequency, and Need for Blood Transfusion score at the day of blood sampling. The presence of internal organ manifestations in the HHT group was recorded. RESULTS: Pentraxin 3 (PTX3) was the only factor that was significantly higher in the HHT patients than the controls and showed significant correlation to the epistaxis severity grade and the hemoglobin level. The VEGF level was higher in the HHT patients compared to controls but not to a significant degree. In addition, a significant correlation of the level of VEGF and the grade of epistaxis could not be observed. Also, no significant correlations were observed between the presence of internal organ manifestations and the level of angiogenic factors. CONCLUSIONS: PTX3, at least partly reflecting vascular inflammation, can be a potential biomarker for the severity of HHT associated epistaxis. The serum level of VEGF was not correlated with the severity of epistaxis in the HHT patients. LEVEL OF EVIDENCE: 2 Laryngoscope, 129:E44-E49, 2019.
Assuntos
Proteína C-Reativa/metabolismo , Epistaxe/etiologia , Epistaxe/metabolismo , Componente Amiloide P Sérico/metabolismo , Telangiectasia Hemorrágica Hereditária/complicações , Telangiectasia Hemorrágica Hereditária/metabolismo , Biomarcadores/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
AIM: To explore the association between vitamin D levels and mild versus severe epistaxis, as well as the overall epistaxis severity score (ESS) in patients with hereditary hemorrhagic telangiectasia. PATIENTS & METHODS: A retrospective chart review of 198 patients was performed to explore the relationship between vitamin D levels and the ESS. Vitamin D levels were also compared with those with mild epistaxis to those with severe epistaxis. RESULTS: A significant difference was found between patient's vitamin D levels and their associated ESS and duration of epistaxis. Patients with mild epistaxis had higher levels of vitamin D than patients with severe epistaxis. CONCLUSION: Vitamin D is associated with features of hereditary hemorrhagic telangiectasia including ESS, bleeding time and epistaxis severity.
Assuntos
Epistaxe/complicações , Epistaxe/metabolismo , Telangiectasia Hemorrágica Hereditária/complicações , Vitamina D/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Adulto JovemRESUMO
Hereditary hemorrhagic telangiectasia is an autosomal dominant trait affecting approximately 1 in 5000 people. A pathogenic DNA sequence variant in the ENG, ACVRL1 or SMAD4 genes, can be found in the majority of patients. The 12th International Scientific HHT Conference was held on June 8-11, 2017 in Dubrovnik, Croatia to present and discuss the latest scientific achievements, and was attended by over 200 scientific and clinical researchers. In total 174 abstracts were accepted of which 58 were selected for oral presentations. This article covers the basic science and clinical talks, and discussions from three theme-based workshops. We focus on significant emergent themes and unanswered questions. Understanding these topics and answering these questions will help to define the future of HHT research and therapeutics, and ultimately bring us closer to a cure.
Assuntos
Telangiectasia Hemorrágica Hereditária , Receptores de Activinas Tipo II/genética , Receptores de Activinas Tipo II/metabolismo , Malformações Arteriovenosas/genética , Malformações Arteriovenosas/metabolismo , Malformações Arteriovenosas/patologia , Malformações Arteriovenosas/terapia , Croácia , Endoglina/genética , Endoglina/metabolismo , Epistaxe/genética , Epistaxe/metabolismo , Variação Genética , Humanos , Proteína Smad4/genética , Proteína Smad4/metabolismo , Telangiectasia Hemorrágica Hereditária/genética , Telangiectasia Hemorrágica Hereditária/metabolismo , Telangiectasia Hemorrágica Hereditária/patologia , Telangiectasia Hemorrágica Hereditária/terapiaRESUMO
BACKGROUND: Oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC-ox) induces specific morbidity with hemorrhagic complications (HC). The aim of this study was to identify preoperative, intraoperative and postoperative HC predictive factors after HIPEC-ox. METHODS: A prospective single center study that included all consecutive patients treated with curative-intent HIPEC-ox, whatever the origin of peritoneal disease, was conducted. All patients underwent systematic blood tests exploring primary hemostasis and endothelial activation before surgical incision (D0) and on postoperative days 2 (POD2) and 5 (POD5). RESULTS: Between May 2012 and August 2015, 47 patients were enrolled in the study. The overall HC rate was 38%. Major morbidity was significantly higher in patients with HC. Patients presenting HC were significantly more often affected with pseudomyxoma peritonei and had less preoperative chemotherapy. Multivariate analysis showed that a higher plasmatic level of Von Willebrand factor antigen at D0 (D0 VWF:Ag) was a protective predictive factor for HC (p = 0.049, HR: 0.97 CI 95% [0.94-1.00]). A D0 VWF:Ag level below 138% had a sensitivity of 87.5%, a specificity of 67% and an area under the curve of 80.3% (CI 95% [66.5-94], p < 0.01) for predicting HC. CONCLUSIONS: Through the identification of prognostic factors, this study highlighted a subgroup of patients with low risk of HC after HIPEC-ox. Based on these results, we propose a routine preoperative dosage of VWF that would help the surgeon to select the most suitable patients for HIPEC-ox.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Procedimentos Cirúrgicos de Citorredução , Hipertermia Induzida/métodos , Compostos Organoplatínicos/administração & dosagem , Neoplasias Peritoneais/terapia , Hemorragia Pós-Operatória/epidemiologia , Fator de von Willebrand/metabolismo , Adulto , Idoso , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Epistaxe/epidemiologia , Epistaxe/metabolismo , Epistaxe/prevenção & controle , Feminino , Hemorragia Gastrointestinal/epidemiologia , Hemorragia Gastrointestinal/metabolismo , Hemorragia Gastrointestinal/prevenção & controle , Humanos , Infusões Parenterais , Neoplasias Intestinais/patologia , Neoplasias Intestinais/terapia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Oxaliplatina , Doenças Peritoneais/epidemiologia , Doenças Peritoneais/metabolismo , Doenças Peritoneais/prevenção & controle , Neoplasias Peritoneais/secundário , Hemorragia Pós-Operatória/metabolismo , Hemorragia Pós-Operatória/prevenção & controle , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Neoplasias Uterinas/patologia , Neoplasias Uterinas/terapia , Fator de von Willebrand/uso terapêuticoRESUMO
CONCLUSION: This immunohistochemical study of estrogen and progesterone receptors could not confirm a significant expression in nasal telangiectasias. Thus, a specific effect of these hormones or anti-hormone therapy on malformed nasal vessels has to be questioned and only offered under strict clinical control. OBJECTIVE: The efforts to control recurrent epistaxis in hereditary hemorrhagic telangiectasia (HHT) using alternative methods are very intense. Hormone or anti-hormone therapy has frequently been postulated and the reported results are controversial. Therefore it was important to find an explanation regarding a possible impact of hormonal therapies by immunohistochemical evaluation of progesterone and estrogen receptor expression on nasal telangiectasias of affected patients. METHODS: Tissue samples of nasal mucosa with evidence of telangiectasias from 14 patients with HHT were analyzed for the expression of progesterone and estrogen receptors on the nuclei of endothelial cells of the malformed vessels using immunohistochemistry. RESULTS: Progesterone receptors were not detected in any of the cases and only two cases showed a weak expression of estrogen receptors with an immunoreactive score of 2/12.
Assuntos
Imuno-Histoquímica/métodos , Mucosa Nasal/irrigação sanguínea , Receptores de Estrogênio/biossíntese , Receptores de Progesterona/biossíntese , Telangiectasia Hemorrágica Hereditária/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Epistaxe/tratamento farmacológico , Epistaxe/etiologia , Epistaxe/metabolismo , Estrogênios/uso terapêutico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Progesterona/uso terapêutico , Progestinas/uso terapêutico , Prognóstico , Estudos Retrospectivos , Telangiectasia Hemorrágica Hereditária/complicações , Telangiectasia Hemorrágica Hereditária/tratamento farmacológico , Telangiectasia/complicações , Telangiectasia/tratamento farmacológico , Telangiectasia/metabolismoRESUMO
BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular dysplasia and severe, recurrent epistaxis is a common clinical phenotype associated with HHT. An intranasal treatment regime of diluted Avastin™ (Bevacizumab; recombinant humanized anti-vascular epithelial growth factor immunoglobin G1) using apulsatile nasal irrigator has proven efficacious in clinical practice. However, concerns regarding the stability of Avastin™ following dilution and prolonged storage in standard containers used for drug delivery, such as polyethylene bottles, have so far prevented a more widespread clinical use. Compatibility with the preservative benzalkonium chloride was also unknown. OBJECTIVE: This study aimed at determining, whether dilution, prolonged refrigerated storage and the presence of the preservative benzalkonium chloride - as required for novel Avastin™ formulations - affected the biochemical and electrochemical properties of the drug. METHODS: We performed a detailed biochemical and electrochemical analysis of Avastin™, including native and sodium dodecyl sulfate polyacrylamide gel electrophoresis, enzyme-linked immunosorbent assay and isoelectric focusing. RESULTS: We did not detect any evidence of degeneration or aggregation following dilution and prolonged, refrigerated storage or from the presence of benzalkonium chloride. All biochemical and electrochemical properties of Avastin™ after dilution and prolonged, refrigerated storage were undistinguishable from control. CONCLUSIONS: Our data provide important insight into the stability of Avastin™ and allow the consideration of novel Avastin™ formulations, including its use in a metered-dose nasal spray for the treatment of HHT and other applications.
Assuntos
Receptores de Activinas Tipo II/imunologia , Inibidores da Angiogênese/imunologia , Anticorpos Monoclonais Humanizados/imunologia , Compostos de Benzalcônio/química , Epistaxe/tratamento farmacológico , Telangiectasia Hemorrágica Hereditária/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptores de Activinas Tipo II/genética , Administração Intranasal , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Bevacizumab , Estabilidade de Medicamentos , Eletroforese em Gel de Poliacrilamida , Ensaio de Imunoadsorção Enzimática , Epistaxe/complicações , Epistaxe/imunologia , Epistaxe/metabolismo , Humanos , Focalização Isoelétrica , Sprays Nasais , Polietileno/química , Conservantes Farmacêuticos/química , Telangiectasia Hemorrágica Hereditária/complicações , Telangiectasia Hemorrágica Hereditária/imunologia , Telangiectasia Hemorrágica Hereditária/metabolismo , Fator A de Crescimento do Endotélio Vascular/imunologiaRESUMO
Objetivos. Comparar el abordaje transesfenoidal endonasal endoscópico con el abordaje transesfenoidal sublabial microquirúrgico. Valoración del grado de resección tumoral, grado de invasividad tumoral, complicaciones y estancia postoperatoria de ambos grupos. Material y métodos. Estudio prospectivo no randomizado de 50 pacientes intervenidos en nuestro centro entre 2002 y 2006 de lesiones en la región selar con diferentes grados de invasión del seno cavernoso según la clasificación de Knosp. Entre las variables a estudio se incluyeron los grados de invasión, los grados de resección postoperatoria (total, subtotal y parcial), lesión del nervio óptico, panhipopituitarismo postoperatorio, fístula de LCR, déficit de pares craneales, epistaxis, meningitis, diabetes insípida y lesión de arteria caró- tida. Nuestra serie consta de 27 hombres y 23 mujeres, con una edad media de 48 años (19-80 años). En 23 casos se utilizó una vía transesfenoidal sublabial microquirúrgica (2 pacientes fueron excluidos) y en 25 casos se realizó un abordaje transesfenoidal endoscópico. El seguimiento medio fue de 12 meses. Resultados. En nuestra experiencia la técnica endoscópica presenta un porcentaje de exéresis completa superior al de la técnica clásica (60% frente a 34,8%) que también se hace evidente en el caso de la resección subtotal (32% frente 26%) existiendo una diferencia estadísticamente significativa (p=0,033). En contraposición no encontramos diferencias en cuanto a complicaciones. También hemos evidenciado que existe una diferencia estadísticamente significativa en cuanto a la estancia postoperatoria (p=0,001), reduciéndose ésta a la mitad (3 días) con la técnica endoscópica. Si bien no hemos encontrado diferencias significativas en cuanto al grado de invasividad tumoral y al grado de resección, un mayor grado de invasividad aumenta en 3,59 veces el riesgo de poco éxito de la cirugía. Discusión y conclusiones. En nuestra experiencia con la técnica endoscópica obtenemos un mayor grado de resección quirúrgica y una estancia postoperatoria menor. No hemos observado diferencias en cuanto a complicaciones (AU)
Objective. Compare the standard transsphenoidal sublabial microscopic approach with the endoscopic transsphenoidal approach concerning the tumoral invasiveness and resection, complications of the approaches and time of post operative hospitalisation. Material and methods. We realized a prospective, non randomised study with 50 patients. They were operated between 2002 and 2006. All the patients had sellar lesions with different grades of invasiveness of the cavernous sinus as classified by Knosp. The variables included in our study were tumoral invasiveness and operative resection (total, subtotal and partial), optic nerve lesion, postoperative panhypopituitarism, CSF fistula, cranial nerves deficits, epistaxis, meningitis, diabetes insipidus and carotid artery lesion. Our series included 27 males and 23 females ranging from 19 to 80 years old (48 mean). In 23 patients we used the standard sublabial microscopic approach (two patients were excluded) and for 25 patients we used the endoscopic approach. The mean follow up was of 12 months. Results. In our experience the endoscopic technique presents a higher percentage of total resection comparing to the sublabial microscopic approach (60% versus 34,8%) and higher percentage of subtotal resections (32% versus 26%) with a statistical significan difference (p=0,033). The time of hospitalisation was significant shorter for the endoscopic approach group (p=0,001), diminishing by half of the time (3 days) of the microscopic approach group. Concerning the tumoral invasiveness and complications we did not appreciate any significant dissimilarity. We appreciated that a higher grade of invasiveness augments by 3,59 the risk of an unsuccessful surgery. Discussion and conclusion. In our experience the endoscopic technique may favour a better tumoral resection and shorter time of hospitalisation. We did not appreciate differences concerning the complications (AU)
Assuntos
Feminino , Humanos , Masculino , Lábio/anormalidades , Lábio/metabolismo , Nervo Óptico/citologia , Nervo Óptico/patologia , Fístula/induzido quimicamente , Epistaxe/sangue , Epistaxe/metabolismo , Meningite/complicações , Meningite/metabolismo , Diabetes Mellitus/sangue , Lábio/patologia , Nervo Óptico/metabolismo , Nervo Óptico/fisiologia , Epistaxe/complicações , Epistaxe/enfermagem , Meningite/genética , Meningite/fisiopatologia , Diabetes Mellitus/patologia , Estudos ProspectivosRESUMO
Recurrent epistaxis is the most frequent clinical manifestation of hereditary haemorrhagic telangiectasia (HHT). Its treatment is difficult. Our objective was to assess the use of tranexamic acid (TA), an antifibrinolytic drug, for the treatment of epistaxis in HHT patients and to investigate in vitro the effects of TA over endoglin and ALK-1 expression and activity in endothelial cells. A prospective study was carried out on patients with epistaxis treated with oral TA in the HHT Unit of Sierrallana Hospital (Cantabria, Spain). Primary cultures of endothelial cells were treated with TA to measure the levels of endoglin and ALK-1 at the cell surface by flow cytometry. RNA levels were also measured by real-time PCR, and the transcriptional effects of TA on reporters for endoglin, ALK-1 and the endoglin/ALK-1 TGF-beta pathway were assessed. The results showed that the fourteen HHT patients treated orally with TA improved, and the frequency and severity of their epistaxis were decreased. No complications derived from the treatment were observed. Cultured endothelial cells incubated with TA exhibited increased levels of endoglin and ALK-1 at the protein and mRNA levels, enhanced TGF-beta signaling, and improved endothelial cell functions like tubulogenesis and migration. In summary, oral administration of TA proved beneficial for epistaxis treatment in selected patients with HHT. In addition to its already reported antifibrinolytic effects, TA stimulates the expression ofALK-1 and endoglin, as well as the activity of the ALK-1/endoglin pathway.
Assuntos
Receptores de Activinas Tipo II/metabolismo , Antifibrinolíticos/uso terapêutico , Antígenos CD/metabolismo , Células Endoteliais/efeitos dos fármacos , Epistaxe/tratamento farmacológico , Receptores de Superfície Celular/metabolismo , Telangiectasia Hemorrágica Hereditária/complicações , Ácido Tranexâmico/uso terapêutico , Receptores de Ativinas Tipo I/metabolismo , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Antifibrinolíticos/administração & dosagem , Antifibrinolíticos/farmacologia , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Endoglina , Células Endoteliais/metabolismo , Epistaxe/etiologia , Epistaxe/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neovascularização Fisiológica/efeitos dos fármacos , Plasminogênio/antagonistas & inibidores , Estudos Prospectivos , Proteínas Serina-Treonina Quinases , RNA Mensageiro/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo I , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Recidiva , Transdução de Sinais/efeitos dos fármacos , Espanha , Fatores de Tempo , Ácido Tranexâmico/administração & dosagem , Ácido Tranexâmico/farmacologia , Transcrição Gênica/efeitos dos fármacos , Fator de Crescimento Transformador beta/metabolismo , Resultado do TratamentoRESUMO
OBJECTIVE: By virtue of no identifiable causes in the majority of children with habitual epistaxis, it continues to be problematic in pediatric clinical practice. The purpose of this study is to explore the possible change of atrial natriuretic peptide (ANP) levels in the children with epistaxis. METHODS: Both the plasma and nasal mucus ANP levels have been determined in 30 sick children by a sensitive radioimmunoassay (RIA) technique. RESULTS: Our results revealed that the plasma and nasal mucus ANP levels were considerably decreased in 24 children with habitual epistaxis when compared with control group (P<0.05), making up 80%, and amongst the interest of these are the nasal mucus ANP levels changing inversely as the times bled from the nose. CONCLUSION: Although the plasma and nasal mucus ANP levels will not establish the diagnosis of its etiology, it is helpful for us to know the cardiovascular status compensating for chronic blood loss in the children with habitual epistaxis.
Assuntos
Fator Natriurético Atrial/metabolismo , Epistaxe/metabolismo , Mucosa Nasal/metabolismo , Adolescente , Fator Natriurético Atrial/sangue , Estudos de Casos e Controles , Doença Crônica , Epistaxe/sangue , Feminino , Habituação Psicofisiológica , Humanos , Masculino , RadioimunoensaioRESUMO
OBJECTIVE: We investigated whether an apoptosis of nasal microvessels contributes to probable mechanism of the onset of epistaxis. STUDY DESIGN AND SETTING: Nasal septal mucosa of Little's areas taken from patients without (n = 19) and with (n = 26) epistaxis were examined. Active caspase-3 in the mucosa was detected according to the methods of immunohistochemistry and Western blotting. On Western blot analysis of the homogenates of the mucosa, we also sought probable signaling factors after caspase-3 activation. RESULTS: Marked activation of caspase-3 was detected in the capillaries and its neighboring muscle cells of Little's area from patients with epistaxis, and the activation was due to enhanced expression of procaspase-3 protein and progressive cleavage of the precursor. As a result of Western blotting of signaling factors, enhanced expressions of caspase-9 and Bax protein in the homogenates of Little's area in epistaxis group were found compared with those in control group. Increased levels of cytochrome c released into a cytosol were also detected in the capillaries in epistaxis group. CONCLUSION: In the present study, caspase-3 activation was found in the capillaries of Little's area from patients with epistaxis, suggesting that an apoptosis of capillaries may contribute to a mechanism of the onset of epistaxis. Moreover, alterations of some apoptotic factors such as caspase-9, Bax, and cytochrome c in the tissues demonstrated participation of mitochondrial disturbance in one of the apoptotic mechanisms. SIGNIFICANCE: Further explorations of the pathobiologic mechanism of capillary apoptosis can lead not only to an identification of risk factors in the onset of epistaxis but also to the development of medical therapy of epistaxis.
Assuntos
Caspases/metabolismo , Epistaxe/metabolismo , Mucosa Nasal/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose/fisiologia , Western Blotting , Capilares/metabolismo , Epistaxe/complicações , Feminino , Genes bcl-2/fisiologia , Humanos , Hipertensão/complicações , Hipertensão/metabolismo , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/irrigação sanguíneaRESUMO
OBJECTIVE: The purpose of this study was to demonstrate silver absorption in blood and hair specimens after septal cauterization with silver nitrate and to discuss the potential toxicity of silver. METHOD: A prospective study of 11 volunteers without any known occupational exposure to silver products or past history of septal cauterization with silver nitrate was undertaken. Subjects were recruited in an academic tertiary care centre from October 1996 to September 1997. The study population consisted of five patients with anterior epistaxis and six healthy volunteers without any bleeding problem. Cauterization was done with one or two silver nitrate applicators directly on the bleeding vessel or Kiesselbach's area. Blood was sampled before cauterization and at specified times after application, while hair strands were sampled only 3 months later. Measurements of silver concentration in whole blood and in hair segments were obtained by inductively coupled plasma mass spectrometry. RESULTS: Silver concentrations in whole blood increased significantly after cauterization (p = .02). The measured peak level seemed to correlate with the number of applicators used. No significant increase in silver concentration was observed in hair samples. CONCLUSIONS: Effective silver absorption occurs with only one or two silver nitrate applicators. Hair has not been as reliable as whole blood to document an acute and fragmentary exposure. The indiscriminate use of silver nitrate is a potential source of silver intoxication.
Assuntos
Anti-Infecciosos Locais/administração & dosagem , Epistaxe/terapia , Nitrato de Prata/administração & dosagem , Prata/metabolismo , Absorção , Adolescente , Adulto , Idoso , Cauterização/métodos , Criança , Epistaxe/metabolismo , Feminino , Cabelo/química , Humanos , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Septo Nasal , Estudos Prospectivos , Prata/sangue , Espectrofotometria AtômicaRESUMO
Air-fluid levels in the sphenoid sinus have been described in association with skull fracture, cerebrospinal fluid rhinorrhea, and sinusitis. The authors have observed this sign in the absence of significant trauma in patients with epistaxis and nasal packing. The fluid is probably normal sinus secretion retained due to prolonged recumbency, although other explanations for its accumulation are discussed.