Accumulating evidence indicates that ataxia-telangiectasia mutated kinase is critical for maintaining cellular homeostasis and that it has both nuclear and cytoplasmic functions.However,the functions of ataxia-telangi...Accumulating evidence indicates that ataxia-telangiectasia mutated kinase is critical for maintaining cellular homeostasis and that it has both nuclear and cytoplasmic functions.However,the functions of ataxia-telangiectasia mutated that when lost lead to cerebellar degeneration are still unknown.In this review,we first describe the role of ataxia-telangiectasia mutated in cerebellar pathology.In addition to its canonical nuclear functions in DNA damage response circuits,ataxia-telangiectasia mutated functions in various cytoplasmic and mitochondrial processes that are critically important for cellular homeostasis.We discuss these functions with a focus on the role of ataxia-telangiectasia mutated in maintaining the homeostatic redox state.Finally,we describe the unique functions of ataxia-telangiectasia mutated in various types of neuronal and glial cells including cerebellar granule neurons,astrocytes,and microglial cells.展开更多
BACKGROUND Type 2 hereditary hemorrhagic telangiectasia(HHT)is a rare autosomal dominant disease and is associated with ALK1 gene mutations.Type 2 HHT patients primarily suffer from recurrent bleeding.There is current...BACKGROUND Type 2 hereditary hemorrhagic telangiectasia(HHT)is a rare autosomal dominant disease and is associated with ALK1 gene mutations.Type 2 HHT patients primarily suffer from recurrent bleeding.There is currently no promising treatment.CASE SUMMARY A 5-year-old Chinese patient(III23)was admitted to Zhongshan Hospital for recurrent melena occurring over 2 mo.She had been experiencing epistaxis for years and had been diagnosed with idiopathic pulmonary hypertension 4 mo before presentation.Abdominal computed tomography examination showed hepatic arteriovenous malformation.Gene testing revealed a c.1121G>A mutation on the ALK1 gene.According to the international diagnostic criteria,this patient was diagnosed with HHT.In addition,8 more family members exhibited HHT symptoms to varying degrees.Gene testing in 5 family members(2 with HHT symptoms and 3 without HHT symptoms)revealed the ALK1 c.1121G>A mutation in the 2 family members with HHT symptoms.This missense mutation results in the substitution of arginine for glutamine at amino acid position 374(R374Q)in the conserved functional kinase domain of ALK1.Biological studies revealed that this mutation decreased the kinase activity of ALK1 and impeded the phosphorylation of its substrate Smad1.Moreover,the R374Q mutant downregulated the protein level of collagen-1,a fibrogenic factor,indicating abnormal fiber generation during vascular formation.CONCLUSION The R374Q mutant of ALK1 and its subsequent influence on fiber generation highly indicated its pathogenic role in this family with type 2 HHT.Detection of this gene mutation will facilitate early diagnosis of suspected type 2 HHT patients,and mechanistic studies will provide insights for future therapy.展开更多
BACKGROUND Hereditary hemorrhagic telangiectasia(HHT)is an autosomal dominant genetic disorder with an incidence of approximately 1 in 5000 in the general population.It is characterized by vasodilation,which affects s...BACKGROUND Hereditary hemorrhagic telangiectasia(HHT)is an autosomal dominant genetic disorder with an incidence of approximately 1 in 5000 in the general population.It is characterized by vasodilation,which affects specific organs,such as the skin,mucous membranes,brain,lungs,gastrointestinal tract,liver,and others.However,HHT rarely involves the portal venous system to cause serious clinical compli-cations.CASE SUMMARY A 68-year-old woman was admitted to the emergency department due to four consecutive days of abdominal pain and bloody stool and was subsequently diagnosed with HHT.Computed tomography angiography confirmed the presence of an arteriovenous fistula(AVFs).Considering this specific manifestation,whole exome sequencing was performed.After a comprehensive evaluation,a selective superior mesenteric artery embolization was prioritized to avoid intestinal ischemia.The postoperative symptoms of the patient were quickly relieved.Unfortunately,two months post-procedure the patient died from intestinal necrosis and abdominal infection related to remaining AVFs.CONCLUSION For patients with diffuse superior mesenteric AVFs,selective mesenteric arterial embolization may lead to positive short-term outcomes.展开更多
Prior to his initial diagnosis, a 21-year-old male had been experiencing facial acne for two years and had been treated by a doctor in private practice. The patient visited our department because the clinical manifest...Prior to his initial diagnosis, a 21-year-old male had been experiencing facial acne for two years and had been treated by a doctor in private practice. The patient visited our department because the clinical manifestations of mandibular acne did not improve. At the time of initial examination, telangiectasia (TE), post-inflammatory erythema (PIE), post-inflammatory hyperpigmentation (PIH), atrophic scars (ASs), and a hypertrophic scar (HS) with induration were observed on the right neck. We diagnosed this as an acne vulgaris complication. HS lesions were topically treated by injecting triamcinolone acetonide, and the patient was prescribed 8.1 g/day of oral Saireito (Japanese herb). Adapalene benzoyl peroxide gel and topical tacrolimus hydrate ointment were used to treat PIE and TE. Both HSs and PIE improved;however, TE and AS did not improve. Currently, the patient is under observation. We consider this to be a very rare concurrent occurrence of diverse complications of acne vulgaris, and present the following case study.展开更多
Hereditary haemorrhagic telangiectasia(HHT) is an autosomal dominant inherited disorder characterised by vascular malformations in predominantly the brain,liverand lungs.Pulmonary hypertension(PH) is increasingly reco...Hereditary haemorrhagic telangiectasia(HHT) is an autosomal dominant inherited disorder characterised by vascular malformations in predominantly the brain,liverand lungs.Pulmonary hypertension(PH) is increasingly recognised as a severe complication of HHT.PH may be categorised into two distinct types in patients with HHT.Post-capillary PH most often results from a high pulmonary blood flow that accompanies the high cardiac output state associated with liver arteriovenous malformations.Less frequently,the HHT-related gene mutations in ENG or ACVRL1 appear to predispose patients with HHT to develop pre-capillary pulmonary arterial hypertension.Differentiation between both forms of PH by right heart catheterisation is essential,since both entities are associated with severe morbidity and mortality with different treatment options.Therefore all HHT patients should be referred to an HHT centre.展开更多
AIM To evaluated vascular dynamic processes in the liver of hereditary hemorrhagic telangiectasia(HHT) patients by ultrasound(US) considering quantitative analytic methods. METHODS The imaging features on US and contr...AIM To evaluated vascular dynamic processes in the liver of hereditary hemorrhagic telangiectasia(HHT) patients by ultrasound(US) considering quantitative analytic methods. METHODS The imaging features on US and contrast-enhanced ultrasound(CEUS) in 18 patients diagnosed with HHT were retrospectively analyzed. Regarding CEUS, realtime contrast harmonic imaging and sulfur hexafluoridefilled microbubbles were used. RESULTS HVa Ms were identified in all 18 patients. By US, the two major Caselitz criteria could be detected in 55.6% patients. "Color spots" were detected in 72.2% of the cases. Respecting sonographic grading criteria by Buscarini, grade 3 could be demonstrated most frequent(40%). By CEUS, all the patients showed quick and early hyperenhancement during the arterial phase. Significant lowest time to peak(TTP) and highest area under the curve(AUC) values were identified in the hepatic artery(TTP: 69.8%; AUC: 100%) and highest TTP and lowest AUC in the hepatic parenchyma and the portal vein. CONCLUSION For the first time we analyzed CEUS findings of a group of HHT patients regarding macro- and microcirculation. Our data demonstrate significant differences in TTP and AUC values in the four selected regions: hepatic artery, shunt region, portal vein and hepatic parenchyma.展开更多
We report a case of severe, refractory gastrointestinal(GI) bleeding in a patient with hereditary hemorrhagic telangiectasia(HHT) whose massive transfusion dependence was lifted shortly after treatment with bevacizuma...We report a case of severe, refractory gastrointestinal(GI) bleeding in a patient with hereditary hemorrhagic telangiectasia(HHT) whose massive transfusion dependence was lifted shortly after treatment with bevacizumab, an anti-vascular endothelial growth factor. The patient's bleeding had been refractory to repeated endoscopic interventions, tranexamic acid, and tamoxifen. However, following treatment with bevacizumab at 5 mg/kg every other week, nearly 300 units of packed red blood cell transfusions were avoided in one year's time. Despite its relatively high cost, bevacizumab may have a more active role in the management of severe GI bleeding in HHT if such remarkable response can be consistently demonstrated.展开更多
Hereditary hemorrhagic telangiectasia(HHT) is arelatively common inherited vascular disorder that was first described in 1864, and is notable for epistaxis, telangiectasia, and arterial venous malformations. While gen...Hereditary hemorrhagic telangiectasia(HHT) is arelatively common inherited vascular disorder that was first described in 1864, and is notable for epistaxis, telangiectasia, and arterial venous malformations. While genetic tests are available, the diagnosis remains clinical, and is based on the Curacao criteria. Patients with HHT are at increased risk for both bleeding and clotting events. Because of these competing complications, hematologists are often faced with difficult clinical decisions. While the majority of management decisions revolve around bleeding complications, it is not infrequent for these patients to require anticoagulation for thrombosis. Any anticoagulation recommendations must take into account the bleeding risks associated with HHT. Recent reviews have found that HHT patients can be safely anticoagulated, with the most frequent complication being worsened epistaxis. Large clinical trials have shown that factor Ⅱa and Ⅹa inhibitors have less intracranial bleeding than warfarin, and basic coagulation research has provided a possible mechanism. This article describes the anticoagulation dilemma posed when a 62-year-old female patient with a history of bleeding events associated with HHT was diagnosed with a pulmonary embolism. The subsequent discussion focuses on the approach to anticoagulation in the HHT patient, and addresses the role of the new oral anticoagulants.展开更多
Hereditary hemorrhagic telangiectasia(HHT)is a rare autosomal-dominantly inherited disease that occurs in approximately one in 5000 to 8000 people.Clinical diagnosis of HHT is made when a person presents three of the ...Hereditary hemorrhagic telangiectasia(HHT)is a rare autosomal-dominantly inherited disease that occurs in approximately one in 5000 to 8000 people.Clinical diagnosis of HHT is made when a person presents three of the following four criteria:family history,recurrent nosebleeds,mucocutaneous telangiectasis,and arteriovenous malformations(AVM)in the brain,lung,liver and gastrointestinal(GI)tract.Although epistaxis is themost common presenting symptom,AVMs affecting the lungs,brain and GI tract provoke a more serious outcome.Heterozygous mutations in endoglin,activin receptor-like kinase 1(ACVRL1;ALK1),and SMAD4,the genes involved in the transforming growth factor-βfamily signaling cascade,cause HHT.We report here the case of a 63 year-old male patient who presented melena and GI bleeding episodes,proven to be caused by bleeding from multiple gastric angiodysplasia.Esophagogastroduodenoscopy revealed multiple angiodysplasia throughout the stomach.Endoscopic argon plasma coagulation was performed to control bleeding from a gastric angiodysplasia.The patient has been admitted several times with episodes of hemoptysis and hematochezia.One year ago,the patient was hospitalized due to right-sided weakness,which was caused by left basal ganglia hemorrhage as the part of HHT presentation.In family history,the patient's mother and elder sister had died,due to intracranial hemorrhage,and his eldest son has been suffered from recurrent epistaxis for 20 years.A genetic study revealed a mutation in exon 3 of ALK1(c.199C>T;p.Arg67Trp)in the proband and his eldest son presenting epistaxis.展开更多
Primary biliary cirrhosis is a slowly progressive cholestatic autoimmune liver disease that mainly affects middle-aged women with an estimated prevalence ranging from 6.7 to 402 cases per million. Hereditary hemorrhag...Primary biliary cirrhosis is a slowly progressive cholestatic autoimmune liver disease that mainly affects middle-aged women with an estimated prevalence ranging from 6.7 to 402 cases per million. Hereditary hemorrhagic telangiectasia, or Rendu-Osler-Weber disease, is an autosomal dominant disorder characterized by angiodysplastic lesions (telangiectases and arteriovenous malformations) that can affect many organs, including liver, with a prevalence of 1-2 cases per 10000. We describe the coexistence, for the first time to our knowledge, of these two rare diseases in a 50-year old Caucasian woman. In this setting, the relevance of an accurate medical history, the role of liver histology and the characterization of liver involvement through dynamic imaging techniques can be emphasized.展开更多
Introduction: Ataxia telangiectasia (AT) is a rare disease characterized by immunodeficiency and neurological manifestations. Ataxia, resulting from cerebella atrophy, runs a progressive incapacitating course. Clinica...Introduction: Ataxia telangiectasia (AT) is a rare disease characterized by immunodeficiency and neurological manifestations. Ataxia, resulting from cerebella atrophy, runs a progressive incapacitating course. Clinical monitoring of the disease course is mandatory for early treatment. Aim: To study clinical severity of AT and correlate it with the degree of cerebellar atrophy. Patients and Methods: We retrospectively studied all children (less than 14 years) with AT seen at Hamad General Hospital Clinics between 1998-2013. We collected basic demographic data, parental consan-guinity, family history, AT clinical severity scores, and reviewed CBC with differential counts;alpha-fetoprotein, serum immunoglobulins and lymphocyte subsets. Cranial MRI scans of each subject were reviewed by a neuroradiologist. Cerebellar atrophy was visually and semi-quantitatively scored. Results: We analyzed data on 18 AT children (10 males and 8 females), mean age of 76.9 months. 77.8% had a positive family history of AT and 41.7% parental consanguinity. Lymphopenia was observed in 77.8% and high serum alpha-fetoprotein in 87.5% of children. Clinical severity of ataxia was 17.1 ± 8.4 (mean ± SD);86.7% of patients were moderate-severe. MRI cerebellar atrophy score was 1.9 ± 1.3 (mean ± SD), and moderate in 51% of patients. AT clinical severity score correlated (coefficient r = 0.566) but not statistically significant p = 0.088) with MRI cerebellar atrophy scores. Conclusions: Moderate to severe ataxia and marked cerebellar atrophy are quite common in AT children. There is a correlation between AT clinical severity and cerebellar atrophy. Larger prospective studies might further determine the significance of our observations and help practicing practitioners monitor the progression of the disease.展开更多
BACKGROUND Hereditary hemorrhagic telangiectasia(HHT)is a rare autosomal dominant genetic disease.Very few patients suffering from HHT present with associated pulmonary arterial hypertension(PAH),which may result in a...BACKGROUND Hereditary hemorrhagic telangiectasia(HHT)is a rare autosomal dominant genetic disease.Very few patients suffering from HHT present with associated pulmonary arterial hypertension(PAH),which may result in a poor prognosis.Here,we report a case of HHT with PAH.The patient’s clinical manifestations and treatment as well as genetic analysis of family members are reviewed,in order to raise awareness of this multimorbidity.CASE SUMMARY A 45-year-old Chinese woman was admitted to the hospital to address a complaint of intermittent shortness of breath,which had lasted over the past 2 years.She also had a 30-year history of recurrent epistaxis and 5-year history of anemia.She reported that the shortness of breath had aggravated gradually over the 2 years.Physical examination discovered anemia and detected gallop rhythm in the precordium.Chest computerized tomography and cardiac ultrasound demonstrated PAH and hepatic arteriovenous malformation.The formal clinical diagnosis was HHT combined with PAH.The patient was treated with ambrisentan and her condition improved for a time.She died half a year after the diagnosis.Genetic testing revealed the patient and some family members to carry an activin A receptor-like type 1 mutation(c.1232G>A,p.Arg411Gln);the family was thus identified as an HHT family.CONCLUSION We report a novel gene mutation(c.1232G>A,p.Arg411Gln)in a Chinese HHT patient with PAH.展开更多
Ataxia Telangiectasia (AT) is a rare autosomal recessive multisystem disease. The diagnosis is often made on a clinical triad that combines neurological signs dominated by a progressive cerebellar ataxia, oculocutaneo...Ataxia Telangiectasia (AT) is a rare autosomal recessive multisystem disease. The diagnosis is often made on a clinical triad that combines neurological signs dominated by a progressive cerebellar ataxia, oculocutaneous signs (telangiectasia, coffee stain milk), immunodeficiency (humoral and cellular) with sinopulmonary infections and elevated alphaphetoprotein. The diagnosis of AT is usually early, however, some forms may be revealed late. We reported a case of a 19-year-old patient, admitted for severe pneumonia with Klebsiella Pneumonia. In its history, it was found a notion of recurrent respiratory infections and bronchiectasis. In its clinical examination, it had been discovered cerebellar ataxia and occulocutaneous telangiectasia. The determination of plasmatic alphafoetoprotein was elevated, and the search of immunodeficiency showed a mixed deficit (humoral and cellular) suggesting the diagnosis of AT.展开更多
BACKGROUND Epistaxis can be an isolated finding or a manifestation of a systemic disease.Some of the potential etiologies are usage of anticoagulants,bleeding disorders,vascular aneurysms,nasal neoplasm,hypertension a...BACKGROUND Epistaxis can be an isolated finding or a manifestation of a systemic disease.Some of the potential etiologies are usage of anticoagulants,bleeding disorders,vascular aneurysms,nasal neoplasm,hypertension and nasal steroids.Hereditary hemorrhagic telangiectasia(HHT)as a cause of recurrent epistaxis is uncommon.CASE SUMMARY In this report,we describe an 18-year-old adolescent with recurrent epistaxis,mucocutaneous telangiectasia and family history of HHT,consistent with HHT.CONCLUSION Timely diagnosis is needed not only to treat the epistaxis but also to be vigilant for other serious manifestations of this condition.展开更多
Background:Apolipoprotein B mRNA editing catalytic polypeptide(APOBEC),an endogenous mutator,induces DNA damage and activates the ataxia telangiectasia and Rad3-related(ATR)-checkpoint kinase 1(Chk1)pathway.Although c...Background:Apolipoprotein B mRNA editing catalytic polypeptide(APOBEC),an endogenous mutator,induces DNA damage and activates the ataxia telangiectasia and Rad3-related(ATR)-checkpoint kinase 1(Chk1)pathway.Although cisplatin-based therapy is the mainstay for muscle-invasive bladder cancer(MIBC),it has a poor survival rate.Therefore,this study aimed to evaluate the efficacy of an ATR inhibitor combined with cisplatin in the treatment of APOBEC catalytic subunit 3B(APOBEC3B)expressing MIBC.Methods:Immunohistochemical staining was performed to analyze an association between APOBEC3B and ATR in patients with MIBC.The APOBEC3B expression in MIBC cell lines was assessed using real-time polymerase chain reaction and western blot analysis.Western blot analysis was performed to confirm differences in phosphorylated Chk1(pChk1)expression according to the APOBEC3B expression.Cell viability and apoptosis analyses were performed to examine the anti-tumor activity of ATR inhibitors combined with cisplatin.Results:There was a significant association between APOBEC3B and ATR expression in the tumor tissues obtained from patients with MIBC.Cells with higher APOBEC3B expression showed higher pChk1 expression than cells expressing low APOBEC3B levels.Combination treatment of ATR inhibitor and cisplatin inhibited cell growth in MIBC cells with a higher APOBEC3B expression.Compared to cisplatin single treatment,combination treatment induced more apoptotic cell death in the cells with higher APOBEC3B expression.Conclusion:Our study shows that APOBEC3B’s higher expression status can enhance the sensitivity of MIBC to cisplatin upon ATR inhibition.This result provides new insight into appropriate patient selection for the effective application of ATR inhibitors in MIBC.展开更多
文摘Accumulating evidence indicates that ataxia-telangiectasia mutated kinase is critical for maintaining cellular homeostasis and that it has both nuclear and cytoplasmic functions.However,the functions of ataxia-telangiectasia mutated that when lost lead to cerebellar degeneration are still unknown.In this review,we first describe the role of ataxia-telangiectasia mutated in cerebellar pathology.In addition to its canonical nuclear functions in DNA damage response circuits,ataxia-telangiectasia mutated functions in various cytoplasmic and mitochondrial processes that are critically important for cellular homeostasis.We discuss these functions with a focus on the role of ataxia-telangiectasia mutated in maintaining the homeostatic redox state.Finally,we describe the unique functions of ataxia-telangiectasia mutated in various types of neuronal and glial cells including cerebellar granule neurons,astrocytes,and microglial cells.
文摘BACKGROUND Type 2 hereditary hemorrhagic telangiectasia(HHT)is a rare autosomal dominant disease and is associated with ALK1 gene mutations.Type 2 HHT patients primarily suffer from recurrent bleeding.There is currently no promising treatment.CASE SUMMARY A 5-year-old Chinese patient(III23)was admitted to Zhongshan Hospital for recurrent melena occurring over 2 mo.She had been experiencing epistaxis for years and had been diagnosed with idiopathic pulmonary hypertension 4 mo before presentation.Abdominal computed tomography examination showed hepatic arteriovenous malformation.Gene testing revealed a c.1121G>A mutation on the ALK1 gene.According to the international diagnostic criteria,this patient was diagnosed with HHT.In addition,8 more family members exhibited HHT symptoms to varying degrees.Gene testing in 5 family members(2 with HHT symptoms and 3 without HHT symptoms)revealed the ALK1 c.1121G>A mutation in the 2 family members with HHT symptoms.This missense mutation results in the substitution of arginine for glutamine at amino acid position 374(R374Q)in the conserved functional kinase domain of ALK1.Biological studies revealed that this mutation decreased the kinase activity of ALK1 and impeded the phosphorylation of its substrate Smad1.Moreover,the R374Q mutant downregulated the protein level of collagen-1,a fibrogenic factor,indicating abnormal fiber generation during vascular formation.CONCLUSION The R374Q mutant of ALK1 and its subsequent influence on fiber generation highly indicated its pathogenic role in this family with type 2 HHT.Detection of this gene mutation will facilitate early diagnosis of suspected type 2 HHT patients,and mechanistic studies will provide insights for future therapy.
基金the Youth Independent Innovation Science Project of PLA General Hospital,No.22QNFC058.
文摘BACKGROUND Hereditary hemorrhagic telangiectasia(HHT)is an autosomal dominant genetic disorder with an incidence of approximately 1 in 5000 in the general population.It is characterized by vasodilation,which affects specific organs,such as the skin,mucous membranes,brain,lungs,gastrointestinal tract,liver,and others.However,HHT rarely involves the portal venous system to cause serious clinical compli-cations.CASE SUMMARY A 68-year-old woman was admitted to the emergency department due to four consecutive days of abdominal pain and bloody stool and was subsequently diagnosed with HHT.Computed tomography angiography confirmed the presence of an arteriovenous fistula(AVFs).Considering this specific manifestation,whole exome sequencing was performed.After a comprehensive evaluation,a selective superior mesenteric artery embolization was prioritized to avoid intestinal ischemia.The postoperative symptoms of the patient were quickly relieved.Unfortunately,two months post-procedure the patient died from intestinal necrosis and abdominal infection related to remaining AVFs.CONCLUSION For patients with diffuse superior mesenteric AVFs,selective mesenteric arterial embolization may lead to positive short-term outcomes.
文摘Prior to his initial diagnosis, a 21-year-old male had been experiencing facial acne for two years and had been treated by a doctor in private practice. The patient visited our department because the clinical manifestations of mandibular acne did not improve. At the time of initial examination, telangiectasia (TE), post-inflammatory erythema (PIE), post-inflammatory hyperpigmentation (PIH), atrophic scars (ASs), and a hypertrophic scar (HS) with induration were observed on the right neck. We diagnosed this as an acne vulgaris complication. HS lesions were topically treated by injecting triamcinolone acetonide, and the patient was prescribed 8.1 g/day of oral Saireito (Japanese herb). Adapalene benzoyl peroxide gel and topical tacrolimus hydrate ointment were used to treat PIE and TE. Both HSs and PIE improved;however, TE and AS did not improve. Currently, the patient is under observation. We consider this to be a very rare concurrent occurrence of diverse complications of acne vulgaris, and present the following case study.
文摘Hereditary haemorrhagic telangiectasia(HHT) is an autosomal dominant inherited disorder characterised by vascular malformations in predominantly the brain,liverand lungs.Pulmonary hypertension(PH) is increasingly recognised as a severe complication of HHT.PH may be categorised into two distinct types in patients with HHT.Post-capillary PH most often results from a high pulmonary blood flow that accompanies the high cardiac output state associated with liver arteriovenous malformations.Less frequently,the HHT-related gene mutations in ENG or ACVRL1 appear to predispose patients with HHT to develop pre-capillary pulmonary arterial hypertension.Differentiation between both forms of PH by right heart catheterisation is essential,since both entities are associated with severe morbidity and mortality with different treatment options.Therefore all HHT patients should be referred to an HHT centre.
文摘AIM To evaluated vascular dynamic processes in the liver of hereditary hemorrhagic telangiectasia(HHT) patients by ultrasound(US) considering quantitative analytic methods. METHODS The imaging features on US and contrast-enhanced ultrasound(CEUS) in 18 patients diagnosed with HHT were retrospectively analyzed. Regarding CEUS, realtime contrast harmonic imaging and sulfur hexafluoridefilled microbubbles were used. RESULTS HVa Ms were identified in all 18 patients. By US, the two major Caselitz criteria could be detected in 55.6% patients. "Color spots" were detected in 72.2% of the cases. Respecting sonographic grading criteria by Buscarini, grade 3 could be demonstrated most frequent(40%). By CEUS, all the patients showed quick and early hyperenhancement during the arterial phase. Significant lowest time to peak(TTP) and highest area under the curve(AUC) values were identified in the hepatic artery(TTP: 69.8%; AUC: 100%) and highest TTP and lowest AUC in the hepatic parenchyma and the portal vein. CONCLUSION For the first time we analyzed CEUS findings of a group of HHT patients regarding macro- and microcirculation. Our data demonstrate significant differences in TTP and AUC values in the four selected regions: hepatic artery, shunt region, portal vein and hepatic parenchyma.
文摘We report a case of severe, refractory gastrointestinal(GI) bleeding in a patient with hereditary hemorrhagic telangiectasia(HHT) whose massive transfusion dependence was lifted shortly after treatment with bevacizumab, an anti-vascular endothelial growth factor. The patient's bleeding had been refractory to repeated endoscopic interventions, tranexamic acid, and tamoxifen. However, following treatment with bevacizumab at 5 mg/kg every other week, nearly 300 units of packed red blood cell transfusions were avoided in one year's time. Despite its relatively high cost, bevacizumab may have a more active role in the management of severe GI bleeding in HHT if such remarkable response can be consistently demonstrated.
文摘Hereditary hemorrhagic telangiectasia(HHT) is arelatively common inherited vascular disorder that was first described in 1864, and is notable for epistaxis, telangiectasia, and arterial venous malformations. While genetic tests are available, the diagnosis remains clinical, and is based on the Curacao criteria. Patients with HHT are at increased risk for both bleeding and clotting events. Because of these competing complications, hematologists are often faced with difficult clinical decisions. While the majority of management decisions revolve around bleeding complications, it is not infrequent for these patients to require anticoagulation for thrombosis. Any anticoagulation recommendations must take into account the bleeding risks associated with HHT. Recent reviews have found that HHT patients can be safely anticoagulated, with the most frequent complication being worsened epistaxis. Large clinical trials have shown that factor Ⅱa and Ⅹa inhibitors have less intracranial bleeding than warfarin, and basic coagulation research has provided a possible mechanism. This article describes the anticoagulation dilemma posed when a 62-year-old female patient with a history of bleeding events associated with HHT was diagnosed with a pulmonary embolism. The subsequent discussion focuses on the approach to anticoagulation in the HHT patient, and addresses the role of the new oral anticoagulants.
基金Supported by A grant of the South Korea Healthcare technology R and D Project,Ministry for Health,Welfare and Family Affairs,South Korea,No.A080588-23in part by a grant from the World Class University(WCU by Korean Ministry of Education,Science and Technology)(to Oh SP)
文摘Hereditary hemorrhagic telangiectasia(HHT)is a rare autosomal-dominantly inherited disease that occurs in approximately one in 5000 to 8000 people.Clinical diagnosis of HHT is made when a person presents three of the following four criteria:family history,recurrent nosebleeds,mucocutaneous telangiectasis,and arteriovenous malformations(AVM)in the brain,lung,liver and gastrointestinal(GI)tract.Although epistaxis is themost common presenting symptom,AVMs affecting the lungs,brain and GI tract provoke a more serious outcome.Heterozygous mutations in endoglin,activin receptor-like kinase 1(ACVRL1;ALK1),and SMAD4,the genes involved in the transforming growth factor-βfamily signaling cascade,cause HHT.We report here the case of a 63 year-old male patient who presented melena and GI bleeding episodes,proven to be caused by bleeding from multiple gastric angiodysplasia.Esophagogastroduodenoscopy revealed multiple angiodysplasia throughout the stomach.Endoscopic argon plasma coagulation was performed to control bleeding from a gastric angiodysplasia.The patient has been admitted several times with episodes of hemoptysis and hematochezia.One year ago,the patient was hospitalized due to right-sided weakness,which was caused by left basal ganglia hemorrhage as the part of HHT presentation.In family history,the patient's mother and elder sister had died,due to intracranial hemorrhage,and his eldest son has been suffered from recurrent epistaxis for 20 years.A genetic study revealed a mutation in exon 3 of ALK1(c.199C>T;p.Arg67Trp)in the proband and his eldest son presenting epistaxis.
文摘Primary biliary cirrhosis is a slowly progressive cholestatic autoimmune liver disease that mainly affects middle-aged women with an estimated prevalence ranging from 6.7 to 402 cases per million. Hereditary hemorrhagic telangiectasia, or Rendu-Osler-Weber disease, is an autosomal dominant disorder characterized by angiodysplastic lesions (telangiectases and arteriovenous malformations) that can affect many organs, including liver, with a prevalence of 1-2 cases per 10000. We describe the coexistence, for the first time to our knowledge, of these two rare diseases in a 50-year old Caucasian woman. In this setting, the relevance of an accurate medical history, the role of liver histology and the characterization of liver involvement through dynamic imaging techniques can be emphasized.
文摘Introduction: Ataxia telangiectasia (AT) is a rare disease characterized by immunodeficiency and neurological manifestations. Ataxia, resulting from cerebella atrophy, runs a progressive incapacitating course. Clinical monitoring of the disease course is mandatory for early treatment. Aim: To study clinical severity of AT and correlate it with the degree of cerebellar atrophy. Patients and Methods: We retrospectively studied all children (less than 14 years) with AT seen at Hamad General Hospital Clinics between 1998-2013. We collected basic demographic data, parental consan-guinity, family history, AT clinical severity scores, and reviewed CBC with differential counts;alpha-fetoprotein, serum immunoglobulins and lymphocyte subsets. Cranial MRI scans of each subject were reviewed by a neuroradiologist. Cerebellar atrophy was visually and semi-quantitatively scored. Results: We analyzed data on 18 AT children (10 males and 8 females), mean age of 76.9 months. 77.8% had a positive family history of AT and 41.7% parental consanguinity. Lymphopenia was observed in 77.8% and high serum alpha-fetoprotein in 87.5% of children. Clinical severity of ataxia was 17.1 ± 8.4 (mean ± SD);86.7% of patients were moderate-severe. MRI cerebellar atrophy score was 1.9 ± 1.3 (mean ± SD), and moderate in 51% of patients. AT clinical severity score correlated (coefficient r = 0.566) but not statistically significant p = 0.088) with MRI cerebellar atrophy scores. Conclusions: Moderate to severe ataxia and marked cerebellar atrophy are quite common in AT children. There is a correlation between AT clinical severity and cerebellar atrophy. Larger prospective studies might further determine the significance of our observations and help practicing practitioners monitor the progression of the disease.
文摘BACKGROUND Hereditary hemorrhagic telangiectasia(HHT)is a rare autosomal dominant genetic disease.Very few patients suffering from HHT present with associated pulmonary arterial hypertension(PAH),which may result in a poor prognosis.Here,we report a case of HHT with PAH.The patient’s clinical manifestations and treatment as well as genetic analysis of family members are reviewed,in order to raise awareness of this multimorbidity.CASE SUMMARY A 45-year-old Chinese woman was admitted to the hospital to address a complaint of intermittent shortness of breath,which had lasted over the past 2 years.She also had a 30-year history of recurrent epistaxis and 5-year history of anemia.She reported that the shortness of breath had aggravated gradually over the 2 years.Physical examination discovered anemia and detected gallop rhythm in the precordium.Chest computerized tomography and cardiac ultrasound demonstrated PAH and hepatic arteriovenous malformation.The formal clinical diagnosis was HHT combined with PAH.The patient was treated with ambrisentan and her condition improved for a time.She died half a year after the diagnosis.Genetic testing revealed the patient and some family members to carry an activin A receptor-like type 1 mutation(c.1232G>A,p.Arg411Gln);the family was thus identified as an HHT family.CONCLUSION We report a novel gene mutation(c.1232G>A,p.Arg411Gln)in a Chinese HHT patient with PAH.
文摘Ataxia Telangiectasia (AT) is a rare autosomal recessive multisystem disease. The diagnosis is often made on a clinical triad that combines neurological signs dominated by a progressive cerebellar ataxia, oculocutaneous signs (telangiectasia, coffee stain milk), immunodeficiency (humoral and cellular) with sinopulmonary infections and elevated alphaphetoprotein. The diagnosis of AT is usually early, however, some forms may be revealed late. We reported a case of a 19-year-old patient, admitted for severe pneumonia with Klebsiella Pneumonia. In its history, it was found a notion of recurrent respiratory infections and bronchiectasis. In its clinical examination, it had been discovered cerebellar ataxia and occulocutaneous telangiectasia. The determination of plasmatic alphafoetoprotein was elevated, and the search of immunodeficiency showed a mixed deficit (humoral and cellular) suggesting the diagnosis of AT.
文摘BACKGROUND Epistaxis can be an isolated finding or a manifestation of a systemic disease.Some of the potential etiologies are usage of anticoagulants,bleeding disorders,vascular aneurysms,nasal neoplasm,hypertension and nasal steroids.Hereditary hemorrhagic telangiectasia(HHT)as a cause of recurrent epistaxis is uncommon.CASE SUMMARY In this report,we describe an 18-year-old adolescent with recurrent epistaxis,mucocutaneous telangiectasia and family history of HHT,consistent with HHT.CONCLUSION Timely diagnosis is needed not only to treat the epistaxis but also to be vigilant for other serious manifestations of this condition.
基金supported by St.Vincent’s Hospital,the Research Institute of Medical Science(Grant Number:SVHR-2021-03).
文摘Background:Apolipoprotein B mRNA editing catalytic polypeptide(APOBEC),an endogenous mutator,induces DNA damage and activates the ataxia telangiectasia and Rad3-related(ATR)-checkpoint kinase 1(Chk1)pathway.Although cisplatin-based therapy is the mainstay for muscle-invasive bladder cancer(MIBC),it has a poor survival rate.Therefore,this study aimed to evaluate the efficacy of an ATR inhibitor combined with cisplatin in the treatment of APOBEC catalytic subunit 3B(APOBEC3B)expressing MIBC.Methods:Immunohistochemical staining was performed to analyze an association between APOBEC3B and ATR in patients with MIBC.The APOBEC3B expression in MIBC cell lines was assessed using real-time polymerase chain reaction and western blot analysis.Western blot analysis was performed to confirm differences in phosphorylated Chk1(pChk1)expression according to the APOBEC3B expression.Cell viability and apoptosis analyses were performed to examine the anti-tumor activity of ATR inhibitors combined with cisplatin.Results:There was a significant association between APOBEC3B and ATR expression in the tumor tissues obtained from patients with MIBC.Cells with higher APOBEC3B expression showed higher pChk1 expression than cells expressing low APOBEC3B levels.Combination treatment of ATR inhibitor and cisplatin inhibited cell growth in MIBC cells with a higher APOBEC3B expression.Compared to cisplatin single treatment,combination treatment induced more apoptotic cell death in the cells with higher APOBEC3B expression.Conclusion:Our study shows that APOBEC3B’s higher expression status can enhance the sensitivity of MIBC to cisplatin upon ATR inhibition.This result provides new insight into appropriate patient selection for the effective application of ATR inhibitors in MIBC.
