RESUMO
In pilot work, we showed that somatic nerve transfers can restore motor function in long-term decentralized dogs. We continue to explore the effectiveness of motor reinnervation in 30 female dogs. After anesthesia, 12 underwent bilateral transection of coccygeal and sacral (S) spinal roots, dorsal roots of lumbar (L)7, and hypogastric nerves. Twelve months postdecentralization, eight underwent transfer of obturator nerve branches to pelvic nerve vesical branches, and sciatic nerve branches to pudendal nerves, followed by 10 mo recovery (ObNT-ScNT Reinn). The remaining four were euthanized 18 mo postdecentralization (Decentralized). Results were compared with 18 Controls. Squat-and-void postures were tracked during awake cystometry. None showed squat-and-void postures during the decentralization phase. Seven of eight ObNT-ScNT Reinn began showing such postures by 6 mo postreinnervation; one showed a return of defecation postures. Retrograde dyes were injected into the bladder and urethra 3 wk before euthanasia, at which point, roots and transferred nerves were electrically stimulated to evaluate motor function. Upon L2-L6 root stimulation, five of eight ObNT-ScNT Reinn showed elevated detrusor pressure and four showed elevated urethral pressure, compared with L7-S3 root stimulation. After stimulation of sciatic-to-pudendal transferred nerves, three of eight ObNT-ScNT Reinn showed elevated urethral pressure; all showed elevated anal sphincter pressure. Retrogradely labeled neurons were observed in L2-L6 ventral horns (in laminae VI, VIII, and IX) of ObNT-ScNT Reinn versus Controls in which labeled neurons were observed in L7-S3 ventral horns (in lamina VII). This data supports the use of nerve transfer techniques for the restoration of bladder function.NEW & NOTEWORTHY This data supports the use of nerve transfer techniques for the restoration of bladder function.
Assuntos
Canal Anal , Neurônios Motores , Transferência de Nervo , Recuperação de Função Fisiológica , Uretra , Bexiga Urinária , Animais , Transferência de Nervo/métodos , Cães , Feminino , Bexiga Urinária/inervação , Uretra/inervação , Canal Anal/inervação , Canal Anal/cirurgia , Neurônios Motores/fisiologia , Regeneração Nervosa/fisiologia , Nervo Pudendo/cirurgia , Nervo Pudendo/fisiopatologiaRESUMO
AIM: The "2022 ACC/AHA Guideline for the Diagnosis and Management of Aortic Disease" provides recommendations to guide clinicians in the diagnosis, genetic evaluation and family screening, medical therapy, endovascular and surgical treatment, and long-term surveillance of patients with aortic disease across its multiple clinical presentation subsets (ie, asymptomatic, stable symptomatic, and acute aortic syndromes). METHODS: A comprehensive literature search was conducted from January 2021 to April 2021, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, CINHL Complete, and other selected databases relevant to this guideline. Additional relevant studies, published through June 2022 during the guideline writing process, were also considered by the writing committee, where appropriate. Structure: Recommendations from previously published AHA/ACC guidelines on thoracic aortic disease, peripheral artery disease, and bicuspid aortic valve disease have been updated with new evidence to guide clinicians. In addition, new recommendations addressing comprehensive care for patients with aortic disease have been developed. There is added emphasis on the role of shared decision making, especially in the management of patients with aortic disease both before and during pregnancy. The is also an increased emphasis on the importance of institutional interventional volume and multidisciplinary aortic team expertise in the care of patients with aortic disease.
Assuntos
Doenças da Aorta , Doença da Válvula Aórtica Bicúspide , Cardiologia , Feminino , Humanos , Gravidez , American Heart Association , Doenças da Aorta/diagnóstico , Doenças da Aorta/terapia , Relatório de Pesquisa , Estados UnidosRESUMO
Very little is known about the physiological role of nicotinic receptors in canine bladders, although functional nicotinic receptors have been reported in bladders of many species. Utilizing in vitro methods, we evaluated nicotinic receptors mediating bladder function in dogs: control (9 female and 11 male normal controls, 5 sham operated), Decentralized (9 females, decentralized 6-21 mo), and obturator-to-pelvic nerve transfer reinnervated (ObNT-Reinn; 9 females; decentralized 9-13 mo, then reinnervated with 8-12 mo recovery). Muscle strips were collected, mucosa-denuded, and mounted in muscle baths before incubation with neurotransmitter antagonists, and contractions to the nicotinic receptor agonist epibatidine were determined. Strip response to epibatidine, expressed as percent potassium chloride, was similar (â¼35% in controls, 30% in Decentralized, and 24% in ObNT-Reinn). Differentially, epibatidine responses in Decentralized and ObNT-Reinn bladder strips were lower than controls after tetrodotoxin (TTX, a sodium channel blocker that inhibits axonal action potentials). Yet, in all groups, epibatidine-induced strip contractions were similarly inhibited by mecamylamine and hexamethonium (ganglionic nicotinic receptor antagonists), SR 16584 (α3ß4 neuronal nicotinic receptor antagonist), atracurium and tubocurarine (neuromuscular nicotinic receptor antagonists), and atropine (muscarinic receptor antagonist), indicating that nicotinic receptors (particularly α3ß4 subtypes), neuromuscular and muscarinic receptors play roles in bladder contractility. In control bladder strips, since tetrodotoxin did not inhibit epibatidine contractions, nicotinic receptors are likely located on nerve terminals. The tetrodotoxin inhibition of epibatidine-induced contractions in Decentralized and ObNT-Reinn suggests a relocation of nicotinic receptors from nerve terminals to more distant axonal sites, perhaps as a compensatory mechanism to recover bladder function.
Assuntos
Transferência de Nervo , Receptores Nicotínicos , Cães , Animais , Feminino , Masculino , Bexiga Urinária , Tetrodotoxina/farmacologia , Canal Anal , Neurônios MotoresRESUMO
The aim of this study was to investigate layer and species variations in detrusor muscle strip responses to myogenic, neurogenic, and nicotinic, and muscarinic receptor stimulations. Strips from bladders of 9 dogs and 6 human organ transplant donors were dissected from inner and outer longitudinal muscle layers, at least 1 cm above urethral orifices. Strips were mounted in muscle baths and maximal responses to neurogenic stimulation using electrical field stimulation (EFS) and myogenic stimulation using potassium chloride (KCl, 120 mM) determined. After washing and re-equilibration was completed, responses to nicotinic receptor agonist epibatidine (10 µM) were determined followed by responses to EFS and muscarinic receptor agonist bethanechol (30 µM) in continued presence of epibatidine. Thereafter, strips and full-thickness bladder sections from four additional dogs and three human donors were examined for axonal density and intramural ganglia. In dog bladders, contractions to KCl, epibatidine, and bethanechol were 1.5- to 2-fold higher in the inner longitudinal muscle layer, whereas contractions to EFS were 1.5-fold higher in the outer (both pre- and post-epibatidine). Human bladders showed 1.2-fold greater contractions to epibatidine in the inner layer and to EFS in the outer, yet no layer differences to KCl or bethanechol were noted. In both species, axonal density was 2- to 2.5-fold greater in the outer layer. Dogs had more intramural ganglia in the adventitia/serosa layer, compared with more internal layers and to humans. These findings indicate several layer-dependent differences in receptor expression or distribution, and neurogenic responses in dog and human detrusor muscles, and myogenic/muscarinic differences between dog versus humans.
Assuntos
Receptores Nicotínicos , Bexiga Urinária , Animais , Betanecol/metabolismo , Betanecol/farmacologia , Cães , Estimulação Elétrica , Humanos , Agonistas Muscarínicos/farmacologia , Contração Muscular , Músculo Liso , Nicotina/farmacologia , Cloreto de Potássio/metabolismo , Cloreto de Potássio/farmacologia , Receptores Muscarínicos/metabolismo , Receptores Nicotínicos/metabolismo , Bexiga Urinária/metabolismoRESUMO
Aortopathy is a term most commonly used to describe a group of genetic diseases that predispose patients to an elevated risk of aortic events including aneurysm and acute aortic syndrome. Types of genetic aortopathy are classified as either heritable or congenital, with heritable thoracic aortic disease (HTAD) further subclassified into syndromic HTAD or nonsyndromic HTAD, the former of which is associated with specific phenotypic features. Radiologists may be the first physicians to encounter features of genetic aortopathy, either incidentally or at the time of an acute aortic event. Identifying patients with genetic aortopathy is of substantial importance to clinicians who manage thoracic aortic disease, because aortic diameter thresholds for surgical intervention are often lower than those for nongenetic aortopathy related to aging and hypertension. In addition, when reparative surgery is performed, the approach and extent of the repair may differ in patients with genetic aortopathy. The radiologist should also be familiar with competing diagnoses that can result in acute aortic events, mainly acquired inflammatory and noninflammatory thoracic aortic disease, because these conditions may be associated with increased risks of similar pathologic endpoints. Because many imaging and phenotypic features of various types of genetic aortopathy overlap, diagnosis and determination of appropriate follow-up recommendations can be challenging. A multidisciplinary approach with the use of imaging is often required and, once the diagnosis is made, imaging has additional importance because of the need for lifelong follow-up. ©RSNA, 2022.
Assuntos
Doenças da Aorta , Aorta , Aorta Torácica/diagnóstico por imagem , Doenças da Aorta/complicações , Doenças da Aorta/diagnóstico por imagem , Doenças da Aorta/genética , Valva Aórtica/anormalidades , Valva Aórtica/patologia , Valva Aórtica/cirurgia , Diagnóstico por Imagem , Humanos , SíndromeRESUMO
BACKGROUND: In individuals with heritable thoracic aortic disease (HTAD), endovascular repair for treatment of aortic aneurysm and dissection may be lifesaving, but is associated with increased risk of failure of endovascular repair and adverse outcomes. This study reports our experience with early and late outcomes of endovascular aortic and branch vessel repair in patients with HTAD. METHODS: A retrospective case series was performed by chart review of individuals with HTAD followed at Washington University School of Medicine/Barnes-Jewish Hospital who underwent endovascular aortic and/or branch vessel repair. Clinical features, imaging characteristics, and short- and long-term outcomes were collected. RESULTS: Twenty-nine patients with HTAD (20 male; mean age 45 ± 13 years) underwent 37 endovascular procedures between 2006 and 2020 with mean follow up of 54 ± 41 months. Seven patients underwent two or more separate endovascular procedures. Each procedure was considered separate for data collection and analysis. Underlying conditions included Marfan syndrome (n = 16 procedures), Loeys-Dietz syndrome (n = 14 procedures), vascular Ehlers-Danlos syndrome (n = 3 procedures), and nonsyndromic HTAD (n = 4 procedures). Twenty patients (69%) had prior open surgical aortic repair. Indications for endovascular aortic repair (n = 31) included urgent repairs of acute complications of aortic dissection (n = 10) or aneurysm rupture (n = 3), and elective aortic repair (n = 18; 10 chronic dissections and eight chronic aneurysms). Six patients underwent elective endovascular repair of six branch vessel aneurysms or dissections. Six patients underwent hybrid open surgical and endovascular repair. Of the 37 procedures, 25 (68%) proximal landing zones were in the native aorta or branch vessel, 11 (30%) were in a surgical graft or elephant trunk and one was in a previously placed endograft. Thirty-six (97%) procedures were technically successful, and none required emergency surgical conversion. Two patients died: one from sepsis and one from presumed late pseudoaneurysm rupture, for a 5% per-procedure mortality rate. Two procedures were complicated by stroke and one patient developed paraparesis. Of the 31 aortic procedures, seven aortic endografts (23%) developed a stent-induced new entry (SINE) discovered with imaging at 20 ± 15 days post-procedure. Seven endografts (23%) developed a Type I endoleak and eight (26%) developed a Type II endoleak. No Type III endoleaks were seen. Within 30 days, two endografts (of 37, 5%) required reintervention. After 30 days, fifteen additional endografts (of 37, 41%) required reintervention. Two patients (of 6, 33%) who underwent hybrid repair required reintervention. CONCLUSIONS: This study is the largest single-center case series examining outcomes of HTAD patients following endovascular repair. Urgent and elective endovascular repairs in patients with HTAD can manage acute and chronic complications of aortic aneurysm and dissection with relatively low risk. However, risk of early and late endoleaks and SINE is high. Close post-procedural surveillance is required, and many individuals will require additional interventions. Hybrid repair shows promise and requires further investigation.
Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Implante de Prótese Vascular , Procedimentos Endovasculares , Humanos , Masculino , Pré-Escolar , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/genética , Aneurisma da Aorta Torácica/cirurgia , Endoleak/etiologia , Prótese Vascular/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Complicações Pós-Operatórias , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/genética , Dissecção Aórtica/cirurgia , Procedimentos Endovasculares/efeitos adversosRESUMO
We determined the effect of pelvic organ decentralization and reinnervation 1 yr later on urinary bladder histology and function. Nineteen canines underwent decentralization by bilateral transection of all coccygeal and sacral (S) spinal roots, dorsal roots of lumbar (L)7, and hypogastric nerves. After exclusions, eight were reinnervated 12 mo postdecentralization with obturator-to-pelvic and sciatic-to-pudendal nerve transfers, then euthanized 8-12 mo later. Four served as long-term decentralized only animals. Before euthanasia, pelvic or transferred nerves and L1-S3 spinal roots were stimulated and maximum detrusor pressure (MDP) recorded. Bladder specimens were collected for histological and ex vivo smooth muscle contractility studies. Both reinnervated and decentralized animals showed less or denuded urothelium, fewer intramural ganglia, and more inflammation and collagen, than controls, although percent muscle was maintained. In reinnervated animals, pgp9.5+ axon density was higher compared with decentralized animals. Ex vivo smooth muscle contractions in response to KCl correlated positively with submucosal inflammation, detrusor muscle thickness, and pgp9.5+ axon density. In vivo, reinnervated animals showed higher MDP after stimulation of L1-L6 roots compared with their transected L7-S3 roots, and reinnervated and decentralized animals showed lower MDP than controls after stimulation of nerves (due likely to fibrotic nerve encapsulation). MDP correlated negatively with detrusor collagen and inflammation, and positively with pgp9.5+ axon density and intramural ganglia numbers. These results demonstrate that bladder function can be improved by transfer of obturator nerves to pelvic nerves at 1 yr after decentralization, although the fibrosis and inflammation that developed were associated with decreased contractile function.
Assuntos
Músculo Liso/fisiopatologia , Transferência de Nervo , Traumatismos da Medula Espinal/fisiopatologia , Nervos Espinhais/fisiopatologia , Bexiga Urinária/inervação , Animais , Cães , Estimulação Elétrica/métodos , Contração Muscular/fisiologia , Regeneração Nervosa/fisiologia , Transferência de Nervo/métodos , Raízes Nervosas Espinhais/fisiopatologia , Bexiga Urinária/fisiopatologiaRESUMO
This study determined the effect of pelvic organ decentralization and reinnervation 1 yr later on the contribution of muscarinic and purinergic receptors to ex vivo, nerve-evoked, bladder smooth muscle contractions. Nineteen canines underwent decentralization by bilateral transection of all coccygeal and sacral (S) spinal roots, dorsal roots of lumbar (L)7, and hypogastric nerves. After exclusions, 8 were reinnervated 12 mo postdecentralization with obturator-to-pelvic and sciatic-to-pudendal nerve transfers then euthanized 8-12 mo later. Four served as long-term decentralized only animals. Controls included six sham-operated and three unoperated animals. Detrusor muscle was assessed for contractile responses to potassium chloride (KCl) and electric field stimulation (EFS) before and after purinergic receptor desensitization with α, ß-methylene adenosine triphosphate (α,ß-mATP), muscarinic receptor antagonism with atropine, or sodium channel blockade with tetrodotoxin. Atropine inhibition of EFS-induced contractions increased in decentralized and reinnervated animals compared with controls. Maximal contractile responses to α,ß-mATP did not differ between groups. In strips from decentralized and reinnervated animals, the contractile response to EFS was enhanced at lower frequencies compared with normal controls. The observation of increased blockade of nerve-evoked contractions by muscarinic antagonist with no change in responsiveness to purinergic agonist suggests either decreased ATP release or increased ecto-ATPase activity in detrusor muscle as a consequence of the long-term decentralization. The reduction in the frequency required to produce maximum contraction following decentralization may be due to enhanced nerve sensitivity to EFS or a change in the effectiveness of the neurotransmission.
Assuntos
Neurônios Motores/efeitos dos fármacos , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Bexiga Urinária/fisiologia , Trifosfato de Adenosina/farmacologia , Animais , Atropina/farmacologia , Estimulação Elétrica/métodos , Antagonistas Muscarínicos/farmacologia , Contração Muscular/fisiologia , Músculo Liso/fisiologia , Transferência de Nervo/métodos , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/inervaçãoRESUMO
Bladder dysfunction is associated with the overexpression of the intermediate filament (IF) proteins desmin and vimentin in obstructed bladder smooth muscle (BSM). However, the mechanisms by which these proteins contribute to BSM dysfunction are not known. Previous studies have shown that desmin and vimentin directly participate in signal transduction. In this study, we hypothesized that BSM dysfunction associated with overexpression of desmin or vimentin is mediated via c-Jun N-terminal kinase (JNK). We employed a model of murine BSM tissue in which increased expression of desmin or vimentin was induced by adenoviral transduction to examine the sufficiency of increased IF protein expression to reduce BSM contraction. Murine BSM strips overexpressing desmin or vimentin generated less force in response to KCl and carbachol relative to the levels in control murine BSM strips, an effect associated with increased JNK2 phosphorylation and reduced myosin light chain (MLC20 ) phosphorylation. Furthermore, desmin and vimentin overexpressions did not alter BSM contractility and MLC20 phosphorylation in strips isolated from JNK2 knockout mice. Pharmacological JNK2 inhibition produced results qualitatively similar to those caused by JNK2 knockout. These findings suggest that inhibition of JNK2 may improve diminished BSM contractility associated with obstructive bladder disease.
Assuntos
Desmina/biossíntese , Sistema de Sinalização das MAP Quinases , Proteína Quinase 9 Ativada por Mitógeno/metabolismo , Contração Muscular , Músculo Liso/metabolismo , Bexiga Urinária/metabolismo , Vimentina/biossíntese , Animais , Desmina/genética , Camundongos , Camundongos Knockout , Proteína Quinase 9 Ativada por Mitógeno/genética , Músculo Liso/citologia , Bexiga Urinária/citologia , Vimentina/genéticaRESUMO
Fibromuscular dysplasia (FMD) is a heterogeneous group of non-atherosclerotic and non-inflammatory arterial diseases that primarily involves the renal and cerebrovascular arteries. Grange syndrome is an autosomal-recessive condition characterized by severe and early-onset vascular disease similar to FMD and variable penetrance of brachydactyly, syndactyly, bone fragility, and learning disabilities. Exome-sequencing analysis of DNA from three affected siblings with Grange syndrome identified compound heterozygous nonsense variants in YY1AP1, and homozygous nonsense or frameshift YY1AP1 variants were subsequently identified in additional unrelated probands with Grange syndrome. YY1AP1 encodes yin yang 1 (YY1)-associated protein 1 and is an activator of the YY1 transcription factor. We determined that YY1AP1 localizes to the nucleus and is a component of the INO80 chromatin remodeling complex, which is responsible for transcriptional regulation, DNA repair, and replication. Molecular studies revealed that loss of YY1AP1 in vascular smooth muscle cells leads to cell cycle arrest with decreased proliferation and increased levels of the cell cycle regulator p21/WAF/CDKN1A and disrupts TGF-ß-driven differentiation of smooth muscle cells. Identification of YY1AP1 mutations as a cause of FMD indicates that this condition can result from underlying genetic variants that significantly alter the phenotype of vascular smooth muscle cells.
Assuntos
Displasia Fibromuscular/genética , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Mutação , Proteínas Nucleares/genética , Fatores de Transcrição/genética , Adolescente , Adulto , Osso e Ossos/patologia , Braquidactilia/genética , Pontos de Checagem do Ciclo Celular/genética , Proteínas de Ciclo Celular , Exoma/genética , Feminino , Genes Recessivos , Heterozigoto , Homozigoto , Humanos , Deficiências da Aprendizagem/genética , Masculino , Pessoa de Meia-Idade , Linhagem , Sindactilia/genética , SíndromeRESUMO
Loeys-Dietz syndrome is a heritable disorder of the connective tissue leading to multisystem involvement including craniofacial features, skeletal abnormalities, cutaneous findings and early-onset and aggressive disease of the aorta and its branches. There are multiple types of Loeys-Dietz syndrome related to pathogenic variants in TGFBR1, TGFBR2, SMAD3, TGFB2, and TGFB3. Individuals with Loeys-Dietz syndrome may be misdiagnosed as having Marfan syndrome due to shared phenotypic features and aortic root dilation. However, ectopia lentis has been an important discriminating feature, being unique to Marfan syndrome and not reported to be associated with Loeys-Dietz syndrome. We report the case of a 46-year-old woman with Loeys-Dietz syndrome type 4 due to a pathogenic variant in TGFB2 who was diagnosed with ectopia lentis at age 44. The patient underwent whole exome sequencing and no other pathogenic variants were found to explain the ectopia lentis. Our findings indicate that ectopia lentis may be an uncommon finding in Loeys-Dietz syndrome type 4 and emphasize the importance of genetic testing in familial thoracic aortic aneurysm disease.
Assuntos
Aneurisma da Aorta Torácica/genética , Ectopia do Cristalino/genética , Síndrome de Loeys-Dietz/genética , Fator de Crescimento Transformador beta2/genética , Adulto , Aneurisma da Aorta Torácica/complicações , Aneurisma da Aorta Torácica/diagnóstico , Aneurisma da Aorta Torácica/patologia , Ectopia do Cristalino/complicações , Ectopia do Cristalino/diagnóstico , Ectopia do Cristalino/patologia , Feminino , Humanos , Síndrome de Loeys-Dietz/complicações , Síndrome de Loeys-Dietz/diagnóstico , Síndrome de Loeys-Dietz/patologia , Masculino , Pessoa de Meia-Idade , Mutação/genéticaRESUMO
AIMS: We sought to determine whether somatic lumbar nerve transfer to the pelvic nerve's anterior vesical branch after sacral decentralization for detrusor muscle reinnervation also leads to aberrant innervation of the bladder outlet. METHODS: Twenty-six female mongrel hound dogs underwent transection of sacral dorsal and ventral spinal roots (ie, sacral decentralization). Immediately afterward, 12 received genitofemoral nerve transfer and 9 received femoral nerve branch transfer. Five were left sacrally decentralized. Controls included 3 sham-operated and 6 unoperated. Eight months postsurgery, the bladder and urethra were injected with retrograde tracing dyes cystoscopically. After 3 weeks, detrusor and urethral pressures were assayed electrophysiologically immediately before euthanasia and characterization of neural reinnervation. RESULTS: Electrical stimulation of spinal cords or roots did not lead to increased urethral sphincter pressure in nerve transfer animals, compared with decentralized animals, confirming a lack of functional reinnervation of the bladder outlet. In contrast, mean detrusor pressure increased after lumbar cord/root stimulation. In sham/unoperated animals, urethral and bladder dye injections resulted in labeled neurons in sacral level neural structures (dorsal root ganglia [DRG], sympathetic trunk ganglia [STG], and spinal cord ventral horns); labeling absent in decentralized animals. Urethral dye injections did not result in labeling in lumbar or sacral level neural structures in either nerve transfer group while bladder dye injections lead to increased labeled neurons in lumbar level DRG, STG, and ventral horns, compared to sacrally decentralized animals. CONCLUSION: Pelvic nerve transfer for bladder reinnervation does not impact urethral sphincter innervation.
Assuntos
Transferência de Nervo/métodos , Nervos Espinhais/transplante , Uretra/inervação , Bexiga Urinária/inervação , Animais , Cães , Estimulação Elétrica , Feminino , Neurônios/fisiologiaRESUMO
Acute aortic dissection (AAD) is a life-threatening condition associated with high morbidity and mortality rates, and it remains a challenge to diagnose and treat. The International Registry of Acute Aortic Dissection was established in 1996 with the mission to raise awareness of this condition and provide insights to guide diagnosis and treatment. Since then, >7300 cases have been included from >51 sites in 12 countries. Although presenting symptoms and physical findings have not changed significantly over this period, the use of computed tomography in the diagnosis has increased, and more patients are managed with interventional procedures: surgery in type A AAD and endovascular therapy in type B AAD; with these changes in care, there has been a significant decrease in overall in-hospital mortality in type A AAD but not in type B AAD. Herein, we summarized the key lessons learned from this international registry of patients with AAD over the past 20 years.
Assuntos
Aneurisma Aórtico , Dissecção Aórtica , Doença Aguda , Idoso , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/mortalidade , Dissecção Aórtica/cirurgia , Aneurisma Aórtico/diagnóstico por imagem , Aneurisma Aórtico/mortalidade , Aneurisma Aórtico/cirurgia , Aortografia/métodos , Implante de Prótese Vascular , Angiografia por Tomografia Computadorizada , Procedimentos Endovasculares , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Sistema de Registros , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
PURPOSE: Smooth muscle dysfunction syndrome (SMDS) due to heterozygous ACTA2 arginine 179 alterations is characterized by patent ductus arteriosus, vasculopathy (aneurysm and occlusive lesions), pulmonary arterial hypertension, and other complications in smooth muscle-dependent organs. We sought to define the clinical history of SMDS to develop recommendations for evaluation and management. METHODS: Medical records of 33 patients with SMDS (median age 12 years) were abstracted and analyzed. RESULTS: All patients had congenital mydriasis and related pupillary abnormalities at birth and presented in infancy with a patent ductus arteriosus or aortopulmonary window. Patients had cerebrovascular disease characterized by small vessel disease (hyperintense periventricular white matter lesions; 95%), intracranial artery stenosis (77%), ischemic strokes (27%), and seizures (18%). Twelve (36%) patients had thoracic aortic aneurysm repair or dissection at median age of 14 years and aortic disease was fully penetrant by the age of 25 years. Three (9%) patients had axillary artery aneurysms complicated by thromboembolic episodes. Nine patients died between the ages of 0.5 and 32 years due to aortic, pulmonary, or stroke complications, or unknown causes. CONCLUSION: Based on these data, recommendations are provided for the surveillance and management of SMDS to help prevent early-onset life-threatening complications.
Assuntos
Actinas/genética , Aneurisma da Aorta Torácica/genética , Permeabilidade do Canal Arterial/genética , Oftalmopatias Hereditárias/genética , Midríase/genética , Adolescente , Adulto , Aneurisma da Aorta Torácica/diagnóstico , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/fisiopatologia , Arginina/genética , Criança , Pré-Escolar , Permeabilidade do Canal Arterial/diagnóstico , Permeabilidade do Canal Arterial/diagnóstico por imagem , Permeabilidade do Canal Arterial/fisiopatologia , Oftalmopatias Hereditárias/diagnóstico , Oftalmopatias Hereditárias/diagnóstico por imagem , Oftalmopatias Hereditárias/fisiopatologia , Predisposição Genética para Doença , Testes Genéticos , Humanos , Lactente , Prontuários Médicos , Músculo Liso/diagnóstico por imagem , Músculo Liso/fisiopatologia , Midríase/diagnóstico , Midríase/diagnóstico por imagem , Midríase/fisiopatologia , Adulto JovemRESUMO
AIMS: To assess bladder smooth muscle function and innervation after long-term lower spinal root transection in canines. METHODS: Thirteen female mixed-breed hound dogs underwent bladder decentralization, which included transection of all sacral dorsal and ventral roots caudal to L7 and hypogastric nerves, bilaterally (n = 3); all sacral roots and hypogastric nerves plus transection of L7 dorsal roots, bilaterally (n = 4); or a sham operation (n = 6). At a year after initial surgery, bladder function was assessed in vivo by stimulation of the pelvic plexus. The bladder tissue was harvested for ex vivo smooth muscle contractility studies. Remaining bladder was evaluated for nerve morphology immunohistochemically using neuronal marker PGP9.5, apoptotic activity using terminal deoxynucleotidyl transferase dUTP nick end labeling, and histopathology using a hematoxylin and eosin stain. RESULTS: Sacral root decentralization did not reduce maximum strength of pelvic plexus stimulation-induced bladder contraction, although long-term sacral dorsal and ventral root plus L7 dorsal root transection significantly decreased contraction strength. Electric field stimulation-induced contractions of the detrusor from all decentralized animals were preserved, compared to controls. Viable nerves and intramural ganglia were visualized in the bladder wall, regardless of group. There was no difference in amount of apoptosis in bladder smooth muscle between groups. CONCLUSION: Bladder smooth muscle cells maintain their function after long-term bladder decentralization. While pelvic plexus-induced bladder contractions were less robust at 1 year after lower spinal root transection, the absence of atrophy and preservation of at least some nerve activity may allow for successful surgical reinnervation after long-term injury.
Assuntos
Estado de Descerebração/fisiopatologia , Músculo Liso/fisiopatologia , Bexiga Urinária/lesões , Bexiga Urinária/inervação , Animais , Cães , Estimulação Elétrica , Feminino , Plexo Hipogástrico/lesões , Marcação In Situ das Extremidades Cortadas , Contração Muscular , Músculo Liso/inervação , Regeneração Nervosa , Raízes Nervosas Espinhais/lesões , Raízes Nervosas Espinhais/fisiopatologiaRESUMO
BACKGROUND: Aortic-root dissection is the leading cause of death in Marfan's syndrome. Studies suggest that with regard to slowing aortic-root enlargement, losartan may be more effective than beta-blockers, the current standard therapy in most centers. METHODS: We conducted a randomized trial comparing losartan with atenolol in children and young adults with Marfan's syndrome. The primary outcome was the rate of aortic-root enlargement, expressed as the change in the maximum aortic-root-diameter z score indexed to body-surface area (hereafter, aortic-root z score) over a 3-year period. Secondary outcomes included the rate of change in the absolute diameter of the aortic root; the rate of change in aortic regurgitation; the time to aortic dissection, aortic-root surgery, or death; somatic growth; and the incidence of adverse events. RESULTS: From January 2007 through February 2011, a total of 21 clinical centers enrolled 608 participants, 6 months to 25 years of age (mean [±SD] age, 11.5±6.5 years in the atenolol group and 11.0±6.2 years in the losartan group), who had an aortic-root z score greater than 3.0. The baseline-adjusted rate of change in the mean (±SE) aortic-root z score did not differ significantly between the atenolol group and the losartan group (-0.139±0.013 and -0.107±0.013 standard-deviation units per year, respectively; P=0.08). Both slopes were significantly less than zero, indicating a decrease in the aortic-root diameter relative to body-surface area with either treatment. The 3-year rates of aortic-root surgery, aortic dissection, death, and a composite of these events did not differ significantly between the two treatment groups. CONCLUSIONS: Among children and young adults with Marfan's syndrome who were randomly assigned to losartan or atenolol, we found no significant difference in the rate of aortic-root dilatation between the two treatment groups over a 3-year period. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov number, NCT00429364.).
Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Aorta/efeitos dos fármacos , Aneurisma Aórtico/prevenção & controle , Atenolol/uso terapêutico , Losartan/uso terapêutico , Síndrome de Marfan/tratamento farmacológico , Antagonistas Adrenérgicos beta/efeitos adversos , Adulto , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Aorta/crescimento & desenvolvimento , Aorta/cirurgia , Insuficiência da Valva Aórtica , Atenolol/efeitos adversos , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Modelos Lineares , Losartan/efeitos adversos , Masculino , Síndrome de Marfan/mortalidade , Síndrome de Marfan/fisiopatologia , Resultado do Tratamento , Adulto JovemAssuntos
Doenças da Aorta/genética , Doenças Raras/genética , Doenças da Aorta/diagnóstico , Doenças da Aorta/terapia , Pesquisa Biomédica/economia , Financiamento Governamental/organização & administração , Fundações/organização & administração , Humanos , National Institutes of Health (U.S.)/economia , Doenças Raras/diagnóstico , Doenças Raras/terapia , Estados UnidosRESUMO
AIMS: Complete spinal cord injury does not block perceptual responses or inferior solitary nucleus activation after genital self-stimulation, even though the vagus is not thought to innervate pelvic structures. We tested if vagus nerve endings sprout after bladder decentralization to innervate genitourinary structures in canines with decentralized bladders. METHODS: Four reinnervation surgeries were performed in female hounds: bilateral genitofemoral nerve transfer to pelvic nerve with vesicostomy (GNF-V) or without (GFN-NV); and left femoral nerve transfer (FNT-V and FNT-NV). After 8 months, retrograde dyes were injected into genitourinary structures. Three weeks later, at euthanasia, reinnervation was evaluated as increased detrusor pressure induced by functional electrical stimulation (FES). Controls included un-operated, sham-operated, and decentralized animals. RESULTS: Increased detrusor pressure was seen in 8/12 GFNT-V, 4/5 GFNT-NV, 5/5 FNT-V, and 4/5 FNT-NV animals after FES, but not decentralized controls. Lumbar cord segments contained cells labeled from the bladder in all nerve transfer animals with FES-induced increased detrusor pressure. Nodose ganglia cells labeled from the bladder were observed in 5/7 nerve transfer animals (1/2 GNT-NV; 4/5 FNT-V), and from the clitoris were in 6/7 nerve transfer animals (2/2 GFNT-NV; 4/5 FNT-V). Dorsal motor nucleus vagus cells labeled from the bladder were observed in 3/5 nerve transfer animals (1/2 GFNT-NV; 2/3 FNT-V), and from the clitoris in 4/5 nerve transfer animals (1/2 GFNT-NV; 3/3 FNT-V). Controls lacked this labeling. CONCLUSIONS: Evidence of vagal nerve sprouting to the bladder and clitoris was observed in canines with lower motoneuron lesioned bladders. Neurourol. Urodynam. 36:91-97, 2017. © 2015 Wiley Periodicals, Inc.
Assuntos
Clitóris/inervação , Neurônios Motores , Transferência de Nervo/métodos , Bexiga Urinária/inervação , Nervo Vago/crescimento & desenvolvimento , Animais , Clitóris/crescimento & desenvolvimento , Cães , Estimulação Elétrica , Feminino , Nervo Femoral/cirurgia , Regeneração Nervosa , Gânglio Nodoso/citologia , Gânglio Nodoso/crescimento & desenvolvimento , Pressão , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/cirurgia , Bexiga Urinária/crescimento & desenvolvimento , Bexiga Urinária/fisiopatologiaRESUMO
BACKGROUND: Marfan syndrome (MFS) leads to aortic root aneurysm, while descending thoracic aortic aneurysm (TAA) occurs less commonly. Abdominal aortic aneurysm (AAA) is rarely reported in MFS. Risk factors for AAA are poorly understood and there are no guidelines for AAA screening in MFS. We sought to characterize AAA among Marfan patients in our center. METHODS: The records of 12 adults with MFS and AAA disease were reviewed. Clinical features, imaging, operative reports, and outcomes were analyzed. RESULTS: Twelve adults with MFS and AAA were studied; age at AAA diagnosis was 44 ± 15 years (range 18-63). Nine patients smoked cigarettes. Eleven patients underwent prior aortic root replacement at age 31 ± 15 years. The size of AAA was 5.0 ± 1.3 cm (range 3.5-7.5) at the time of diagnosis. The AAA was suprarenal in 5, juxtarenal in 2, and infrarenal in 5 patients. Two patients had a descending TAA. Branch vessel aneurysms were present in 7 patients. Five patients underwent open surgical repair, 5 underwent endovascular repair, and 5 are being treated medically. One patient died suddenly with AAA size 5.7 cm, 2 months before death. Three patients subsequently developed type B aortic dissection, from 3 months to 9 years after AAA diagnosis. CONCLUSIONS: Adults with MFS are at risk for developing AAA. Evaluation for AAA is recommended in adults with MFS and prior root replacement, especially if descending aortic or branch vessel aneurysm is present or the patient smokes cigarettes.