Introdução: O tratamento alternativo de Redução septal percutânea (RSP) em pacientes com cardiomiopatia hipertrófica obstrutiva é relativamente novo e há poucos trabalhos publicados sobre a evolução tardia. Objetivos: Avaliar nos pacientes com cardiomiopatia hipertrófica obstrutiva sintomáticos e refratários ao tratamento clínico, tratados com RSP, a sobrevida cardíaca e global, qualidade de vida, eventos maiores e as alterações encontradas no eletrocardiograma (ECG), ecocardiograma(ECO) e Holter 24h antes e na evolução tardia de até 15 anos. Método: Foram incluídos pacientes consecutivos que realizaram RSP no Instituto Dante Pazzanese de Cardiologia e no Hospital do Coração de Outubro de 1998 até junho de 2013. Todos os pacientes realizaram exame clínico, ECG e ECO, e a maioria Holter 24h e responderam o questionário DASI antes e pós-RSP. Os dados qualitativos foram descritos em frequências absolutas e relativas e os quantitativos resumidos em médias ± desvios padrão. Para as variáveis quantitativas foram utilizados modelos ANOVA com medidas repetidas, seguidos pelo método de comparações múltiplas de Bonferroni. O nível de significância de 0,05 foi aceito. Resultados: Dos 56 pacientes incluidos, 28 (50%) eram homens, a idade média foi 53,2 ±15,5 anos sendo 2 crianças e 11 (19,6%) tinham coronariopatia. A maioria estava em classe funcional III-IV, o gradiente médio basal por ECO foi 92,8 ± 3,3 mmHg, a espessura do septo 23,9 ± 0,6 e 62,5% tinha insuficiência mitral (IM) moderada. Durante a internação 1 (1,7%)paciente implantou marcapasso. Durante o seguimento de 7,4 ± 4 anos ocorreram 3 implantes de CDI, 2 por prevenção secundaria e 1 marcapasso, 1 nova RSP, 3 cirurgias de miectomias e houve 7 (12,5%) óbitos, apenas 2 de causa cardíaca. O tempo médio de sobrevida, estimado pelo método de Kaplan Meier foi de 13,3 anos (IC95% 12,2 a 14,5 anos), com expectativa de sobrevida de 96,4% em 1 ano, 87,7% em 5 anos e 81,0% a os 12 anos pós-RSP. Houve melhora significativa na qualidade de vida pelo questionário DASI e na classe funcional da NYHA que passou de 3,6 ± 0,5 para 1,2 ± 0,5 no pós-RSP. Na última avaliação do ECO o gradiente 9,37 ± 6,7 mmHg, o septo 12,87 ± 0,98 mm e a IM foi discreta em 90% todos com p < 0,001. Das variáveis analisadas somente o gradiente no estresse, p=0,039 e a massa p=0,024 foram associados a pior prognóstico. Conclusões: A redução septal percutânea mostrou, na evolução tardia com 100% de seguimento, ser uma técnica segura, eficaz em manter os benefícios tardiamente com baixa mortalidade, oferecendo melhora significativa da classe funcional e da qualidade de vida para os pacientes. / Introduction: Percutaneous septal Reduction (PSR) is a relatively new alternative treatment in patients with obstructive hypertrophic cardiomyopathy and there are few published studies on late evolution. Objectives: Evaluate in symptomatic patients with hypertrophic obstructive cardiomyopathy refractory to medical treatment and who underwent PSR, cardiac and overall survival, quality of life, major events and changes found on the electrocardiogram (ECG), echocardiography (ECHO) and Holter 24h before and after PSR during an evolution up to 15 years. Method: Consecutive patients who were submitted to RSP in Dante Pazzanese Institute of Cardiology and Heart Hospital from October 1998 were included. All patients went through clinical, ECG and ECHO examination, and nearly all answered DASI questionnaire, 24-hour Holter monitoring before and after PSR. Qualitative data were described as absolute and relative frequencies and quantitative summarized as means ± standard deviations. ANOVA models were used for quantitative variables with repeated measures, followed by Bonferroni method for multiple comparison. Significance level of 0.05 was accepted. Results: From 56 patients included, 28 (50%) were men , the mean age was 53.2 ± 15.5 years with 2 children and 11 (19.6%) had coronary artery disease . Most were in functional class III - IV from NYHA, the mean baseline ECO gradient was 92.8 ± 3.3 mmHg, the septal thickness 23.9 ± 0.6mm and 62.5 % had moderate mitral regurgitation (MR). During hospitalization 1 (1.7%) patient required permanent pacemaker. During follow-up of 7.4 ± 4 years, 3 patient required ICD implantation, 2 (for secondary prevention), 1 permanent pacemaker, 1 new RSP, 3 myectomy surgery. There were 7 (12.5%) deaths but only 2 of cardiac causes. The median survival time estimated by the Kaplan Meier was 13.3 years (95% CI 12.2 to 14.5 years), with expected survival of 96.4% at 1 year, 87.7% at 5 years and 81.0% at 12 years post-PSR. Significant improvement was seen in quality of life inferred by DASI questionnaire answers and NYHA functional class from 3.6 ± 0.5 to 1.2 ± 0.5. In last evaluation we found statistical significant reduction in ECO gradient 9.37 ± 6.7 mmHg, septum thikness 12.87 ± 0.98 mm and MR was mild in 90 % of patients. Of the variables analyzed only stress gradient (p = 0.039) and mass (p = 0.024) were associated with worse prognosis. Conclusions: The results of this study suggest that percutaneous septal reduction in late evolution with no loses in follow-up, is a safe technique, effective in reducing ventricular gradient and preserving the benefits in long-term evolution with low mortality, offering significant improvement in functional class and quality of life for patients.

Rare lipoprotein A (RlpA) has been studied previously only in Escherichia coli, where it localizes to the septal ring and scattered foci along the lateral wall, but mutants have no phenotypic change. In this thesis, we show rlpA mutants of Pseudomonas aeruginosa form chains of short, fat cells when grown in media of low osmotic strength. These morphological defects indicate RlpA is needed for efficient separation of daughter cells and maintenance of rod shape. Analysis of peptidoglycan sacculi from a ΔrlpA mutant revealed increased tetra and hexasaccharides that lack stem peptides (hereafter called "naked glycans"). Incubation of these sacculi with purified RlpA resulted in release of naked glycans containing 1,6-anhydro N-acetylmuramic acid ends. RlpA did not degrade sacculi from wild-type cells unless the sacculi were subjected to a limited digestion with an amidase to remove some of the stem peptides. Collectively, these findings indicate RlpA is a lytic transglycosylase with a strong preference for naked glycan strands. We propose that RlpA activity is regulated in vivo by substrate availability, and that amidases and RlpA work in tandem to degrade peptidoglycan in the division septum and lateral wall. Our discovery that RlpA from P. aeruginosa is a lytic transglycosylase motivated us to reinvestigate RlpA from E. coli. We confirmed predictions that RlpA of E. coli is an outer membrane protein and determined its abundance to be about 600 molecules per cell. However, multiple efforts to demonstrate that E. coli RlpA is a lytic transglycosylase were unsuccessful and the function of this protein in E. coli remains obscure.

No description available.

Diss. (sammanfattning) Göteborg : Göteborgs universitet, 2007. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 6 uppsatser.

Thesis (doctoral)--Rijksuniversiteit te Groningen.

Made available in DSpace on 2016-06-02T19:22:49Z (GMT). No. of bitstreams: 1 1829.pdf: 1302384 bytes, checksum: f53ef9f9cd782da76b146d55e3808620 (MD5) Previous issue date: 2008-04-30 / Universidade Federal de Minas Gerais / Peripheral injection of pilocarpine (PILO, 1 mg/Kg of body weight), muscarinic cholinergic agonist, induce salivation, water intake and pressor response. The medial septal area (MSA) is an important brain area involved in cardiovascular regulation and hydroelectrolytic control. In this present study, we investigated: 1) the effect of MSA electrolytic lesion or the blockade of muscarinic cholinergic receptors into MSA on salivation, water intake and cardiovascular responses induced by peripheral pilocarpine; 2) the role of the sympathetic nervous system and/or vasopressin on the cardiovascular responses induced by peripheral pilocarpine; 3) the effect of injection of pilocarpine into MSA on salivation, water intake and cardiovascular responses. Male Holtzman rats weighing 280 to 320 g were submitted to 1 or 15 days MSA electrolytic lesion (2 mA x 5 s) or stainless steel guide cannulas were stereotaxically implanted into the MSA. We observed that peripheral pilocarpine (1 mg/kg of body weight) induces salivary secretion, water intake and an increase in mean arterial pressure (MAP) . This increase in MAP is due to an activation of simpathetic nervous system, since it was significantly reduced by previous treatment with prazosin (1 mg/kg of body weight), but not by vasopressin V1a receptor antagonist (10 µg/kg of body weigh). The salivary secretion and dipsogenic response induced by peripheral pilocarpine was reduced by MSA eletrolytic lesion or MSA muscarinic cholinergic blockade. Nonetheless, the pressor response induced by peripheral pilocarpine was not depend of MSA, since MSA eletrolytic lesion or muscarinic cholinergic receptors blockade did not change this response. Pilocarpine injection into MSA induced water intake (200 e 500 nmol/0,5 µL), salivary secretion (500 nmol/0,5 µL) and MAP increase (500 nmol/0,5 µL). Our results show that peripheral or MSA injection of pilocarpine induce salivary secretion, water intake and pressor response. The pressor response induced by peripheral pilocarpine is due to sympathetic activation. The MSA and its muscarinic cholinergic receptors are involved in the salivary secretion and water intake, but not in the control of pressor response induced by peripheral pilocarpine, suggesting that MSA has a differencial control on the responses induced by peripheral pilocarpine. / A injeção periférica de pilocarpina (PILO, 1 mg/kg de peso corporal), agonista colinérgico muscarínico, induz salivação, ingestão de água e resposta pressora. A área septal medial (ASM) é uma importante área cerebral envolvida com a regulação cardiovascular e com o controle do balanço hidroeletrolítico. No presente estudo, investigamos: 1) o efeito da lesão eletrolítica da ASM ou do bloqueio dos receptores colinérgicos muscarínicos da ASM na salivação, na ingestão de água e nas respostas cardiovasculares induzida pela pilocarpina periférica; 2) a participação do sistema nervoso simpático e da vasopressina sobre as respostas cardiovasculares induzidas pela pilocarpina periférica; 3) os efeitos da injeção de pilocarpina na ASM sobre a salivação, ingestão de água e respostas cardiovasculares. Ratos Holtzman (280 - 320 g), foram submetidos à lesão eletrolítica (2 mA x 5 s) da ASM (1 ou 15 dias) ou ao implante de cânula-guia de aço inoxidável na ASM. Verificamos que a injeção periférica de pilocarpina (1 mg/kg de peso corporal) produz secreção salivar, ingestão de água e aumento da pressão arterial média (PAM). Este aumento da pressão arterial é decorrente da ativação do sistema nervoso simpático, pois foi reduzida significantemente pelo tratamento prévio com prazosin (1 mg/kg de peso corporal), mas não pelo antagonista do receptor V1a de vasopressina (10 µg/kg de peso corporal). A salivação e a resposta dipsogênica induzidas pela pilocarpina periférica foram reduzidas pela lesão eletrolítica ou pelo bloqueio colinérgico muscarínico da ASM. Entretanto, a resposta pressora induzida pela pilocarpina periférica não depende da ASM, já que a lesão eletrolítica ou o bloqueio de receptores colinérgicos muscarínicos da ASM não alteraram esta resposta. A injeção de pilocarpina na ASM induz resposta dipsôgenica (200 e 500 nmol/0,5 µL), salivação (500 nmol/0,5 µL) e resposta pressora (500 nmol/0,5 µL). Nossos resultados mostram que a pilocarpina periférica ou na ASM induz salivação, ingestão de água e resposta pressora. A resposta pressora induzida pela pilocarpina periférica é decorrente de um aumento na atividade simpática. A ASM e seus receptores colinérgicos muscarínicos participam do controle da secreção salivar e ingestão de água, mas não da resposta pressora induzida pela pilocarpina periférica, sugerindo um controle diferencial da ASM nas respostas induzidas pela administração periférica de pilocarpina.

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13331号 / 論医博第2199号 / 新制||医||1044(附属図書館) / (主査)教授 湊谷 謙司, 教授 横出 正之, 教授 戸口田 淳也 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

Introduction: Transseptal puncture (TSP) is challenging in patients with prior percutaneous atrial septal defect (ASD) occluder. We aimed to perform a systematic review and meta-analysis of the safety and efficacy of catheter ablation for atrial fibrillation (AF) in patients with percutaneous ASD occluder. Methods: We searched PubMed, Medline, Embase, Ovid, and Cochrane for studies reporting results of AF ablation (freedom from AF, fluoroscopy/procedure time, and complications) in patients with percutaneous ASD occluders. Results: Three studies with a total of 64 patients met inclusion criteria. The success rate of TSP was 100%. All patients (but one) underwent TSP under fluoroscopic and intracardiac echocardiography guidance. Freedom from AF was achieved in 77.7% (95% confidence interval [CI]: 65.7–86.3) patients. In the subgroup analysis, comparing septal versus device puncture, no significant difference in recurrence of AF was observed (23.07% vs. 16.66%; risk ratio: 1.18; 95% CI: 0.35–4.00; p =.79, respectively). The total fluoroscopy time was not significantly different in patients with TSP via native septum or device (43.50 vs. 70.67 min; p =.44), total procedural time was significantly longer with TSP via the closure device (237.3 vs. 180 min; p =.004) compared with the native septum. There were no device dislodgement or residual interatrial shunt during the follow-up period. Conclusion: Catheter ablation for AF in patients with prior percutaneous ASD closure device is feasible and safe with favorable long-term outcomes.

The physiological significance of noradrenergic sympathohabenular ingrowth following medial septal lesions was investigated. Following septal lesions, sympathetic fibers originating in the superior cervical ganglia are known to sprout into the medial habenular nuclei, and into the hippocampal formation. Previous work involving sympathohippocampal ingrowth showed that firing rates in septal animals with no ingrowth showed that firing rates in septal animals with no ingrowth were higher than rates of septal animals with ingrowth and controls. Those results suggested that sympathetic ingrowth in the hippocampus had some functional capability in a modulatory manner. The primary aim of the present study was to determine if the peripheral sympathetic ingrowth into the medial habenular nuclei following a septal lesion is functionally significant. The results showed that firing rates of neurons of the medial habenulae in animals receiving septal lesions were significantly higher than rates of control animals and septal lesioned + ganglionectomized animals.