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1.
Nat Commun ; 12(1): 6876, 2021 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-34824236

RESUMO

Compositional changes of cell types are main drivers of biological processes. Their detection through single-cell experiments is difficult due to the compositionality of the data and low sample sizes. We introduce scCODA ( https://github.com/theislab/scCODA ), a Bayesian model addressing these issues enabling the study of complex cell type effects in disease, and other stimuli. scCODA demonstrated excellent detection performance, while reliably controlling for false discoveries, and identified experimentally verified cell type changes that were missed in original analyses.


Assuntos
Análise de Célula Única/métodos , Teorema de Bayes , Benchmarking , Perfilação da Expressão Gênica , Humanos , Modelos Estatísticos , Tamanho da Amostra , Análise de Célula Única/normas
2.
Integr Org Biol ; 1(1): obz015, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-33791530

RESUMO

The relationship between form and function is thought to play an integral role in structuring broad-scale patterns of morphological evolution and resource utilization. In ecomorphological studies, mechanical performance is widely understood to constrain the evolution of form and function. However, the relationship between form, function, and resource utilization is less clear. Additionally, seasonal fluctuations in resource availability may further complicate patterns of resource use. How organisms cope with these complexities, and the effect of these factors on broadscale patterns of morphological evolution is also poorly understood. Here we use three-dimensional geometric morphometrics, biomechanics, stable isotope analysis, and gut-content analysis to study trophic evolution in a clade of riverine-adapted electric fishes from a region with high seasonal variability; the Amazon River. We find significant and phylogenetically structured relationships among measures of trophic ecology and skull shape. We also recover a significant relationship between the mechanical advantage of the mandible and trophic position, where species feeding at higher trophic levels have narrower jaws with lower mechanical advantages, and species feeding at lower trophic levels have deeper jaws with higher mechanical advantages. Our results indicate that selection is driving the evolution of mandible shape and performance toward specialization on different trophic ecologies.


Ecomorfologia de Peixes Elétricos Neotropicais: Uma Abordagem Integrativa para Testar as Relações Entre Forma, Função, e Ecologia Trófica Acredita-se que a relação entre forma e função desempenhe um papel integral na estruturação de padrões de larga-escala de evolução morfológica e utilização de recursos. Em estudos ecomorfológicos, se é amplamente atribuído ao desempenho mecânico a restrição da evolução da forma e da função. Em estudos de sistemas complexos, como mandíbulas de peixes, a ideia de que a morfologia está relacionada ao desempenho é frequentemente estabelecida, mas sua relação com a utilização de recursos é menos clara. Aqui, nós usamos morfometria geométrica tridimensional, biomecânica, análise de isótopos estáveis e análise de conteúdo intestinal para estudar a evolução trófica em um clado de peixes elétricos adaptados a rios, da região da bacia Amazônica. Encontramos relações significativas e estruturadas filogeneticamente entre medidas de ecologia trófica e forma do crânio. Também recuperamos uma relação significativa entre a vantagem mecânica da mandíbula e posição trófica, onde as espécies que se alimentam em níveis tróficos superiores têm mandíbulas mais estreitas com menores vantagens mecânicas, e as espécies que se alimentam em níveis tróficos inferiores têm mandíbulas mais profundas com maiores vantagens mecânicas. Nossos resultados indicam que a seleção está conduzindo a evolução da forma e desempenho da mandíbula para a especialização em diferentes ecologias tróficas. Translated to Portuguese by J.P. Fontenelle (jp.fontenelle@mail.utoronto.ca).

3.
Internist (Berl) ; 56(8): 900-6, 2015 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-26219619

RESUMO

In addition to cardiac and pulmonary diseases there is a broad variety of different underlying causes of dyspnea. The spectrum includes the different forms of anemia, all causes of upper airway obstructions, neuromuscular diseases and psychopathological disorders. This article gives a brief review of the entire spectrum by providing information about differential diagnostics as well as the main therapeutic principles. A field of growing interest is dyspnea in the context of palliative care.


Assuntos
Obstrução das Vias Respiratórias/complicações , Obstrução das Vias Respiratórias/diagnóstico , Dispneia/diagnóstico , Dispneia/etiologia , Transtornos Mentais/diagnóstico , Doenças Neuromusculares/diagnóstico , Obstrução das Vias Respiratórias/terapia , Diagnóstico Diferencial , Dispneia/terapia , Humanos , Transtornos Mentais/complicações , Transtornos Mentais/terapia , Doenças Neuromusculares/complicações , Doenças Neuromusculares/terapia , Cuidados Paliativos/métodos
4.
Allergy ; 68(5): 562-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23480774

RESUMO

Schnitzler's syndrome is characterized by recurrent urticarial rash and monoclonal gammopathy, associated with clinical and biological signs of inflammation and a long-term risk of AA amyloidosis and overt lymphoproliferation. An extensive literature review was performed, and the following questions were addressed during an expert meeting: In whom should Schnitzler's syndrome be suspected? How should the diagnosis of Schnitzler's syndrome be established? How should a patient with Schnitzler's syndrome be treated? How should a patient with Schnitzler's syndrome be followed up?. A diagnosis of Schnitzler's syndrome is considered definite in any patient with two obligate criteria: a recurrent urticarial rash and a monoclonal IgM gammopathy, and two of the following minor criteria: recurrent fever, objective signs of abnormal bone remodeling, elevated CRP level or leukocytosis, and a neutrophilic infiltrate on skin biopsy. It is considered probable, if only 1 minor criterion is present. In patients with monoclonal IgG gammopathies, diagnosis is definite if three minor criteria are present and possible if two are present. First-line treatment in patients with significant alteration of quality of life or persistent elevation of markers of inflammation should be anakinra. Follow-up should include clinical evaluation, CBC and CRP every 3 months and MGUS as usually recommended.


Assuntos
Síndrome de Schnitzler/diagnóstico , Síndrome de Schnitzler/tratamento farmacológico , Seguimentos , Humanos
5.
Tissue Antigens ; 82(4): 243-51, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24461003

RESUMO

A major challenge in epitope-based vaccine (EV) design stems from the vast genomic variation of pathogens and the diversity of the host cellular immune system. Several computational approaches have been published to assist the selection of potential T cell epitopes for EV design. So far, no thorough comparison between the current methods has been realized. Using human immunodeficiency virus as test case, different EV selection algorithms were evaluated with respect to their ability to select small peptides sets with broad coverage of allelic and pathogenic diversity. The methods were compared in terms of in silico measurements simulating important vaccine properties like the ability of inducing protection against a multivariant pathogen in a population; the predicted immunogenicity; pathogen, allele, and population coverage; as well as the conservation of selected epitopes. Additionally, we evaluate the use of human leukocyte antigen (HLA) supertypes with regards to their applicability for population-spanning vaccine design. The results showed that in terms of induced protection methods that simultaneously aim to optimize pathogen and HLA coverage significantly outperform methods focusing on pathogen coverage alone. Moreover, supertype-based approaches for coverage of HLA diversity were showed to yield only satisfying results in populations in which the supertype representatives are prevalent.


Assuntos
Vacinas contra a AIDS/imunologia , Antígenos Virais/imunologia , Epitopos de Linfócito T/imunologia , Infecções por HIV/prevenção & controle , HIV-1/imunologia , Peptídeos/imunologia , Algoritmos , Alelos , Antígenos Virais/genética , Simulação por Computador , Epitopos de Linfócito T/genética , Frequência do Gene , Infecções por HIV/virologia , HIV-1/genética , Antígenos HLA/genética , Antígenos HLA/imunologia , Interações Hospedeiro-Patógeno , Humanos , Modelos Imunológicos , Peptídeos/genética , Linfócitos T/imunologia , Linfócitos T/virologia , Vacinas de Subunidades Antigênicas
6.
Chemistry ; 18(24): 7506-15, 2012 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-22504878

RESUMO

Short-lived pivaloylmetals, (H(3)C)(3)C-COM, were established as the reactive intermediates arising through thermal heterolytic expulsion of O=CtBu(2) from the overcrowded metal alkoxides tBuC(=O)-C(-OM)tBu(2) (M = MgX, Li, K). In all three cases, this fission step is counteracted by a faster return process, as shown through the trapping of tBu-COM by O=C(tBu)-C(CD(3))(3) with formation of the deuterated starting alkoxides. If generated in the absence of trapping agents, all three tBu-COM species "dimerize" to give the enediolates MO-C(tBu)=C(tBu)-OM along with O=CtBu(2) (2 equiv). A common-component rate depression by surplus O=CtBu(2) proves the existence of some free tBu-COM (separated from O=CtBu(2)); but companion intermediates with the traits of an undissociated complex such as tBu-COM & O=CtBu(2) had to be postulated. The slow fission step generating tBu-COMgX in THF levels the overall rates of dimerization, ketone addition, and deuterium incorporation. Formed by much faster fission steps, both tBu-COLi and tBu-COK add very rapidly to ketones and dimerize somewhat slower (but still fairly fast, as shown through trapping of the emerging O=CtBu(2) by H(3)CLi or PhCH(2)K, respectively). At first sight surprisingly, the rapid fission, return, and dimerization steps combine to very slow overall decay rates of the precursor Li and K alkoxides in the absence of trapping agents: A detailed study revealed that the fast fission step, generating tBu-COLi in THF, is followed by a kinetic partitioning that is heavily biased toward return and against the product-forming dimerization. Both tBu-COLi and tBu-COK form tBu-CH=O with HN(SiMe(3))(3), but only tBu-COK is basic enough for being protonated by the precursor acyloin tBuC(=O)-C(-OH)tBu(2) .

7.
Gynecol Obstet Fertil ; 38(11): 660-2, 2010 Nov.
Artigo em Francês | MEDLINE | ID: mdl-21030284

RESUMO

OBJECTIVES: To evaluate the effect of Temozolomide on female fertility and the relevance of our coverage in preservation of fertility. PATIENTS AND METHODS: From 2005 to 2009, 24 patients treated with Temozolomide for a low-grade glioma were included in the study (12 women who underwent a fertility preservation consultation and 12 women who did not). A retrospective study of their medical records and sending a questionnaire were undertaken to assess their fertility after treatment. RESULTS: Of the 24 patients, 15 patients had no fertility preservation and the remaining nine had a cryopreservation of embryos with or without an oocyte cryopreservation. Four patients are or have been pregnant (delivery, spontaneous miscarriage, pregnancy being in the group of preserving fertility and a current pregnancy in the group where no fertility preservation has been achieved). DISCUSSION: First study on the effect of Temozolomide on female fertility. CONCLUSION: Temozolomide is not totally gonadotoxic.


Assuntos
Antineoplásicos Alquilantes/efeitos adversos , Dacarbazina/análogos & derivados , Glioma/tratamento farmacológico , Infertilidade Feminina/induzido quimicamente , Adulto , Antineoplásicos Alquilantes/uso terapêutico , Criopreservação , Dacarbazina/efeitos adversos , Dacarbazina/uso terapêutico , Embrião de Mamíferos , Feminino , Humanos , Infertilidade Feminina/prevenção & controle , Oócitos , Gravidez , Resultado da Gravidez , Técnicas de Reprodução Assistida , Estudos Retrospectivos , Temozolomida
8.
Artigo em Alemão | MEDLINE | ID: mdl-20652484

RESUMO

The evaluation of the German Mammography Screening Program requires record linkage with data from cancer registries in order to measure the number of false-negative mammograms and interval cancers. This study aims at evaluating the performance of the established linkage method based on identifiers encrypted by the standard procedure of the German cancer registries. In addition, the results are compared with an alternative method based on plain text identifiers. A total of 16,572 records from the Bremen Mammography Screening Pilot Study were linked with data from the Bremen Cancer Registry. Based on a gold standard set of matching record pairs, homonym and synonym errors were determined. Given the customary threshold value in cancer registries, the plain text method showed a lower rate of synonym errors (2.1-5.1%) and a lower rate of homonym errors (0.01-0.15%). As 10.4 million women are invited to take part biennially in screening, the corresponding figures would be 3,237 homonym errors for the standard procedure and 294 using the plain text method provided equivalent conditions. The 11-fold increase in the homonym error rate documents the trade-off for better data protection using encrypted data.


Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias da Mama/prevenção & controle , Detecção Precoce de Câncer/estatística & dados numéricos , Detecção Precoce de Câncer/normas , Mamografia/estatística & dados numéricos , Mamografia/normas , Registro Médico Coordenado/normas , Sistema de Registros/estatística & dados numéricos , Sistema de Registros/normas , Erros de Diagnóstico , Reações Falso-Negativas , Feminino , Alemanha , Humanos , Garantia da Qualidade dos Cuidados de Saúde/normas , Garantia da Qualidade dos Cuidados de Saúde/estatística & dados numéricos
9.
Ann Dermatol Venereol ; 135(11): 765-8, 2008 Nov.
Artigo em Francês | MEDLINE | ID: mdl-19061657

RESUMO

BACKGROUND: The entity called pseudolymphomatous folliculitis (PLF) is a cutaneous pseudolymphoma. We report a new case of PLF with an atypical clinical presentation. CASE REPORT: A 6-year-old child was examined for an asymptomatic, hypochromic lesion of the face progressing for three months. The histology showed the activated pilosebaceous units with characteristic perifollicular infiltration by T-cells associated with dendritic cells expressing CD1a and protein S100. The outcome was spontaneously favourable. All of the foregoing elements supported a diagnosis of PLF. DISCUSSION: PLF is defined as a clinical-pathological entity among the cutaneous pseudolymphomas. The usual clinical aspect is that of a solitary red-to-violaceous asymptomatic nodule measuring less than 1.5cm in diameter. Histology shows follicular invasion characterized by lymphocytic infiltration into pilosebaceous units, creating architectural distortion; this infiltration is associated to perifollicular dendritic cells expressing CD1a and protein S100. We report this new case of PLF because of its peculiar clinical presentation. However, FPL remains a controversial entity, since the follicular location of the pseudolymphomatous lymphocytic infiltration seems poorly specific in facial lesions.


Assuntos
Amoxicilina/uso terapêutico , Foliculite/patologia , Pseudolinfoma/patologia , Dermatopatias/patologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/patologia , Criança , Células Dendríticas/imunologia , Células Dendríticas/patologia , Progressão da Doença , Foliculite/tratamento farmacológico , Foliculite/imunologia , Humanos , Inflamação/patologia , Masculino , Pseudolinfoma/tratamento farmacológico , Pseudolinfoma/imunologia , Dermatopatias/tratamento farmacológico , Dermatopatias/imunologia
10.
Gynecol Obstet Fertil ; 35(9): 853-60, 2007 Sep.
Artigo em Francês | MEDLINE | ID: mdl-17707674

RESUMO

Cancer is not the only disease where the question of the female fertility preservation is asked. In autoimmune diseases, alkylating agents are also used and it is now established that 20 g as a cumulative dose of cyclophosphamide is associated with premature ovarian failure in 50% of 20-year-old patients. Several strategies are discussed and offered to these patients to prevent the ovarian failure: GnRH agonist treatment, in vitro fertilization and embryos cryopreservation, oocytes cryopreservation and ovarian cortex cryopreservation. These techniques might also be associated one with the other. A survey was conducted in France in order to assess the practices realised in these diseases. Four centres were asked for these diseases, concerning 17 patients (mean age: 26.2 +/- 1.8 SEM [15-43]) and systemic lupus erythematosus was the most frequent disease (7/17). Ovarian cortex cryopreservation was realised for 6 patients. Embryos or oocytes cryopreservation was realised for 2 patients including one where ovarian cortex cryopreservation was associated. In 10 cases, considering the treatment and the patient's wish no fertility preservation was realised. Female fertility preservation in autoimmune diseases is a difficult question and a national registry, such as the one conducted by the GRECOT, can help to answer this question.


Assuntos
Doenças Autoimunes/complicações , Fertilidade/fisiologia , Adulto , Doenças Autoimunes/tratamento farmacológico , Ciclofosfamida/efeitos adversos , Feminino , França , Humanos , Infertilidade Feminina/etiologia , Infertilidade Feminina/prevenção & controle , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Insuficiência Ovariana Primária/induzido quimicamente
12.
Endoscopy ; 38(12): 1201-5, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17163319

RESUMO

BACKGROUND: Barrett's adenocarcinoma is being diagnosed increasingly. We examine possible differences between long segment and short-segment Barrett esophagus (LSBE and SSBE) in long-term follow-up on the basis of our histopathology registry. METHODS AND PATIENTS: All Barrett's esophagus patients diagnosed histologically between 1990 and 1995 (n = 1071) were selected. Long-term follow-up data from endoscopy with biopsy were sought on all patients without neoplasia on initial endoscopic biopsy (n = 1003). A total of 255 individuals (25.4 %) were regarded as drop-outs (201 lost and 54 without further endoscopy). Of the remaining 748 patients with follow up for more than 5 years, 315 had documented LSBE, 246 had SSBE, and 187 had no length of Barrett esophagus recorded (NLBE). RESULTS: In the study cases (male : female ratio 2.1 : 1, mean age +/- SD 60.9 +/- 14.2 years), the biopsy procedure was fully compliant with guidelines in only 32.5 %. Only 5 cases (0.6 %) had visible lesions reported on endoscopy, but all were negative for neoplasia. Over a mean follow-up of 78.2 +/- 35.6 months (range 0-240), 7 new cases of low grade intraepithelial neoplasia (LGIN) and 15 cancer cases developed, accounting for a yearly incidence of 0.2 % (LGIN) or 0.4 % (cancer) after an initial negative endoscopy. When the cases with initial diagnosis of neoplasia were included, this yearly incidence rose to 0.5 % (LGIN), 0.3 % (high grade intraepithelial neoplasia [HGIN]) or 1.7 % (cancer). Differences between SSBE and LSBE were only encountered for cancer incidence. CONCLUSION: The yearly incidence of Barrett esophagus cancer varies between 0.4 % and 1.7 %. Despite the limitations of this retrospective and pathology-based study, the observed risk of developing cancer in Barrett esophagus without neoplasia is comparable to that found in other studies, mainly from the US and the UK, and varies between 0.7 % and 1.0 % of yearly incidence.


Assuntos
Esôfago de Barrett/epidemiologia , Esôfago de Barrett/patologia , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/patologia , Esofagoscopia/métodos , Esôfago/patologia , Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Biópsia/normas , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco
13.
Phys Rev Lett ; 97(7): 076103, 2006 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-17026251

RESUMO

High dry friction requires intimate contact between two surfaces and is generally obtained using soft materials with an elastic modulus less than 10 MPa. We demonstrate that high-friction properties similar to rubberlike materials can also be obtained using microfiber arrays constructed from a stiff thermoplastic (polypropylene, 1 GPa). The fiber arrays have a smaller true area of contact than a rubberlike material, but polypropylene's higher interfacial shear strength provides an effective friction coefficient of greater than 5 at normal loads of 8 kPa. At the pressures tested, the fiber arrays showed more than an order of magnitude increase in shear resistance compared to the bulk material. Unlike softer materials, vertical fiber arrays of stiff polymer demonstrate no measurable adhesion on smooth surfaces due to high tensile stiffness.

14.
Clin Exp Dermatol ; 31(5): 659-61, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16780496

RESUMO

Pyoderma gangrenosum (PG) is an uncommon ulcerative condition. It is most commonly associated with inflammatory bowel disease, haematological malignancies and autoimmune disease. We report on two patients have developed PG during the initial course of Graves' disease (GD), prior to treatment of this condition. The lesions completely cleared with treatment by colchicine in the first case and with oral ciclosporin in the second case. The report emphasizes that a diagnostics of PG should be considered in patients with GD and skin ulcers.


Assuntos
Doença de Graves/complicações , Úlcera da Perna/etiologia , Pioderma Gangrenoso/etiologia , Administração Oral , Adulto , Biópsia , Colchicina/uso terapêutico , Ciclosporina/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Feminino , Supressores da Gota/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Úlcera da Perna/tratamento farmacológico , Úlcera da Perna/patologia , Pioderma Gangrenoso/tratamento farmacológico , Pioderma Gangrenoso/patologia , Resultado do Tratamento
15.
J Ethnopharmacol ; 89(2-3): 251-60, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-14611888

RESUMO

A selection of 32 fungal strains, belonging to 8 genera of entomopathogenic Deuteromycetes collected in various provinces of China, were screened for activities on targets involved in degenerative diseases of the central nervous system. The strains were grown under various fermentation conditions, and a total of 256 different extracts were obtained. The bioassays included functional screens for NMDA antagonistic activity in stably transfected fibroblasts, for neuritogenic activities in PC-12 cells, and tests for MAO inhibitory and radical scavenging properties. Several extracts with promising activities were identified. Some Paecilomyces extracts induced pronounced axonal-like outgrowths in PC-12 cells. In Paecilomyces militaris RCEF 0095, the neuritogenic activity could be linked to yellow pigments. Three Beauveria and Paecilomyces strains showed radical scavenging properties, which could be localized in the extract by a bioautographic assay on TLC. An extract obtained from the mycelium of Paecilomyces tenuipes RCEF 0275 showed moderate MAO inhibitory activity, whereas extracts of Sporothrix chondracris RCEF 0187 antagonized NMDA receptor mediated cell toxicity.


Assuntos
Antifúngicos/uso terapêutico , Fármacos do Sistema Nervoso Central/uso terapêutico , Doenças do Sistema Nervoso Central/tratamento farmacológico , Fungos Mitospóricos/metabolismo , Animais , Sobrevivência Celular , Células Cultivadas , Cromatografia em Camada Fina , Avaliação Pré-Clínica de Medicamentos , Fermentação , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Sequestradores de Radicais Livres/uso terapêutico , Mitocôndrias Hepáticas/metabolismo , Monoaminoxidase/metabolismo , Ratos
16.
Dtsch Med Wochenschr ; 128(4): 135-40, 2003 Jan 24.
Artigo em Alemão | MEDLINE | ID: mdl-12589582

RESUMO

BACKGROUND: There are two different tracks in undergraduate medical education at the Charité, a traditional (TT) one and a reformed one (RT) which was implemented in 1999. We report a survey reflecting on possible differences between students joining the two tracks. METHODS: During the winter term 2001/02 a questionnaire was sent to all 223 newly enrolled medical students. Three groups were distinguished: those following either the traditional or the reformed course (TT or RT), or those who followed the TT, although they had applied for it, because there were not enough vacancies in the RT. PARTICIPANTS: 150 (63% female; average age: 21.5 years) of 223 first year medical students. RESULTS: Applicants for the RT did not differ significantly from those of the other groups with respect to school-leaving grades, their choice of main courses at school an their motivation to study medicine. But they differed in the demands that they placed on their instruction. The wish for a good practical medical training, advancing their individual potential and the ability to select for themselves any instructional priorities were of greater importance for those choosing the RT than those who preferred the TT. More students of the RT than the TT would again have chosen to study medicine and less often stated that they had considered giving up their medical course. CONCLUSION: Students have different expectations concerning medical curricula. The possibility to choose between different ways of studying may help to meet different expectations.


Assuntos
Educação de Graduação em Medicina , Estudantes de Medicina , Adulto , Currículo , Feminino , Alemanha , Humanos , Masculino , Inquéritos e Questionários
17.
Circulation ; 104(21): 2533-8, 2001 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-11714646

RESUMO

BACKGROUND: Defibrillation thresholds (DFT) with standard implantable cardioverter-defibrillator leads in the right ventricle (RV) may be determined by weak shock field intensity in the myocardium of the left ventricle (LV). Adding a shocking electrode in a coronary vein on the middle of the LV free wall, thereby establishing biventricular defibrillation, substantially reduced defibrillation requirements in animals. We investigated the feasibility of this approach in 24 patients receiving an implantable cardioverter-defibrillator using a prototype over-the-wire temporary LV defibrillation lead. METHODS AND RESULTS: The LV lead was inserted through the coronary sinus, using a guide catheter and guidewire, into a posterior or lateral coronary vein whose location was determined by retrograde venography. Paired DFT testing compared a standard system (RV to superior vena cava plus can emulator [SVC+Can], 60% tilt biphasic shock) to a system including the LV lead. The biventricular system was tested with a dual-shock waveform (20% tilt monophasic shock from LV-->SVC+Can, then 60% tilt biphasic shock from RV-->SVC+Can). Twenty patients completed DFT testing. Venography and LV lead insertion time was 46+/-40 minutes. The biventricular system reduced mean DFT by 45% (8.9+/-1.1 J versus 4.9+/-0.5 J, P<0.001). Twelve patients (60%) had a standard system DFT >/=8 J, and the biventricular system gave a lower DFT in all patients. There were no adverse events related to the use of the LV lead, which was removed after testing. CONCLUSIONS: Internal defibrillation using a transvenously inserted LV lead is feasible, produces significantly lower DFTs, and seems safe under the conditions tested. Biventricular defibrillation may be a useful option for reducing DFTs or could be added to an LV pacing lead for heart failure.


Assuntos
Vasos Coronários , Desfibriladores Implantáveis , Ventrículos do Coração , Angiografia Coronária , Eletrofisiologia , Estudos de Viabilidade , Feminino , Insuficiência Cardíaca/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Função Ventricular
18.
Europace ; 3(4): 278-84, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11678385

RESUMO

AIMS: Improvements in the size and shape of implantable cardioverter defibrillators (ICDs) might be obtained by using one capacitor instead of the series connection of two capacitors traditionally used in ICDs. The aim of this study was to determine whether a biphasic waveform delivered from a single 336 microF capacitor had the same defibrillation efficacy as a standard biphasic waveform. METHODS AND RESULTS: Randomized, paired defibrillation threshold testing was acutely performed in 54 patients undergoing ICD implantation. A standard 140 microF 80% tilt biphasic waveform (two 280 microF capacitors connected in series) was compared with an experimental biphasic waveform delivered from a single 336 microF capacitor at either 60% tilt (33 patients) or 80% tilt (21 patients). All waveforms had a 60/40 phase1/phase2 duration ratio. Compared with the standard waveform, the 60% tilt experimental waveform had a lower delivered energy (6.7 +/- 2.8 vs 7.9 +/- 3.3 joules, P<0.02), lower peak voltage (218 +/- 43 vs 333 +/- 68 V, P<0.01), and a slightly longer pulse duration (13.4 +/- 1.4 vs 10.7 +/- 1.1 ms, P<0.01). Conversely, the 80% tilt experimental waveform had a higher delivered energy (9.1 +/- 3.5 vs 6.3 +/- 2.4 joules, P<0.01), a lower peak voltage (234 +/- 44 vs 302 +/- 51 V, P<0.01) and a much longer pulse duration (25.7 +/- 2.5 vs 1.13 +/- 1 ms, P<0.01). CONCLUSION: Waveforms delivered from a large capacitance are feasible but require a lower tilt. This technique may allow smaller, thinner ICDs without jeopardizing defibrillation success.


Assuntos
Desfibriladores Implantáveis/normas , Capacitância Elétrica , Idoso , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
19.
Circulation ; 104(4): 442-7, 2001 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-11468207

RESUMO

BACKGROUND: The coronary venous system is increasingly used for left ventricular or biventricular pacing in patients with severe heart failure. The present study investigated the structure of the coronary veins in patients presenting with structural heart disease and malignant ventricular tachyarrhythmias. The availability of veins for possible lead placement was assessed. METHODS AND RESULTS: The number, relative size, and location of coronary veins were evaluated by retrograde venography in 129 patients undergoing cardioverter-defibrillator implantation. Detailed x-ray image analysis was performed in 86 patients, for whom optimal coronary sinus occlusion and vein visualization was achieved. The anterior interventricular vein and the middle cardiac vein were visible in 85 (99%) of 86 patients and in 86 (100%) of 86 patients, respectively. Between these 2 veins, at least 1 additional prominent vein was visible in 85 (99%) of 86 patients. Just 1 vein was present in 44 (51%) of 86 patients. Two veins were observed in 40 (46%) of 86 patients, and >2 veins were visualized in 2 (2%) of 86 patients. Venous anatomy allowed positioning of a 0.014-in guidewire in a coronary vein in 115 (93%) of 124 patients. CONCLUSIONS: The presence, diameter, angulation, and tortuosity of veins as visualized by retrograde venography determine their acceptability for the placement of a lead in a predetermined location. Despite the considerable variability of the coronary venous system among patients, a lateral vessel for lead introduction was available in 82%, and a posterior or lateral vessel was available in 99% of individuals within a patient population that could potentially benefit from a lead on the left ventricle.


Assuntos
Vasos Coronários/fisiopatologia , Flebografia/métodos , Taquicardia Ventricular/fisiopatologia , Idoso , Vasos Coronários/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Veias/patologia , Veias/fisiopatologia
20.
Clin Endocrinol (Oxf) ; 54(5): 627-32, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11380493

RESUMO

OBJECTIVE: Type 1 angiotensin II (Ang II) receptors transduce most of the known actions of Ang II, including steroidogenesis and trophic actions on the adrenal cortex. We investigated the type 1 Ang II receptor expression in adrenocortical tissues to define its regulation in adrenocortical neoplasms and to compare its expression with that of the ACTH receptor (ACTH-R). PATIENTS AND MEASUREMENTS: Poly A RNA was extracted from tumour tissue and electrophoresed through a 1.0% agarose gel, blotted and hybridized with alpha32P-CTP labelled PCR generated type 1 Ang II receptor cDNA probe. Receptor autoradiography was performed on slices from normal adrenals and tumour tissue by incubation with 125I-Sar1, Ile8-Ang II with and without pretreatment with cold Ang II or with the selective type 1 receptor antagonist losartan. RESULTS: Ang II type 1 receptor mRNA was high in cortisol producing (CPA; n = 5) and aldosterone producing (APA; n = 4) adenomas (normal adrenals 100 +/- 12% vs. 180 +/- 16% in CPA and 154 +/- 26% in APA, mean +/- SEM), but was low in nonfunctioning adenomas (NFA; n = 2; 2 +/- 1%). ACTH receptor mRNA followed a similar pattern (CPA 178 +/- 17, APA 196 +/- 30, NFA 0%, carcinomas 56 +/- 11%) with a good correlation between Ang II type 1 receptor and ACTH-R mRNA of r = 0.692, P = 0.0019. Receptor autoradiography in normal adrenals demonstrated Ang II type 1 receptors predominantly in the zona glomerulosa. In tumour tissue, mainly type 1 receptor expression was found confirming the Northern blot data. CONCLUSIONS: Angiotensin II type 1 receptor and ACTH receptor expression seems to be correlated with the functional status of adrenocortical tumours, suggesting regulation by similar factors. The predominant receptor expressed in adrenocortical tumours is the Angiotensin II type 1 receptor whereas type 2 receptor expression is minimal.


Assuntos
Adenoma/química , Neoplasias do Córtex Suprarrenal/química , RNA Mensageiro/análise , Receptores de Angiotensina/metabolismo , Receptores da Corticotropina/metabolismo , Adenoma/metabolismo , Adolescente , Neoplasias do Córtex Suprarrenal/metabolismo , Adulto , Idoso , Aldosterona/metabolismo , Autorradiografia , Northern Blotting , Feminino , Humanos , Hidrocortisona/metabolismo , Masculino , Pessoa de Meia-Idade , Receptor Tipo 1 de Angiotensina , Receptor Tipo 2 de Angiotensina , Receptores de Angiotensina/genética , Receptores da Corticotropina/genética
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