RESUMO
BACKGROUND: Women comprise almost 50% of patients undergoing transcatheter aortic valve replacement (TAVR) and previous studies have indicated higher rates of procedural complications and bleeding in women compared to men. It is unknown whether men and women demonstrate a differential response to bivalirudin versus unfractionated heparin (UFH) in TAVR. We sought to evaluate outcomes by sex and type of anticoagulant from the Bivalirudin Versus Heparin Anticoagulation in Transcatheter Aortic Valve Replacement (BRAVO-3) trial of transfemoral TAVR. METHODS: BRAVO-3 was a randomized multicenter trial comparing transfemoral TAVR with bivalirudin versus UFH (31 centers, n = 802). The primary endpoint was 48 h major bleeding defined as Bleeding Academic Research Consortium (BARC) type ≥3b. Major adverse cardiovascular events (MACE) were a composite of 30-day death, myocardial infarction, or stroke. Net adverse cardiovascular events (NACE) were a composite of BARC ≥3b bleeding or 30-day MACE. We examined the outcomes in men and women. RESULTS: The total cohort included 49% women (n = 391, 195 received bivalirudin and 196 UFH) and 51% men (n = 411, 209 received bivalirudin and 202 UFH). Women were older than men with fewer comorbidities including coronary artery disease, atrial fibrillation, diabetes but similar EuroSCORE I. Women received smaller sheath and device sizes compared with men without differences in the use of vascular closure devices. At 48-hr post-TAVR there was no difference in bleeding or vascular complications in women compared to men. The use of bivalirudin did not result in significantly lower bleeding at 48 hr or 30-days compared to UFH. CONCLUSIONS: There was no difference in early outcomes with bivalirudin versus UFH in men or women undergoing contemporary TAVR. © 2016 Wiley Periodicals, Inc.
Assuntos
Anticoagulantes/uso terapêutico , Antitrombinas/uso terapêutico , Estenose da Valva Aórtica/terapia , Valva Aórtica , Cateterismo Cardíaco , Implante de Prótese de Valva Cardíaca , Heparina/uso terapêutico , Fragmentos de Peptídeos/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Antitrombinas/efeitos adversos , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/mortalidade , Estenose da Valva Aórtica/fisiopatologia , Cateterismo Cardíaco/efeitos adversos , Cateterismo Cardíaco/instrumentação , Cateterismo Cardíaco/métodos , Cateterismo Cardíaco/mortalidade , Europa (Continente) , Feminino , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/instrumentação , Implante de Prótese de Valva Cardíaca/métodos , Implante de Prótese de Valva Cardíaca/mortalidade , Hemorragia/induzido quimicamente , Heparina/efeitos adversos , Hirudinas/efeitos adversos , Humanos , Masculino , Estudos Multicêntricos como Assunto , Infarto do Miocárdio/etiologia , América do Norte , Fragmentos de Peptídeos/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Acidente Vascular Cerebral/etiologia , Fatores de Tempo , Resultado do TratamentoRESUMO
Descending necrotising mediastinitis is a rare complication of odontogenic infection. The key to diagnosis is to maintain a high index of suspicion when antibiotics and adequate surgical drainage do not lead to resolution of symptoms. Open thoracic operation to drain mediastinal collections is potentially lethal and interventional radiological techniques are thought to reduce mortality. We report the use of interventional radiology in the diagnosis, monitoring and treatment of this condition and illustrate our experience with three case reports.
Assuntos
Infecção Focal Dentária/complicações , Mediastinite/terapia , Radiologia Intervencionista , Abscesso/microbiologia , Abscesso/terapia , Adulto , Drenagem , Seguimentos , Humanos , Angina de Ludwig/microbiologia , Angina de Ludwig/terapia , Masculino , Mediastinite/microbiologia , Pessoa de Meia-Idade , Pescoço/microbiologia , Derrame Pleural/microbiologia , Derrame Pleural/terapia , Radiografia Intervencionista , Infecções Estreptocócicas/terapia , Tomografia Computadorizada por Raios X , Ultrassonografia de Intervenção , Estreptococos Viridans/isolamento & purificaçãoRESUMO
The two most important beta-turn features in peptides and proteins are the type I and type II turns, which differ mainly in the orientation of the central peptide unit. Facile conformational interconversion is possible, in principle, by a flip of the central peptide unit. Homologous crystal structures afford an opportunity to structurally characterize both possible conformational states, thus allowing identification of sites that are potentially stereochemically mobile. A representative data set of 250 high-resolution (=2.0 A), non-homologous protein crystal structures and corresponding variant and homologous entries, obtained from the Brookhaven Protein Data Bank, was examined to identify turns that are assigned different conformational types (type I/type II) in related structures. A total of 55 examples of beta-turns were identified as possible candidates for a stereochemically mobile site. Of the 55 examples, 45 could be classified as a potential site for interconversion between type I and type II beta-turns, while ten correspond to flips from type I' to type II' structures. As a further check, the temperature factors of the central peptide unit carbonyl oxygen atom of the 55 examples were examined. The analysis reveals that the turn assignments are indeed reliable. Examination of the secondary structures at the flanking positions of the flippable beta-turns reveals that seven examples occur in the loop region of beta-hairpins, indicating that the formation of ordered secondary structures on either side of the beta-turn does not preclude local conformational variations. In these beta-turns, Pro (11 examples), Lys (nine examples) and Ser (seven examples) were most often found at the i+1 position. Glycine was found to occur overwhelmingly at position i+2 (28 examples), while Ser (seven examples) and Asn (six examples) were amongst the most frequent residues. Activation energy barriers for the interconversion between type I and type II beta-turns were computed using the peptide models Ac-Pro-Aib-NHMe and Ac-Pro-Gly-NHMe within the framework of the AM1 semi-empirical molecular orbital procedure. In order to have a uniform basis for comparison and to eliminate the distracting influence of the deviation of backbone dihedral angles from that expected for ideal beta-turns, the dihedral angles phii+1 and psii+2 were fixed at the ideal values (phii+1=-60 degrees and psii+2=0 degrees). The other two angles (psii+1 and phii+2) were varied systematically to go from type II to type I beta-turn structures. The computational results suggest that there exists one stereospecific, concerted flip of the central peptide unit involving correlated single bond rotation that can occur with an activation barrier of the order of 3 kcal/mol. The results presented here suggest that conformational variations in beta-turns are observed in protein crystal structures and such changes may be an important dynamic feature in solution.
Assuntos
Modelos Moleculares , Conformação Proteica , Proteínas/química , Modelos Químicos , Peptídeos/químicaRESUMO
Quantum and statistical mechanics have been used to determine energy profiles for the SN2 reaction of Cl- + CH3Cl in the gas phase, in aqueous solution, and in liquid DMF. The energy profile in the gas phase has the characteristic double-well form featuring unsymmetrical ion-dipole complexes as minima and a symmetrical transition state. Hydration causes the reaction surface to become almost unimodal and increases the barrier significantly. The reaction profile in DMF is intermediate between those for the gas phase and aqueous solution. The ion-dipole complexes are still free energy minima in DMF. Thus, the reaction in DMF involves initial formation of the complex before the rate-determining step. The computed results are shown to be in good accord with experimental free energies of activation. The same technique has been applied to the addition reaction of OH- + H2C = O in the gas phase and aqueous solution. Ab initio 6-31 + G* calculations indicate that the reaction proceeds essentially without activation in the gas phase. Hydration introduces a substantial energy barrier. The transition state in water has been located at a C-O separation of roughly 2 A. A key finding for both reactions is that the activation barriers induced by hydration result primarily from change in strengths rather than in numbers of solute-water hydrogen bonds along the reaction paths.
Assuntos
Química , Simulação por Computador , Modelos Moleculares , Conformação Molecular , Fenômenos Químicos , Soluções , TermodinâmicaRESUMO
The alkali ions present in the supercages of zeolites X and Y interact with included guest molecules through quadrupolar (cation-pi), and dipolar (cation-carbonyl) interactions. The presence of such interactions can be inferred through solid-state NMR spectra of the guest molecules. Alkali ions, as illustrated in this article, can be exploited to control the photochemical and photophysical behaviors of the guest molecules. For example, molecules that rarely phosphoresce can be induced to do so within heavy cation-exchanged zeolites. The nature (electronic configuration) of the lowest triplet state of carbonyl compounds can be altered with the help of light alkali metal ions. This state switch (n pi*-pi pi*) helps to bring out reactivity that normally remains dormant. Selectivity obtained during the singlet oxygen oxidation of olefins within zeolites illustrates the remarkable control that can be exerted on photoreactions with the help of a confined medium that also has active sites. The reaction cavities of zeolites, like enzymes, are not only well-defined and confined, but also have active sites that closely guide the reactant molecule from start to finish. The examples provided here illustrate that zeolites are far more useful than simple shape-selective catalysts.
Assuntos
Zeolitas/química , Sítios de Ligação , Cátions/química , Fenômenos Químicos , Físico-Química , Cristalografia/métodos , Transporte de Elétrons , Elétrons , Espectroscopia de Ressonância Magnética , Teste de Materiais/métodos , Modelos Químicos , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Fotoquímica , Espectrometria de Fluorescência , Relação Estrutura-Atividade , Zeolitas/antagonistas & inibidoresRESUMO
OBJECTIVE: The purpose of this study was to determine the efficacy of oxypentifylline in the treatment of recurrent oral aphthous ulcers and to compare the results with those of previous studies. STUDY DESIGN: A 6-week open trial and a patient survey regarding pain were conducted at the Oral and Maxillofacial Surgery Unit, City General Hospital, Carlisle. Twenty-four patients (11 male and 13 female) were selected from sequential referrals involving complaints of recurrent oral ulcers. A 2-week pretrial period was used to record data pertaining to the occurrence, duration, and pain associated with ulcers. A 4-week period of treatment with oxypentifylline (400 mg administered orally 3 times daily) was followed by an assessment of improvement at the end of 6 weeks. RESULTS: The results were comparable to those of previous studies, with positive responses seen in 63.6% of male patients and 61.5% of female patients. However, recurrence of ulcers was noted in all patients once the drug was discontinued. This was attributed to the small size of the patient sample studied and to the relatively short duration of treatment. No significant side effects were noted. CONCLUSIONS: Double-blind, controlled studies are indicated for a definitive assessment of the efficacy of oxypentifylline in the management of recurrent oral aphthous ulcers. The encouraging results of this study support the suggestion that the use of oxypentifylline be considered in refractory cases of recurrent oral aphthous ulcers.
Assuntos
Adjuvantes Imunológicos/uso terapêutico , Pentoxifilina/uso terapêutico , Estomatite Aftosa/tratamento farmacológico , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Lacrimal gland tumours are rare. We present a case of a lacrimal gland pleomorphic adenoma in a 19-year-old man. The tumour was removed and he has made an uncomplicated recovery, with no sign of recurrence after nine months of follow-up. We will keep him under long-term review.
Assuntos
Adenoma Pleomorfo/diagnóstico , Doenças do Aparelho Lacrimal/diagnóstico , Adenoma Pleomorfo/patologia , Adulto , Blefaroptose/etiologia , Assimetria Facial/etiologia , Seguimentos , Humanos , Doenças do Aparelho Lacrimal/patologia , Masculino , Acuidade VisualRESUMO
BACKGROUND: Total knee arthroplasty (TKA) and total hip arthroplasty (THA) are the most widely practiced surgical options for arthritis all over the world and its application is rising in India. Indian Society of Hip and Knee Surgeons (ISHKS) has established a joints registry and has been collecting data for last 6 years. MATERIALS & METHODS: All members of ISHKS are encouraged to actively participate in the registry. A simple two page knee and hip form can be downloaded from the website www.ishks.com. The information collected includes patient demographics, indication for surgery, implant details and in case of revision arthroplasty: the details of implants removed and the cause of failure of primary arthroplasty. These forms are mailed to the central registry office and the data is fed in computerized registry. Data collection started in October 2006. RESULTS: Joint registry is a very important initiative of ISHKS and till date, have data of 34,478 TKAs and 3604 THAs, contributed by 42 surgeons across India. Some important observations have emerged. Data of 34,478 TKAs was assessed: These included 8612 males (25%) and 25,866 females (75%). Average age was 64.4 years (Osteoarthritis range: 45 to 88 years; Rheumatoid arthritis range: 22 to 74 years). Average body mass index was 29.1 (Range: 18.1 to 42.9). The indication for TKA was osteoarthritis in 33,444 (97%) and rheumatoid arthritis in 759 (2.2%). Total of 3604 THA procedures were recorded. These included 2162 (60%) male patients and 1442 (40%) female patients. Average age was 52 years (Range 17 to 85 years) and average BMI was 25.8 (Range: 17.3 to 38.5). The indications for THA was AVN in 49%. CONCLUSION: The registry will become more meaningful in years to come. Active participation of all arthroplasty surgeons across India is vital for the success of the joints registry.
RESUMO
Apolar, neutral peptides have been shown to ionize extremely well under the conditions used for electrospray ionization mass spectrometry (ESIMS). Peptides for which the conformations have been independently determined in solution and in crystals have been examined by ESIMS. Studies of peptide helices ranging from 7 to 18 residues reveal that shorter helices yield exclusively singly charged ions, while in larger helices multiply charged species are detectable. Multiple sites for protonation/metallation are introduced in the helix by proline insertion or by changing the chirality in the residue. The preferred site of cation binding to helices may be the C-terminus end, where three free CO groups are available for chelation. Ab initio and DFT calculations at several levels have been carried out for the binding of H+, Li+, Na+, and K+ to CHO-(Gly)3)-OMe. The results reveal that metallation in helices is favoured by chelation to carbonyl groups at the C-terminus, while protonation involved two carbonyl groups and thus favour a 10-membered cyclic hydrogen-bonded structure. In -strands, metallation/protonation occurs at isolated carbonyl groups. Collision induced fragmentation of hydrophobic peptides under ESI conditions reveals that helix fragmentation occurs predominantly from the C-terminus, while in -hairpins cleavage occurs simultaneously at multiple sites.
Assuntos
Metais Alcalinos/química , Oligopeptídeos/química , Aminoácidos Neutros/química , Sítios de Ligação , Glicina/química , Modelos Moleculares , Estrutura Secundária de Proteína , Prótons , Espectrometria de Massas por Ionização por Electrospray , Eletricidade EstáticaRESUMO
Structure-function studies have shown that it is possible to convert a sodium channel to a calcium-selective channel by a single amino acid substitution in the selectivity filter locus. Ion permeation through the "model selectivity filter" was modeled with a reduced set of functional groups representative of the constituent amino acid side chains. Force-field minimizations were conducted to obtain the energy profile of the cations as they get desolvated and bind to the "model selectivity filter." The calculations suggest that the ion selectivity in the calcium channel is due to preferential binding, whereas in the sodium channel it is due to exclusion. Energetics of displacement of a bound cation from the calcium "model selectivity filter" by another cation suggest that "multi-ion mechanism" reduces the activation barrier for ion permeation. Thus, the simple model captures qualitatively most of the conduction characteristics of sodium and calcium channels. However, the computed barriers for permeation are fairly large, suggesting that ion interaction with additional residues along the transport path may be essential to effect desolvation.
Assuntos
Canais de Cálcio/química , Canais de Sódio/química , Cátions/química , Simulação por Computador , Ativação do Canal Iônico , Modelos Biológicos , Modelos MolecularesRESUMO
Through a systematic study of several diphenylcyclopropane derivatives, we have inferred that the cations present within a zeolite control the excited-state chemistry of these systems. In the parent 1,2-diphenylcylopropane, the cation binds to the two phenyl rings in a sandwich-type arrangement, and such a mode of binding prevents cis-to-trans isomerization. Once an ester or amide group is introduced into the system (derivatives of 2beta,3beta-diphenylcyclopropane-1alpha-carboxylic acid), the cation binds to the carbonyl group present in these chromophores and such a binding has no influence on the cis-trans isomerization process. Cation-reactant structures computed at density functional theory level have been very valuable in rationalizing the observed photochemical behavior of diphenylcyclopropane derivatives included in zeolites. While the parent system, 1,2-diphenylcylopropane, has been extensively investigated in the context of chiral induction in solution, owing to its failure to isomerize from cis to trans, the same could not be investigated in zeolites. However, esters of 2beta,3beta-diphenylcyclopropane-1alpha-carboxylic acid could be studied within zeolites in the context of chiral induction. Chiral induction as high 20% ee and 55% de has been obtained with selected systems. These numbers, although low, are much higher than what has been obtained in solution with the same system or with the parent system by other investigators (maximum approximately 10% ee).