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1.
Anaesthesist ; 63(2): 114-21, 2014 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-24352743

RESUMO

BACKGROUND: The profession of the anesthetist in Germany includes the disciplines anesthesia, intensive care, emergency and pain medicine. Despite the versatility and competence of the profession, patients do not appear to have recognized anesthesiology as a medical discipline or anesthetists as medical doctors. AIM: This study was conducted with the aim of estimating how previous experience and information gathered before contact with the anesthetist for premedication have influenced and changed the perception of patients with regards to the professional fields and the characteristics of anesthetists. MATERIAL AND METHODS: A total of 3,950 patients from 3 German hospitals were asked to answer a questionnaire handed out by the assistance nurse in the premedication area prior to the medical consultation with the duty anesthetist. The questions involved the patient perception of the discipline, the characteristics of anesthetists and also evaluated the patient previous experience and provision of information. According to the answers 1,753 patients were considered eligible for the study and were categorized into subgroups I-IV (group I interested and experienced with operations, group II interested but inexperienced, group III uninterested but experienced and group IV neither interested nor experienced) for statistical analysis. RESULTS: Of the respondents 56.2 % had obtained previous information from a general practitioner followed by acquaintances (21.4 %) and the internet (19.9 %), which significantly differed with age. Interested and experienced patients showed the best perception of the profession. Often, the knowledge of interested and uninterested persons did not significantly differ. Interested patients and those with experience of anesthesiology had the best knowledge of anesthesiology. Performing anesthesia was most often identified by all groups (50.9-95.3 %) as a function of anesthetists while the other professional fields were recognized correctly by only 5.8-26.6 %. Depending on the group 41.0-84.4 % regarded anesthetists as medical doctors. Only 15.0-78.3 % of other attributes were associated with anesthetists. CONCLUSION: Unfortunately, the perception of patients on the versatility and characteristics of anesthetists are poorly developed. However, the knowledge differs significantly depending on previous experience and gathered information. Interestingly patients with previous experience mostly showed better knowledge compared to interested patients. Results suggest that personal interaction, patient-physician communication in general and improved collaboration between general practitioners and anesthetists are the key elements for better patient knowledge, which could lead to increased patient satisfaction.


Assuntos
Anestesiologia/tendências , Médicos , Papel Profissional , Adulto , Fatores Etários , Idoso , Coleta de Dados , Feminino , Alemanha , Humanos , Internet , Masculino , Pessoa de Meia-Idade , Enfermeiras e Enfermeiros , Pacientes , Relações Médico-Paciente , Medicação Pré-Anestésica , Fatores Socioeconômicos , Inquéritos e Questionários , Recursos Humanos
2.
Nat Genet ; 24(2): 127-31, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10655056

RESUMO

Hereditary human retinal degenerative diseases usually affect the mature photoreceptor topography by reducing the number of cells through apoptosis, resulting in loss of visual function. Only one inherited retinal disease, the enhanced S-cone syndrome (ESCS), manifests a gain in function of photoreceptors. ESCS is an autosomal recessive retinopathy in which patients have an increased sensitivity to blue light; perception of blue light is mediated by what is normally the least populous cone photoreceptor subtype, the S (short wavelength, blue) cones. People with ESCS also suffer visual loss, with night blindness occurring from early in life, varying degrees of L (long, red)- and M (middle, green)-cone vision, and retinal degeneration. The altered ratio of S- to L/M-cone photoreceptor sensitivity in ESCS may be due to abnormal cone cell fate determination during retinal development. In 94% of a cohort of ESCS probands we found mutations in NR2E3 (also known as PNR), which encodes a retinal nuclear receptor recently discovered to be a ligand-dependent transcription factor. Expression of NR2E3 was limited to the outer nuclear layer of the human retina. Our results suggest that NR2E3 has a role in determining photoreceptor phenotype during human retinogenesis.


Assuntos
Mutação , Receptores Citoplasmáticos e Nucleares/genética , Células Fotorreceptoras Retinianas Cones/fisiopatologia , Degeneração Retiniana/genética , Deleção de Sequência , Fatores de Transcrição/genética , Sequência de Aminoácidos , Substituição de Aminoácidos , Animais , Galinhas , Drosophila/genética , Feminino , Humanos , Íntrons , Masculino , Camundongos , Dados de Sequência Molecular , Receptores Nucleares Órfãos , Linhagem , Polimorfismo Conformacional de Fita Simples , Retina/metabolismo , Retina/patologia , Retina/fisiopatologia , Células Fotorreceptoras Retinianas Cones/patologia , Degeneração Retiniana/patologia , Degeneração Retiniana/fisiopatologia , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Síndrome , Xenopus laevis
3.
Nat Genet ; 28(2): 188-91, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11381270

RESUMO

Bardet-Biedl syndrome (BBS, MIM 209900) is a heterogeneous autosomal recessive disorder characterized by obesity, pigmentary retinopathy, polydactyly, renal malformations, mental retardation, and hypogenitalism. The disorder is also associated with diabetes mellitus, hypertension, and congenital heart disease. Six distinct BBS loci map to 11q13 (BBS1), 16q21 (BBS2), 3p13-p12 (BBS3), 15q22.3-q23 (BBS4), 2q31 (BBS5), and 20p12 (BBS6). Although BBS is rare in the general population (<1/100,000), there is considerable interest in identifying the genes causing BBS because components of the phenotype, such as obesity and diabetes, are common. We and others have demonstrated that BBS6 is caused by mutations in the gene MKKS (refs. 12,13), mutation of which also causes McKusick-Kaufman syndrome (hydrometrocolpos, post-axial polydactyly, and congenital heart defects). MKKS has sequence homology to the alpha subunit of a prokaryotic chaperonin in the thermosome Thermoplasma acidophilum. We recently identified a novel gene that causes BBS2. The BBS2 protein has no significant similarity to other chaperonins or known proteins. Here we report the positional cloning and identification of mutations in BBS patients in a novel gene designated BBS4.


Assuntos
Síndrome de Bardet-Biedl/genética , Obesidade/genética , Proteínas/genética , Clonagem Molecular , Consanguinidade , Etiquetas de Sequências Expressas , Humanos , Proteínas Associadas aos Microtúbulos , Dados de Sequência Molecular , Mutação
4.
Anaesthesia ; 67(9): 991-8, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22698066

RESUMO

Deep neuromuscular blockade during certain surgical procedures may improve operating conditions. Sugammadex can be used to reverse deep neuromuscular blockade without waiting for spontaneous recovery. This randomised study compared recovery times from neuromuscular blockade induced by rocuronium 0.6 mg.kg(-1), using sugammadex 4 mg.kg(-1) administered at 1-2 post-tetanic count (deep blockade) or neostigmine 50 µg.kg(-1) (plus atropine 10 µg.kg(-1)) administered at the re-appearance of the second twitch of a train-of-four stimulation (moderate blockade), in patients undergoing laparoscopic surgery. The primary efficacy variable was the time from the start of sugammadex/neostigmine administration to recovery of the train-of-four ratio to 0.9. Patients receiving sugammadex recovered 3.4 times faster than patients receiving neostigmine (geometric mean (95% CI) recovery times of 2.4 (2.1-2.7) and 8.4 (7.2-9.8) min, respectively, p<0.0001). Moreover, 94% (62/66) of sugammadex-treated patients recovered within 5 min, vs 20% (13/65) of neostigmine-treated patients, despite the difference in the depth of neuromuscular blockade at the time of administration of both drugs. The ability to provide deep neuromuscular blockade throughout the procedure but still permit reversal at the end of surgery may enable improved surgical access and an enhanced visual field.


Assuntos
Inibidores da Colinesterase/uso terapêutico , Laparoscopia/métodos , Neostigmina/uso terapêutico , Bloqueio Neuromuscular/métodos , gama-Ciclodextrinas/uso terapêutico , Adulto , Idoso , Androstanóis/antagonistas & inibidores , Anestesia , Período de Recuperação da Anestesia , Anestésicos Intravenosos , Inibidores da Colinesterase/efeitos adversos , Estimulação Elétrica , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Neostigmina/efeitos adversos , Fármacos Neuromusculares não Despolarizantes/antagonistas & inibidores , Segurança do Paciente , Propofol , Rocurônio , Tamanho da Amostra , Sugammadex , Brometo de Vecurônio/antagonistas & inibidores , Adulto Jovem , gama-Ciclodextrinas/efeitos adversos
5.
Kidney Int ; 80(10): 1080-91, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21775973

RESUMO

Prior small studies have shown multiple benefits of frequent nocturnal hemodialysis compared to conventional three times per week treatments. To study this further, we randomized 87 patients to three times per week conventional hemodialysis or to nocturnal hemodialysis six times per week, all with single-use high-flux dialyzers. The 45 patients in the frequent nocturnal arm had a 1.82-fold higher mean weekly stdKt/V(urea), a 1.74-fold higher average number of treatments per week, and a 2.45-fold higher average weekly treatment time than the 42 patients in the conventional arm. We did not find a significant effect of nocturnal hemodialysis for either of the two coprimary outcomes (death or left ventricular mass (measured by MRI) with a hazard ratio of 0.68, or of death or RAND Physical Health Composite with a hazard ratio of 0.91). Possible explanations for the left ventricular mass result include limited sample size and patient characteristics. Secondary outcomes included cognitive performance, self-reported depression, laboratory markers of nutrition, mineral metabolism and anemia, blood pressure and rates of hospitalization, and vascular access interventions. Patients in the nocturnal arm had improved control of hyperphosphatemia and hypertension, but no significant benefit among the other main secondary outcomes. There was a trend for increased vascular access events in the nocturnal arm. Thus, we were unable to demonstrate a definitive benefit of more frequent nocturnal hemodialysis for either coprimary outcome.


Assuntos
Hemodiálise no Domicílio , Falência Renal Crônica/terapia , Adulto , Idoso , Desenho de Equipamento , Feminino , Hemodiálise no Domicílio/efeitos adversos , Hemodiálise no Domicílio/instrumentação , Hemodiálise no Domicílio/mortalidade , Humanos , Hiperfosfatemia/etiologia , Hiperfosfatemia/terapia , Hipertensão/etiologia , Hipertensão/terapia , Hipertrofia Ventricular Esquerda/diagnóstico , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/terapia , Falência Renal Crônica/sangue , Falência Renal Crônica/complicações , Falência Renal Crônica/mortalidade , Falência Renal Crônica/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , América do Norte , Cooperação do Paciente , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
6.
Am J Transplant ; 10(3): 477-89, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20055812

RESUMO

Because the vagus nerve is implicated in control of inflammation, we investigated if brain death (BD) causes impairment of the parasympathetic nervous system, thereby contributing to inflammation. BD was induced in rats. Anaesthetised ventilated rats (NBD) served as control. Heart rate variability (HRV) was assessed by ECG. The vagus nerve was electrically stimulated (BD + STIM) during BD. Intestine, kidney, heart and liver were recovered after 6 hours. Affymetrix chip-analysis was performed on intestinal RNA. Quantitative PCR was performed on all organs. Serum was collected to assess TNFalpha concentrations. Renal transplantations were performed to address the influence of vagus nerve stimulation on graft outcome. HRV was significantly lower in BD animals. Vagus nerve stimulation inhibited the increase in serum TNFalpha concentrations and resulted in down-regulation of a multiplicity of pro-inflammatory genes in intestinal tissue. In renal tissue vagal stimulation significantly decreased the expression of E-selectin, IL1beta and ITGA6. Renal function was significantly better in recipients that received a graft from a BD + STIM donor. Our study demonstrates impairment of the parasympathetic nervous system during BD and inhibition of serum TNFalpha through vagal stimulation. Vagus nerve stimulation variably affected gene expression in donor organs and improved renal function in recipients.


Assuntos
Morte Encefálica/diagnóstico , Inflamação/patologia , Estimulação do Nervo Vago/métodos , Anestesia , Animais , Regulação para Baixo , Eletrocardiografia/métodos , Frequência Cardíaca , Mucosa Intestinal/metabolismo , Masculino , Ratos , Ratos Endogâmicos F344 , Ratos Endogâmicos Lew , Fator de Necrose Tumoral alfa/sangue , Nervo Vago/patologia
7.
J Eur Acad Dermatol Venereol ; 24(12): 1400-5, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20384691

RESUMO

BACKGROUND AND OBJECTIVE: Tumescent local anaesthesia (TLA) with high prilocaine doses leads to formation of methemoglobin (MHb) which is known to be a potent activator of pro-inflammatory endothelial cell response in vitro. As TLA is widely used for large dermatological resections, the aim of this study was to investigate the effects of high prilocaine doses on the systemic inflammatory response in vivo and its clinical relevance. METHODS: This prospective study examines the influence of MHb on serum interleukin (IL)-6, IL-8 and tumour necrosis tumour necrosis (TNF)-α levels up to 72 h after application of TLA with prilocaine in doses higher than 600 mg. RESULTS: A total of 30 patients received prilocaine in a median dose of 1500 mg (range: 880-4160 mg) for large resections. Peak prilocaine serum concentration was reached 4 h (0.72 ± 0.07 µg/mL), the maximum concentration of MHb (7.43 ± 0.87%) and IL-6 (28.4 ± 4.1 U/L) 12 h after TLA application. TNF-α and IL-8 release were not found significantly increased. Three patients developed MHb concentrations >15%. CONCLUSIONS: This clinical study shows for the first time that a high prilocaine serum concentration leads in vivo to elevated systemic levels of IL-6 but not of IL-8 and TNF-α because of initial high MHb levels. Because of possible and unpredictable high MHb concentrations, TLA should only be performed with prilocaine in doses of 2.5 mg/kg. In general, new solutions of TLA are necessary to achieve adequate anaesthesia for large dermatological resections to decrease the risk of methemoglobinaemia.


Assuntos
Anestésicos Locais/administração & dosagem , Interleucina-6/sangue , Interleucina-8/sangue , Prilocaína/administração & dosagem , Fator de Necrose Tumoral alfa/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anestésicos Locais/sangue , Proteína C-Reativa/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prilocaína/sangue , Estudos Prospectivos , Adulto Jovem
8.
Skin Pharmacol Physiol ; 23(4): 177-82, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20185975

RESUMO

The evaluation of the benefit/risk ratio (BRR) for topical glucocorticoids (TGC) allows the comparison of active ingredients and thereby includes aspects of dosage (blanching response, BR) as well as adverse effects (skin atrophy). In the present study, the BRR of hydrocortisone aceponate, prednicarbate and betamethasone valerate was investigated according to an adapted procedure for investigating the BR. The main difference is the longer application period of the investigational substance without occlusion. Thus, the pharmacokinetic characteristics of all of the systems are considered more intensely and the penetration conditions are designed in a realistic way, namely oriented towards the preparation in order to improve the significance and relevance of the BRR for practical use. The results demonstrate that the investigated substances also show differences in the extent of the BR, but on the other hand they show that the improved penetration characteristics of the double-esterified compounds are clearly less effective. In comparison to the BRR, this results to a large extent in a balanced picture without relevant advantages for single preparations. Nevertheless, the already mentioned positive characteristics of the investigated TGC and the positive practical clinical experiences have been approved. Further investigations have to show whether the method presented here for investigating the BR offers advantages in the comparative assessment of TGC.


Assuntos
Glucocorticoides/administração & dosagem , Glucocorticoides/metabolismo , Hidrocortisona/análogos & derivados , Absorção Cutânea/efeitos dos fármacos , Absorção Cutânea/fisiologia , Administração Tópica , Adulto , Método Duplo-Cego , Feminino , Seguimentos , Glucocorticoides/uso terapêutico , Humanos , Hidrocortisona/administração & dosagem , Hidrocortisona/metabolismo , Hidrocortisona/uso terapêutico , Masculino , Pessoa de Meia-Idade , Padrões de Referência , Fatores de Risco , Adulto Jovem
9.
J Chemother ; 32(3): 151-155, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32124685

RESUMO

Staphylococcus pseudintermedius is a well known commensal organism of dogs but also a canine opportunistic pathogen. Reports of this organism being recovered from specimens from humans might suggest an increase prevalence in human infections and/or improved diagnostic leading to more accurate identification. Here we report a case of persistent S. pseudintermedius infection in an adult female oncology patient including colonization of the tip of an indwelling catheter. Diligence by laboratories in correctly isolating and identifying this pathogen (including susceptibility testing) is essential for optimal patient care.


Assuntos
Antineoplásicos/uso terapêutico , Zoonoses Bacterianas/diagnóstico , Neoplasias Retais/tratamento farmacológico , Infecções Estafilocócicas/diagnóstico , Staphylococcus , Animais , Zoonoses Bacterianas/transmissão , Cateteres de Demora/microbiologia , Cães , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Animais de Estimação , Infecções Estafilocócicas/transmissão
10.
Colorectal Dis ; 11(2): 162-7, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18462237

RESUMO

OBJECTIVE: 'Fast-track' rehabilitation has been shown to accelerate recovery, reduce general morbidity and decrease hospital stay after elective colonic surgery. Despite this evidence, there is no information on the acceptance and utilization of these concepts among the entirety of Austrian and German surgeons. METHOD: In 2006, a questionnaire concerning perioperative routines in elective, open colonic resection was sent to the chief surgeons of 1270 German and 120 Austrian surgical centres. RESULTS: The response rate was 63% in Austria (76 centres) and 30% in Germany (385 centres). Mechanical bowel preparation is used by the majority (Austria, 91%; Germany, 94%); the vertical incision is the standard method of approach to the abdomen in Austria (79%) and Germany (83%), nasogastric decompression tubes are rarely used, one-third of the questioned surgeons in both countries use intra-abdominal drains. Half of the surgical centres allow the intake of clear fluids on the day of surgery and one-fifth offer solid food on that day. Epidural analgesia is used in three-fourths of the institutions. CONCLUSION: Although there is an evident benefit of fast-track management, the survey shows that they are not yet widely used as a routine in Austria and Germany.


Assuntos
Colectomia/reabilitação , Assistência Perioperatória/métodos , Padrões de Prática Médica , Anestesia Epidural/estatística & dados numéricos , Áustria , Cirurgia Colorretal , Alemanha , Pesquisas sobre Atenção à Saúde , Humanos , Tempo de Internação
11.
Mol Inform ; 38(10): e1900014, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31166649

RESUMO

We report the building, validation and release of QSPR (Quantitative Structure Property Relationship) models aiming to guide the design of new solvents for the next generation of Li-ion batteries. The dataset compiled from the literature included oxidation potentials (Eox ), specific ionic conductivities (κ), melting points (Tm ) and boiling points (Tb ) for 103 electrolytes. Each of the resulting consensus models assembled 9-19 individual Support Vector Machine models built on different sets of ISIDA fragment descriptors.(1) They were implemented in the ISIDA/Predictor software. Developed models were used to screen a virtual library of 9965 esters and sulfones. The most promising compounds prioritized according to theoretically estimated properties were synthesized and experimentally tested.


Assuntos
Simulação por Computador , Avaliação Pré-Clínica de Medicamentos , Eletrólitos/química , Eletrólitos/síntese química , Solventes/química , Solventes/síntese química , Condutividade Elétrica , Fontes de Energia Elétrica , Técnicas Eletroquímicas , Eletrólitos/análise , Ésteres/síntese química , Ésteres/química , Lítio/química , Modelos Moleculares , Estrutura Molecular , Relação Quantitativa Estrutura-Atividade , Software , Solventes/análise , Sulfonas/síntese química , Sulfonas/química , Máquina de Vetores de Suporte
12.
JDR Clin Trans Res ; 4(4): 323-332, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30931720

RESUMO

INTRODUCTION: School screening and the note home (pinned to a backpack) informing parents/caregivers that their child needs to see a dentist have not been effective. OBJECTIVES: The Family Access to a Dentist Study (FADS) evaluated the effectiveness of school interventions based on the common-sense model of self-regulation (CSM) among K-4 children needing restorative treatment. METHODS: FADS was a multisite double-blind randomized controlled trial with 5 arms. FADS tested a CSM-driven referral letter and dental information guide (DIG) to move caregivers from inaccurate to accurate perceptions of dental caries. Six school districts from Ohio and Washington (14 schools) participated in school years 2015 to 2016 and 2016 to 2017. A total of 611 caregivers were randomized, and 86% (n = 597 children) completed the exit examination. The primary outcome was receipt of care based on a change in oral health status determined clinically within 1 school year. RESULTS: In accordance with our primary aims, 5 arms were collapsed into 3: CSM letter and reduced CSM letter (combined), CSM letter + DIG and reduced CSM letter + reduced DIG (combined), and standard letter. Among all sites, 39.7% received restorative care (237 of 597). Combined analysis of sites revealed that the CSM referral letter (with and without the DIG) did not increase dental visits when compared with the standard letter. However, for combined sites (East Cleveland, Ohio; Washington), the CSM + DIG increased dental visits when compared with standard letter in univariate analysis (51.3% vs. 40.9%), indicating 1.6-times increased odds of a dental visit (95% CI, 0.97 to 2.58) after imputation and adjustment for covariates. The CSM + DIG group had 1.9-times increased odds (95% CI, 1.21 to 3.08) of care when compared the CSM letter alone. CONCLUSION: A CSM-driven approach to informing caregivers of the chronic nature of caries with resources in an illustrative manner can increase the benefit of school oral health screening (ClinicalTrials.gov NCT02395120). KNOWLEDGE TRANSFER STATEMENT: A school dental referral (note home) that tells a parent that the child has cavities has not been effective. In this trial, a referral based on the common-sense model of self-regulation increased follow-up care for children with restorative needs.


Assuntos
Cárie Dentária , Criança , Método Duplo-Cego , Família , Humanos , Ohio , Washington
13.
Kidney Int ; 73(11): 1310-5, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18337713

RESUMO

The Modification of Diet in Renal Disease (MDRD) Study examined the effects of strict blood pressure control and dietary protein restriction on the progression of kidney disease. Here, we retrospectively evaluated outcomes of nondiabetic participants with stages 2-4 chronic kidney disease (CKD) from randomized and nonrandomized cohorts of the MDRD Study. Kidney failure and survival status through December of 2000, were obtained from the US Renal Data System and the National Death Index. Event rates were calculated for kidney failure, death, and a composite outcome of death and kidney failure. In the 1666 patients, rates for kidney failure were four times higher than that for death. Kidney failure was a more likely event than death in subgroups based on baseline glomerular filtration rate, proteinuria, kidney disease etiology, gender, and race. It was only among those older than 65 that the rate for death approximated that for kidney failure. In contrast to other populations with CKD, our study of relatively young subjects with nondiabetic disease has found that the majority of the participants advanced to kidney failure with a low competing risk of death. In such patients, the primary emphasis should be on delaying progression of kidney disease.


Assuntos
Dieta com Restrição de Proteínas , Nefropatias/dietoterapia , Nefropatias/fisiopatologia , Insuficiência Renal/mortalidade , Adolescente , Adulto , Idoso , Determinação da Pressão Arterial , Doença Crônica , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Nefropatias/complicações , Masculino , Pessoa de Meia-Idade , Insuficiência Renal/etiologia , Estudos Retrospectivos , Fatores Sexuais , Resultado do Tratamento
14.
Clin Exp Immunol ; 152(2): 311-9, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18341609

RESUMO

Hypothermic preservation of solid allografts causes profound damage of vascular endothelial cells. This, in turn, might activate innate immunity. In the present study we employed an in vitro model to study to what extent supernatants of damaged endothelial cells are able to activate innate immunity and to study the nature of these signals. The expression of high mobility group box 1 (HMGB1) and adhesion molecules on human umbilical vein endothelial cell was studied by immunofluorescence, fluorescence activated cell sorter and Western blotting. Cytokine production was performed by enzyme-linked immunosorbent assay. HMGB1 expression was lost completely in endothelial cells after hypothermic preservation. This was associated with cell damage as it occurred only in untreated endothelial cell but not in cells rendered resistant to hypothermia-mediated damage by dopamine treatment. Only supernatants from hypothermia susceptible cells up-regulated the expression of interleukin (IL)-8 and adhesion molecules in cultured endothelial cells in an HMGB1-dependent manner. In whole blood assays, both supernatants of hypothermia susceptible and resistant cells inhibited tumour necrosis factor (TNF)-alpha production concomitantly with an increased IL-10 secretion. The activity of the supernatants was already found after 6 h of hypothermic preservation, and paralleled the decrease in intracellular adenosine triphosphate (ATP) levels. Modulation of TNF-alpha and IL-10 production by these supernatants was abrogated completely by prior treatment with adenosine deaminase and was similar to the response of an A2R agonist. Our study demonstrates that both HMGB1 and adenosine are released during hypothermic preservation. While release of HMGB1 is caused by cell damage, release of adenosine seems to be related to ATP hydrolysis, occurring in both susceptible and resistant cells.


Assuntos
Adenosina/metabolismo , Endotélio Vascular/metabolismo , Proteína HMGB1/metabolismo , Refrigeração , Moléculas de Adesão Celular/metabolismo , Células Cultivadas , Células Endoteliais/imunologia , Células Endoteliais/metabolismo , Endotélio Vascular/citologia , Endotélio Vascular/imunologia , Humanos , Interleucina-10/biossíntese , Interleucina-8/metabolismo , Lipopolissacarídeos/imunologia , Fator de Necrose Tumoral alfa/biossíntese
15.
Am J Cardiovasc Drugs ; 7(6): 449-52, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-18076212

RESUMO

OBJECTIVE: Resistant hypertension is an important clinical problem that is poorly studied and not well managed. The objective of this study was to identify factors associated with successful treatment of resistant hypertension in a specialty clinic. METHODS: This was a retrospective observational study examining the medical records of patients seen at a specialty hypertension clinic at the University of Rochester, Rochester, New York, USA, in the year 2005. The records of 68 patients were reviewed. Those presenting with resistant hypertension (defined as BP > or =140/90mm Hg and receiving at least three antihypertensive medications, including a diuretic) were identified. Change in medication type and dosage, BP reduction, and percentage of patients at Joint National Committee (JNC)-7 goal were noted. RESULTS: Twenty-eight patients were included in the analysis. Mean age was 62.5 +/- 11.6 years, 54% were women, and mean presenting BP was 175.4 +/- 23.5/87.5 +/- 14.6mm Hg. After an average of 6.2 +/- 3.2 visits over a mean of 13.9 +/- 13.5 months, mean BP was reduced to 145.3 +/- 27.7/73.9 +/- 13.6mm Hg (paired t-test: p = 0.001 SBP, p = 0.0001 DBP), and 44.8% of the patients were at their JNC-7 goal. Change in the mean number of antihypertensive medications was not significantly different between the initial and final clinic visits (4.1 +/- 1.2 vs 4.2 +/- 1.0; p = 0.627). Combination pill use increased from four patients (14%) at initial visit to 19 (68%) at final visit. Numbers of patients treated with diuretics, beta-adrenoceptor antagonists, calcium channel antagonists (CCB), and minoxidil increased at the final clinic visit. Significant dose-related changes included the up-titration of CCBs to high doses, and the initiation of moderate doses of thiazide diuretics; mainly chlorthalidone (67% final visit vs 0% at initial visit). CONCLUSIONS: Patients referred to a specialty clinic for the control of resistant hypertension achieved significant reductions in BP with frequent visits, combination pills, and greater use and higher doses of CCBs and thiazide diuretics.


Assuntos
Anti-Hipertensivos/uso terapêutico , Resistência a Medicamentos , Hipertensão/tratamento farmacológico , Antagonistas Adrenérgicos beta/uso terapêutico , Instituições de Assistência Ambulatorial , Bloqueadores dos Canais de Cálcio/administração & dosagem , Bloqueadores dos Canais de Cálcio/uso terapêutico , Clortalidona/administração & dosagem , Clortalidona/uso terapêutico , Diuréticos/administração & dosagem , Diuréticos/uso terapêutico , Quimioterapia Combinada , Feminino , Hospitais Especializados , Humanos , Masculino , Pessoa de Meia-Idade , Minoxidil/uso terapêutico , Assistência Centrada no Paciente , Estudos Retrospectivos
16.
J Physiol Pharmacol ; 58 Suppl 5(Pt 2): 501-11, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18204164

RESUMO

The isolation perfusion model, including transbronchial ventilation of human lung, offers the possibility to study pharmacological interactions under physiological conditions. In view of the increasing importance of targeted therapy of lung diseases, this model of perfusion might attract major interest, particularly, in lung cancer. Our study investigated physiological, histological, and immunohistochemical alterations of lung and tumor tissue during isolated perfusion of lung lobectomy specimens to explore potential limitations of this model. Right after resection, 16 human lung resection specimens for primary lung cancer were isolated, ventilated, and perfused under physiological conditions with a modified Krebs-Henseleit solution over a period of 10, 60, 90, 120, and 240 min. Perfusion pressure, pH, lung weight gain, and histological edema formation were measured continuously before and during perfusion. After perfusion, lung and tumor tissue was investigated by hematoxylin-and-eosin stained sections. Immunohistochemistry of NADH, PECAM-1, angiotensin-converting-enzyme and NF-kappabeta were performed to determine lung tissue viability and changes at the endothelial layer. We found that perfusion up to 120 min could be performed with completely stable physiological conditions. Beyond that time span, edema formation and weight gain of the resection specimen started and were followed by an increase in inspiratory pressure and pulmonary artery pressure. Perfusion of more than 4 h led to a significant edema formation in lung tissue accompanied by loss of viability and significant histological alterations. We conclude that isolated ventilation and perfusion of human lung resections within the setup chosen is reliable for pharmacological studies up to a period of 120 min. Thereafter, edema formation and endothelial damage develop and limit the interpretation and reliability of drug delivery studies.


Assuntos
Neoplasias Pulmonares/patologia , Pulmão/anatomia & histologia , Idoso , Endotélio/metabolismo , Endotélio/patologia , Água Extravascular Pulmonar/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Técnicas In Vitro , Pulmão/cirurgia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão/fisiologia , Peptidil Dipeptidase A/metabolismo , Perfusão , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Pneumonectomia , Edema Pulmonar/patologia , Respiração Artificial , Volume de Ventilação Pulmonar
17.
Trends Neurosci ; 24(2): 79-85, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11164937

RESUMO

The NGF family of neurotrophins has a crucial role in regulating neuron numbers during vertebrate development. Six years ago the prediction was made that invertebrates with simple nervous systems, such as Caenorhabditis elegans, would lack neurotrophins. Surprisingly, it now appears that not only C. elegans but also Drosophila melanogaster, lack homologs of the neurotrophins or their trk receptors. Furthermore, functional studies indicate that control of neuronal numbers in Drosophila is primarily dependent on steroids. By contrast, a recognizable trk homolog exists in molluscs, a phylum that includes species with the most complex nervous systems in the invertebrate kingdom. This suggests that neurotrophic signaling mechanisms might be one of the prerequisites for evolution of complex nervous systems. Expansion of the genome projects to other invertebrates, such as molluscs and coelenterates, should provide new insights on the molecular correlates of building complex brains.


Assuntos
Encéfalo/crescimento & desenvolvimento , Evolução Molecular , Invertebrados/crescimento & desenvolvimento , Fatores de Crescimento Neural/fisiologia , Filogenia , Animais , Caenorhabditis elegans/crescimento & desenvolvimento , Drosophila melanogaster/crescimento & desenvolvimento , Hormônios/fisiologia , Humanos , Fator de Crescimento Neural/fisiologia , Neurônios/fisiologia , Receptores Proteína Tirosina Quinases/fisiologia
18.
Cancer Res ; 42(1): 207-18, 1982 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-7032691

RESUMO

The tumor-induced marrow and red blood cell cytolysis assays have been used to explore the mechanism of cancer cell destruction of normal cells. Previously, we suggested that tumor-induced cytolysis was caused by tumor cell membrane-bound serine proteases. In this study, we have shown that concentrations of the broad-spectrum serine protease inhibitor diisopropylfluorophosphate that did not inhibit tumor cell DNA and protein synthesis completely abrogated tumor-induced red blood cell cytolysis. In addition, tumor cell membranes isolated by differential and sucrose density gradient centrifugation and characterized by electron microscopy and enzyme marker analysis were cytolytic for rat 59Fe-labeled red blood cells. The specific activity expressed as release index (%) per microgram of protein was 1.620 for the tumor cell membrane preparations as compared to 0.002 for intact Walker 256 tumor cells. Tumor cell membranes solubilized in Triton X-100 had activity in the p-toluenesulfonyl-L-arginine methyl ester assay for trypsin-like enzymes and the N-benzoyl-L-tyrosine ethyl ester assay for chymotrypsin-like enzymes. The enzyme activities demonstrated in these assays could be inhibited by N-alpha-p-tosyl-L-lysine chloromethyl ketone HCl and L-1-tosylamide-alpha-phenyl-ethyl chloromethyl ketone, respectively. Using [3H]diisopropylfluorophosphate affinity labeling of the tumor cell membrane proteins followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, we have identified membrane-bound serine protease(s) that appear to be responsible for tumor-induced marrow and red blood cell cytolysis.


Assuntos
Carcinoma 256 de Walker/enzimologia , Membrana Celular/enzimologia , Endopeptidases/metabolismo , Animais , Células da Medula Óssea , Carcinoma 256 de Walker/ultraestrutura , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Citotoxicidade Imunológica/efeitos dos fármacos , Hemólise , Isoflurofato/farmacologia , Masculino , Ratos , Serina Endopeptidases
19.
Cancer Res ; 46(11): 5963-8, 1986 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-3530442

RESUMO

A prospective randomized trial of preoperative intratumoral therapy with Bacillus Calmette-Guérin (BCG) was conducted in non-small cell lung cancer patients. Eighty-eight patients (48 BCG-treated and 40 control subjects) were entered into the study; three control subjects were removed from data analysis because histology revealed pathology other than non-small cell lung cancer. There were no differences between BCG-treated and control patients in sex, age, cigarettes smoked per day, pack-years of cigarette smoking, white blood cell count, or number of peripheral blood lymphocytes. Toxicity of BCG was limited to transient malaise and fever (average peak temperature, 38.7 degrees C). There was no significant difference in outcome (recurrence or survival) between BCG-treated and control groups with Stage I or Stage III tumors; there were too few Stage II tumors for separate statistical analysis. Outcome was not affected within or between the two treatment groups by tuberculin skin test status. Combining both treatment groups, Stage III patients had a worse outcome than did Stage I-II patients, non-squamous cell tumor patients (large cell and adenocarcinoma) had worse outcomes than did squamous cell tumor patients, and men had a worse outcome than women. We conclude that, although preoperative intratumoral BCG therapy is safe, it does not lengthen disease-free interval or prolong survival in patients with non-small cell lung cancer.


Assuntos
Carcinoma/terapia , Neoplasias Pulmonares/terapia , Mycobacterium bovis/imunologia , Vacinas Bacterianas/administração & dosagem , Carcinoma/cirurgia , Terapia Combinada , Feminino , Humanos , Imunoterapia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos
20.
Med Klin Intensivmed Notfmed ; 111(4): 325-9, 2016 May.
Artigo em Alemão | MEDLINE | ID: mdl-26153466

RESUMO

Treatment of a patient with acute cardiac failure due to a contusio cordis after polytrauma by an interdisciplinary team is reported. Shortly after admission to our shock room, the patient developed cardiogenic shock caused by an extended coronary dissection. After interim cardiopulmonary resuscitation, the patient was stabilized by venoarterial extracorporeal membrane oxygenation (ECMO) and subsequent complex coronary artery intervention in the heart catheter laboratory. Despite the increased left ventricular function which enabled partial weaning from the ECMO, the patient died of multiple organ failure 10 days after admission.


Assuntos
Dissecção Aórtica/complicações , Dissecção Aórtica/terapia , Aneurisma Coronário/complicações , Aneurisma Coronário/terapia , Oxigenação por Membrana Extracorpórea , Insuficiência Cardíaca/terapia , Traumatismos Cardíacos/complicações , Traumatismos Cardíacos/terapia , Comunicação Interdisciplinar , Colaboração Intersetorial , Traumatismo Múltiplo/terapia , Cateterismo Cardíaco , Procedimentos Endovasculares , Evolução Fatal , Humanos , Masculino , Pessoa de Meia-Idade
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