RESUMO
SERCA2a gene transfer ameliorates heart failure pathologic processes in left ventricular myocardium. We sought to assess the simultaneous molecular changes that occur in the right ventricle. Sprague-Dawley rats underwent aortic banding and were followed by echocardiography for development of heart failure. After a decrease in fractional shortening of 25 % from baseline, intracoronary injection of adenoviral-SERCA2a or adenoviral-beta-galactosidase was performed. Successful gene transfer was confirmed by immunoblotting. Rats were randomly euthanized on post-operative day 7 or 21. Protein analysis including right ventricular levels of SERCA2a, betaARK1, inflammatory mediators (IL-1, IL-6 and TNF-alpha), apoptotic markers (Bax, Bak and Bcl-2) and MAPK (Jnk, p38 and Erk) was performed. Adenoviral-SERCA2a-treated animals showed increased right ventricular expression of SERCA2a compared with controls. Decreased levels of inflammatory markers were also demonstrated in this group. Expression of pro-apoptotic markers was similarly improved. Levels of MAPK were increased compared with the control group. These differences were most significant 7 days after gene transfer, but the majority of these changes persisted at 21 days. These results suggest that attenuation of pathologic mechanisms of calcium cycling, inflammation and apoptosis also occur in the right ventricular myocardium after SERCA2a gene transfer during heart failure. These findings support a therapeutic role for genetic manipulation of this pathway in patients with right ventricular or biventricular failure.
Assuntos
Técnicas de Transferência de Genes , Insuficiência Cardíaca/terapia , Ventrículos do Coração/fisiopatologia , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/genética , Adenoviridae/genética , Adenoviridae/metabolismo , Animais , Biomarcadores/metabolismo , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Ventrículos do Coração/patologia , Humanos , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Transgenes , Replicação ViralRESUMO
The limited effectiveness of therapy for patients with advanced stage head and neck squamous cell carcinoma (HNSCC) or recurrent disease is a reflection of an incomplete understanding of the molecular basis of HNSCC pathogenesis. MUC4, a high molecular weight glycoprotein, is differentially overexpressed in many human cancers and implicated in cancer progression and resistance to several chemotherapies. However, its clinical relevance and the molecular mechanisms through which it mediates HNSCC progression are not well understood. This study revealed a significant upregulation of MUC4 in 78% (68/87) of HNSCC tissues compared with 10% positivity (1/10) in benign samples (P=0.006, odds ratio (95% confidence interval)=10.74 (2.0-57.56). MUC4 knockdown (KD) in SCC1 and SCC10B HNSCC cell lines resulted in significant inhibition of growth in vitro and in vivo, increased senescence as indicated by an increase in the number of flat, enlarged and senescence-associated ß-galactosidase (SA-ß-Gal)-positive cells. Decreased cellular proliferation was associated with G0/G1 cell cycle arrest and decrease expression of cell cycle regulatory proteins like cyclin E, cyclin D1 and decrease in BrdU incorporation. Mechanistic studies revealed upregulation of p16, pRb dephosphorylation and its interaction with histone deacetylase 1/2. This resulted in decreased histone acetylation (H3K9) at cyclin E promoter leading to its downregulation. Orthotopic implantation of MUC4 KD SCC1 cells into the floor of the mouth in nude mice resulted in the formation of significantly smaller tumors (170±18.30 mg) compared to those (375±17.29 mg) formed by control cells (P=0.00007). In conclusion, our findings showed that MUC4 overexpression has a critical role by regulating proliferation and cellular senescence of HNSCC cells. Downregulation of MUC4 may be a promising therapeutic approach for treating HNSCC patients.
Assuntos
Carcinoma de Células Escamosas/patologia , Senescência Celular , Neoplasias de Cabeça e Pescoço/patologia , Mucina-4/fisiologia , Proteínas de Neoplasias/fisiologia , Proteína do Retinoblastoma/fisiologia , Animais , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Montagem e Desmontagem da Cromatina , Ciclina E/análise , Inibidor p16 de Quinase Dependente de Ciclina , Humanos , Camundongos , Mucina-4/análise , Invasividade Neoplásica , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
We report the first case of hexasomy 12p mosaicism due to 2 copies of an apparent i(12p) [46,XX/48,XX, +i(12p), +i(12p)]. In every cell that contained the i(12p), 2 copies of the marker were found. The hexasomy was found in amniocytes (16%) and skin fibroblasts (95%) but not in peripheral blood lymphocytes. The chromosomal origin of the marker was confirmed with the use of in situ hybridization of alpha-satellite specific for the centromere of chromosome 12. The present case was diagnosed following chromosome analysis for anomalies on ultrasound. The hexasomy 12p patient showed striking phenotypic similarities with severely affected tetrasomy 12p cases and died shortly after birth. We propose that the more severe presentation of this case is due to the 4 extra copies of 12p.
Assuntos
Aneuploidia , Aberrações Cromossômicas/diagnóstico por imagem , Cromossomos Humanos Par 12 , Diagnóstico Pré-Natal , Adulto , Aberrações Cromossômicas/genética , Transtornos Cromossômicos , Feminino , Doenças Fetais/diagnóstico por imagem , Doenças Fetais/genética , Humanos , Hibridização in Situ Fluorescente , Recém-Nascido , Mosaicismo , Gravidez , UltrassonografiaRESUMO
A fetus with lobar holoprosencephaly and lumbosacral meningomyelocele associated with duplication of the short arm of chromosome 3 is reported. The anomalies were detected on fetal ultrasound at 20 weeks' gestation and the autopsy findings correlated well with the prenatal findings. The fetal karyotype was 46,XY,der(3)del(3)(p26) dup(3)(p26p21.3). The association of holoprosencephaly with duplication 3p is well known, but to the best of our knowledge this is the first reported association of meningomyelocele with 3p duplication. These findings suggest that a gene or genes with a crucial role in central nervous system development are located on the short arm of chromosome 3.
Assuntos
Anormalidades Múltiplas/genética , Cromossomos Humanos Par 3 , Holoprosencefalia/genética , Meningomielocele/genética , Anormalidades Múltiplas/diagnóstico por imagem , Adulto , Feminino , Feto , Idade Gestacional , Holoprosencefalia/diagnóstico por imagem , Humanos , Cariotipagem , Meningomielocele/diagnóstico por imagem , Gravidez , Ultrassonografia Pré-NatalRESUMO
BACKGROUND: We are developing a miniaturized centrifugal blood pump for use as a temporary cardiac assist device in neonatal and pediatric sized patients. This pump has a very low priming volume of 13 mL. A small motor stator has also been designed, which resulted in a device that can be placed very close to the patient, thereby minimizing overall circuit volume. METHODS: Testing to date has included in vitro hemodynamic performance, in vitro hemolysis generation, and in vivo evaluation in 5 lambs weighing 5.5 to 21 kg. Two lambs underwent peripheral cannulation from external jugular vein to carotid artery, whereas 3 others were cannulated from left atrium to carotid artery. RESULTS: In vitro data demonstrated pump capacity spanning 0.3 to 3.0 L/min and very low hemolysis generation at these conditions. In vivo, the pump functioned satisfactorily for periods up to 148 hours, and the bypass appeared to be well tolerated by the animals. Plasma free hemoglobin levels remained less than 25 mg/dL during all animal experiments. All devices were thrombus-free at explantation. CONCLUSIONS: We conclude that this device has merit as an alternative to current oversized systems used for neonatal and pediatric cardiac assistance. In addition, a chronic neonatal lamb model in which to evaluate pediatric circulatory assist devices has been developed successfully.
Assuntos
Coração Auxiliar , Animais , Criança , Pré-Escolar , Desenho de Equipamento , Coração Auxiliar/efeitos adversos , Hemodinâmica , Humanos , Técnicas In Vitro , Lactente , Recém-Nascido , OvinosRESUMO
This paper summarizes the authors' in vivo experience in evaluating a miniature centrifugal blood pump designed for pediatric/neonatal ventricular support. Left ventricular bypass was accomplished in two adult sheep and five juvenile lambs (5.5-80.0 kg) via either central (left ventricle to carotid artery) or peripheral (jugular vein to carotid artery) cannulation. Animals were weaned from mechanical ventilation and continuously monitored. Hemodynamic parameters remained within a normal range over the duration of the bypass. Two of five lambs were electively killed at 8, and 76 hours; the remaining three lambs died from respiratory complications at 33, 44, and 156 hours. There were no mechanical complications, and blood seal integrity was confirmed beyond 6 days. The pump speed was maintained at 3,000-4,500 rpm with pump flow rates between 0.4-1.5 L/min. Average plasma free hemoglobin was below 20 mg/dl in the five lamb experiments. Renal, hepatic, and hematologic indices also remained within physiologic ranges. Histopathologic analyses of major organs revealed renal cortical infarctions in two of five lambs. Examination of the pump surfaces after explant indicated small areas of thrombus in the housing adjacent to the outflow ports in two experiments. These encouraging results support further testing and refinement of this miniature centrifugal pump.
Assuntos
Coração Auxiliar/normas , Animais , Contagem de Células Sanguíneas , Nitrogênio da Ureia Sanguínea , Centrifugação , Criança , Creatinina/sangue , Derivação Cardíaca Esquerda , Coração Auxiliar/efeitos adversos , Hematócrito , Hemodinâmica/fisiologia , Hemoglobinas/análise , Hemoglobinas/metabolismo , Humanos , Recém-Nascido , Complicações Pós-Operatórias/mortalidade , Ovinos , Trombose/etiologia , Trombose/fisiopatologiaRESUMO
The efficacy of an innovative intravenous membrane oxygenator (IMO) was tested acutely (6-8 hrs) in seven calves. The IMO prototypes consisted of a central polyurethane balloon within a bundle of hollow fibers with a membrane surface area of 0.14 m2. The IMO devices were inserted through the external jugular vein into the inferior vena cava of anesthetized calves (68.9 +/- 2.3 kg). Rhythmic balloon pulsation (60-120 bpm) was controlled with an intra-aortic balloon pump console. Oxygen sweep gas was delivered through the device at 3.0 L/min. Gas concentrations were monitored continuously by mass spectroscopy. The principal results were as follows: 1) oxygen and carbon dioxide exchange ranged from 125 to 150 ml/min/m2 and 150 to 200 ml/min/m2, respectively; 2) there was at least a 30-50% augmentation of gas exchange with balloon pulsation; 3) maximum exchange occurred with 60-90 bpm balloon pulsations; and 4) hemodynamic parameters remained unchanged. There were no device related complications, and the feasibility of insertion of the device by a cervical cut-down was established. These acute in vivo experiments show that the Pittsburgh IMO device can exchange oxygen and carbon dioxide gases in vivo at levels consistent with this current prototype design, and that intravenous balloon pulsation significantly enhances gas exchange without causing any end-organ damage.
Assuntos
Oxigenadores de Membrana , Adulto , Animais , Engenharia Biomédica , Dióxido de Carbono , Bovinos , Desenho de Equipamento , Estudos de Avaliação como Assunto , Feminino , Humanos , Oxigênio , Troca Gasosa Pulmonar , Síndrome do Desconforto Respiratório/terapiaRESUMO
The authors analyzed factors that may influence the outcome of adult patients with respiratory failure who were treated with ECMO. Between December 1990 and July 1995, the authors used ECMO to support 33 patients (age range, 17-56 years) with respiratory failure from adult respiratory distress syndrome (ARDS; n = 9), primary graft failure after lung transplantation (n = 16), late graft failure after lung transplantation (n = 5), and miscellaneous reasons (n = 3). Twenty (61%) patients were successfully weaned from ECMO, and 13 (39%) survived to hospital discharge. Venoarterial ECMO was used in 46% of survivors, compared with 60% of nonsurvivors (p = 0.43). The time on mechanical support before ECMO and the duration on ECMO for survivors and nonsurvivors was 2.9 +/- 1.8 days vs 5.0 +/- 1.3 days (p = 0.35), and 6.5 +/- 1.8 days vs 5.7 +/- 1.1 days (p = 0.68), respectively. Compared with the nonsurvivors, survivors had higher PF ratios (PaO2/FIO2; 104 +/- 33 vs 81 +/- 8, p = 0.43) before ECMO was initiated, although the differences were not significant. Among the patients who received ECMO for primary graft failure, 75% were weaned from ECMO, and 56% survived to discharge. ECMO is beneficial for adult patients with respiratory failure, especially those with primary graft failure after lung transplantation.
Assuntos
Oxigenação por Membrana Extracorpórea , Síndrome do Desconforto Respiratório/terapia , Insuficiência Respiratória/terapia , Doença Aguda , Adulto , Oxigenação por Membrana Extracorpórea/métodos , Feminino , Humanos , Transplante de Pulmão/efeitos adversos , Masculino , Síndrome do Desconforto Respiratório/fisiopatologia , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/fisiopatologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
This paper summarizes the authors' in vivo experience to date with an implantable axial flow blood pump designed for long-term ventricular support. This small, valveless pump with blood-lubricated bearings has been implanted in six calves (83 +/- 6 kg) as a left ventricular assist device (LVAS). The left ventricle and descending thoracic aorta were cannulated by left thoracotomy, and the pump was placed in a subcutaneous pocket below the costal margin. Animals remained hemodynamically stable throughout the course of support during partial left ventricular bypass. Five animals were killed after 15, 27, 52, 57, and 181 days. The longest survivor (181 days) demonstrated normal pump function at the time death. Pump speed was maintained at 10,100 +/- 100 rpm, with an average pump flow rate of 4.9 +/- 0.5 L/min under resting physiologic conditions. Average plasma free hemoglobin was 17.4 +/- 7.5 mg/dl. Renal, hepatic, and hematologic indices remained within physiologic range in all of these animals, except during the immediate postoperative period. Histopathologic analyses of major organs after death revealed small renal cortical infarcts in five of six animals; the remaining organs were normal. These animal studies support the feasibility of this small implanted axial flow pump for long-term ventricular assistance.
Assuntos
Coração Auxiliar , Animais , Aorta Torácica/fisiologia , Velocidade do Fluxo Sanguíneo , Bovinos , Estudos de Viabilidade , Coração Auxiliar/efeitos adversos , Hematócrito , Hemodinâmica/fisiologia , Hemoglobinas/metabolismo , Córtex Renal/patologia , Lubrificação , Toracotomia , Tromboembolia/etiologiaRESUMO
Circulatory assist devices are used to treat patients awaiting cardiac transplantation to preserve life as well as to permit recovery of end-organ function. The efficacy of pulseless perfusion versus pulsatile perfusion in the recovery of end-organ function has not been fully determined. In this study, the efficacy of pulseless perfusion compared to pulsatile perfusion on the recovery of renal function after a 30 min period of normothermic ischemia was examined. Pigs were randomly assigned to four groups. In all groups, acute renal ischemia was induced by clamping both renal arteries for 30 min. Reperfusion for 120 min was performed using either pulsatile perfusion or pulseless perfusion at 65 +/- 1.6 mm Hg (Groups I [pulsatile] and II [pulseless]) and at 40 +/- 1.1 mm Hg (Groups III [pulsatile] and IV [pulseless]). After reperfusion, renal blood flow, hemodynamic power (pressure * flow: hemodynamic power), oxygen consumption (VO2), tissue ATP, and urine output (UO) in Groups I, II, and III were significantly higher than in Group IV (p < .01 by ANOVA). Histopathologic examinations were not significantly different between groups. Under hypotensive conditions, pulsatile perfusion improves hemodynamic power delivery to the organ compared to pulseless perfusion. These results suggest that a pulseless pump is acceptable as an assist device when normal flow or perfusion pressure is maintained.
Assuntos
Coração Auxiliar , Hemodinâmica , Rim/fisiologia , Animais , Transplante de Coração , Humanos , Isquemia/fisiopatologia , Rim/fisiopatologia , Consumo de Oxigênio , Fluxo Pulsátil , Suínos , Resistência Vascular/fisiologiaRESUMO
The role of pulsatile flow as a physiologic stimulus for endothelium mediated vasoregulation is poorly understood. Furthermore, non pulsatile flow, which is associated with increased vascular resistance and end-organ failure, has been demonstrated to lead to a decrease in nitric oxide (NO) production in vitro. Anesthetized pigs (23.4 +/- 0.3 kg) were placed on cardiopulmonary bypass using either non pulsatile or pulsatile perfusion for 60 min. In both groups, animals were maintained with a constant mean aortic flow (1.0-1.3 L/min). Serum samples obtained during bypass were assayed for the stable end-products of NO (nitrate [NO3-] and nitrite [NO2-]) by a method based on the Greiss reaction. Systemic vascular resistance was higher after 60 min in the non pulsatile (3712.5 +/- 481.2 dyne sec cm(-5)) vs the pulsatile group (2672.6 +/- 427.0 dyne sec cm(-5)), but not statistically significant (p > .05). However, NO production was decreased in the non pulsatile flow group (27 +/- 6%) vs the pulsatile flow group (14 +/- 5%) at a statistically significant level (p < .005). The results suggest that non pulsatile flow is associated with diminished endothelial shear stress and a reduction in endothelial nitric oxide production. This may contribute to the detrimental physiologic effects observed in prolonged non pulsatile flow states.
Assuntos
Ponte Cardiopulmonar/métodos , Óxido Nítrico/fisiologia , Vasodilatação/fisiologia , Animais , Ponte Cardiopulmonar/efeitos adversos , Estudos de Avaliação como Assunto , Feminino , Nitratos/sangue , Nitritos/sangue , Fluxo Pulsátil , Suínos , Resistência Vascular/fisiologiaRESUMO
BACKGROUND: Couples who have had multiple miscarriages are at risk for carrying a balanced translocation since these carriers may produce unbalanced gametes. Small imbalances may lead to offspring with multiple congenital anomalies. This report emphasizes the importance of obtaining cytogenetics studies in couples with recurrent spontaneous abortions. CASE: A couple was referred for cytogenetic prenatal testing because of a history of recurrent miscarriages and an infant who died at 6 weeks of age with multiple congenital anomalies. Although the parental chromosomes were previously reported to be normal in another laboratory, the pedigree was consistent with a chromosomal etiology, and parental blood samples were reevaluated. The father was found to carry a subtle reciprocal translocation t(7;11)(q35;q23.3). Slides were obtained from the previous miscarriages and the infant who died. On reexamination, one miscarriage and the infant were found to be chromosomally unbalanced, carrying the derivative 7, resulting in partial monosomy for 7q and partial trisomy for 11q. The other miscarriage had a chromosomally normal female karyotype. Maternal cell contamination could not be excluded in that case. The current pregnancy was found to carry the balanced translocation. Since the rearrangement was quite small and subtle, fluorescence in situ hybridization (FISH) using "painting" probes for chromosomes 7 and 11 was used to confirm the balanced state in the fetus. CONCLUSION: This family illustrates the importance of performing high-quality chromosome studies on people who have spontaneous abortions and children with multiple congenital anomalies. The use of FISH probes was helpful in confirming this subtle rearrangement.
Assuntos
Anormalidades Múltiplas/genética , Aborto Habitual/genética , Translocação Genética , Adulto , Cromossomos Humanos Par 11 , Cromossomos Humanos Par 7 , Feminino , Fluorescência , Testes Genéticos , Humanos , Hibridização In Situ , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Cariotipagem , Masculino , Linhagem , Gravidez , Diagnóstico Pré-NatalRESUMO
The effects of prolonged, submaximal exercise by seven healthy, untrained individuals on the generation of H2O2 by neutrophils was studied. Hydrogen peroxide generation by neutrophils isolated from pre-exercise (control) and post-exercise blood samples was measured 10, 15 and 20 minutes following stimulation with phorbol myristate acetate (PMA). Exercise was associated with a significant elevation in the number of circulating neutrophils and a diminished capacity for neutrophil H2O2 generation following PMA stimulation. Addition of post-exercise plasma to neutrophils isolated from pre-exercise blood caused a small reduction in H2O2 generation, suggesting the presence of an inhibitory factor(s) in the plasma during physical exercise. These results support the concept that exercise may contribute to an attenuation of oxygen-dependent neutrophil killing.
Assuntos
Exercício Físico/fisiologia , Peróxido de Hidrogênio/metabolismo , Neutrófilos/metabolismo , Reação de Fase Aguda/imunologia , Adulto , Feminino , Humanos , Contagem de Leucócitos , Masculino , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Ésteres de Forbol/farmacologiaRESUMO
As part of an interdisciplinary research project, the performance response of sows and their litters to the probiotic strain Enterococcus faecium NCIMB 10415, as well as some health characteristics of the piglets, were studied. Gestating sows (n = 26) were randomly allotted into 2 groups. The probiotic was administered by dietary supplementation to 1 group of sows and their respective litters (probiotic group), whereas the second group (control group) received no probiotic supplementation. The duration of the treatment was nearly 17 wk for sows (d 90 ante partum until d 28 postpartum) and 6 wk for piglets (d 15 to 56). Body weight and feed consumption were recorded weekly. The frequency of 4 toxin and 5 adhesion genes of putative pathogenic Escherichia coli was monitored weekly (d 7 to 35) by multiplex PCR assays, and fecal consistency of weaned piglets was studied daily. Probiotic treatment of lactating sows led to an overall pre-weaning mortality of 16.2% compared with 22.3% in the control group (P = 0.44). Animal losses during the first 3 d of the suckling period were decreased in the probiotic group (P = 0.09). For piglets (n = 153), which were weaned at 28 d, there were no overall treatment differences in BW gain, feed intake, or feed efficiency. Probiotic supplementation, however, led to nearly a 40% reduction (P = 0.012). The actual percentage of piglets with postweaning diarrhea in the probiotic group was 21% compared with 38% in the control group (P = 0.05). The study on virulence factors of dominant fecal E. coli isolates revealed a high diversity with varying frequency and distribution of each single pathogenicity gene. The 440 isolates carried 29 different pathogenicity gene combinations as well as each of the 9 pathogenicity genes alone. Altogether, isolates with more than 2 pathogenicity genes were quite rare (< or = 10%), and up until d 28 isolates without any pathogenicity gene occurred most frequently. Depending on the time of sampling, one-third or more of all isolates contained est2 or est1b as single gene or in combination with other pathogenicity genes.
Assuntos
Enterococcus faecium/fisiologia , Escherichia coli/patogenicidade , Probióticos/administração & dosagem , Suínos/fisiologia , Fatores de Virulência/genética , Ração Animal/análise , Animais , Animais Recém-Nascidos/fisiologia , Animais Lactentes/fisiologia , Peso Corporal/fisiologia , Diarreia/epidemiologia , Diarreia/prevenção & controle , Diarreia/veterinária , Escherichia coli/genética , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/prevenção & controle , Infecções por Escherichia coli/veterinária , Fezes/química , Fezes/microbiologia , Feminino , Incidência , Lactação/fisiologia , Gravidez , Distribuição Aleatória , Suínos/crescimento & desenvolvimento , Suínos/microbiologia , Doenças dos Suínos/epidemiologia , Doenças dos Suínos/prevenção & controle , Fatores de Tempo , Virulência/genética , DesmameRESUMO
Previously, we reported that the combination of plasmapheresis (PP) and intravenous immunoglobulin (IVIg) allow sensitized patients to undergo orthotopic heart transplantation (OHT), even across a positive crossmatch. In the current study, the effect of that combination, PP+IVIg, on survival of a larger group of such recipients is investigated. The latter group (I) consisted of 35 sensitized patients who received PP+IVIG together with standard immunosuppressive drugs. Rejection was seen in 11 patients, findings strongly suggestive of a vascular (humoral) being identified in five of those cases. Four deaths occurred, two of them in the immediate post-operative period, one after almost six months, and one after almost two yr post-OHT. Follow-up range 4.5 months to 7.8 yr post-OHT (average=1.1 yr). Patient survival was analyzed after generation of a Kaplan-Meier plot. Comparison with a control OHT group (II) given standard immunosuppressive drugs only (N=276) showed enhanced survival of group I (p=0.0414 by log-rank test). We conclude that the combination of PP and IVIG (i) is associated with declines in T- and B-percent-reactive antibody and in crossmatch positivity, and (ii) is very useful in the management of the sensitized cardiac patient undergoing OHT, often allowing a successful outcome to transplantation in the face of a positive crossmatch.
Assuntos
Transplante de Coração/fisiologia , Imunoglobulinas Intravenosas/uso terapêutico , Plasmaferese , Biópsia , Rejeição de Enxerto/epidemiologia , Transplante de Coração/imunologia , Transplante de Coração/mortalidade , Transplante de Coração/patologia , Teste de Histocompatibilidade , Humanos , Imunossupressores/uso terapêutico , Isoanticorpos/sangue , Análise de SobrevidaRESUMO
Transhiatal esophagectomy is gaining increasing use as the preferred technique for esophagectomy. In this article, the indications, diagnostic evaluation, and technical details of the operative procedure for transhiatal esophagectomy are reviewed. Results of large clinical series are discussed and the potential pitfalls and risks of the procedure are reviewed. Current controversies and future trends are also discussed.
Assuntos
Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Quimioterapia Adjuvante , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Esofagoscopia , Humanos , Estadiamento de Neoplasias , Complicações Pós-Operatórias , Radioterapia Adjuvante , Resultado do TratamentoRESUMO
When erythrocytes are incubated with 32Pi, incorporation of label into phosphoproteins is a gradual process, increasing for at least 2 hours. Membrane phospholipids also are labeled. Exogenous protein kinase substrates are unlabeled in these incubations. This suggests that labeling by 32Pi occurs into polypeptides inside the erythrocytes. When erythrocytes are incubated with [gamma-32P]ATP and active protein kinase, membrane polypeptides are not labeled. Only exogenously added protein kinase substrates and the regulatory subunit of protein kinase (and its contaminants) are labeled. This suggests that labeling from [gamma-32P]ATP and active protein kinase occurs in the compartment outside the erythrocytes. Apyrase (EC 3.6.1.5) eliminates such labeling, demonstrating that it was occurring in the compartment external to the erythrocytes. However, in incubations of cells with 32Pi, apyrase has no effect on the incorporation into membrane polypeptides and phospholipids, demonstrating that this labeling occurs on the inside of the membrane. Thus, additions of apyrase to intact particles incubated with protein kinase substrates and 32Pi provides a method for identifying internally exposed polypeptides in the plasma membranes of a variety of systems.
Assuntos
Membrana Eritrocítica/ultraestrutura , Proteínas de Membrana/análise , Apirase/metabolismo , Membrana Eritrocítica/análise , Humanos , Fosfolipídeos/análise , Fosfoproteínas/análise , Fosforilação , Proteínas Quinases/metabolismo , Espectrina/análiseRESUMO
The intestinal bacterium Enterococcus faecium NCIMB 10415 (E. faecium SF68) has been used for more than a decade as a probiotic strain in animal nutrition as well as in the prevention and treatment of diarrhoea in humans. Beneficial effects have been shown in feeding and clinical trials. However, the strain has no selective growth markers and monitoring in the intestinal tract is impossible by cultivation. Using specific nucleotide sequences, in this study a probe for colony hybridization was constructed in order to quantify this probiotic strain in feed and intestinal and faecal samples from piglets and sows. The probiotic strain showed almost constant amounts in sow faeces (1.8 x 10(5) cfu/g wet weight), while contents in digesta and piglet faeces varied on a lower level depending on gut section and piglet age. The ratio of specific probiotic counts and total enterococci was much lower than in sow faeces however the strain could be detected reliably in faeces already on the 14th day of life. The application of the colony hybridization method enables for the first time the selective detection of the widely used probiotic E. faecium NCIMB 10415 strain among total Enterococcus spp. counts of digesta, faeces and feed. It is now possible to monitor the presence of the probiotic in the intestinal tract and faeces. Results of this study have implications for the proposed modes of action of probiotics in animal nutrition.
Assuntos
Sistema Digestório/microbiologia , Enterococcus faecium/crescimento & desenvolvimento , Probióticos/administração & dosagem , Suínos , Fatores Etários , Ração Animal , Fenômenos Fisiológicos da Nutrição Animal , Animais , Animais Recém-Nascidos , Contagem de Colônia Microbiana/veterinária , Sondas de DNA , Enterococcus faecium/fisiologia , Fezes/microbiologia , Feminino , Trânsito Gastrointestinal , Masculino , Suínos/crescimento & desenvolvimento , Suínos/microbiologiaRESUMO
The purpose of this study was to evaluate the surgical outcome of completion thyroidectomy in patients with presumed unilateral well-differentiated thyroid cancer (WDTC). The medical records of all patients having had unilateral thyroid lobectomy for WDTC, who subsequently underwent completion thyroidectomy, were reviewed. From 1980 to 1991, 60 patients with WDTC underwent completion thyroidectomy. Forty-seven patients had presumed unilateral WDTC, with no evidence of residual disease prior to their completion thyroidectomy. Twenty-five (53%) of these patients were found to have residual neoplastic disease in the neck. In 20 (43%) of 47 patients, a focus of cancer was found in the remaining thyroid lobe and in 5 additional patients no cancer was found in the contralateral lobe, however, unsuspected nodal disease was found. The remaining 13 of the 60 patients presented with either regional recurrence (n = 12) or distant metastases (n = 1) at the time of their completion thyroidectomy. All (92%) but 1 of these 13 patients had cancer in the remaining thyroid lobe. Multifocal disease in the primary lobe was associated with bilateral thyroid cancer (p less than 0.01). Complications were infrequent; transient hypocalcemia occurred in 5 (8%) patients, permanent hypoparathyroidism occurred in 1 (1.7%) patient, and transient recurrent laryngeal nerve palsy occurred in 3 (5%) patients. Residual WDTC was found in 37 (62%) of 60 patients undergoing completion thyroidectomy. Multifocal disease in the primary resected lobe was associated with a high incidence of contralateral thyroid cancer. Completion thyroidectomy is a safe procedure and may prevent the development of regional recurrence by eliminating an unsuspected focus of cancer.