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1.
Eur J Clin Microbiol Infect Dis ; 33(10): 1861-7, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24859907

RESUMEN

The fully human anti-lipopolysaccharide (LPS) immunoglobulin M (IgM) monoclonal antibody panobacumab was developed as an adjunctive immunotherapy for the treatment of O11 serotype Pseudomonas aeruginosa infections. We evaluated the potential clinical efficacy of panobacumab in the treatment of nosocomial pneumonia. We performed a post-hoc analysis of a multicenter phase IIa trial (NCT00851435) designed to prospectively evaluate the safety and pharmacokinetics of panobacumab. Patients treated with panobacumab (n = 17), including 13 patients receiving the full treatment (three doses of 1.2 mg/kg), were compared to 14 patients who did not receive the antibody. Overall, the 17 patients receiving panobacumab were more ill. They were an average of 72 years old [interquartile range (IQR): 64-79] versus an average of 50 years old (IQR: 30-73) (p = 0.024) and had Acute Physiology and Chronic Health Evaluation II (APACHE II) scores of 17 (IQR: 16-22) versus 15 (IQR: 10-19) (p = 0.043). Adjunctive immunotherapy resulted in an improved clinical outcome in the group receiving the full three-course panobacumab treatment, with a resolution rate of 85 % (11/13) versus 64 % (9/14) (p = 0.048). The Kaplan-Meier survival curve showed a statistically significantly shorter time to clinical resolution in this group of patients (8.0 [IQR: 7.0-11.5] versus 18.5 [IQR: 8-30] days in those who did not receive the antibody; p = 0.004). Panobacumab adjunctive immunotherapy may improve clinical outcome in a shorter time if patients receive the full treatment (three doses). These preliminary results suggest that passive immunotherapy targeting LPS may be a complementary strategy for the treatment of nosocomial O11 P. aeruginosa pneumonia.


Asunto(s)
Anticuerpos Antibacterianos/administración & dosificación , Anticuerpos Monoclonales/administración & dosificación , Factores Inmunológicos/administración & dosificación , Inmunoterapia/métodos , Neumonía Bacteriana/terapia , Pseudomonas aeruginosa/inmunología , Adulto , Anciano , Anticuerpos Antibacterianos/efectos adversos , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/farmacocinética , Infección Hospitalaria/microbiología , Infección Hospitalaria/terapia , Femenino , Humanos , Inmunoglobulina M/administración & dosificación , Inmunoglobulina M/efectos adversos , Factores Inmunológicos/efectos adversos , Factores Inmunológicos/farmacocinética , Masculino , Persona de Mediana Edad , Neumonía Bacteriana/microbiología , Estudios Prospectivos , Pseudomonas aeruginosa/clasificación , Serogrupo , Resultado del Tratamiento
2.
Chemosphere ; 95: 519-26, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24176656

RESUMEN

The present study precisely describes the solubility patterns of commercial uncoated and organic coated ZnO NPs (nc-NPs and c-NPs, respectively) in a natural carbonate-rich water and the physicochemical processes involved. NPs transformation rates were determined with the Donnan Membrane approach (DMT, to obtain Zn(2+) concentration) and ultrafiltration (i.e. Zn(2+) and Zn bound to small organic ligands) and modeled with VMinteQ. XPS measurements evidenced the presence on native nc-NPs of a Zn(OH)2 layer which accounts for almost 22% of total Zn. This Zn(OH)2 phase is more soluble than ZnO, and could control the early dissolution steps of the nc-NPs in our system. Indeed, nc-NPs display a fast (<1 h) dissolution step reaching 19 µM Zn in solution (<1% of the total initial zinc concentration). Comparatively, c-NPs progressively release zinc during the first 48 h, to finally reach a maximum of 197 µM (10% of total Zn), which is 10 times the maximum value measured for nc-NPs. Over the long term, dissolved Zn concentrations decrease in both systems, corresponding to the neoformation of carbonate phases observed by TEM imaging. The kinetic modeling allows highlighting two different ranges of time, corresponding to (i) first 10h with a fast precipitation (kp(')=-182.10(-4)) related to a highly oversaturated solution with respect to carbonate zinc mineral and (ii) a second slower precipitation step (kp(')=-8.10(-4)), related to the embedding of NPs in the precipitated carbonate matrix. The steady state is reached after 3 months of interaction.


Asunto(s)
Monitoreo del Ambiente , Nanopartículas/análisis , Ríos/química , Contaminantes Químicos del Agua/análisis , Óxido de Zinc/análisis , Carbonatos/química , Cinética , Solubilidad
3.
Vaccine ; 24(44-46): 6632-5, 2006 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-16828206

RESUMEN

The antigen used in influenza vaccines is directly derived from influenza viruses. It is produced in embryonated chicken eggs for both inactivated and live attenuated influenza vaccines. As a consequence, all influenza vaccines contain varying amounts of residual egg proteins, depending on the specific manufacturing process of the vaccine. The degree of purity of influenza vaccines can be assessed by quantifying the total amount of protein in relation to the amount of specific antigen. Alternatively, ovalbumin can be used as surrogate marker, representing the amount of egg-derived proteins present in the vaccine. Egg proteins, such as ovalbumin, are classified as sensitising agents. Their presence in a vaccine may be linked to adverse reactions. Such a vaccine is not suitable for subjects with a known history of egg-allergy. This population is currently excluded from influenza vaccination programs. Influenza vaccines are intended for annual re-immunisation. This repeated administration may lead to an immunity against ovalbumin and other egg proteins, which in turn may provoke increased local and systemic reactions and a reduced tolerability profile of the product. Comparing several influenza vaccines present on the market, ELISA and Western blot analysis showed clearly a very low level of ovalbumin in Inflexal V. Furthermore, data showed, that Inflexal V is the influenza vaccine with the lowest ovalbumin content.


Asunto(s)
Vacunas contra la Influenza/química , Ovalbúmina/análisis , Cultivo de Virus , Western Blotting , Ensayo de Inmunoadsorción Enzimática , Vacunas contra la Influenza/inmunología , Ovalbúmina/efectos adversos , Ovalbúmina/inmunología
4.
Am J Cardiol ; 88(9A): 1L-20L, 2001 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-11694220

RESUMEN

Angiotensin-converting enzyme (ACE) is primarily localized (>90%) in various tissues and organs, most notably on the endothelium but also within parenchyma and inflammatory cells. Tissue ACE is now recognized as a key factor in cardiovascular and renal diseases. Endothelial dysfunction, in response to a number of risk factors or injury such as hypertension, diabetes mellitus, hypercholesteremia, and cigarette smoking, disrupts the balance of vasodilation and vasoconstriction, vascular smooth muscle cell growth, the inflammatory and oxidative state of the vessel wall, and is associated with activation of tissue ACE. Pathologic activation of local ACE can have deleterious effects on the heart, vasculature, and the kidneys. The imbalance resulting from increased local formation of angiotensin II and increased bradykinin degradation favors cardiovascular disease. Indeed, ACE inhibitors effectively reduce high blood pressure and exert cardio- and renoprotective actions. Recent evidence suggests that a principal target of ACE inhibitor action is at the tissue sites. Pharmacokinetic properties of various ACE inhibitors indicate that there are differences in their binding characteristics for tissue ACE. Clinical studies comparing the effects of antihypertensives (especially ACE inhibitors) on endothelial function suggest differences. More comparative experimental and clinical studies should address the significance of these drug differences and their impact on clinical events.


Asunto(s)
Peptidil-Dipeptidasa A/fisiología , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Sistema Cardiovascular/enzimología , Sistema Cardiovascular/fisiopatología , Enfermedad Coronaria/tratamiento farmacológico , Enfermedad Coronaria/enzimología , Enfermedad Coronaria/fisiopatología , Endotelio Vascular/fisiopatología , Corazón/fisiopatología , Humanos , Riñón/enzimología , Riñón/fisiopatología , Enfermedades Renales/enzimología , Enfermedades Renales/fisiopatología , Miocardio/enzimología , Peptidil-Dipeptidasa A/genética , Disfunción Ventricular Izquierda/fisiopatología
5.
Ann Thorac Surg ; 72(5): 1760-1, 2001 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11722091

RESUMEN

Amiodarone-induced pulmonary toxicity is usually seen in cardiac surgical patients who have received large doses of amiodarone for ventricular arrhythmias over prolonged periods. In this report, we describe a case of amiodarone-induced pulmonary toxicity after a short course of therapy for postoperative atrial fibrillation.


Asunto(s)
Amiodarona/efectos adversos , Antiarrítmicos/efectos adversos , Enfermedades Pulmonares/inducido químicamente , Enfermedad Aguda , Anciano , Amiodarona/administración & dosificación , Antiarrítmicos/administración & dosificación , Humanos , Masculino
6.
Ann Thorac Surg ; 72(2): 548-53; discussion 553-4, 2001 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-11515896

RESUMEN

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors differ in their ability to inhibit tissue ACE. This study was, therefore, undertaken to determine whether high tissue affinity ACE inhibitors would improve endothelial function and thereby decrease tissue necrosis during ischemia. METHODS: In a porcine model, the second and third diagonal vessels were occluded for 90 minutes, followed by 45 minutes of cardioplegic arrest and 180 minutes of reperfusion. During the period of coronary occlusion, 10 pigs received enalaprilat (low affinity tissue ACE inhibitor), 0.05 mg/kg intravenously, 10 received quinaprilat (high affinity tissue ACE inhibitor), 10 mg intravenously, and 10 others received no ACE inhibitor. RESULTS: Wall motion scores (4, normal, to -1, dyskinesia) were higher in animals treated with ACE inhibitors (3.20+/-0.15 SE enalaprilat versus 3.08+/-0.23 quinaprilat versus 1.52+/-0.07 no ACE; both p < 0.0001 from no ACE). Endothelial-dependent relaxation to bradykinin was best preserved in the quinaprilat-treated hearts (32.1%+/-7.6% enalaprilat versus 65.8%+/-12.6% quinaprilat versus 30.6%+/-10.7% no ACE; p < 0.0001 from no ACE; p < 0.005 from enalaprilat). This was associated with a greater reduction in infarct size: area necrosis/area risk 24.3%+/-0.8% enalaprilat (p < 0.0001 from no ACE) versus 14.3%+/-3.2% quinaprilat (p < 0.0001 from no ACE; p < 0.005 from enalaprilat) versus 40.0%+/-1.7% no ACE. CONCLUSIONS: ACE inhibitors with higher affinity to tissue ACE result in better preservation of endothelial function and less tissue necrosis during coronary revascularization.


Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Enalaprilato/farmacología , Endotelio Vascular/efectos de los fármacos , Isoquinolinas/farmacología , Infarto del Miocardio/patología , Daño por Reperfusión Miocárdica/patología , Tetrahidroisoquinolinas , Animales , Infusiones Intravenosas , Contracción Miocárdica/efectos de los fármacos , Miocardio/patología , Necrosis , Porcinos
8.
Mech Dev ; 104(1-2): 89-98, 2001 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-11404083

RESUMEN

At weaning, milk producing mammary epithelial cells undergo apoptosis and are removed by phagocytosis. Here, we show that mouse mammary gland involution is associated with mitochondrial cytochrome c release and processing of numerous caspases, including caspase-1, -3, -7, -8 and -9. Induction of caspase-3-like activity paralleled cleavage of poly-(ADP--ribose) polymerase. Dexamethasone inhibited processing of caspase-3, -7 and -8 and apoptosis, but had no effect on caspase-1 accumulation and cytochrome c release. In Bcl-2 transgenic animals, cytochrome c release, caspase activation and apoptosis were impaired. Thus, the pro-apoptotic signaling pathway in mammary epithelial cells during involution involves the release of cytochrome c and activation of caspases. It is inhibited by Bcl-2 at the mitochondrial level and by dexamethasone at a post-mitochondrial level.


Asunto(s)
Caspasas/metabolismo , Grupo Citocromo c/metabolismo , Glándulas Mamarias Animales/fisiología , Destete , Animales , Apoptosis , Western Blotting , Caspasa 1/metabolismo , Caspasa 3 , Caspasa 7 , Caspasa 8 , Caspasa 9 , Dexametasona/farmacología , Activación Enzimática , Glucocorticoides/farmacología , Inmunohistoquímica , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Fagocitosis , Poli(ADP-Ribosa) Polimerasas/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Transducción de Señal , Espectrometría de Fluorescencia , Factores de Tiempo
9.
J Thorac Cardiovasc Surg ; 121(5): 943-50, 2001 May.
Artículo en Inglés | MEDLINE | ID: mdl-11326238

RESUMEN

OBJECTIVE: This study was undertaken to determine whether early discharge after coronary artery bypass grafting allows patients to return home earlier or merely increases the use of outpatient nursing and inpatient rehabilitation services. METHODS: Patterns of discharge were analyzed in 407 patients undergoing bypass grafting in 1990, when there were no early extubations or fast track protocols, and compared with 379 patients in 1998, when these protocols were used. RESULTS: Patients in 1998 had a higher prevalence of class IV angina (35.3% vs 22.8%; P =.006), urgent/emergency surgery (58.3% vs 44.9%; P =.015), and lower ejection fractions (48.9% +/- 16.4% vs 52.9% +/- 13.5%; P =.0002). Despite these increased risk factors, 1998 patients spent less time receiving ventilatory support (10.2 +/- 9.2 vs 26.7 +/- 15.7 hours; P <.001) and had a shorter length of stay (5.4 +/- 2.5 vs 9.2 +/- 4.3 days; P <.001). However, fewer 1998 patients were discharged home (56.7% vs 97.0%; P <.0001). A higher percentage of 1998 patients (43.3% vs 2.9%; P <.00001) were discharged to extended care facilities where their average length of stay was 10.6 +/- 15.1 days. Readmission to the Boston Medical Center was also more common in 1998 patients (5.3% vs 0.5%; P <.0001). CONCLUSIONS: Early extubation and fast track protocols have resulted in earlier discharge from acute care facilities. However, the anticipated earlier return to home has been offset by the increased use of outpatient nursing services, discharges to extended care facilities, and hospital readmissions.


Asunto(s)
Puente de Arteria Coronaria , Tiempo de Internación , Alta del Paciente/tendencias , Femenino , Servicios de Atención de Salud a Domicilio/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Cuidados Posoperatorios , Respiración Artificial , Factores de Riesgo , Instituciones de Cuidados Especializados de Enfermería/estadística & datos numéricos
11.
Adv Exp Med Biol ; 480: 195-201, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-10959427

RESUMEN

At weaning most of the alveolar epithelial cells in the mammary gland die by apoptosis and are removed by phagocytosis. Caspases are a family of aspartate specific cysteine proteases. Activation of caspases is generally thought to represent a major and irreversible event in the apoptotic process. We analyzed caspase expression and activation during mammary gland involution. A quantitative RT-PCR based approach revealed that levels of mRNA expression of several caspases are induced during involution. Using an antibody that specifically recognizes activated caspases we measured a transient induction of caspase activity in situ and found a maximal activation at days two and three of involution. These data were corroborated by monitoring caspase-3 like activity in mammary extracts with a synthetic DEVD-afc peptide as caspase-3 substrate. Using Fas-deficient mice we present evidence that the Fas signaling pathway is not essential for caspase activation and apoptosis during mammary gland involution. In summary, signaling pathways during involution seem to involve activation of caspases as intraepithelial triggers of mammary epithelial cell apoptosis.


Asunto(s)
Caspasas/fisiología , Glándulas Mamarias Animales/fisiología , Animales , Activación Enzimática/fisiología , Femenino , Lactancia/fisiología , Ratones
12.
Ann Thorac Surg ; 70(1): 145-50, 2000 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-10921699

RESUMEN

BACKGROUND: This study was undertaken to determine whether glucose-insulin-potassium (GIK) would improve myocardial performance and limit morbidity after coronary artery bypass grafting in diabetic patients. METHODS: Forty consecutive coronary artery bypass grafting patients with medically treated diabetes mellitus were prospectively randomly assigned to either a GIK group (n = 20; 500 mL D5W + 80 U regular insulin + 40 mEq KCl 30 mL/hour) or a no-GIK group (n = 20; D5W at 30 mL/hour). The GIK was begun at anesthetic induction and continued for 12 hours postoperatively. RESULTS: Patients treated with GIK had higher postoperative cardiac indices (2.88 +/- 0.50 versus 2.20 +/- 0.39 L/minute per square meter; p < 0.0001), lower inotrope scores (0.40 +/- 0.68 versus 1.25 +/- 1.44; p = 0.05), less weight gain (5.80 +/- 3.76 versus 13.85 +/- 6.52 pounds; p < 0.0001), and had shorter times of ventilator support (8.35 +/- 2.60 versus 13.45 +/- 7.33 hours; p = 0.0128). They had a significantly lower prevalence of atrial fibrillation (15% versus 60%; p = 0.003), and shorter hospital stays (6.70 +/- 1.52 versus 10.15 +/- 6.62 days; p = 0.02). CONCLUSIONS: Substrate enhancement with GIK in diabetic patients improved myocardial performance and resulted in faster recovery after coronary artery bypass grafting.


Asunto(s)
Soluciones Cardiopléjicas/administración & dosificación , Puente de Arteria Coronaria , Complicaciones de la Diabetes , Complicaciones Posoperatorias/prevención & control , Anciano , Femenino , Glucosa/administración & dosificación , Humanos , Insulina/administración & dosificación , Masculino , Complicaciones Posoperatorias/epidemiología , Potasio/administración & dosificación , Estudios Prospectivos , Resultado del Tratamiento
13.
Int J Cancer ; 85(4): 578-83, 2000 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-10699933

RESUMEN

The erbB-2/neu oncogene is frequently over-expressed in many different tumors in humans, including those of breast and ovary. The oncogene encodes a receptor tyrosine kinase closely related to the epidermal-growth-factor receptor. We studied effects on differentiation and cell death of erbB-2/neu during mammary-gland development in transgenic mice expressing an activated, oncogenic rat erbB-2/neu gene controlled by the mammary-gland-specific promoter from mouse-mammary-tumor virus (MMTV-LTR). Transgenic animals develop mammary cancer after repeated pregnancies and lactation. We present evidence that over-expression of erbB-2/neu in these mice is restricted to tumor cells. Tumor cells fail to differentiate and express milk proteins such as beta-casein and whey acidic protein (WAP) during lactation. Epithelial-cell apoptosis during normal involution is characterized by non-random DNA degradation into oligonucleosomal fragments. Tumor cells were mostly refractory to this developmentally controlled programmed cell death. Distinct areas within tumors, however, showed spontaneous cell death as measured by in situ TUNEL staining that co-localized with caspase-3-like activity. Our results indicate that the control of developmental cell death during involution is disturbed in erbB-2/neu-induced tumors although cell death and caspase activation can take place.


Asunto(s)
Apoptosis , Genes erbB-2 , Glándulas Mamarias Animales/citología , Neoplasias Mamarias Experimentales/genética , Receptor ErbB-2/genética , Animales , Cruzamientos Genéticos , Células Epiteliales/citología , Células Epiteliales/fisiología , Femenino , Humanos , Lactancia , Masculino , Glándulas Mamarias Animales/crecimiento & desarrollo , Glándulas Mamarias Animales/fisiología , Neoplasias Mamarias Experimentales/patología , Ratones , Ratones Transgénicos , Embarazo , Ratas
14.
J Card Surg ; 15(4): 229-38, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-11758057

RESUMEN

BACKGROUND: Methods to improve hemostasis in aortic surgery continue to evolve. Use of heparin-bonded cardiopulmonary bypass circuits (HBC) has been shown previously to effectively reduce bleeding and improve outcomes in coronary and valve operations. OBJECTIVE: To evaluate the impact of HBC on bleeding and transfusion requirements in proximal aortic surgery. METHODS: Data on 140 consecutive patients undergoing 144 operations of the proximal aorta were collected. Between July 1987 and July 1994, conventional cardiopulmonary bypass circuits (CONV) were used (n = 53). In July 1994, we switched to "tip-to-tip" HBC (n = 91). This study compared clinical outcomes and transfusion requirements between these two groups. RESULTS: Indications for surgery, baseline characteristics, and operative profile of the study groups were similar. Overall operative mortality and reoperation for bleeding were 9% and 13%, respectively. Compared with CONV, use of HBC was associated with decreased mortality (3% vs 18%, p = 0.004), reoperation for bleeding (7% vs 24%, p = 0.005), and hospital length of hospital stay (10 +/- 11 vs 20 +/- 30 days, p = 0.002). Although the incidence of allogeneic blood transfusion was similar (HBC 75% vs CONV 87%, p = 0.12), the magnitude of blood products utilization was much lower in the HBC group (total blood products per patient: 24 +/- 29 vs 49 +/- 47 donor units, p = 0.0002). In the multivariate analyses, use of HBC was identified as an independent predictor of reduced mortality, morbidity, and reduced magnitude of allogeneic blood transfusions. CONCLUSION: Use of HBC in proximal aortic surgery resulted in reduced bleeding and blood transfusion, improving clinical outcomes. Undoubtedly, multiple factors account for the overall improved results. However, use of HBC is an important component of an overall blood conservation strategy.


Asunto(s)
Aneurisma de la Aorta/cirugía , Disección Aórtica/cirugía , Pérdida de Sangre Quirúrgica/prevención & control , Transfusión Sanguínea , Implantación de Prótesis Vascular , Puente Cardiopulmonar/instrumentación , Heparina , Estudios de Casos y Controles , Femenino , Hemostasis Quirúrgica , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento
15.
Ann Thorac Surg ; 68(5): 1644-7, 1999 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-10585035

RESUMEN

BACKGROUND: This study was undertaken to determine the impact of the use and availability of coronary stents on outcomes in patients requiring emergent coronary artery bypass graft (CABG) surgery following a failed percutaneous transluminal coronary angioplasty (PTCA). METHODS: Patients were divided into two groups based on the year of their CABG for a failed PTCA and the availability of stents: group 1, 1992 to 1994, stents not available (n = 34); and group 2, 1995 to 1997, stents available (n = 26). RESULTS: CABG patients in the group where stents were not available were more likely to have had an abrupt coronary occlusion (26 of 34 versus 3 of 26; p < 0.0001) and less likely to have had a dissection (8 of 34 versus 23 of 26; p < 0.0001) as their indication for emergent CABG. Patients in the stent era had a lower incidence of perioperative myocardial infarction (5 of 26 versus 17 of 34; p < 0.01) and a decreased mortality rate (0 of 26 versus 6 of 34; p < 0.03). In the 9 patients where stents were employed, patency of the lumen was restored in 8 patients and there was only 1 myocardial infarction. CONCLUSIONS: Stents have had a favorable impact on patients requiring an emergent CABG following a failed PTCA.


Asunto(s)
Angioplastia Coronaria con Balón , Disección Aórtica/cirugía , Aneurisma Coronario/cirugía , Puente de Arteria Coronaria , Urgencias Médicas , Infarto del Miocardio/cirugía , Stents , Anciano , Disección Aórtica/mortalidad , Aneurisma Coronario/mortalidad , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/mortalidad , Evaluación de Procesos y Resultados en Atención de Salud , Complicaciones Posoperatorias/mortalidad , Estudios Retrospectivos , Tasa de Supervivencia , Insuficiencia del Tratamiento
16.
Ann Thorac Surg ; 68(5): 1849-50, 1999 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-10585075

RESUMEN

Early calcification of aortic allografts is usually seen in children less than 3 years of age. We describe a case of a 22-year-old intravenous drug user who developed calcific aortic valve stenosis less than 3 years after an allograft root replacement for endocarditis.


Asunto(s)
Insuficiencia de la Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/patología , Válvula Aórtica/trasplante , Calcinosis/patología , Endocarditis Bacteriana/cirugía , Complicaciones Posoperatorias/patología , Infecciones Estafilocócicas/cirugía , Adulto , Válvula Aórtica/patología , Humanos , Masculino , Reoperación , Trasplante Homólogo
17.
Circulation ; 100(13): 1438-42, 1999 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-10500046

RESUMEN

BACKGROUND: Activation of complement during revascularization of ischemic myocardium accentuates myocardial dysfunction. Soluble human complement receptor type 1 (sCR1) is a potent inhibitor of complement, as are heparin-bonded (HB) cardiopulmonary bypass (CPB) circuits. This study sought to determine whether total complement inhibition with the combination of sCR1 and HB-CPB limits damage during the revascularization of ischemic myocardium. METHODS AND RESULTS: In 40 pigs, the second and third diagonal coronary arteries were occluded for 90 minutes, followed by 45 minutes of cardioplegic arrest and 180 minutes of reperfusion. In 10 pigs, sCR1 (10 mg/kg) was infused 5 minutes after the onset of coronary occlusion (sCR1), 10 received HB-CPB only (HB-CPB), 10 received sCR1 and HB-CPB (sCR1+HB), and 10 received neither sCR1 or HB-CPB (unmodified). Addition of sCR1 to the HB group resulted in less myocardial tissue acidosis (DeltapH = -0.72+/-0.03 for unmodified; -0.46+/-0.05 for HB; -0.18+/-0.04 for sCR1; -0.13+/-0.01 for sCR1+HB), better recovery of wall motion scores (4 = normal to -1 = dyskinesia; 1.67+/-0.17 for unmodified; 2.80+/-0.08 for HB; 3.35+/-0.10 for sCR1; 3.59+/-0.08 for sCR1+HB), less lung water accumulation (5.46+/-0.28% for unmodified; 2.39+/-0.34% for HB; 1.22+/-0.07% for sCR1; 1.24+/-0.13% for sCR1+HB), and smaller infarct size (area necrosis/area risk = 44.6+/-0.7% for unmodified; 33.2+/-1.9% for HB; 19.0+/-2.4% for sCR1; 20+/-1.0% for sCR1+HB) (P<0.05 versus unmodified; P<0.05 versus unmodified and HB groups). CONCLUSIONS: Total complement inhibition with sCR1 and sCR1+HB circuits optimizes recovery during the revascularization of ischemic myocardium.


Asunto(s)
Anticoagulantes/farmacología , Puente Cardiopulmonar , Proteínas Inactivadoras de Complemento/farmacología , Heparina/farmacología , Isquemia Miocárdica/patología , Daño por Reperfusión Miocárdica/patología , Receptores de Complemento/fisiología , Animales , Agua Corporal/metabolismo , Proteínas del Sistema Complemento/análisis , Corazón/fisiopatología , Humanos , Concentración de Iones de Hidrógeno , Pulmón/metabolismo , Infarto del Miocardio/patología , Isquemia Miocárdica/sangre , Isquemia Miocárdica/fisiopatología , Daño por Reperfusión Miocárdica/sangre , Daño por Reperfusión Miocárdica/fisiopatología , Miocardio/metabolismo , Solubilidad , Porcinos
18.
J Mammary Gland Biol Neoplasia ; 4(2): 145-52, 1999 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-10426393

RESUMEN

Maintenance of mammary epithelial differentiation and milk production during lactation is a consequence of milk removal and the presence of lactogenic hormones, particularly glucocorticoids, insulin and prolactin. After weaning the fall in lactogenic hormones and milk stasis lead to involution, a process that is mainly characterized by three events: (i) downregulation of milk protein gene expression, (ii) loss of epithelial cells by apoptosis and, (iii) tissue remodeling and preparation of the gland for a new pregnancy. Each of these processes is likely to depend on the activity of specific sets of transcription factors in the mammary epithelium and stroma that ensure the timely and spatially coordinated expression of critical gene products such as mediators of apoptosis (e.g., caspase-1 and regulators of tissue remodeling events (e.g., matrix metalloproteinases). Here we describe signal transduction events such as activation of protein kinase A and JNK and changes in the activity of several transcription factors including Stat5, Stat3, NF1, Oct-1, and AP-1 during the early and late phases of mammary gland involution. We discuss their possible role in regulating and coordinating involution with emphasis on the apoptotic process of involution.


Asunto(s)
Regulación de la Expresión Génica , Lactancia/fisiología , Glándulas Mamarias Animales/fisiología , Leche/metabolismo , Factores de Transcripción/metabolismo , Animales , Apoptosis , Diferenciación Celular , Células Epiteliales/citología , Células Epiteliales/fisiología , Femenino , Glándulas Mamarias Animales/citología , Ratones , Embarazo
19.
Ann Thorac Surg ; 67(4): 1030-7, 1999 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-10320247

RESUMEN

BACKGROUND: This study evaluated the impact of recent advances (particularly noninvasive diagnosis, retrograde cerebral perfusion, heparin-bonded circuits, and use of collagen-impregnated grafts and antifibrinolytic agents) on clinical outcomes of patients undergoing proximal aortic operations. METHODS: One hundred eight consecutive patients undergoing 111 proximal aortic operations over 10 years were studied. The cohort was divided into two groups: early, 1987 to 1993 and late, 1994 to 1997. RESULTS: Baseline patients profiles, indications for operation (aneurysm, 66 patients; dissection, 45 patients), priority of the operation, and surgical procedures were comparable for both groups. Mortality and morbidity for the entire cohort were 13.5% (15 of 111) and 66% (73 of 111), respectively. Compared with the early group, the late group was characterized by significantly higher use of noninvasive diagnostic modalities (69% versus 10%), exclusive use of heparin-bonded circuits and collagen-impregnated grafts (100% versus 0% for both), use of antifibrinolytic agents (79% versus 8%), and the introduction of retrograde cerebral perfusion (43% versus 0%) (p<0.00001 for all). These changes in practice were associated with a substantial decrease in operative mortality (26% [13 of 49] versus 3% [2 of 62], p = 0.001), overall morbidity (77% [38 of 49] versus 56% [35 of 62], p = 0.02), blood transfusions (55.6+/-48 donor units versus 29.3+/-35 donor units, p = 0.003), and a shorter hospital stay (21.6+/-31 days versus 12.1+/-15 days, p = 0.07). Average long-term follow-up for 99% (107 of 108) of patients was 29.6+/-30 months (1 to 120 months). Ten-year actuarial survival was 57.3%+/-8% with 93% being in New York Heart Association functional class I or II. CONCLUSIONS: Recent advances, particularly noninvasive diagnosis and improved operative management, have led to a substantial reduction in mortality and morbidity after proximal aortic operation. Improved short- and long-term outcomes were achieved both in acute dissection and aneurysm procedures, although patients remain at risk for long-term distal aortic complications.


Asunto(s)
Aorta/cirugía , Aneurisma de la Aorta/cirugía , Disección Aórtica/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Disección Aórtica/diagnóstico , Antifibrinolíticos/administración & dosificación , Aneurisma de la Aorta/diagnóstico , Aortografía , Transfusión Sanguínea , Colágeno/administración & dosificación , Femenino , Heparina/administración & dosificación , Humanos , Tiempo de Internación , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
20.
Ann Thorac Surg ; 67(4): 1097-103, 1999 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-10320257

RESUMEN

BACKGROUND: Compared to men, women undergoing coronary artery bypass grafting appear to have a higher morbidity and mortality, particularly in the perioperative period. This study was designed to answer the questions of whether such differences in clinical outcomes between men and women still exist with improvements in surgical techniques and determine whether it is gender or associated comorbid conditions in women that lead to higher morbidity. METHODS: An analysis of a single center's contemporary experience (1994 to 1997) of 1,743 consecutive patients undergoing primary coronary artery bypass grafting was performed. Only reoperations were excluded. Data were collected prospectively and presented as mean +/- standard deviation (p<0.05). RESULTS: Women represented 30.0% of patients. Compared with men, women were older (68.4 versus 63.8 years; p<0.05), and had more urgent surgical interventions (70.0% versus 56.7%; p<0.05), a higher incidence of diabetes (42.1% versus 26.7%; p<0.05), hypertension (82.0% versus 73.9%; p<0.05), lower body surface area (1.73+/-0.18 m2 versus 2.03+/-0.19 m2; p<0.05), and hematocrit (31.7%+/-3.9% versus 36.2%+/-3.9%; p<0.05). Ejection fraction, incidence of previous myocardial infarction, chronic obstructive pulmonary disease, left main (LM) disease, renal insufficiency, extent of coronary disease, and preoperative intraaortic balloon pump were similar. Women received fewer arterial grafts (91.0% versus 95.5%; p<0.05) and distal anastomoses (3.31+/-0.88 versus 3.49+/-0.94 p<0.05). Despite these differences, there were no statistical differences in the incidence of postoperative death (1.5% versus 1.0%), myocardial infarction (0.6% versus 0.6%), or cerebrovascular accident/transient ischemic attack (1.1% versus 0.4%) between men and women. Women had a higher inotropic support (10.2% versus 4.4%; p<0.05) and longer hospital stays (7.3+/-5.7 days versus 6.3+/-4.2 days; p<0.05). Using multivariate analysis, female gender was not an independent predictor of death or postoperative complications but was a predictor of length of hospital stay, use of arterial grafts, and extent of coronary revascularization. CONCLUSIONS: After accounting for differences in their risk variables, the incidences of death, perioperative myocardial infarction and cerebrovascular accident/ transient ischemic attack after coronary artery bypass grafting in women and men were not statistically significant. Perioperative complications are related to comorbid risk factors but not to female gender itself. Further studies are warranted.


Asunto(s)
Puente de Arteria Coronaria , Tiempo de Internación , Factores de Edad , Anciano , Superficie Corporal , Cardiotónicos/uso terapéutico , Puente de Arteria Coronaria/mortalidad , Complicaciones de la Diabetes , Femenino , Hematócrito , Humanos , Hipertensión/complicaciones , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Estudios Prospectivos , Factores de Riesgo , Factores Sexuales , Resultado del Tratamiento
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