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1.
Chest ; 120(6): 1869-76, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11742915

RESUMO

STUDY OBJECTIVE: The impact of stable, chronic heart failure on baseline pulmonary function remains controversial. Confounding influences include previous coronary artery bypass or valve surgery (CABG), history of obesity, stability of disease, and smoking history. DESIGN: To control for some of the variables affecting pulmonary function in patients with chronic heart failure, we analyzed data in four patient groups, all with left ventricular (LV) dysfunction (LV ejection fraction [LVEF] < or =35%): (1) chronic heart failure, nonsmokers, no CABG (n = 78); (2) chronic heart failure, nonsmokers, CABG (n = 46); (3) chronic heart failure, smokers, no CABG (n = 40); and (4) chronic heart failure, smokers, CABG (n = 48). Comparisons were made with age- and gender-matched patients with a history of coronary disease but no LV dysfunction or smoking history (control subjects, n = 112) and to age-predicted norms. RESULTS: Relative to control subjects and percent-predicted values, all groups with chronic heart failure had reduced lung volumes (total lung capacity [TLC] and vital capacity [VC]) and expiratory flows (p < 0.05). CABG had no influence on lung volumes and expiratory flows in smokers, but resulted in a tendency toward a reduced TLC and VC in nonsmokers. Smokers with chronic heart failure had reduced expiratory flows compared to nonsmokers (p < 0.05), indicating an additive effect of smoking. Diffusion capacity of the lung for carbon monoxide (DLCO) was reduced in smokers and in subjects who underwent CABG, but not in patients with chronic heart failure alone. There was no relationship between LV size and pulmonary function in this population, although LV function (cardiac index and stroke volume) was weakly associated with lung volumes and DLCO. CONCLUSIONS: We conclude that patients with chronic heart failure have primarily restrictive lung changes with smoking causing a further reduction in expiratory flows.


Assuntos
Ponte de Artéria Coronária , Doença das Coronárias/fisiopatologia , Implante de Prótese de Valva Cardíaca , Medidas de Volume Pulmonar , Complicações Pós-Operatórias/fisiopatologia , Fumar/efeitos adversos , Disfunção Ventricular Esquerda/fisiopatologia , Idoso , Doença das Coronárias/diagnóstico , Feminino , Hemodinâmica/fisiologia , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Fatores de Risco , Fumar/fisiopatologia , Disfunção Ventricular Esquerda/diagnóstico , Função Ventricular/fisiologia
2.
J Heart Lung Transplant ; 20(7): 770-2, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11448808

RESUMO

Post-transplant lymphoproliferative disorder (PTLD) is a frequent and often fatal complication of organ transplantation. It most often results from an Epstein-Barr virus (EBV)-transformed B-cell clone, which expresses B-cell surface markers such as CD20. We describe a case of a heart transplant recipient who EBV seroconverted post-transplant and subsequently developed subcutaneous and lymphatic B-cell lymphoma, successfully treated with CD20 antibody (rituximab). The patient has been in remission during 10 months of clinical follow-up.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Infecções por Vírus Epstein-Barr/etiologia , Transplante de Coração/efeitos adversos , Transtornos Linfoproliferativos/tratamento farmacológico , Transtornos Linfoproliferativos/etiologia , Anticorpos Monoclonais Murinos , Antígenos CD20/análise , Biomarcadores Tumorais/análise , Criança , Infecções por Vírus Epstein-Barr/sangue , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Humanos , Terapia de Imunossupressão/efeitos adversos , Transtornos Linfoproliferativos/diagnóstico , Masculino , Rituximab
3.
J Heart Lung Transplant ; 20(3): 350-7, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11257562

RESUMO

BACKGROUND: The sequelae of severe brain injury include myocardial dysfunction. We sought to describe the prevalence and characteristics of myocardial dysfunction seen in the context of brain-injury-related brain death and to compare these abnormalities with myocardial pathologic changes. METHODS: We examined the clinical course, electrocardiograms, head computed tomography scans, and echocardiographic data of 66 consecutive patients with brain death who were evaluated as heart donors. In a sub-group of patients, we compared echocardiographic findings with pathologic findings. RESULTS: Echocardiographic systolic myocardial dysfunction was present in 28 (42%) of 66 patients and was not predicted by clinical, electrocardiographic, or head computed tomographic scan characteristics. Ventricular arrhythmias were more common in the patients with, compared to those without, myocardial dysfunction (32% vs 0%; p < 0.001). Myocardial dysfunction was segmental in all 8 patients with spontaneous subarachnoid or intracerebral hemorrhage. In these patients, the left ventricular apex was often spared. Myocardial dysfunction was either segmental or global in 17 patients who suffered head trauma and in 3 patients who died of other central nervous system illnesses. In 11 autopsied hearts, we found poor correlation between echocardiographic dysfunction and pathologic findings. CONCLUSIONS: Systolic myocardial dysfunction is common after brain-injury-related brain death. After spontaneous subarachnoid or intracerebral hemorrhage, the pattern of dysfunction is segmental, whereas after head trauma, it may be either segmental or global. We found poor correlation between the echocardiographic distribution of dysfunction and light microscopic pathologic findings.


Assuntos
Morte Encefálica/fisiopatologia , Lesões Encefálicas/fisiopatologia , Disfunção Ventricular/fisiopatologia , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Hemorragias Intracranianas/diagnóstico por imagem , Hemorragias Intracranianas/fisiopatologia , Masculino , Pessoa de Meia-Idade , Ultrassonografia , Disfunção Ventricular/diagnóstico por imagem
4.
ASAIO J ; 46(5): 569-72, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11016508

RESUMO

Giant cell myocarditis is a highly lethal disorder characterized by rapidly progressive congestive heart failure. The aim of this study was to describe the clinical course of patients with giant cell myocarditis who received a ventricular assist device. Patients with giant cell myocarditis were identified from the Multicenter Giant cell Myocarditis Registry. Bridging to cardiac transplantation in the giant cell myocarditis patients who received a ventricular assist device was compared with bridging in the general population of heart failure patients, as reported in the literature. Median posttransplantation survival for patients with giant cell myocarditis who received and did not receive ventricular assist devices was calculated by the Kaplan-Meier method and compared with use of the log-rank test. Nine patients with giant cell myocarditis who received ventricular assist devices were identified. Seven patients survived to transplantation, four were alive 30 days posttransplantation, and two survived to 1 year. The rate of successful bridging to transplantation in seven of nine patients (78%) is similar to that reported for other ventricular assist device recipients. Posttransplantation survival of 57% (4 of 7) at 30 days and 29% (2 of 7) at 1 year was significantly lower compared with 93% 1-year survival of the 30 patients with giant cell myocarditis who did not receive ventricular assist devices before transplantation (p<0.001). Ventricular assist devices can be an effective bridge to transplantation for patients with heart failure caused by giant cell myocarditis. Although their posttransplantation survival was poor in our series, a few patients had long-term survival.


Assuntos
Insuficiência Cardíaca/cirurgia , Coração Auxiliar , Miocardite/cirurgia , Adolescente , Adulto , Feminino , Insuficiência Cardíaca/mortalidade , Transplante de Coração , Humanos , Masculino , Pessoa de Meia-Idade , Miocardite/mortalidade
5.
Transpl Int ; 13(2): 162-5, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10836655

RESUMO

Radiation-induced heart disease is an increasingly recognized late sequela of mediastinal radiation therapy for malignant neoplasms. We report four cases of heart transplantation for end-stage heart failure induced by mediastinal radiation therapy. Short-term and intermediate-term results are excellent with all four patients currently surviving a mean of 48 months after transplantation. Neither a second malignancy nor recurrence of the primary malignancy has been observed to date. The early results of heart transplantation for end-stage, radiation-induced heart disease are encouraging.


Assuntos
Baixo Débito Cardíaco/etiologia , Baixo Débito Cardíaco/cirurgia , Transplante de Coração , Neoplasias Hematológicas/radioterapia , Radioterapia/efeitos adversos , Adulto , Criança , Neoplasias Hematológicas/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Transplante Homólogo
6.
J Heart Lung Transplant ; 19(4): 330-6, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10775812

RESUMO

BACKGROUND: We determined the type, symptoms, and risk factors for sleep apnea in heart transplant recipients and the response to nasal continuous positive airway pressure. METHODS: A retrospective study on heart transplant recipients with sleep apnea was conducted in a tertiary care medical center with follow-up telephone interviews. Between February 1988 and August 1998, 147 patients underwent orthotopic heart transplantation at our institution. Seventeen patients (11.6%) who were suspected of having sleep apnea underwent polysomnography at a mean interval of 17.5 months after transplantation. RESULTS: All were diagnosed with sleep apnea: 13 had obstructive sleep apnea and 4 had mixed sleep apnea. Mean age at polysomnography was 50.8 years (range, 24-67 years). The patients presented with snoring (100%), excessive daytime somnolence (65%), witnessed apneas (53%), and morning fatigue (53%). Sixteen (94%) had a mean weight gain of 10.4 kg after transplantation, and 1 patient lost 14.6 kg. In the 11 patients with obstructive sleep apnea who underwent nasal continuous positive airway pressure titration, significant improvements occurred in the apnea-hypopnea index (decreased from 37.6 to 10.4; p = 0.01) and mean arousal index (decreased from 44.5 to 19.4; p = 0.01). Only 2 of the 8 patients with sleep apnea for whom nasal continuous positive airway pressure was recommended continued to use it at the time of telephone follow-up. CONCLUSIONS: Sleep apnea, especially obstructive sleep apnea, occurs frequently in heart transplant recipients. Obstructive sleep apnea appears to present in the typical manner, and although a positive response to nasal continuous positive airway pressure can be documented by polysomnography, long-term use of nasal continuous positive airway pressure may be low.


Assuntos
Transplante de Coração/estatística & dados numéricos , Respiração com Pressão Positiva/métodos , Síndromes da Apneia do Sono/epidemiologia , Síndromes da Apneia do Sono/terapia , Adulto , Distribuição por Idade , Idoso , Feminino , Seguimentos , Humanos , Masculino , Máscaras , Pessoa de Meia-Idade , Polissonografia , Prevalência , Probabilidade , Estudos Retrospectivos , Fatores de Risco , Distribuição por Sexo , Síndromes da Apneia do Sono/diagnóstico , Estatísticas não Paramétricas , Inquéritos e Questionários , Taxa de Sobrevida , Resultado do Tratamento
7.
Nucl Med Commun ; 21(1): 55-63, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10717903

RESUMO

Left ventricular function is modified by respiration and pericardial constraint. The aim of this study was to compare left ventricular systolic and diastolic function during inspiration and expiration in four patient groups: patients (1) without cardiac disease, (2) with severe pulmonary disease, (3) with cardiac amyloid and (4) with pericardial constriction (before and after pericardiectomy). Using blood-pool left ventriculography with modified gating, we obtained time-activity curves at the onset of inspiration and expiration. On inspiration and expiration, patients with pericardial constriction and patients with cardiac amyloid were significantly different from those without cardiac disease and those with severe pulmonary disease, in that left ventricular ejection fraction (LVEF) was less, peak filling rate was greater, time to peak filling rate was shorter, and rapid filling fraction was increased. When inspiration and expiration were compared, time to left ventricular peak filling rate was shorter (P = 0.05) on inspiration (118 +/- 48 ms) than on expiration (168 +/- 35 ms) in patients with pericardial constriction. No other measures differed between inspiration and expiration in pericardial constriction, and left ventricular function was unaffected by respiration in the other groups. Time to left ventricular peak filling rate was 49 +/- 69 ms less on inspiration than on expiration in pericardial constriction and this difference was significantly different (P = 0.04) from that in patients with cardiac amyloid (34 +/- 58 ms greater), patients without cardiac disease (2 +/- 69 ms greater) and patients with severe pulmonary disease (19 +/- 63 ms less). In pericardial constriction, pericardial resection caused an increase in LVEF without a change in left ventricular diastolic filling but abolished the differences present between inspiration and expiration in time to left ventricular peak filling rate. This respiratory response in time to left ventricular peak filling rate may be valuable in the diagnosis of pericardial constriction.


Assuntos
Coração/diagnóstico por imagem , Mecânica Respiratória/fisiologia , Função Ventricular Esquerda/fisiologia , Idoso , Amiloidose/diagnóstico por imagem , Amiloidose/fisiopatologia , Feminino , Cardiopatias/diagnóstico por imagem , Cardiopatias/fisiopatologia , Ventrículos do Coração/diagnóstico por imagem , Humanos , Pneumopatias/diagnóstico por imagem , Pneumopatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pericárdio/fisiologia , Ventriculografia com Radionuclídeos , Volume Sistólico/fisiologia
8.
Chest ; 117(2): 321-32, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10669670

RESUMO

We examined the degree of ventilatory constraint in patients with a history of chronic heart failure (CHF; n = 11; mean +/- SE age, 62 +/- 4 years; cardiac index [CI], 2.0 +/- 0.1; and ejection fraction [EF], 24 +/- 2%) and in control subjects (CTLS; n = 8; age, 61 +/- 5 years; CI, 2.6 +/- 0.3) by plotting the tidal flow-volume responses to graded exercise in relationship to the maximal flow-volume envelope (MFVL). Inspiratory capacity (IC) maneuvers were performed to follow changes in end-expiratory lung volume (EELV) during exercise, and the degree of expiratory flow limitation was assessed as the percent of the tidal volume (VT) that met or exceeded the expiratory boundary of the MFVL. CHF patients had significantly (p < 0.05) reduced baseline pulmonary function (FVC, 76 +/- 4%; FEV(1), 78 +/- 4% predicted) relative to CTLS (FVC, 99 +/- 4%; FEV(1), 102 +/- 4% predicted). At peak exercise, oxygen consumption (VO(2)) and minute ventilation (V(E)) were lower in CHF patients than in CTLS (VO(2), 17 +/- 2 vs 32 +/- 2 mL/kg/min; VE, 56 +/- 4 vs 82 +/- 6 L/min, respectively), whereas VE/carbon dioxide output was higher (42 +/- 4 vs 29 +/- 5). In CTLS, EELV initially decreased with light exercise, but increased as VE and expiratory flow limitation increased. In contrast, the EELV in patients with CHF remained near residual volume (RV) throughout exercise, despite increasing flow limitation. At peak exercise, IC averaged 91 +/- 3% and 79 +/- 4% (p < 0.05) of the FVC in CHF patients and CTLS, respectively, and flow limitation was present over > 45% of the VT in CHF patients vs < 25% in CTLS (despite the higher VE in CTLS). The least fit and most symptomatic CHF patients demonstrated the lowest EELV, the greatest degree of flow limitation, and a limited response to increased inspired carbon dioxide during exercise, all consistent with VE constraint. We conclude that patients with CHF commonly breathe near RV during exertion and experience expiratory flow limitation. This results in VE constraint and may contribute to exertional intolerance.


Assuntos
Teste de Esforço , Insuficiência Cardíaca/diagnóstico , Medidas de Volume Pulmonar , Adulto , Idoso , Dióxido de Carbono/sangue , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Volume Residual/fisiologia , Volume Sistólico/fisiologia , Relação Ventilação-Perfusão/fisiologia , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/fisiopatologia , Trabalho Respiratório/fisiologia
9.
Mayo Clin Proc ; 74(12): 1221-6, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10593350

RESUMO

Giant cell myocarditis (GCM) is a rare and frequently fatal disorder with no proven treatment. Case reports and data from a rat model of GCM suggest that immunosuppressive therapy directed against T lymphocytes may have clinical benefit. We describe a 47-year-old man with severe acute heart failure due to GCM in whom the left ventricular ejection fraction normalized and the myocardial inflammatory infiltrate resolved rapidly after treatment with muromonab-CD3, cyclosporine, azathioprine, and corticosteroids. Three previously published cases with less impressive responses to treatment including muromonab-CD3 and a critical review of the published data on immunosuppressive therapy are included in this report. The response to immunosuppressive therapy is highly variable, and direct comparisons between immunosuppressive regimens do not exist. Therefore, despite individual reports of dramatic improvement after immunosuppressive treatment, firm conclusions cannot be made about the benefit of immunosuppression for GCM. The benefits of immunosuppressive therapy must be confirmed in a prospective, randomized trial.


Assuntos
Células Gigantes/patologia , Imunossupressores/uso terapêutico , Miocardite/tratamento farmacológico , Miocardite/imunologia , Adulto , Anti-Inflamatórios/uso terapêutico , Azatioprina/uso terapêutico , Ciclosporina/uso terapêutico , Quimioterapia Combinada , Feminino , Glucocorticoides/uso terapêutico , Humanos , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Muromonab-CD3/uso terapêutico , Miocardite/patologia , Miocardite/fisiopatologia , Prednisona/uso terapêutico , Modelos de Riscos Proporcionais , Volume Sistólico , Resultado do Tratamento
10.
J Biol Chem ; 274(52): 36905-11, 1999 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-10601243

RESUMO

Mannose 6-phosphate receptors (MPRs) deliver soluble acid hydrolases to the lysosome in higher eukaryotic cells. The two MPRs, the cation-dependent MPR (CD-MPR) and the insulin-like growth factor II/cation-independent MPR, carry out this process by binding with high affinity to mannose 6-phosphate residues found on the N-linked oligosaccharides of their ligands. To elucidate the key amino acids involved in conveying this carbohydrate specificity, site-directed mutagenesis studies were conducted on the extracytoplasmic domain of the bovine CD-MPR. Single amino acid substitutions of the residues that form the binding pocket were generated, and the mutant constructs were expressed in transiently transfected COS-1 cells. Following metabolic labeling, mutant CD-MPRs were tested for their ability to bind pentamannosyl phosphate-containing affinity columns. Of the eight amino acids mutated, four (Gln-66, Arg-111, Glu-133, and Tyr-143) were found to be essential for ligand binding. In addition, mutation of the single histidine residue, His-105, within the binding site diminished the binding of the receptor to ligand, but did not eliminate the ability of the CD-MPR to release ligand under acidic conditions.


Assuntos
Receptor IGF Tipo 2/química , Sequência de Aminoácidos , Animais , Sítios de Ligação , Células COS , Bovinos , Concentração de Íons de Hidrogênio , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Relação Estrutura-Atividade
11.
J Am Soc Echocardiogr ; 12(10): 859-63, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10511656

RESUMO

Noncompaction of the ventricular myocardium is a rare congenital cardiomyopathy resulting from an arrest in normal endomyocardial embryogenesis. The characteristic echocardiographic findings consist of multiple, prominent myocardial trabeculations and deep intertrabecular recesses communicating with the left ventricular cavity. The disease uniformly affects the left ventricle, with or without concomitant right ventricular involvement, and results in systolic and diastolic ventricular dysfunction and clinical heart failure. Noncompaction was initially described in children. However, recent studies have characterized this disease in the adult population, in whom this process may be more prevalent than currently appreciated. We describe an illustrative case of isolated noncompaction of the ventricular myocardium in a 57-year-old woman with the typical clinical and echocardiographic features of the disease. The literature on the topic is reviewed.


Assuntos
Cardiopatias Congênitas/diagnóstico por imagem , Diagnóstico Diferencial , Ecocardiografia Doppler em Cores , Ecocardiografia Transesofagiana , Feminino , Coração/embriologia , Cardiopatias Congênitas/embriologia , Cardiopatias Congênitas/patologia , Ventrículos do Coração/patologia , Humanos , Pessoa de Meia-Idade , Miocárdio/patologia
12.
J Biol Chem ; 274(42): 29889-96, 1999 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-10514470

RESUMO

Mannose 6-phosphate receptors (MPRs) play an important role in the targeting of newly synthesized soluble acid hydrolases to the lysosome in higher eukaryotic cells. These acid hydrolases carry mannose 6-phosphate recognition markers on their N-linked oligosaccharides that are recognized by two distinct MPRs: the cation-dependent mannose 6-phosphate receptor and the insulin-like growth factor II/cation-independent mannose 6-phosphate receptor. Although much has been learned about the MPRs, it is unclear how these receptors interact with the highly diverse population of lysosomal enzymes. It is known that the terminal mannose 6-phosphate is essential for receptor binding. However, the results from several studies using synthetic oligosaccharides indicate that the binding site encompasses at least two sugars of the oligosaccharide. We now report the structure of the soluble extracytoplasmic domain of a glycosylation-deficient form of the bovine cation-dependent mannose 6-phosphate receptor complexed to pentamannosyl phosphate. This construct consists of the amino-terminal 154 amino acids (excluding the signal sequence) with glutamine substituted for asparagine at positions 31, 57, 68, and 87. The binding site of the receptor encompasses the phosphate group plus three of the five mannose rings of pentamannosyl phosphate. Receptor specificity for mannose arises from protein contacts with the 2-hydroxyl on the terminal mannose ring adjacent to the phosphate group. Glycosidic linkage preference originates from the minimization of unfavorable interactions between the ligand and receptor.


Assuntos
Manose/química , Oligossacarídeos/metabolismo , Receptor IGF Tipo 2/metabolismo , Animais , Sítios de Ligação , Cátions , Bovinos , Ligantes , Modelos Moleculares , Dados de Sequência Molecular , Oligossacarídeos/química , Fosforilação , Conformação Proteica
13.
Int J Cardiol ; 72(1): 27-37, 1999 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-10636630

RESUMO

We hypothesized that, within the normal range of resting heart rate, heart rate and left ventricular ejection fraction would be inversely correlated and heart rate and left ventricular filling would be correlated in patients with dilated cardiomyopathy and not correlated in patients with normal cardiac function. At rest, heart rate, left ventricular ejection fraction, and three measures of diastolic filling (time to peak filling rate, peak filling rate, and first half filling fraction) were recorded using radionuclide ventriculography in subjects with no cardiac disease, patients with idiopathic dilated cardiomyopathy, and patients with dilated cardiomyopathy associated with ischemic heart disease. Heart rate had significant inverse correlations with left ventricular ejection fraction (r=-0.55, P=0.0007) and time to peak filling rate (r=-0.47, P=0.005) and a positive correlation with peak filling rate (r=0.73, P<0.0001) in patients with idiopathic dilated cardiomyopathy; heart rate was correlated only weakly with these measures in the absence of cardiac disease and essentially was not correlated in dilated cardiomyopathy due to ischemic heart disease. The change in resting heart rate with left ventricular ejection fraction and time to peak filling rate were significantly (P<0.05) different between patients with no cardiac disease and those with idiopathic dilated cardiomyopathy. Thus, resting heart rate correlated significantly with left ventricular ejection fraction and diastolic filling in patients with idiopathic dilated cardiomyopathy.


Assuntos
Cardiomiopatia Dilatada/fisiopatologia , Frequência Cardíaca , Volume Sistólico , Adulto , Fatores Etários , Idoso , Ecocardiografia Doppler , Feminino , Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Ventriculografia com Radionuclídeos , Fatores Sexuais
15.
Mol Pharmacol ; 54(5): 761-9, 1998 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9804611

RESUMO

An aspartate-to-alanine point mutation in the catalytic domain (D853A) of guanylyl cyclase-C (GC-C), the heat-stable enterotoxin (STa) receptor, rendered the enzyme catalytically inactive. Mn2+/Triton X-100-stimulated guanylyl cyclase activity was detected in membranes from COS7 cells overexpressing GC-C but not GC-CD853A. STa treatment of paired cells resulted in cGMP production in those transiently expressing GC-C but not GC-CD853A. GC-C and GC-CD853A showed similar Bmax and Kd values for [125I]STa binding in these cells, indicating that the lack of catalytic activity in the latter was not due to differing expression levels or reduced binding affinity. The involvement of the catalytic domain in aldosteronogenesis was studied in human adrenocortical H295R cells. COS7 and H295R cells infected with vaccinia virus-expressing GC-C and GC-CD853A (VVGC-CD853A) had [125I]STa-binding characteristics akin to those in transfected cells. Immunoblot confirmed that both GC-C and GC-CD853A formed similar higher order oligomers in infected cells. Virus-mediated expression of GC-C in H295R cells revealed concentration-dependent STa-stimulated cGMP formation that was undetectable in VVGC-CD853A-infected cells. STa decreased angiotensin II-stimulated human aldosterone generation in a concentration-dependent manner in vaccinia virus-expressing GC-C-infected cells but not in those infected with VVGC-CD853A. These results demonstrate that a catalytically active guanylyl cyclase is required for the inhibition of aldosteronogenesis.


Assuntos
Aldosterona/biossíntese , Guanilato Ciclase/fisiologia , Receptores de Peptídeos/fisiologia , Angiotensina II/farmacologia , Animais , Toxinas Bacterianas/metabolismo , Toxinas Bacterianas/farmacologia , Sítios de Ligação , Células COS/metabolismo , Células COS/virologia , Células Cultivadas , GMP Cíclico/biossíntese , Enterotoxinas/metabolismo , Enterotoxinas/farmacologia , Proteínas de Escherichia coli , Guanilato Ciclase/genética , Guanilato Ciclase/metabolismo , Humanos , Immunoblotting , Radioisótopos do Iodo , Cinética , Mutação Puntual , Receptores de Enterotoxina , Receptores Acoplados a Guanilato Ciclase , Receptores de Peptídeos/genética , Receptores de Peptídeos/metabolismo , Sensibilidade e Especificidade , Estimulação Química , Transfecção , Vaccinia virus/genética , Vaccinia virus/metabolismo
16.
J Heart Lung Transplant ; 17(7): 732-6, 1998 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9703241

RESUMO

BACKGROUND: Kaposi's sarcoma is an endothelial tumor rarely diagnosed after heart transplantation. We report on a patient originally from Africa in whom Kaposi's sarcoma developed in association with Kaposi's sarcoma-associated herpesvirus. METHODS: A man from Ghana had constitutional symptoms associated with multiple pulmonary nodules that developed 3 months after heart transplantation. Kaposi's sarcoma was diagnosed by thorascopic biopsy. Treatment consisted of reducing immunosuppression therapy and adding famciclovir treatment. Symptoms resolved within 1 month after treatment, and no disease progression was observed for 5 months. The patient died suddenly 8 months after heart transplantation; autopsy revealed occlusion of the left anterior descending coronary artery and grade 3A rejection. Extensive Kaposi's sarcoma was observed in the lungs and gastrointestinal tract at autopsy. RESULTS: Pathologic analysis of the tumor demonstrated features consistent with Kaposi's sarcoma. Polymerase chain reaction and in situ hybridization demonstrated the presence of Kaposi's sarcoma-associated herpesvirus. CONCLUSION: Kaposi's sarcoma rarely is diagnosed after transplantation. Patients infected with Kaposi's sarcoma-associated herpesvirus may be at increased risk. Screening for Kaposi's sarcoma-associated herpesvirus may be indicated in patients at risk. The role of antiviral medications and immunization in the treatment and prevention of the disorder is unknown.


Assuntos
Transplante de Coração , Herpesvirus Humano 8/isolamento & purificação , Neoplasias Pulmonares/virologia , Complicações Pós-Operatórias/virologia , Sarcoma de Kaposi/virologia , 2-Aminopurina/análogos & derivados , 2-Aminopurina/uso terapêutico , Antivirais/uso terapêutico , Famciclovir , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Fatores de Risco
17.
Am J Cardiol ; 80(11): 1491-2, 1997 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-9399732
18.
Am J Med Sci ; 314(3): 139-52, 1997 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9298040

RESUMO

Cardiac transplantation is a proven, effective therapy for selected patients with end-stage congestive heart failure. Recipient selection is performed by a multidisciplinary team consisting of transplant physicians and surgeons. Clinicians responsible for patient assessment must establish the severity of cardiac dysfunction, formulate a prognosis, and stratify patients according to risk for mortality. Patients whose survival and quality of life are most limited without cardiac transplantation are candidates for therapy. The scarcity of organ donors makes careful screening of potential recipients necessary to identify those individuals most likely to obtain a long-term benefit. Recipient selection criteria and management strategies are evolving because of extended waiting times and high mortality caused by the lack of sufficient numbers of donors. Alternative therapies should be applied wherever possible.


Assuntos
Administração de Caso , Insuficiência Cardíaca/cirurgia , Transplante de Coração , Seleção de Pacientes , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Arritmias Cardíacas/mortalidade , Arritmias Cardíacas/prevenção & controle , Causas de Morte , Doenças Transmissíveis/etiologia , Enalapril/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/etiologia , Transplante de Coração/efeitos adversos , Coração Auxiliar , Hemodinâmica , Humanos , Hipertensão Pulmonar/cirurgia , Expectativa de Vida , Prognóstico , Fatores de Risco , Listas de Espera
19.
Transplantation ; 63(11): 1607-10, 1997 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-9197354

RESUMO

BACKGROUND: The current success of cardiac transplantation is in part attributable to the development of effective immunosuppressive agents such as cyclosporine. However, concern remains regarding the potential for cyclosporine-induced nephrotoxicity. Animal studies and early reports of renal protective effects of pentoxifylline in bone marrow transplant recipients prompted a randomized trial in cardiac transplant recipients. METHODS: Twenty-nine patients were randomized to receive pentoxifylline 400 mg p.o. t.i.d. or matching placebo for 1 year after cardiac transplantation. Renal function was assessed preoperatively and at 1, 6, and 12 months postoperatively. Glomerular filtration rate and renal plasma flow were measured with iothalamate and para-aminohippurate, respectively. Serum creatinine was also measured. Ambulatory blood pressure monitoring after withdrawal of antihypertensives for 3 days was performed 12 months postoperatively. RESULTS: Twenty-seven patients completed the study. Glomerular filtration rate rose between 1 and 6 months after transplantation, presumably due to the reduction in goal cyclosporine level in that period, and then fell modestly between 6 and 12 months, presumably due to ongoing nephrotoxic effects of cyclosporine. No difference in glomerular filtration rate or creatinine was seen between pentoxifylline and placebo groups at any interval. Renal plasma flow increased modestly between baseline and 6 months in the pentoxifylline group, but not in the placebo group, and then fell between 6 and 12 months. Serum creatinine increased between baseline and 6 months in both groups, apparently due to increased body weight. Results of 18-hr ambulatory blood pressure monitoring obtained 1 year after transplantation was not different between groups. CONCLUSIONS: Renal function declines only modestly in the first year after cardiac transplantation. Pentoxifylline did not attenuate this process and had no effect on blood pressure. The modest decline in renal function may be related to current immunosuppressive strategies.


Assuntos
Pressão Sanguínea , Transplante de Coração , Rim/fisiologia , Pentoxifilina/farmacologia , Vasodilatadores/farmacologia , Adulto , Idoso , Monitorização Ambulatorial da Pressão Arterial , Peso Corporal/fisiologia , Ciclosporina/administração & dosagem , Ciclosporina/efeitos adversos , Ciclosporina/farmacologia , Método Duplo-Cego , Sinergismo Farmacológico , Transplante de Coração/fisiologia , Humanos , Hipertensão/induzido quimicamente , Imunossupressores/efeitos adversos , Imunossupressores/farmacologia , Nefropatias/induzido quimicamente , Pessoa de Meia-Idade , Aumento de Peso/fisiologia
20.
J Heart Lung Transplant ; 16(5): 573-5, 1997 May.
Artigo em Inglês | MEDLINE | ID: mdl-9171279

RESUMO

A 47-year-old man with cirrhotic liver disease complicated by encephalopathy and class IV congestive heart failure caused by genetic hemochromatosis underwent combined orthotopic heart and liver transplantation. The patient remains well, working full time, 4 years after operation. Combined heart and liver transplantation is an effective therapy for selected patients with concurrent heart and liver failure caused by systemic iron overload.


Assuntos
Insuficiência Cardíaca/cirurgia , Transplante de Coração/métodos , Hemocromatose/complicações , Hemocromatose/genética , Cirrose Hepática/cirurgia , Transplante de Fígado/métodos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/etiologia , Encefalopatia Hepática/etiologia , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/etiologia , Masculino , Pessoa de Meia-Idade
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