RESUMO
CONTEXT: Resistance to thyroid hormone (RTH) is an inherited syndrome of reduced tissue responsiveness to thyroid hormone, which is usually due to mutations in the thyroid hormone receptor ß gene (THRB). Few studies have been conducted to investigate bone and mineral metabolism in RTH. OBJECTIVE: The objective of the study was to evaluate the clinical and biochemical parameters related to bone and mineral metabolism in RTH due to mutations in the THRB gene (RTHß). DESIGN AND PARTICIPANTS: We conducted a cross-sectional study on 14 patients with RTHß (RTHG), eight adults and six children, and 24 control subjects (CG). OUTCOMES: Serum measures included total calcium (TCa), inorganic phosphate (iP), alkaline phosphatase (AP), parathyroid hormone (PTH), 25-hydroxyvitamin D (25OHD), osteocalcin (OC), carboxyterminal telopeptide (CTX), and fibroblast growth factor 23 (FGF-23). We estimated the renal threshold phosphate concentration (TmPO4/GFR) and assessed bone mass using dual X-ray absorptiometry. RESULTS: Adults and children with RTH showed higher serum levels of TCa than controls (P=.029 and, P=.018 respectively). However, only children with RTH exhibited lower serum levels of iP than controls (P=.048). FGF-23 was higher in RTHß children (P=.04). RTHß adults had lower whole-body (P=.01) and lumbar spine (P=.01) bone mineral density than control subjects. The same pattern was observed when the results were expressed as Z-scores between groups, with a lower value in RTHG than in CG for the lumbar spine of adults (P=.03). No difference was observed between groups in PTH, 25OHD, AP, OC, and CTX. CONCLUSION: Biochemical abnormalities are seen in children with RTH (Low iP, high FGF23), while high calcium (with normal UCa) is seen in RTH subjects of all ages, and later on, in adult life, low BMD is seen. Considering that the TRα1 isoform is the predominant TR in the skeleton, we hypothesize that probably these patients may exhibit enhanced calcium flux from bone to circulation. Our data represent a challenge for new studies to unveil the control of calcium and phosphorus homeostasis and fracture risk in these patients.
Assuntos
Cálcio/sangue , Genes erbA , Fósforo/sangue , Receptores beta dos Hormônios Tireóideos/genética , Síndrome da Resistência aos Hormônios Tireóideos/genética , Hormônios Tireóideos/metabolismo , Adolescente , Adulto , Idoso , Densidade Óssea/fisiologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Adulto JovemRESUMO
OBJECTIVE: To compare inverted-L mini-sternotomy performed above the sternal furcula with conventional sternotomy in patients with aortic valve diseases who undergo surgical treatment. METHODS: We operated upon 30 patients who had aortic valve lesions that had clinical and hemodynamic findings. All patients underwent inverted-L sternotomy, which extended from above the manubrium of the sternum to the 3rd right intercostal space, without opening the pleural cavity. Their ages ranged from 32 to 76 years, and 18 were males and 12 were females. We used negative pressure in a venous 1/4-inch cannula, and the patients were maintained in Trendelemburg's position. Twenty-seven patients received bioprostheses with diameters ranging from 23 to 29mm. Three patients underwent only removal of the calcifications of the aortic valve leaflets and aortic commissurotomy. RESULTS: The mean duration of anoxic cardiac arrest was 63.11min. Access was considered good in all patients. One death was due to pulmonary and renal problems not related to the incision. All patients had a better recovery in the intensive care unit, got out of bed sooner, coughed more easily, and performed prophylactic physiotherapeutic maneuvers for respiratory problems more easily and with less pain in the incision. Early ambulation was more easily carried out by all patients. CONCLUSION: Mini-sternotomy proved to be better than the conventional sternotomy because it provided more comfort for the patients in the early postoperative period, with less pain and greater desire for early ambulation and all its inherent advantages.
Assuntos
Valva Aórtica/cirurgia , Doenças das Valvas Cardíacas/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Esterno/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND: There is controversy regarding the role of reparative techniques for rheumatic-mitral valve disease. We have analyzed the late results of mitral valve repair in a group of patients with rheumatic mitral valve insufficiency. METHODS: From March 1980 to December 1997, 201 patients with rheumatic fever underwent mitral valve repair at the Heart Institute, Hospital das Clínicas, Medical School, University of São Paulo. The mean age of patients was 26.9 +/- 15.4 years, with 59.7% of the patients being female. Other diagnoses were present in 67.7% of patients; the most common was tricuspid regurgitation (31.3%). Mitral valve repair techniques included: 1) Carpentier ring annuloplasty in 75 patients (37.3%); 2) posterior annuloplasty with bovine patch in 68 patients (33.8%); 3) posterior segmental annuloplasty in 16 patients (7.9%); 4) quadrangular resection of the posterior leaflet with ring plication in 11 patients (5.5%); 5) partial resection of the anterior leaflet in 6 patients (3%); 6) De Vega's annuloplasty in 6 patients (3%); 7) Kay's annuloplasty in 5 patients (2.5%); 8) Reed's annuloplasty in 4 patients (2%); and 9) miscellaneous techniques in 10 patients (4.9%). Combined techniques were used in 94 patients (46.8%), the most frequent of which was chordal shortening (48 patients, 23.9%). Other non-mitral cardiac procedures were performed in 113 patients (56.2%). Actuarial survival and event-free curves (Kaplan-Meier method) were compared by linear regression analysis. RESULTS: The in-hospital mortality rate was 2.0% (four patients). The causes of death were multiorgan failure in two patients and low cardiac output in the other two patients. In the late postoperative period, 83.9% of the patients were in New York Heart Association (NYHA) functional class 1. The actuarial survival was 93.9% +/- 1.9% at a mean of 125 months. Twenty-three patients were reoperated in the postoperative period at a mean interval of 35.7 months. Survival free from reoperation was 43.3% +/- 13.7% at 125 months. When analyzing the patients according to age, actuarial survival was 91.3% +/- 3.8% in the group of patients younger than 16 years (Group 1), compared with 95.6% +/- 2.7% in the group older than 16 years (Group 2), with a statistically significant difference of p < 0.0001. Survival free from reoperation was 50.8% +/- 16.9% in Group 1 and 47.0% +/- 14.9% in Group 2 (p < 0.0001). CONCLUSIONS: Late results obtained with mitral valve repair for rheumatic mitral valve insufficiency were satisfactory and exceeded those reported for mitral valve replacement in the same population.
Assuntos
Próteses Valvulares Cardíacas , Insuficiência da Valva Mitral/mortalidade , Insuficiência da Valva Mitral/cirurgia , Valva Mitral/cirurgia , Cardiopatia Reumática/cirurgia , Adolescente , Adulto , Idoso , Brasil , Procedimentos Cirúrgicos Cardíacos/métodos , Criança , Pré-Escolar , Ecocardiografia Doppler , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/diagnóstico por imagem , Estudos Retrospectivos , Cardiopatia Reumática/diagnóstico por imagem , Cardiopatia Reumática/mortalidade , Taxa de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Because cardiac decompensation is subtle, the best time to perform aortic valve replacement surgery may be difficult to determine. We investigated the relation of symptoms to left ventricular (LV) function and the timing of valve replacement in patients with aortic regurgitation (AR) of largely rheumatic origin. METHODS: Sixty-eight initially asymptomatic patients (mean age 29 years) with severe chronic AR were monitored for 36 months. Assessments included baseline and yearly echocardiograms and radioisotope ventriculography (resting and exercise) and clinical examinations every 6 months. RESULTS: Forty-seven patients (69%) remained asymptomatic and 21 (31%) had symptoms develop after 24 to 36 months. Compared with symptomatic patients, asymptomatic patients had significantly (P <.05) lower baseline LV end-diastolic diameter, end-systolic diameter, end-systolic stress, and volume/mass ratio but greater shortening fraction and ejection fraction (EF) at rest. These variables remained stable without statistically significant change until surgical correction in symptomatic patients. Percent variation of EF from rest to exercise increased in patients who remained asymptomatic (EF 2.8% +/- 10.6%) but decreased in those who became symptomatic (EF -4.2% +/- 13%; P <.05). Twenty symptomatic patients (New York Heart Association class III/IV, angina and/or syncope) had valve replacement surgery, after which all were in New York Heart Association class I/II and had significant decreases of LV end-diastolic and end-systolic diameters and an increase on percent variation of EF from rest to exercise (P <.0001). CONCLUSIONS: Development of symptoms did not correlate with change in any ventricular function indexes. Surgery on appearance of symptoms restored LV function to near normal.
Assuntos
Insuficiência da Valva Aórtica/cirurgia , Implante de Prótese de Valva Cardíaca , Próteses Valvulares Cardíacas , Função Ventricular Esquerda , Adulto , Valva Aórtica/cirurgia , Insuficiência da Valva Aórtica/diagnóstico por imagem , Insuficiência da Valva Aórtica/fisiopatologia , Bioprótese , Ecocardiografia , Teste de Esforço , Feminino , Seguimentos , Humanos , Masculino , Seleção de Pacientes , Doenças Reumáticas/complicaçõesRESUMO
Binding properties of the subtypes of adenosine A2 receptors in membrane preparations and the effects of adenosine receptor ligands on cAMP accumulation in slices from the optic tectum of neonatal chicks have been investigated. [3H]2-[4-(2-p-carboxyethyl)phenylamino]-5'-N-ethylcarboxaminoadenosin e (CGS 21680), a selective ligand for adenosine A2a receptors, did not bind to optic tectal membranes, as observed with rat striatal membranes. CGS 21680 also did not induce cyclic AMP accumulation in optic tectum slices. However, 5'-N-ethylcarboxamidoadenosine (NECA), 2-chloro-adenosine or adenosine induced a 2.5- to 3-fold increase on cyclic AMP accumulation in this preparation. [3H]NECA binds to fresh non-washed-membranes obtained from optic tectum of chicks, displaying one population of binding sites, which can be displaced by NECA, 8-phenyltheophylline, 2-chloro-adenosine, but is not affected by CGS 21680. The estimated K(D) value was 400.90 +/- 80.50 nM and the Bmax was estimated to be 2.51 +/- 0.54 pmol/mg protein. Guanine nucleotides, which modulate G-proteins activity intracellularly, are also involved in the inhibition of glutamate responses by acting extracellularly. Moreover, we have previously reported that guanine nucleotides potentiate, while glutamate inhibits, adenosine-induced cyclic AMP accumulation in slices from optic tectum of chicks. However, the guanine nucleotides, GMP or GppNHp and the metabotropic glutamate receptors agonist, 1S,3R-ACPD did not alter the [3H]NECA binding observed in fresh non-washed-membranes. Therefore, the adenosine A2 receptor found in the optic tectum must be the adenosine A2b receptor which is available only in fresh membrane preparations, and its not modulated by guanine nucleotides or glutamate analogs.
Assuntos
Receptores Purinérgicos P1/metabolismo , Colículos Superiores/metabolismo , Adenosina/análogos & derivados , Adenosina/metabolismo , Adenosina-5'-(N-etilcarboxamida)/metabolismo , Animais , Membrana Celular/metabolismo , Galinhas , AMP Cíclico/metabolismo , Cicloleucina/análogos & derivados , Cicloleucina/farmacologia , Técnicas In Vitro , Fenetilaminas/metabolismo , Ensaio Radioligante , Ratos , Colículos Superiores/efeitos dos fármacosRESUMO
Glutamate and adenosine both modulate adenylyl cyclase activity through interaction of their specific receptors with stimulatory or inhibitory G-proteins. Guanine nucleotides (GN), which modulate G-protein activity intracellularly, are also involved in the inhibition of glutamate responses, acting from the outside of the cells. We had previously reported that glutamate inhibits adenosine-induced cyclic AMP (cAMP) accumulation in slices obtained from the optic tectum of chicks. In the present study we investigated the interaction of GN with these two neurotransmitters and found that GN inhibit the inhibitory effect of glutamate on adenosine-induced cAMP accumulation and potentiate adenosine-induced cAMP accumulation. These effects were observed with 5'-guanylylimidodiphosphate (GppNHp) or GMP, but not with guanosine (the nucleoside). Besides, these interactions of GN occur via a metabotropic glutamate receptor (mGluR) sensitive to (1 S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1 S,3R-ACPD) but not to L-2-amino-4-phosphonobutyrate (L-AP4). These effects were partially modulated by a mGluR antagonist, (RS)-alpha-methyl-4-carboxyphenylglycine ((RS)M-CPG), and by an adenosine receptor antagonist, 8-phenyltheophylline. GN only potentiated the adenosine response when adenosine was acting through its receptor positively linked to adenylyl cyclase. Therefore, the data show that guanine nucleotides not only inhibit glutamate-induced responses, but also stimulate adenosine-induced responses, a fact that may contribute to the understanding of the physiological functions of guanine nucleotides.
Assuntos
Adenosina/fisiologia , AMP Cíclico/metabolismo , Glutamatos/fisiologia , Nucleotídeos de Guanina/fisiologia , Colículos Superiores/efeitos dos fármacos , Animais , Benzoatos/farmacologia , Galinhas , Antagonistas de Aminoácidos Excitatórios/farmacologia , Glicina/análogos & derivados , Glicina/farmacologia , Técnicas In Vitro , Receptores de Glutamato Metabotrópico/antagonistas & inibidores , Receptores de Glutamato Metabotrópico/fisiologia , Colículos Superiores/metabolismoRESUMO
PURPOSE: To compare immediate and late (12 months) follow-up of clinical and Doppler echocardiographic results between percutaneous mitral balloon valvuloplasty and open commissurotomy in a prospective and randomized trial. METHODS: Eighty eight symptomatic patients with severe mitral stenosis and favorable anatomy were randomized in a prospective trial comparing the two procedures. All patients were submitted to clinical and Doppler echocardiographic evaluation before the procedures and immediate and twelve months thereafter. RESULTS: Mean mitral gradient (mmHg) decreased from 12.2 +/- 5.8 to 5.80 +/- 2.7 (p < 0.001) in commissurotomy group (CG) and from 11.7 +/- 6.1 to 5.0 +/- 2.4 (p < 0.001) in the balloon valvuloplasty group (VG). Mitral valve are (cm2) increased from 0.98 +/- 0.21 to 2.52 +/- 0.46 in CG and from 1.05 +/- 0.25 to 2.18 +/- 0.40 in VG (p < 0.001). In both groups there was a slight decrease in mitral valve area at 12 month follow-up. There was no death in either group. One patient in the VG had moderate mitral regurgitation and underwent surgery. At the 12 month follow-up, all patients in CG and 97.7% of patients in VG were in New York Heart Association functional class I or II. CONCLUSION: Both procedures were safe and showed similar immediate improvement in mitral gradient and functional class. Mitral valve area had a greater increase immediately after commissurotomy, however, there was a significantly greater reduction in the CG after 12 months of follow-up, when compared to balloon valvuloplasty. In both groups, mitral gradient remained reduced and most patients did not change functional class during the follow-up.
Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Cateterismo , Estenose da Valva Mitral/terapia , Adolescente , Adulto , Ecocardiografia Doppler , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estenose da Valva Mitral/cirurgiaRESUMO
Metabotropic glutamate receptors (mGluRs) have been shown to modulate adenylate cyclase activity via G-proteins. In the present study we report similar results to the previously observed in the literature, showing that glutamate and the metabotropic agonists, 1S,3R-ACPD or quisqualate induced cAMP accumulation in hippocampal slices of young rats. Moreover, guanine nucleotides GTP, GDP or GMP, inhibited the glutamate-induced cAMP accumulation. By measuring LDH activity in the buffer surrounding the slices, we showed that the integrity of the slices was maintained, indicating that the effect of guanine nucleotides was extracellular. GMP, GDPbeta-S or Gpp(NH)p abolished quisqualate-induced cAMP accumulation. GDPbeta-S or Gpp(NH)p but not GMP inhibited 1S,3R-ACPD-induced cAMP accumulation. The response evoked by glutamate was also abolished by the mGluR antagonists: L-AP3 abolished glutamate-induced cAMP accumulation in a dose-dependent manner and MCPG was effective only at the 2 mM dose. DNQX was ineffective. We are reporting here, an inhibition induced by guanine nucleotides, via an extracellular site (s), similar to the observed with classical glutamate antagonists on a cellular response evoked by mGluR agonists.
Assuntos
AMP Cíclico/antagonistas & inibidores , Nucleotídeos de Guanina/farmacologia , Receptores de Glutamato Metabotrópico/metabolismo , Animais , AMP Cíclico/metabolismo , Cicloleucina/análogos & derivados , Cicloleucina/farmacologia , Ácido Glutâmico/farmacologia , Guanosina Difosfato/análogos & derivados , Guanosina Difosfato/farmacologia , Guanosina Monofosfato/farmacologia , Guanosina Trifosfato/farmacologia , Guanilil Imidodifosfato/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/crescimento & desenvolvimento , Hipocampo/metabolismo , Neurotoxinas/farmacologia , Ácido Quisquálico/farmacologia , Ratos , Ratos Wistar , Tionucleotídeos/farmacologiaRESUMO
BACKGROUND: From March 1982 to December 1995, 2,607 Fisics-Incor bovine pericardial bioprostheses were implanted in 2,259 patients. Mean age was 47.2 +/- 17.5 years, and 55% were male. Rheumatic fever was present in 1,301 (45.7%) patients. METHODS: One thousand and seventy-three aortic valve replacements, 1,085 mitral replacements, 27 tricuspid replacements, 195 mitral-aortic replacements, and 16 other combined valve replacements were carried out. Combined procedures were performed in 788 (32.9%) patients, the most frequent being tricuspid valve repair (9.2%) and coronary artery bypass grafting (7.7%). RESULTS: Hospital mortality was 8.6% (194 patients), 8.6% for the mitral group, 4.7% for the aortic group, and 12.8% for double-valve replacements. The linear rates for calcification, thromboembolism, rupture, leak and endocarditis were, respectively, 1.1%, 0.2%, 0.9%, 0.1% and 0.5% patient-year. The actuarial survival curve was 56.7 +/- 5.4% in 15 years. Survival free from endocarditis was 91.92%, survival free from thromboembolism was 95 +/- 1.7%, survival free from rupture was 43.7 +/- 9.8%, survival free from leak was 98.9 +/- 4.5%, and survival free from calcification was 48.8 +/- 7.9% in 15 years. In the late postoperative period, 1,614 (80.6%) patients were in New York Heart Association functional Class I. CONCLUSIONS: We conclude that the results with the Fisics-Incor bovine pericardial prostheses were satisfactory in our group of patients.