RESUMEN
BACKGROUND: PM00104 binds guanines at DNA minor grooves, impacting DNA replication and transcription. A phase I study was undertaken to investigate safety, dose-limiting toxicities (DLTs), recommended phase II dose (RP2D), pharmacokinetics (PKs) and preliminary antitumour activity of PM00104 as a 1- or 3-h infusion three-weekly. METHODS: Patients with advanced solid tumours received PM00104 in a dose escalation trial, as guided by toxicity and PK data. RESULTS: A total of 47 patients were treated; 27 patients on the 1-h schedule (0.23-3.6 mg m(-2)) and 20 patients on the 3-h schedule (1.8-3.5 mg m(-2)). Dose-limiting toxicities comprised reversible nausea, vomiting, fatigue, elevated transaminases and thrombocytopenia, establishing the 1-h schedule RP2D at 3.0 mg m(-2). With the 3-h schedule, DLTs of reversible hypotension and neutropenia established the RP2D at 2.8 mg m(-2). Common PM00104-related adverse events at the RP2D comprised grade 1-2 nausea, fatigue and myelosuppression. In both schedules, PKs increased linearly, but doses over the 1-h schedule RP2D resulted in higher than proportional increases in exposure. A patient with advanced urothelial carcinoma had RECIST shrinkage by 49%, and three patients had RECIST stable disease ≥6 months. CONCLUSION: PM00104 is well tolerated, with preliminary evidence of antitumour activity observed. The 1-h 3-weekly schedule is being assessed in phase II clinical trials.
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Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Tetrahidroisoquinolinas/administración & dosificación , Tetrahidroisoquinolinas/uso terapéutico , Adulto , Anciano , Antineoplásicos/efectos adversos , Antineoplásicos/farmacocinética , Progresión de la Enfermedad , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Humanos , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Neoplasias/clasificación , Tetrahidroisoquinolinas/efectos adversos , Tetrahidroisoquinolinas/farmacocinética , Adulto JovenRESUMEN
PURPOSE: To determine the mass balance, excretion and metabolism of the small molecule flavonoid tumour vascular disrupting agent ASA404 in patients with advanced cancer. METHODS: Seven cancer patients were given a single dose of 3,000 mg [(14)C] ASA404 by intravenous infusion over 20 min prior to collection of samples of plasma, urine and faeces. Pharmacokinetic samples were analysed by HPLC, liquid scintillation counting, mass spectrometry, glusulase treatment and comparison to authentic standards. Descriptive pharmacokinetic parameters were generated by noncompartmental analysis. RESULTS: Mass balance was achieved (mean recovery of radioactivity in excreta = 86.9% of the dose) with balanced excretion between urine (mean recovery of radioactivity in urine = 53.9% of dose) and faeces (mean recovery of radioactivity in faeces = 33.3% of dose). ASA404 was eliminated as parent drug, three known metabolites (6-methylhydroxy-ASA404, ASA404 acyl glucuronide and 6-methylhydroxy-ASA404 acyl glucuronide) and two novel metabolites (an ASA404 dimer and an ASA404 dimer glucuronide conjugate). Unchanged ASA404 was the major radioactivity component detected in plasma within the first 24 h after dosing. At later time points, irreversibly protein bound ASA404 and all of the metabolites that had been detected in excreta contributed to total plasma radioactivity. CONCLUSION: This study defined the substantial excretion of ASA404, mainly as metabolites, in both urine (over half of the dose) and faeces (about one-third of the dose) after intravenous administration. Two novel metabolites were identified that were not reported by previous studies using nonradioactive techniques.
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Antineoplásicos/farmacocinética , Neoplasias/tratamiento farmacológico , Anciano , Antineoplásicos/uso terapéutico , Radioisótopos de Carbono , Cromatografía Líquida de Alta Presión/métodos , Femenino , Humanos , Infusiones Intravenosas , Masculino , Espectrometría de Masas , Persona de Mediana Edad , Neoplasias/patología , Unión Proteica , Factores de Tiempo , XantonasRESUMEN
BACKGROUND: This phase Ib trial assessed safety, tolerability, and maximum tolerated dose (MTD) of figitumumab (CP-751,871), a fully human monoclonal antibody targeting the insulin-like growth factor type 1 receptor (IGF-IR), in combination with docetaxel. METHODS: Patients with advanced solid tumours were treated with escalating dose levels of figitumumab plus 75 mg m(-2) docetaxel every 21 days. Safety, efficacy, pharmacokinetics (PKs), and biomarker responses were evaluated. RESULTS: In 46 patients, no dose-limiting toxicities were attributable to the treatment combination. Grade 3 and 4 toxicities included neutropaenia (n=28), febrile neutropaenia (n=11), fatigue (n=10), leukopaenia (n=7), diarrhoea (n=5), hyperglycaemia, lymphopaenia, cellulitis, DVT, and pain (all n=1). The MTD was not reached. Four partial responses were observed; 12 patients had disease stabilisation of > or =6 months. Pharmacokinetic and biomarker analyses showed a dose-dependent increase in plasma exposure, and complete sIGF-IR downregulation at doses of >or =3 mg kg(-1). Pharmacokinetics of docetaxel in combination was similar to when given alone. Out of 18 castration-resistant prostate cancer patients, 10 (56%) had > or =5 circulating tumour cells (CTCs) per 7.5 ml of blood at baseline: 6 out of 10 (60%) had a decline from > or =5 to <5 CTCs and 9 out of 10 (90%) had a > or =30% decline in CTCs after therapy. CONCLUSIONS: Figitumumab and docetaxel in combination are well tolerated. Further evaluation is warranted.
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Anticuerpos Monoclonales/toxicidad , Neoplasias/tratamiento farmacológico , Taxoides/uso terapéutico , Adulto , Anciano , Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/uso terapéutico , Antineoplásicos/toxicidad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidad , Celulitis (Flemón)/inducido químicamente , Docetaxel , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Inmunoglobulinas Intravenosas , Linfopenia/inducido químicamente , Masculino , Persona de Mediana Edad , Neutropenia/inducido químicamente , Neoplasias de la Próstata/tratamiento farmacológico , Receptor IGF Tipo 1/antagonistas & inhibidores , Taxoides/farmacocinéticaRESUMEN
BACKGROUND: Histone deacetylase blockade can promote heat shock protein 90 (HSP90) acetylation, abrogating androgen receptor signaling. A phase II trial of the histone deacetylase inhibitor (HDACi) romidepsin was conducted in patients with progressing, metastatic, castration-resistant prostate cancer (CRPC). PATIENTS AND METHODS: A dose of 13 mg/m(2) was administered i.v. over 4 h on days 1, 8 and 15 every 28 days. The primary end point was rate of disease control defined as no evidence of radiological progression at 6 months. A sample size of 16 assessable patients in stage 1 and nine assessable patients in stage 2 was selected; progression to stage 2 required one or more patients with disease control in stage 1 (H(o) = 0.10, H(a) = 0.30; alpha and beta = 0.10). RESULTS: Thirty-five patients were enrolled. Two patients achieved a confirmed radiological partial response (RECIST) lasting > or = 6 months, along with a confirmed prostate-specific antigen decline of > or = 50%. Eleven patients experienced toxicity necessitating early discontinuation. The commonest adverse events were nausea (30 patients; 85.7%), fatigue (28 patients; 80.0%), vomiting (23 patients; 65.7%) and anorexia (20 patients; 57.1%). There was no significant cardiac toxicity. CONCLUSIONS: At the dose and schedule selected, romidepsin demonstrated minimal antitumor activity in chemonaive patients with CRPC. Further studies of improved HDACi, alone and in combination with other therapies, should nevertheless be investigated.
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Antibióticos Antineoplásicos/uso terapéutico , Depsipéptidos/uso terapéutico , Inhibidores de Histona Desacetilasas/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Hormonales/uso terapéutico , Castración , Resistencia a Antineoplásicos , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/patologíaRESUMEN
OBJECTIVES: To investigate modifiable risk and preventive factors of work-related eye injuries. METHODS: A case-crossover study conducted to explore the associations between transient risk factors and work-related eye injuries. Patients seen at seven medical centres in Taiwan with work-related eye injuries over a 4-year period were enrolled in the study. Clinical information was collected from medical charts and detailed information on exposure to eight potentially modifiable factors during the 60 minutes prior to the occurrence of each injury, as well as during the same time interval on the last work day prior to the injury, were obtained using questionnaire surveys. Matched-pair interval analysis was adopted to assess the odds ratios (ORs) for work-related eye injuries given exposure to the eight modifiable factors. RESULTS: A total of 283 subjects were interviewed. Most of these injured workers were young, male, and self-employed or small enterprise workers. The most common injury type was photokeratitis (33.2%), mainly caused by welding (30.4%). The OR for a work-related eye injury was increased with the performance of an unfamiliar task (57.0), operation of a faulty tool or piece of equipment (48.5), distractions (24.0), being rushed (13.0), or fatigued (10.0), and a poor work environment (4.3). Wearing eye protection devices was found to have a significant protective effect on workers who might otherwise have been exposed to eye injuries (OR = 0.4; 95% CI 0.2 to 0.7). CONCLUSION: Potential modifiable risk and preventive factors for work-related eye injuries were identified using a case-crossover study. This information should be helpful in the development of preventive strategies.
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Accidentes de Trabajo , Lesiones Oculares/etiología , Exposición Profesional/efectos adversos , Accidentes de Trabajo/prevención & control , Accidentes de Trabajo/estadística & datos numéricos , Adolescente , Adulto , Anciano , Estudios Cruzados , Lesiones Oculares/epidemiología , Lesiones Oculares/prevención & control , Dispositivos de Protección de los Ojos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Exposición Profesional/estadística & datos numéricos , Oportunidad Relativa , Estudios Retrospectivos , Factores de Riesgo , Taiwán/epidemiología , Adulto JovenRESUMEN
BACKGROUND: The purpose of this study was to evaluate the association of circulating tumour cell (CTC) counts, before and after commencing treatment, with overall survival (OS) in patients with castration-resistant prostate cancer (CRPC). EXPERIMENTAL DESIGN: A 7.5 ml of blood was collected before and after treatment in 119 patients with CRPC. CTCs were enumerated using the CellSearchSystem. RESULTS: Higher CTC counts associated with baseline characteristics portending aggressive disease. Multivariate analyses indicated that a CTC >or=5 was an independent prognostic factor at all time points evaluated. Patients with baseline CTC >or=5 had shorter OS than those with <5 [median OS 19.5 versus >30 months, hazard ratio (HR) 3.25, P=0.012]; patients with CTC >50 had a poorer OS than those with CTCs 5-50 (median OS 6.3 versus 21.1 months, HR 4.1, P<0.001). Patients whose CTC counts reduced from >or=5 at baseline to <5 following treatment had a better OS compared with those who did not. CTC counts showed a similar, but earlier and independent, ability to time to disease progression to predict OS. CONCLUSION: CTC counts predict OS and provide independent prognostic information to time to disease progression; CTC dynamics following therapy need to be evaluated as an intermediate end point of outcome in randomised phase III trials.
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Células Neoplásicas Circulantes/patología , Orquiectomía , Neoplasias de la Próstata/diagnóstico , Anciano , Anciano de 80 o más Años , Biomarcadores/análisis , Biomarcadores/sangre , Recuento de Células , Ensayos Clínicos Fase I como Asunto , Ensayos Clínicos Fase II como Asunto , Progresión de la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Análisis de Supervivencia , Insuficiencia del TratamientoRESUMEN
Pertuzumab represents the first in a new class of targeted therapeutics known as HER dimerisation inhibitors. We conducted a phase Ib study to determine the maximum-tolerated dose, the dose limiting toxicities (DLT), and pharmacokinetic (PK) interaction of docetaxel when administered in combination with pertuzumab. Initially, two dose levels of docetaxel (60 and 75 mg m(-2)) were explored in combination with a fixed dose of 1050 mg of pertuzumab; then two dose levels of docetaxel (75 and 100 mg m(-2)) were explored in combination following a fixed dose of 420 mg of pertuzumab with a loading dose of 840 mg. Both drugs were administered intravenously every 3 weeks. The latter dose of pertuzumab was allowed after an amendment to the original protocol when phase II data suggesting no difference in toxicity or activity between the 2 doses became available. Two patients out of two treated at docetaxel 75 mg m(-2) in combination with pertuzumab 1050 mg suffered DLT (grade 3 diarrhoea and grade 4 febrile neutropaenia). Two out of five patients treated at docetaxel 100 mg m(-2) in combination with pertuzumab 420 mg with a loading dose of 840 mg suffered DLT (grade 3 fatigue and grade 4 febrile neutropaenia). Stable disease was observed at four cycles in more than half of the patients treated and a confirmed radiological partial response with a >50% decline in PSA in a patient with hormone refractory prostate cancer were observed. There were no pharmacokinetic drug-drug interactions. The recommended phase II dose of this combination was docetaxel 75 mg m(-2) and 420 mg pertuzumab following a loading dose of 840 mg.
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Anticuerpos Monoclonales/administración & dosificación , Antineoplásicos/administración & dosificación , Neoplasias/tratamiento farmacológico , Proteínas Recombinantes/administración & dosificación , Taxoides/administración & dosificación , Adulto , Anciano , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/farmacocinética , Anticuerpos Monoclonales Humanizados , Antineoplásicos/efectos adversos , Antineoplásicos/farmacocinética , Estudios de Cohortes , Progresión de la Enfermedad , Docetaxel , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Quimioterapia Combinada , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Femenino , Estudios de Seguimiento , Humanos , Infusiones Intravenosas , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Receptor ErbB-2/antagonistas & inhibidores , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/farmacocinética , Taxoides/efectos adversos , Taxoides/farmacocinética , Factores de Tiempo , Resultado del TratamientoRESUMEN
In the present studies we have made the novel observation that protease nexin 1 (PN1), a member of the serine protease inhibitor (SERPIN) superfamily, is a potent inhibitor of the blood coagulation Factor XIa (FXIa). The inhibitory complexes formed between PN1 and FXIa are stable when subjected to reducing agents, SDS, and boiling, a characteristic of the acyl linkage formed between SERPINs and their cognate proteases. Using a sensitive fluorescence-quenched peptide substrate, the K(assoc) of PN1 for FXIa was determined to be 7.9 x 10(4) m(-)(1) s(-)(1) in the absence of heparin. In the presence of heparin, this rate was accelerated to 1.7 x 10(6), M(-)(1) s(-)(1), making PN1 a far better inhibitor of FXIa than C1 inhibitor, which is the only other SERPIN known to significantly inhibit FXIa. FXIa-PN1 complexes are shown to be internalized and degraded by human fibroblasts, most likely via the low density lipoprotein receptor-related protein (LRP), since degradation was strongly inhibited by the LRP agonist, receptor-associated protein. Since FXIa proteolytically modifies the amyloid precursor protein, this observation may suggest an accessory role for PN1 in the pathobiogenesis of Alzheimer's disease.
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Proteínas Portadoras/farmacología , Proteínas Inactivadoras del Complemento 1/farmacología , Factor XIa/fisiología , Heparina/farmacología , Serpinas/fisiología , Precursor de Proteína beta-Amiloide , Línea Celular , Proteína Inhibidora del Complemento C1 , Factor XIa/antagonistas & inhibidores , Humanos , Nexinas de Proteasas , Receptores de Superficie Celular , Inhibidores de Serina Proteinasa/farmacología , Serpina E2RESUMEN
The standard treatment of left main coronary artery (LMCA) disease has been bypass surgery (CABG). Recent reports suggested that stenting of LMCA disease might be feasible. From January 1995 to April 1998, we carried out a prospective study of elective stenting of unprotected LMCA disease to evaluate its immediate and long-term results. Of 61 consecutive patients with unprotected LMCA disease, 6 were excluded. Acute procedural success was 100% for the remaining 55 patients, without any complications such as stent thrombosis, myocardial infarction, CABG, or death. During a mean follow-up of 16.1+/-9.6 months, 11 patients (20%) had symptomatic recurrence, between 2 to 6 months after their procedure. Seven patients underwent CABG, two had repeat intervention, one continued with medical therapy, and one died before planned angiography. There was no late sudden death. Forty-four patients (80%) remained asymptomatic. We conclude that elective stenting may be a safe alternative to CABG in unprotected LMCA disease.
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Angioplastia Coronaria con Balón , Enfermedad Coronaria/terapia , Stents , Anciano , Angiografía Coronaria , Puente de Arteria Coronaria , Enfermedad Coronaria/diagnóstico por imagen , Enfermedad Coronaria/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Diseño de Prótesis , Resultado del TratamientoRESUMEN
For the 12-mo period of 1995, we encountered seven consecutive patients with symptomatic unprotected left main coronary stenosis requiring revascularization. There were five males and two females, age ranging 48-76 years. One patient was referred to coronary bypass surgery. Of the remaining six patients, three refused surgery and the other three, including one with previous bypass surgery and two with previous interventional procedures, preferred percutaneous revascularization. All six had successful elective stenting of their left main coronary stenoses with the new short Palmaz-Schatz stents, P084 and PS104. There were no complications and all remained totally asymptomatic at 3-14 months followup. We conclude that with proper patient selection and the availability of appropriate stents, elective stenting of unprotected left main coronary stenosis is safe with good immediate and medium term results.
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Enfermedad Coronaria/terapia , Stents , Anciano , Angina de Pecho/diagnóstico por imagen , Angina de Pecho/terapia , Angioplastia Coronaria con Balón , Angiografía Coronaria , Enfermedad Coronaria/diagnóstico por imagen , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/terapia , Esfuerzo FísicoRESUMEN
STUDY OBJECTIVE: The aim was to describe the distribution of lipids and apolipoproteins in the Chinese population in Hong Kong. DESIGN: This was a prospective, cross sectional, population based survey. SETTINGS: The study was conducted in a single, self referred, out patient screening centre. PARTICIPANTS: Altogether 825 Chinese adults aged > or = 20 years were screened. One hundred subjects who had previously had lipid measurement and 29 who were taking lipid modifying drugs were excluded but 289 men and 407 women remained for further analysis. MAIN RESULTS: Age standardised mean (SEM) lipids concentrations for Hong Kong Chinese were total cholesterol: men, 5.48 (0.05) mmol/l and women, 5.46 (0.06) mmol/l; triglycerides: men, 1.22 (1.03) mmol/l and women, 1.00 (1.03) mmol/l; high density lipoprotein (HDL) cholesterol: men, 1.25 (0.02) mmol/l and women, 1.42 (0.02) mmol/l; low density lipoprotein (LDL) cholesterol: men, 3.56 (0.05) mmol/l and women, 3.50 (0.06) mmol/l; apolipoprotein A-I (apo A-I): men, 1.34 (0.01) g/l and women, 1.46 (0.01) g/l; and apolipoprotein B (apo B): men, 1.15 (0.02) g/l and women, 1.06 (0.02) g/l. The total to HDL cholesterol ratios were men, 4.62 (0.07) and women, 4.10 (0.08); and apo B to apo A-I ratios (apo B/A) were men, 0.88 (0.02) and women, 0.75 (0.02). While levels of total cholesterol, LDL cholesterol, apo B, triglycerides, total/HDL cholesterol, and apo B/A were positively associated with age in both sexes and were higher in men before the age 50-59 years, they rose steeply thereafter in women to cross over the levels in men. In contrast, HDL cholesterol decreased with age while apo A-I remained constant, and both were consistently higher in women than in men in all age groups. CONCLUSIONS: Hong Kong Chinese have attained lipid profiles similar to those in other developed western populations. Environmental factors seem influential in this regard. Faced with the increasing coronary mortality of recent years, there should be a major effort to reduce the cholesterol concentrations in this population.
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Apolipoproteínas/sangre , Etnicidad , Lípidos/sangre , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Envejecimiento/sangre , China/etnología , Estudios Transversales , Femenino , Hong Kong , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Valores de Referencia , Caracteres Sexuales , Distribución por SexoRESUMEN
Apesar de um longo período refratário atrial pós evento ventricular (PVARP) pode prevenir a ocorrência de taquicardias mediadas pelo marcapasso e também o sincronismo inapropriado com arrtmias atriais na estimulação dupla-câmara(DDD) a limitação da freqüência máxima será necessariamente comprometida. Testamos a possibilidade de utilizar um marcapasso dupla-câmara com sensor de ventilação por minuto (DDDR) e com capacidade de encurtar o PVARP durante o exercício em 13 pacientes com bradicardia (PVARP em repouso = 463 + - 29 ms) a fim de prevenir a limitação prematura da freqüência máxima. O teste de esforço em esteira nos modos DDD e DDDR com este PVARP resultou em freqüências máximas de 98 bpm + - 8 bpm e 142 bpm + - 3 bpm respectivamente (P < 0,0001). Estes resultados foram obtidos graças à incompetênciacronotrópica e à limitação da freqüência máxima no modo DDD, ambas contornadas pelo uso do sensor. Com a finalidade de simular arritmias atriais, foi aplicada estimulação na parece torácica por 30 segundos, a uma freqüência de 250 bpm e com uma sensibilidade atrial unipolar média de 0,82 mV. No modo DDD, ocorreu uma resposta ventricular irregular (as freqüências com um PVARP de 280 ms e 463 ms + - 29 ms foram respectivamente 92 bpm + - 5 bpm e 66 bpm + - 3 bpm (P < 0,0001). No modo DDDR, com PVARP de 463 ms + - 29 ms, ocorreu uma estimulação ventricular regular a 53 bpm + - 2 bpm devida à mudança de modo para VVIR, na presença de eventos repetitivos captados dentro do PVARP. Um paciente desenvolveu fibrilação atrial espontânea durante o seguimento, que foi corretamente identificada pelo algoritmo do marcapasso, resultando na mudança de modo DDDR para VVIR e na preservação da resposta em freqüência. Em conclusão, o PVARP controlado pelo sensor permite a utilização de um PVARP mais longo durante o repouso, sem comprometer a freqüência máxima durante o exercício. Adicionalmente, ao oferecer em proteção contra retrógrada, o PVARP longo e a mudança automática de modo também limitam a freqüência durante as arritmias atriais, permitindo uma resposta ventricular de acordo com a demanda fisiológica...
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Arritmias Cardíacas , Marcapaso Artificial , TaquicardiaRESUMEN
Thrombocytosis is a rare cause of ischemic cardiovascular and cerebrovascular events in patients with intrinsically normal coronary and cerebral vasculature. This report details the occurrence of inferior wall myocardial infarction (MI) consequent upon postsplenectomy thrombocytosis in a thirty-four-year-old man with angiographically normal coronary arteries. The MI was complicated by early left ventricular mural thrombus formation and embolic cerebral infarction. Combined anticoagulant and antiplatelet therapy was required to prevent the recurrence of ischemic events.
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Cardiopatías/etiología , Embolia y Trombosis Intracraneal/etiología , Infarto del Miocardio/etiología , Esplenectomía/efectos adversos , Trombocitosis/etiología , Trombosis/etiología , Adulto , Cardiopatías/diagnóstico por imagen , Humanos , Masculino , Trombosis/diagnóstico por imagen , UltrasonografíaRESUMEN
Although a long postventricular atrial refractory period (PVARP) may prevent the occurrence of pacemaker mediated tachycardias and inadvertent tracking of atrial arrhythmias in dual chamber (DDD) pacing, the maximum upper rate will necessarily be compromised. We tested the feasibility of using minute ventilation sensing in a dual chamber rate adaptive pacemaker (DDDR) to shorten the PVARP during exercise in 13 patients with bradycardias (resting PVARP = 463 +/- 29 msec) to avoid premature upper rate behavior. Graded treadmill exercise tests in the DDD and DDDR modes at this PVARP resulted in maximum ventricular rates of 98 +/- 8 and 142 +/- 3 beats/min, respectively (P < 0.0001), due to chronotropic incompetence and upper rate limitation in the DDD mode, both circumvened with the use of sensor. In order to stimulate atrial arrhythmias, chest wall stimulation was applied for 30 seconds at a rate of 250 beats/min at a mean unipolar atrial sensitivity of 0.82 mV. Irregular ventricular responses occurred in the DDD mode (the rates at a PVARP of 280 and 463 +/- 29 msec were, respectively 92 +/- 5 and 66 +/- 3 msec; P < 0.0001). In the DDDR mode at a PVARP of 463 +/- 29 msec, regular ventricular pacing at 53 +/- 2 beats/min occurred due to mode switching to VVIR mode in the presence of repetitive sensed atrial events within the PVARP. One patient developed spontaneous atrial fibrillation on follow-up, which was correctly identified by the pacemaker algorithm, resulting in mode switch from DDDR to regular VVIR pacing and preservation of rate response. In conclusion, sensor controlled PVARP allows a long PVARP to be used at rest without limiting the maximum rate during exercise. In addition, to offer protection against retrograde conduction, a long PVARP and mode switching also limit the rate during atrial arrhythmias and allow regular ventricular rate responses according to the physiological demands.
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Bradicardia/terapia , Estimulación Cardíaca Artificial/métodos , Bloqueo Cardíaco/terapia , Marcapaso Artificial , Anciano , Algoritmos , Nodo Atrioventricular/fisiopatología , Bradicardia/fisiopatología , Diseño de Equipo , Ejercicio Físico/fisiología , Prueba de Esfuerzo , Bloqueo Cardíaco/fisiopatología , Humanos , Taquicardia/prevención & controlRESUMEN
The role of ventricular rate-adaptive pacing (VVIR) in the elderly was investigated in 12 patients with a mean age of 85 +/- 2 years (range 75-95 years) with implanted activity-initiated VVIR pacemakers. Although four patients had significant extracardiac diseases, all were capable of independent walking and self care. The pacing rate achieved during structured daily activities (walking, climbing stairs, washing, bed-making and scrubbing floors) were compared with those achieved by 10 age-matched healthy subjects. Apart from the more strenuous activities (ascending stairs and floor-scrubbing), the pacing rates achieved by the patients were comparable to those of the healthy subjects and occurred within an appropriate time. In a 4-weekly randomized, double-blind crossover protocol in the VVI and VVIR pacing modes, all patients underwent assessments in a 12-min walking distance test, a 24 h non-invasive ambulatory blood pressure recording and a symptomatic documentation. During VVIR pacing, the 12-min walking distance was significantly improved compared to VVI pacing (556 +/- 52 vs. 545 +/- 55 m, P less than 0.05). There was no difference between the recorded blood pressure and symptom scores between the two pacing modes, although most patients preferred VVIR pacing (P less than 0.05). It is concluded that VVIR pacing in this elderly population can improve exercise capacity, and the patients' preference for the VVIR mode was documented despite the absence of a measurable difference in symptomatology.
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Bradicardia/terapia , Prueba de Esfuerzo , Frecuencia Cardíaca/fisiología , Marcapaso Artificial , Programas Informáticos , Anciano , Anciano de 80 o más Años , Presión Sanguínea/fisiología , Bradicardia/fisiopatología , Método Doble Ciego , Electrocardiografía Ambulatoria/instrumentación , Femenino , Humanos , MasculinoRESUMEN
This report details the clinical, electrocardiographic, and electropharmacological characteristics of an unusual case of bidirectional tachycardia induced by aconites present in a Chinese herbal decoction consumed by a previously healthy subject. The tachycardia showed marked susceptibility to vagotonic maneuvers, cholinesterase inhibition, and adenosine triphosphate. The incessant nature of the tachycardia, rapid recurrence after transient suppression, and failure to respond to direct current cardioversion suggested an automatic tachycardia mechanism consistent with known data on the cellular electrophysiological mechanism of aconitine-mediated arrhythmogenesis. A fascicular or ventricular myocardial origin of the tachycardia with alternating activation patterns, or dual foci with alternate discharge, appeared most plausible. The rootstocks of aconitum plants have been commonly employed in traditional Chinese herbal recipes for "cardiotonic" actions and for relieving "rheumatism." Multiple pitfalls could occur during the processing of these herbs that might have predisposed to aconite poisoning. The need for strict control and surveillance of herbal substances with low margins of safety is highlighted.
Asunto(s)
Aconitum/envenenamiento , Medicamentos Herbarios Chinos/envenenamiento , Taquicardia/inducido químicamente , Antiarrítmicos/uso terapéutico , Cardioversión Eléctrica , Electrocardiografía , Femenino , Flecainida/uso terapéutico , Sistema de Conducción Cardíaco/efectos de los fármacos , Sistema de Conducción Cardíaco/fisiopatología , Humanos , Persona de Mediana Edad , Taquicardia/diagnóstico , Taquicardia/terapiaRESUMEN
The rate adaptive characteristics and pacemaker mediated tachycardia protection algorithm of an accelerometer based DDDR pacemaker were evaluated in 11 patients with bradycardia (seven atrioventricular block, four sick sinus syndrome). Rate adaptive programming was effected by collecting the acceleration level during a 3-minute moderate exercise ("tailoring" of sensor). In comparison with an externally attached piezoelectric sensor, the accelerometer sensor showed lower rate changes during external tapping of the pacemaker (16 +/- 3 vs 29 +/- 4 ppm, P less than 0.02) and applied direct pressure (1 +/- 1 vs 40 +/- 3 beats/min, P less than 0.001) on the pacemaker. At nominal setting, the accelerometer sensor showed improved rate stability and higher rate response to jogging and standing, although responses to other daily activities and treadmill exercise were similar. Apart from changing the rate responsive slope, rate response could be improved by repeat "tailoring" of the sensor at a lower exercise level, resulting in better overall rate response characteristics. The ability of the rate monitoring software to collect acceleration levels for an activity and profile the projected rate response at different rate responsive settings allowed programming to be effected with the minimum amount of exercise testing. The pacemaker also discriminated atrial tachyarrhythmias from normal sinus response using the sensor to judge the appropriateness of the atrial rate, which correctly identified and prevented rapid ventricular tracking in two patients during atrial flutter/fibrillation.
Asunto(s)
Bloqueo Cardíaco/terapia , Marcapaso Artificial , Síndrome del Seno Enfermo/terapia , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Paroxysmal nocturnal hemoglobinuria (PHN) is an acquired chronic hemolytic anemia associated with an unusual susceptibility to hemolytic crisis, infection, and venous thrombosis which would be aggravated by a number of factors including surgery. We report a case of PHN undergoing percutaneous transluminal coronary angioplasty and discuss the corresponding perioperative management.
Asunto(s)
Angioplastia Coronaria con Balón , Ritmo Circadiano/fisiología , Enfermedad Coronaria/terapia , Hematuria/sangre , Adulto , Anemia Hemolítica , Enfermedad Coronaria/sangre , Hemoglobinometría , Humanos , Masculino , Tiempo de Tromboplastina ParcialRESUMEN
A sixty-four-year-old man presented with repolarization abnormalities on the electrocardiogram. Echocardiography and cardiac catheterization revealed that he had the rare combination of apical hypertrophic cardiomyopathy with bilateral coronary-artery-to-pulmonary-artery fistula. An exercise thallium scan was negative, suggesting that the marked electrocardiographic changes were most likely secondary to the apical myocardial hypertrophy, instead of to coronary-steal-induced ischemia.