RESUMEN
A total of 14 Chinese patients with inoperable hepatocellular carcinoma received a liposomal formulation of daunorubicin (DaunoXome) at a dose equivalent to 100 mg/m2 of the free drug every 3 weeks. Altogether, 12 patients were assessable for response; 2 patients had stable disease for 8 weeks, but all eventually developed progressive disease and there was no responder. The drug was well tolerated, with no evidence of cardiac toxicity being observed. Deterioration of liver-function tests was attributed to progressive tumors in the terminal stage of the disease. Pharmacokinetics studies revealed a biexponential decay for daunorubicin in association with mean initial and terminal half-lives of 1.8 and 7.4 h, respectively, and a mean total clearance of 15.0+/-5.5 ml/min. The AUC ratio between the metabolite daunorubicinol and daunorubicin was 0.07. These data differ markedly from the pharmacokinetics of the free drug.
Asunto(s)
Antibióticos Antineoplásicos/administración & dosificación , Carcinoma Hepatocelular/tratamiento farmacológico , Daunorrubicina/administración & dosificación , Neoplasias Hepáticas/tratamiento farmacológico , Adulto , Anciano , Carcinoma Hepatocelular/metabolismo , Daunorrubicina/efectos adversos , Daunorrubicina/farmacocinética , Portadores de Fármacos , Femenino , Humanos , Liposomas , Neoplasias Hepáticas/metabolismo , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVES: To determine the spectrum of serum immunoreactive erythropoietin (SIE) levels amongst HIV-infected children aged < 13 years in relation to the levels among healthy children as well as those with renal failure; to examine the relationship between clinical and laboratory parameters and SIE levels. DESIGN: A cross-sectional study with a descriptive non-interventional format. HIV-infected Canadian subjects were recruited through four tertiary Canadian and one Bahamian centre. Children with renal failure and healthy children were recruited from one of the Canadian centres. METHODS: Study subjects had clinical and laboratory profiles determined at baseline and at each of five follow-up periods over 1 year. SIE levels were measured by radioimmunoassay with a normal range of 12-28 IU/I. Data handling and statistical functions were performed by the Canadian HIV Trials Network. RESULTS: The study enrolled 133 HIV-infected subjects and 38 controls. Of these, 117 HIV-infected subjects, 24 healthy controls, and 11 controls with renal failure were eligible for analysis. The median age of infected subjects was 44 months, whereas that of healthy controls was 56 months, and 95 months for controls with renal failure. The median SIE levels were 14 and 11 IU/I for subjects with renal failure and healthy subjects, respectively. The median SIE level was 61 IU/I among zidovudine (ZDV)-treated subjects and 22 IU/I among ZDV-naive HIV-infected subjects. HIV-infected children almost invariably had SIE levels < 200 IU/I. The median SIE levels amongst HIV-infected subjects whose hemoglobin levels were < 100 g/l were 98 and 31 IU/I for ZDV-treated and ZDV-naive subjects, respectively (P = 0.002). This difference in median SIE levels between ZDV-treated subjects and ZDV-naive subjects was also observed among subjects whose hemoglobin levels were > 100 g/l (median, 58 and 15 IU/l, respectively; P < 0.001). Hemoglobin level was the most important predictor of log10 SIE (P < 0.01 for ZDV-treated and ZDV-naive subjects). CONCLUSIONS: SIE levels amongst HIV-infected children were affected by HIV infection, use of ZDV, and presence or absence of anemia. SIE levels amongst HIV-infected children were generally lower than 200 IU/I. This characterization of SIE levels will facilitate clinical trials of exogenous recombinant human erythropoietin in HIV-infected children with anemia.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Eritropoyetina/sangre , Infecciones por VIH/sangre , Zidovudina/uso terapéutico , Anemia/prevención & control , Bahamas , Canadá , Niño , Preescolar , Estudios Transversales , Femenino , Infecciones por VIH/tratamiento farmacológico , Hemoglobinas/análisis , Humanos , Lactante , Masculino , Insuficiencia Renal/sangreRESUMEN
OBJECTIVES: To determine the spectrum of serum immunoreactive erythropoietin (SIE) levels amongst HIV-infected children aged <13 years in relation to the levels among healthy children as well as those with renal failure; to examine the relationship between clinical and laboratory parameters and SIE levels. DESIGN: A cross-sectional study with a descriptive non-interventional format. HIV-infected Canadian subjects were recruited through four tertiary Canadian and one Bahamian centre. Children with renal failure and healthy children were recruited from one of the Canadian centres. METHODS: Study subjects had clinical and laboratory profiles determined at baseline and at each of five follow-up periods over 1 year. SIE levels were measured by radio-immunoassay with a normal range of 12-28 IU/I. Data handling and statistical functions were performed by the Canadian HIV Trials Network. RESULTS: Ths study enrolled 133 HIV-infected subjects and 38 controls. Of these, 117 HIV-infected subjects, 24 healthy controls, and 11 controls with renal failure were eligible for analysis. The median age of infected subjects was 44 months, whereas that of healthy controls was 56 months, and 95 months for controls with renal failure. The median SIE levels were 14 and 11 IU/I for subjects with renal failure and healthy subjects, respectively. The median SIE level was 61 IU/I among zidovudine (ZDV)-treated subjects and 22 IU/I among ZDV-naive HIV-infected subjects. HIV-infected children almost invariably had SIE levels < 200 IU/I. The median SIE levels amongst HIV-infected subjects whose hemoglobin levels were < 100 g/l were 98 and 31 IU/I for ZDV-treated and ZDV-naive subjects, respectively (P = 0.002). This difference in median SIE levels between ZDV-treated subjects and ZDV-naive subjects was also observed among subjects whose hemoglobin levels were > 100 g/l (median, 58 and 15 IU/I, respectively; P < 0.001). Hemoglobin level was the most important predictor of log10 SIE (P < 0.001 for ZDV-treated and ZDV-naive subjects). CONCLUSIONS: SIE levels amongst HIV-infected children were affected by HIV infection, use of ZDV, and presence or absence of anemia. SIE levels amongst HIV-infected children were generally lower than 200 IU/I. This characterization of SIE levels will facilitate clinical trials of exogenous recombinant human erythropoietin in HIV-infected children with anemia.(Au)
Asunto(s)
Niño , Preescolar , Estudio Comparativo , Femenino , Humanos , Masculino , Lactante , Fármacos Anti-VIH/uso terapéutico , Eritropoyetina/sangre , Zidovudina/uso terapéutico , Infecciones por VIH/sangre , Bahamas , Canadá , Estudios Transversales , Hemoglobinas/análisis , Infecciones por VIH/tratamiento farmacológico , Insuficiencia Renal/sangre , Anemia/prevención & controlRESUMEN
PURPOSE: To compare the safety and efficacy of liposomal daunorubicin (DaunoXome; NeXstar Pharmaceuticals, Inc, Boulder, CO) with a reference regimen of doxorubicin, bleomycin, and vincristine (ABV) in advanced AIDS-related Kaposi's sarcoma (KS). PATIENTS AND METHODS: In a prospective randomized phase III trial, 232 patients were randomized to receive DaunoXome 40 mg/m2 or a combination regimen of doxorubicin 10 mg/m2, bleomycin 15 U, and vincristine 1 mg, administered intravenously every 2 weeks. Treatment was continued until complete response (CR), disease progression, or unacceptable toxicity. RESULTS: Of 232 patients randomized, 227 were treated: 116 with DaunoXome and 111 with ABV. The overall response rate (CR or partial response [PR]) was 25% (three CRs and 26 PRs) for DaunoXome and 28% (one CR and 30 PRs) for ABV. The difference in response rates was not statistically significant. The median survival time was 369 days for DaunoXome patients and 342 days for ABV patients (P = .19). The median time to treatment failure was 115 days for DaunoXome and 99 days for ABV (P = .13). ABV patients experienced significantly more alopecia and neuropathy (P < .0001). DaunoXome patients experienced more grade 4 neutropenia (P = .021). Cardiac function remained stable, with no instances of congestive heart failure on either treatment arm. CONCLUSION: In this large phase III trial, the efficacy of DaunoXome was comparable to that of ABV. Response rates, time to treatment failure, and overall survival were similar on both treatment arms. DaunoXome is a safe and effective primary therapy for advanced AIDS-related KS.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/complicaciones , Antibióticos Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Daunorrubicina/administración & dosificación , Sarcoma de Kaposi/tratamiento farmacológico , Adulto , Alopecia/inducido químicamente , Antibióticos Antineoplásicos/efectos adversos , Antibióticos Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bleomicina/administración & dosificación , Bleomicina/efectos adversos , Canadá , Daunorrubicina/efectos adversos , Daunorrubicina/uso terapéutico , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Portadores de Fármacos , Femenino , Humanos , Liposomas , Masculino , Persona de Mediana Edad , Neutropenia/inducido químicamente , Estudios Prospectivos , Inducción de Remisión , Sarcoma de Kaposi/etiología , Sarcoma de Kaposi/mortalidad , Tasa de Supervivencia , Insuficiencia del Tratamiento , Estados Unidos , Vincristina/administración & dosificación , Vincristina/efectos adversosRESUMEN
OBJECTIVE: To evaluate the efficacy and safety of liposomal encapsulated daunorubicin (DaunoXome) in the treatment of AIDS-associated mucocutaneous Kaposi's sarcoma. DESIGN: A Phase II, multicentre, European, non-comparative, open study to assess the use of DaunoXome in patients with no prior anthracycline chemotherapy for Kaposi's sarcoma. The response rate, time to disease progression, and the incidence and severity of adverse events were documented. SETTING: Hospital-based HIV units. PATIENTS: Thirty HIV-seropositive patients with mucocutaneous Kaposi's sarcoma were enrolled and treated. INTERVENTIONS: Treatment with DaunoXome at a dose of 40 mg/m2 intravenously once every 2 weeks. Treatment with antiretroviral agents and prophylaxis of opportunistic infections where indicated. RESULTS: Of the 30 evaluable patients, 22 patients (73%) achieved a partial response. Median time to treatment response was 30 days (range, 15-202). For patients with a partial response, median time to treatment failure was 153 days (range, 15-558). Patients received a median of 10 cycles (range, 1-44). Adverse events were minimal. The most common side effect was granulocytopenia in 16 patients (53%). CONCLUSION: DaunoXome is an effective and well-tolerated treatment for AIDS-associated mucocutaneous Kaposi's sarcoma and can be administered for prolonged periods. The myelosuppression can be managed by dose reductions and dose not preclude the concurrent use of antiretroviral therapies.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/complicaciones , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/uso terapéutico , Daunorrubicina/administración & dosificación , Daunorrubicina/uso terapéutico , Sarcoma de Kaposi/tratamiento farmacológico , Adulto , Antibióticos Antineoplásicos/efectos adversos , Daunorrubicina/efectos adversos , Progresión de la Enfermedad , Portadores de Fármacos , Humanos , Liposomas , Masculino , Persona de Mediana Edad , Tiempo de Reacción , Inducción de RemisiónAsunto(s)
Infecciones Estreptocócicas/microbiología , Supuración/complicaciones , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , MasculinoRESUMEN
In environments with temperatures above 60 degrees C, thermophilic prokaryotes are the only metabolically active life-forms. By using the SO(4) tracer technique, we studied the activity of sulfate-reducing microorganisms (SRM) in hot sediment from a hydrothermal vent site in the northern part of freshwater Lake Tanganyika (East Africa). Incubation of slurry samples at 8 to 90 degrees C demonstrated meso- and thermophilic sulfate reduction with optimum temperatures of 34 to 45 degrees C and 56 to 65 degrees C, respectively, and with an upper temperature limit of 80 degrees C. Sulfate reduction was stimulated at all temperatures by the addition of short-chain fatty acids and benzoate or complex substrates (yeast extract and peptone). A time course experiment showed that linear thermophilic sulfate consumption occurred after a lag phase (12 h) and indicated the presence of a large population of SRM in the hydrothermal sediment. Thermophilic sulfate reduction had a pH optimum of about 7 and was completely inhibited at pH 8.8 to 9.2. SRM could be enriched from hydrothermal chimney and sediment samples at 60 and 75 degrees C. In lactate-grown enrichments, sulfide production occurred at up to 70 and 75 degrees C, with optima at 63 and 71 degrees C, respectively. Several sporulating thermophilic enrichments were morphologically similar to Desulfotomaculum spp. Dissimilatory sulfate reduction in the studied hydrothermal area of Lake Tanganyika apparently has an upper temperature limit of 80 degrees C.
RESUMEN
The cellular fatty acid compositions were determined for 42 strains of Pseudomonas cepacia from five cystic fibrosis centers in North America. All isolates contained significant (20%) amounts of hexadecanoic (C16:0), and cis-9 hexadecenoic (C16:1 cis9) acids and an isomer of octadecenoic acid (C18:1). None had hydroxy acids containing fewer than 14 carbon atoms. The quantitative data from the fatty acid analysis were highly reproducible and provided a basis for numerical analysis. Five subgroups comprising all the strains were obtained by cluster analysis and further characterized by principal-component analysis. With minor exceptions, the predominant subgroup identified in each center was different from that identified in other centers and accounted for one-half of the isolates within each center. Cellular fatty acid composition is a useful adjunct to biochemical characterization for the identification of P. cepacia isolated from cystic fibrosis patients. Numerical analysis of the fatty acid data can separate P. cepacia into subgroups, which may provide useful epidemiologic information or a basis for further analysis by more complex techniques such as DNA probe analysis.
Asunto(s)
Portador Sano/microbiología , Fibrosis Quística/complicaciones , Ácidos Grasos/análisis , Infecciones por Pseudomonas/microbiología , Pseudomonas/clasificación , Técnicas de Tipificación Bacteriana , Cromatografía de Gases , Análisis por Conglomerados , Humanos , Pseudomonas/análisis , Infecciones por Pseudomonas/complicacionesRESUMEN
Meningococcal disease occurs in both endemic and epidemic forms. Current trends in the epidemiology and control of this disease are reviewed.
Asunto(s)
Infecciones Meningocócicas/epidemiología , Vacunas Bacterianas , Reservorios de Enfermedades , Humanos , Infecciones Meningocócicas/prevención & control , Estados UnidosRESUMEN
Pseudomonas gladioli was isolated from 11 patients with cystic fibrosis. It resembled Pseudomonas cepacia on the selective and differential medium OFPBL, producing yellow colonies after 48 to 72 h of incubation. Isolates were characterized biochemically, by DNA hybridization, and by cellular fatty acid analysis. A review of the clinical status of selected patients colonized by P. gladioli did not reveal any apparent association of this organism with infectious complications of cystic fibrosis. Thus, the clinical implications may differ depending on which of these two closely related species is reported by laboratories. Determination of the fatty acid profile of isolates by gas chromatography may be a useful adjunct to biochemical characterization as a means of identification. In contrast to P. cepacia, most isolates of P. gladioli contained 3-OH C10:0 fatty acid under the growth conditions used.