RESUMEN
AIM: To comprehensively review the health needs of patients living with clinically significant haemoglobinopathies (thalassaemia and sickle-cell disease (SCD)) in New South Wales, Australia. METHODS: A survey-based health needs assessment was undertaken in outpatients cared for at five tertiary institutions in metropolitan and regional centres. Sixty-three of 121 adults (approximately 80-90% of adult patients with transfusion-requiring haemoglobinopathies in New South Wales) completed an in-house and commercial health-related quality assessment survey (SF-36v2). RESULTS: Subjects came from more than eight world regions, with those with SCD being more likely to be born outside of Australia than subjects with thalassaemia (P < 0.001, likelihood ratio 20.64) as well as more likely to have been refugees (26% vs 2%). The population contained socially disadvantaged subjects with 13 subjects (20.6%) having incomes below the Australian poverty line. Complications of thalassaemia were comparable to previous international reports although our subjects had a high rate of secondary amenorrhea (>12 months = 27%) and surgical splenectomy (55.6%). Use of hydroxyurea in SCD was less than expected with only 46.6% of subjects having prior use. Lack of universal access to magnetic resonance imaging-guided chelation (international best practice) was evident, although 65.5% had been able to access magnetic resonance imaging through clinical trial, or self-funding. CONCLUSIONS: Patients with SCD and thalassaemia experience considerable morbidity and mortality and require complex, multidisciplinary care. This study revealed both variance from international best practice and between specialist units. The results of this research may provide the impetus for the development of clinical and research networks to enable the uniform delivery of health services benchmarked against international standards.
Asunto(s)
Encuestas Epidemiológicas/métodos , Hemoglobinopatías/diagnóstico , Hemoglobinopatías/etnología , Adolescente , Adulto , Australia/etnología , Femenino , Hemoglobinopatías/terapia , Humanos , Masculino , Persona de Mediana Edad , Nueva Gales del Sur/etnología , Adulto JovenRESUMEN
BACKGROUND: Venom-induced consumption coagulopathy (VICC) is a major effect of snake envenoming. OBJECTIVES: To investigate whether fresh frozen plasma (FFP) given after antivenom resulted in more rapid correction of coagulation. PATIENTS/METHODS: This was a multicenter open-label randomized controlled trial in patients with VICC of FFP vs. no FFP within 4 h of antivenom administration. Patients (> 2 years) recruited to the Australian snakebite project with VICC (International Normalized Ratio [INR] > 3) were eligible. Patients were randomized 2 : 1 to receive FFP or no FFP. The primary outcome was the proportion with an INR of < 2 at 6 h after antivenom administration. Secondary outcomes included time from antivenom administration to discharge, adverse effects, major hemorrhage, and death. RESULTS: Of 70 eligible patients, 65 consented to be randomized: 41 to FFP, and 24 to no FFP. Six hours after antivenom administration, more patients randomized to FFP had an INR of < 2 (30/41 [73%] vs. 6/24 [25%]; absolute difference, 48%; 95% confidence interval 23-73%; P = 0.0002). The median time from antivenom administration to discharge was similar (34 h, range 14-230 h vs. 39 h, range 14-321 h; P = 0.44). Seven patients developed systemic hypersensitivity reactions after antivenom administration - two mild and one severe (FFP arm), and three mild and one severe (no FFP). One serious adverse event (intracranial hemorrhage and death) occurred in an FFP patient with pre-existing hypertension, who was hypertensive on admission, and developed a headache 6 h after FFP administration. Post hoc analysis showed that the median time from bite to FFP administration was significantly shorter for non-responders to FFP than for responders (4.7 h, interquartile range [IQR] 4.2-6.7 h vs. 7.3 h, IQR 6.1-8 h; P = 0.002). CONCLUSIONS: FFP administration after antivenom administration results in more rapid restoration of clotting function in most patients, but no decrease in discharge time. Early FFP administration (< 6-8 h) post-bite is less likely to be effective.
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Antivenenos/uso terapéutico , Coagulación Sanguínea/efectos de los fármacos , Transfusión Sanguínea/métodos , Coagulación Intravascular Diseminada/terapia , Plasma , Mordeduras de Serpientes/terapia , Venenos de Serpiente , Adolescente , Adulto , Animales , Antivenenos/efectos adversos , Australia , Terapia Combinada , Coagulación Intravascular Diseminada/sangre , Coagulación Intravascular Diseminada/etiología , Coagulación Intravascular Diseminada/mortalidad , Femenino , Hemorragia/etiología , Hemorragia/mortalidad , Hemorragia/prevención & control , Humanos , Relación Normalizada Internacional , Tiempo de Internación , Masculino , Persona de Mediana Edad , Alta del Paciente , Mordeduras de Serpientes/sangre , Mordeduras de Serpientes/complicaciones , Mordeduras de Serpientes/mortalidad , Factores de Tiempo , Tiempo de Tratamiento , Resultado del Tratamiento , Adulto JovenRESUMEN
Factor replacement with BIOSTATE(®), a factor VIII (FVIII)/von Willebrand factor concentrate, forms the mainstay of treatment for children with von Willebrand disorder (VWD) in Australia and New Zealand. However, published data on the clinical efficacy and safety of BIOSTATE in the VWD paediatric population are limited. We retrospectively assessed the efficacy and safety of BIOSTATE in 43 children with VWD who received treatment for surgery, non-surgical bleeds or continuous prophylaxis at eight paediatric haemophilia centres in Australia and New Zealand. Data were collected on patient demographics, disease history, treatment history, dosage, administration, adverse reactions, concomitant medications and excessive bleeding events. BIOSTATE provided excellent/good haemostatic efficacy in 90% of surgical procedures (n = 42) with a mean daily FVIII dose of 47 IU FVIII:C kg(-1) and a median treatment duration of 3 days. Excellent/good haemostatic efficacy was achieved in 94% of non-surgical bleeding events (n = 72) with a mean FVIII dose of 45 IU FVIII:C kg(-1) day(-1) and a median treatment duration of 1 day. There were no bleeding events attributable to lack of efficacy. One case of nausea, possibly related to BIOSTATE administration, was reported. These results suggest that BIOSTATE is safe and effective for the treatment and prophylaxis of bleeding in children with VWD.
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Factor VIII/uso terapéutico , Hemorragia/prevención & control , Hemostáticos/uso terapéutico , Enfermedades de von Willebrand/tratamiento farmacológico , Factor de von Willebrand/uso terapéutico , Adolescente , Niño , Preescolar , Combinación de Medicamentos , Femenino , Hemostasis Quirúrgica/métodos , Humanos , Lactante , MasculinoRESUMEN
BACKGROUND: Limited information exists on the dynamics of hemostasis in patients with venom-induced consumption coagulopathy (VICC) from snake envenomation. OBJECTIVE: The aim of the present study was to investigate specific factor deficiencies and their time course in Australasian elapid envenomation. METHODS: We measured coagulation parameters and factor concentrations in patients recruited to the Australian Snakebite Project, an observational cohort study. There were 112 patients with complete VICC, defined as an international normalized ratio (INR) > 3, and 18 with partial VICC. Serial citrated plasma samples were collected from 0.5 to 60 h post-bite. INR, activated partial thromboplastin time (aPTT), coagulation factors (F)I, II, V, VII, VIII, IX, X, von Willebrand factor antigen (VWF:Ag) and D-dimer concentrations were measured. RESULTS: Complete VICC was characterized by near/total depletion of fibrinogen, FV and FVIII, with an INR and aPTT that exceeded the upper limits of detection, within 2 h of snakebite. Prothrombin levels never fell below 60% of normal, suggesting that the toxins were rapidly eliminated or inactivated and re-synthesis of clotting factors occurred irrespective of antivenom. Partial VICC caused limited depletion of fibrinogen and FV, and almost complete consumption of FVIII. Onset of VICC was more rapid with brown snake (Pseudonaja spp.) venom, which contains a group C prothrombin activator toxin, compared with the tiger snake group, which contains a group D prothrombin activator toxin and requires human FVa formation. Resolution of VICC occurred within 24-36 h irrespective of snake type. CONCLUSIONS: These results suggest that Australasian elapid prothrombin activators have a potent but short duration of action. Antivenom is unlikely to be administered in time to prevent VICC.
Asunto(s)
Coagulación Intravascular Diseminada/sangre , Mordeduras de Serpientes/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Antivenenos/farmacología , Australia , Coagulación Sanguínea/efectos de los fármacos , Factores de Coagulación Sanguínea/metabolismo , Niño , Preescolar , Estudios de Cohortes , Coagulación Intravascular Diseminada/etiología , Femenino , Humanos , Relación Normalizada Internacional , Masculino , Persona de Mediana Edad , Tiempo de Tromboplastina Parcial , Factores de Tiempo , PonzoñasRESUMEN
von Willebrand's disease (VWD) is an inherited bleeding disorder characterized by deficient levels of or dysfunctional von Willebrand factor (VWF). This phase II/III open-label, multicentre study evaluated the efficacy and safety of BIOSTATE, a high purity plasma-derived double-virus inactivated FVIII/VWF concentrate, when used in non-surgical bleeds, surgical procedures and prophylactic therapy in VWD patients for whom desmopressin treatment was deemed ineffective, inadequate or contraindicated. Twenty three patients (7 type 1, 9 type 2 and 7 type 3; 12 male, 11 female), who received FVIII/VWF concentrate as part of their VWD management, were recruited prospectively between December 2004 and May 2007 from eight centres in Australia and New Zealand. BIOSTATE dosing was based on pre-treatment FVIII:C and/or VWF:RCo plasma levels and a predetermined dosing guide. Haemostatic efficacy of BIOSTATE was rated as excellent or good for all major and minor surgery events, long-term prophylaxis, and for four of the six assessable non-surgical bleeding events. Blood transfusions were required by two major surgery patients as well as one patient with a non-surgical bleed. The median overall exposure to BIOSTATE across all groups was 8 days, greater in the prophylactic group (range 53-197) compared with major surgery (3-24), minor surgery (1-8) and non-surgical bleeds (1-10). BIOSTATE was shown to be efficacious and well tolerated when treating patients with VWD. This study also provides important insights into dosing regimens with BIOSTATE and the role of monitoring therapy with FVIII:C and VWF:RCo.
Asunto(s)
Factor VIII/uso terapéutico , Enfermedades de von Willebrand/tratamiento farmacológico , Factor de von Willebrand/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Esquema de Medicación , Combinación de Medicamentos , Factor VIII/administración & dosificación , Factor VIII/análisis , Femenino , Hemorragia/prevención & control , Hemostasis/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Inactivación de Virus , Adulto Joven , Factor de von Willebrand/administración & dosificación , Factor de von Willebrand/análisisRESUMEN
Microparticles (MP) are small fragments of cytoplasm shed from a cell surface and their role in the pathophysiology of disease is being extensively investigated. A novel staining technique for quantifying total MP in peripheral blood was evaluated in this study. Evaluation of Bodipy-maleimide (or bio-maleimide) as a stain for quantifying total MP in peripheral blood by flow cytometry. Samples were obtained from 10 healthy donors after informed consent. Plasma was prepared by sequential centrifugation at 1500 g followed by 13,000 g and stained with Annexin V and bio-maleimide. Enumeration beads were added after 15 min of incubation with the stain and samples analyzed on a FACS Canto flow cytometer. Detection and quantification of MP by bio-maleimide staining was comparable with that by Annexin V. The total mean MP level with bio-maleimide staining was 34 +/- 19.7/microl (range of 11.6-68.1/microl) and with Annexin V staining it was 38.9 +/- 29.8/microl (range of 10.6 to 112.9/microl). There was no significant difference using a paired t-test and methods were comparable using a Bland-Altman plot. Bio-maleimide is a useful and inexpensive stain to measure total MP levels in peripheral blood by flow cytometry. This technique could be employed to study thrombotic risks in a variety of disease states.
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Plaquetas/ultraestructura , Compuestos de Boro , Citoplasma/ultraestructura , Citometría de Flujo/métodos , Maleimidas , Coloración y Etiquetado , Adulto , Anciano , Anexina A5 , Membrana Celular/ultraestructura , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recuento de Plaquetas/métodosRESUMEN
Abnormal bleeding may be seen in up to a third of patients with amyloidosis. Factor X deficiency is the commonest acquired coagulopathy in amyloidosis. While mild intracutaneous bleeding is common, spontaneous life-threatening haemorrhage is rare. We report a case of acquired FX deficiency due to amyloid light chain (AL)-amyloidosis presenting with spontaneous retroperitoneal bleeding. The diagnostic and management issues in this patient are discussed.
Asunto(s)
Amiloidosis/complicaciones , Deficiencia del Factor X/etiología , Hemorragia/etiología , Anciano , Anciano de 80 o más Años , Factores de Coagulación Sanguínea/uso terapéutico , Deficiencia del Factor X/diagnóstico , Deficiencia del Factor X/tratamiento farmacológico , Femenino , Humanos , Espacio RetroperitonealRESUMEN
BACKGROUND: Treatment with interferon and subcutaneous cytarabine produces superior cytogenetic responses in chronic myeloid leukaemia (CML) than treatment with interferon alone, but at the expense of greater toxicity. Cytarabine ocfosfate (YNK01) is an oral precursor of cytarabine that may overcome some of the inconvenience and toxicities associated with subcutaneous cytarabine administration. PATIENTS AND METHODS: We studied the efficacy and tolerability of combination therapy with interferon-alpha-2b and YNK01 in patients with newly diagnosed, untreated CML. Forty patients were treated with interferon-alpha-2b (5 MU/m2/day) plus monthly courses of YNK01 (600 mg/day for 10 days) for 1 year. RESULTS: The 6-month complete haematological response rate was 63% and the 1-year major cytogenetic response rate was 30%, with 10% of cytogenetic responses being complete. With a median follow-up of 57 months, the estimated 5-year overall survival was 86% (95% confidence interval 70% to 94%). Treatment tolerability was poor, with toxicity leading to discontinuation of one or both drugs in 60% of cases. The median daily dose of interferon alpha-2b was 7.75 MU and the median dose of YNK01 was 600 mg/day for each 10-day treatment cycle. CONCLUSIONS: Interferon-alpha-2b and YNK01 produce cytogenetic responses comparable to those achieved with interferon-alpha-2b and parenteral cytarabine, although toxicity was excessive. Alternate dosing strategies may enhance the tolerability of YNK01.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Citidina Monofosfato/análogos & derivados , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Administración Oral , Adolescente , Adulto , Anciano , Arabinonucleotidos/administración & dosificación , Citidina Monofosfato/administración & dosificación , Esquema de Medicación , Femenino , Humanos , Inyecciones Subcutáneas , Interferón alfa-2 , Interferón-alfa/administración & dosificación , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Masculino , Persona de Mediana Edad , Proteínas Recombinantes , Resultado del TratamientoRESUMEN
BACKGROUND: The Australian Iron Status Advisory Panel advocates dietary intervention as the first treatment option for mild iron deficiency [serum ferritin (SF) = 10-15 microg/L]. However, there appear to be no studies on the efficacy of dietary treatment for iron deficiency. OBJECTIVE: We compared the effects of iron supplementation and of a high-iron diet on serum ferritin (SF) and hemoglobin in iron-deficient women of childbearing age. DESIGN: Forty-four iron-deficient women (SF <15 microg/L or SF = 15-20 microg/L plus serum iron <10 micromol/L and total-iron-binding capacity >68 micromol/L) and 22 iron-replete women (hemoglobin > or =120 g/L and SF >20 microg/L) matched for age and parity categories were enrolled and completed 7-d weighed food records at baseline. The iron-deficient women were randomly allocated to receive iron supplementation (105 mg/d; supplement group) or a high-iron diet (recommended intake of absorbable iron: 2.25 mg/d; diet group) for 12 wk. Hematologic and dietary assessments were repeated at the end of the intervention and again after a 6-mo follow-up. RESULTS: Mean SF in the supplement group increased from 9.0 +/- 3.9 microg/L at baseline to 24.8 +/- 10.0 microg/L after the intervention and remained stable during follow-up (24.2 +/- 9.8 microg/L), whereas the diet group had smaller increases during the intervention (8.9 +/- 3.1 to 11.0 +/- 5.9 microg/L) but continued to improve during follow-up (to 15.2 +/- 9.5 microg/L). Mean hemoglobin tended to improve in both intervention groups, but the change was only significant in the supplement group. CONCLUSIONS: In iron-deficient women of childbearing age, a high-iron diet produced smaller increases in SF than did iron supplementation but resulted in continued improvements in iron status during a 6-mo. follow-up.
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Anemia Ferropénica/dietoterapia , Ferritinas/sangre , Hemoglobinas/análisis , Deficiencias de Hierro , Hierro de la Dieta/administración & dosificación , Adolescente , Adulto , Anemia Ferropénica/prevención & control , Disponibilidad Biológica , Dieta , Registros de Dieta , Suplementos Dietéticos , Femenino , Ferritinas/metabolismo , Humanos , Absorción Intestinal , Hierro/metabolismo , Hierro de la Dieta/farmacocinética , Estudios Longitudinales , Persona de Mediana Edad , Necesidades Nutricionales , Cooperación del PacienteAsunto(s)
Anemia/tratamiento farmacológico , Transfusión de Eritrocitos/efectos adversos , Eritropoyetina/uso terapéutico , Leucemia Mielomonocítica Crónica/tratamiento farmacológico , Anciano , Anemia/etiología , Hemoglobinas/metabolismo , Hepatomegalia/etiología , Humanos , Leucemia Mielomonocítica Crónica/complicaciones , MasculinoRESUMEN
Acetaminophen may increase International Normalized Ratio (INR) in patients taking anticoagulation medication, and in patients with acetaminophen poisoning without hepatic injury. The objective of this study was to describe and investigate the effect of acetaminophen on INR. The authors studied patients admitted to a regional toxicology treatment center with acetaminophen poisoning with INR and without potentially confounding coingestion or hepatic injury. Exposed and nonexposed (control) cohorts were recruited from admissions with acetaminophen poisoning and psychotropic drug poisoning, respectively. From 1,437 acetaminophen poisonings, after exclusions, there were 143 admissions with 205 estimations of INR. INR showed a time-dependent increase. Fifty percent of all patients and 66% of those with an extrapolated 4-hour acetaminophen concentration > or = 150 mg/L had an abnormal INR at some time. Dose ingested (p = 0.01) and nomogram-based risk (p for trend = 0.005) were correlated with the effect. N-acetylcysteine had a protective effect. Functional factor VII was lower (p = 0.005) in exposed patients (n = 30) than controls (n = 8), and less than antigenic factor VII in exposed patients (p = 0.03). Factor IX was lower (p = 0.02). Factor VIIIc was not significantly different. The authors concluded that an isolated, small rise in INR is common after acetaminophen poisoning without hepatic injury. It appears to be caused by inhibition of Vitamin K-dependent activation of coagulation factors. This effect suggests a possible mechanism for the observed interaction between acetaminophen and warfarin.
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Acetaminofén/envenenamiento , Analgésicos no Narcóticos/envenenamiento , Coagulación Sanguínea/efectos de los fármacos , Factor VII/fisiología , Acetaminofén/efectos adversos , Adolescente , Adulto , Anciano , Analgésicos no Narcóticos/efectos adversos , Anticoagulantes/farmacología , Enfermedad Hepática Inducida por Sustancias y Drogas , Estudios de Cohortes , Interacciones Farmacológicas , Sobredosis de Droga , Factor IX/biosíntesis , Factor IX/fisiología , Factor VII/biosíntesis , Factor VIII/biosíntesis , Factor VIII/fisiología , Femenino , Humanos , Relación Normalizada Internacional , Hepatopatías/sangre , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Tiempo de Protrombina , Estudios RetrospectivosRESUMEN
To determine the safety and efficacy of the combination of idarubicin, cytarabine and etoposide ("ICE") for induction and consolidation treatment of acute myeloid leukemia (AML), and of dose-intensification of cytarabine in this setting, 54 previously untreated patients in three cohorts were studied by sequential dose escalation of cytarabine, in combination with standard doses of idarubicin and etoposide. Cytarabine was given to Cohort 1 at the conventional dosage of 100 mg/m2 per day by continuous infusion for 7 days in induction and 5 days in consolidation; to Cohort 2 at high-dose (HiDAC) (3 g/m2 intravenously twice daily on days 1, 3, 5 and 7) during induction with conventional dosage during consolidation; to Cohort 3 HiDAC was given for both induction and consolidation. In addition, Cohort 3 patients received lenograstim (Granocyte; rHuG-CSF) after both induction and consolidation courses. We found that there was no significant difference between the three cohorts in hematological toxicity in induction, but that HiDAC was associated with a greater incidence of gastro-intestinal toxicities. There was no difference in induction mortality between the three cohorts, which was 11% overall. Consolidation with HiDAC led to a significant increase in hematological toxicity. Overall, the complete remission (CR) rate was 80% with no significant difference between the three regimens. The estimated disease free survival at 3 years was 28%, 67% and 54% respectively for Cohorts 1, 2 and 3 with an estimated overall survival of 38%, 63% and 47%. We conclude that cytarabine dosage can be escalated safely in combination with idarubicin and etoposide in both induction and consolidation. The combination is effective for induction treatment of AML and its side-effects appear similar to those of standard regimens. Whether its use offers long-term benefits compared with standard regimens is the subject of ongoing controlled randomized studies.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Leucemia Mieloide/tratamiento farmacológico , Leucemia Promielocítica Aguda/tratamiento farmacológico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Estudios de Cohortes , Citarabina/administración & dosificación , Citarabina/efectos adversos , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Etopósido/administración & dosificación , Etopósido/efectos adversos , Femenino , Humanos , Idarrubicina/administración & dosificación , Idarrubicina/efectos adversos , Leucemia Mieloide/mortalidad , Leucemia Promielocítica Aguda/mortalidad , Masculino , Persona de Mediana Edad , Inducción de Remisión , Tasa de SupervivenciaAsunto(s)
Antineoplásicos/uso terapéutico , Neoplasias del Sistema Nervioso Central/secundario , Leucemia Promielocítica Aguda/tratamiento farmacológico , Tretinoina/uso terapéutico , Femenino , Humanos , Leucemia Promielocítica Aguda/patología , Persona de Mediana Edad , Recurrencia , Inducción de RemisiónRESUMEN
BACKGROUND: The Hunter Area Pathology Service provides transfusion services to 4 metropolitan and 11 rural hospitals in Australia. To improve blood availability, conserve blood stocks, and reduce crossmatch-to-transfusion ratios, a networked electronic blood release system (EBRS) has been developed for computer cross-matching within the laboratory and at sites remote from the transfusion laboratory. It is innovative, in that non-laboratory staffs have been trained to release computer-matched blood at remote hospitals without transfusion laboratories. STUDY DESIGN AND METHODS: The EBRS software was tested and validated according to the Australian software standards AS 3563.1 and 3563.2 (1991). Over 7000 units were released by the EBRS in a laboratory trial conducted in conjunction with the conventional immediate-spin crossmatch. A further, 12-month study was conducted within the laboratory before the staged implementation of the EBRS at the remote hospitals. RESULTS: The EBRS has resulted in 1) a 25-percent reduction in the number of units requested by the medical staff, resulting from the reduction in time needed to provide compatible blood due to the elimination of the serologic crossmatch; 2) better blood stock management (reducing outdated red cell units by 30%); and 3) significant savings in laboratory workload (savings of approximately 100 hours/month). In addition, the rapid availability of computer-crossmatched red cells in emergency situations has enhanced patient safety. CONCLUSION: The EBRS is a safe and efficient means of providing red cells within the laboratory and at remote hospitals without laboratory services.
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Bancos de Sangre , Tipificación y Pruebas Cruzadas Sanguíneas , Programas Informáticos , Tipificación y Pruebas Cruzadas Sanguíneas/instrumentación , Procesamiento Automatizado de Datos , Humanos , Recursos HumanosAsunto(s)
Anemia Hemolítica/inducido químicamente , Antiulcerosos/efectos adversos , Cuerpos de Heinz , Omeprazol/efectos adversos , Lesión Renal Aguda/inducido químicamente , Anciano , Anemia Hemolítica/sangre , Antiulcerosos/uso terapéutico , Creatinina/sangre , Femenino , Estudios de Seguimiento , Cuerpos de Heinz/efectos de los fármacos , Hemoglobinas/efectos de los fármacos , Hemoglobinas/metabolismo , Humanos , Omeprazol/uso terapéuticoRESUMEN
We report the first documented case of the use of peripheral blood stem cell autografting in the treatment of a Jehovah's Witness with acute myeloblastic leukemia. This case illustrates the complex ethical and clinical issues that arise in the treatment of such patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cristianismo , Ética Médica , Testigos de Jehová , Leucemia Mieloide Aguda/tratamiento farmacológico , Adulto , Humanos , Leucemia Mieloide Aguda/sangre , Recuento de Leucocitos , Masculino , Menores , Autonomía Personal , Recuento de Plaquetas , Inducción de RemisiónRESUMEN
All-trans-retinoic acid (ATRA) is known to induce differentiation of promyelocytes in vitro and also to induce remission of acute promyelocytic leukaemia in vivo. We treated 11 patients with poor prognosis acute promyelocytic leukaemia (APL) with ATRA and obtained seven complete and one partial remission. Remissions took one to three months to achieve and were associated with adverse effects including dry skin and bone pain. In eight patients the white cell count rose above 20 x 10(9)/L within the first ten days of retinoic acid treatment and this was associated with the development of pulmonary leukostasis in three patients which was fatal in one. Another two patients died of intracranial haemorrhage also within the first ten days. ATRA is a promising new agent in the induction therapy of this particular category of acute leukaemia.
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Leucemia Promielocítica Aguda/tratamiento farmacológico , Tretinoina/uso terapéutico , Adulto , Australia , Diferenciación Celular/efectos de los fármacos , Femenino , Humanos , Leucemia Promielocítica Aguda/sangre , Leucemia Promielocítica Aguda/patología , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Inducción de Remisión , Tretinoina/efectos adversosRESUMEN
Using simultaneous multiple peptide synthesis by the multipin approach, the feasibility of systematic large-scale pharmacological screening of peptide ligands was investigated. The method involves the assembly of small quantities of peptides (ca. 50 nmol) on plastic pins derivatized with an ester linker based on glycolate and 4-(hydroxymethyl)benzoate. These esters are stable under peptide synthesis and side-chain deprotection conditions but cleave under relatively mild basic conditions to generate peptides having C-terminal acid, amide and methylamide. A two-step approach to side-chain deprotection and cleavage from the solid support allows potentially toxic reagents to be removed (washed) from the peptide prior to cleavage. Consequently, the resulting peptide solutions can be used in bioassays with minimal processing. A series of angiotensin II and substance P analogs were synthesized and evaluated in an in vivo rat model and in vitro radioreceptor assay, respectively. Structure-activity studies on analogs of these bioactive peptides are well documented. The data obtained were consistent with that reported in the literature.