RESUMO
Due to demographic changes the number of elderly patients undergoing hip replacement surgery is increasing. In order to ensure safe treatment of elderly patients, age-specific medical factors must be taken into consideration. This article presents an overview of these factors. Furthermore, we evaluated our own patients treated between 2010 and 2015 regarding age-related treatment strategies and complication rates. Out of 3166 patients a total of 439 were over 80 years old (average age 84 years). It can be concluded from the scientific literature and from own data that elective hip replacement surgery in elderly patients is a technically safe procedure; however, the risk profile of each patient must be thoroughly analyzed so that in the event of even minor signs of potential complications countermeasures can be taken in good time.
Assuntos
Artroplastia de Quadril/mortalidade , Procedimentos Cirúrgicos Eletivos/mortalidade , Fraturas do Quadril/mortalidade , Fraturas do Quadril/cirurgia , Osteoartrite do Quadril/mortalidade , Osteoartrite do Quadril/cirurgia , Complicações Pós-Operatórias/mortalidade , Idoso , Idoso de 80 Anos ou mais , Artroplastia de Quadril/estatística & dados numéricos , Procedimentos Cirúrgicos Eletivos/estatística & dados numéricos , Feminino , Humanos , Masculino , Complicações Pós-Operatórias/prevenção & controle , Prevalência , Fatores de Risco , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Necrotizing fasciitis is a life-threatening clinical pattern, which may lead to multi-organ failure and death with delayed diagnosis or inadequate treatment. We report on a 68-year old patient who developed necrotizing fasciitis of the right elbow with multiorgan failure and long-term ventilation after an accidental and minor injury. The patient survived as a result of an early diagnosis and surgical intervention. In this case report we want to clarify the diagnosis and treatment of necrotizing fasciitis and give an overview of the recent literature on the topic.
Assuntos
Fasciite Necrosante/diagnóstico , Fasciite Necrosante/cirurgia , Insuficiência de Múltiplos Órgãos/diagnóstico , Insuficiência de Múltiplos Órgãos/terapia , Idoso , Diagnóstico Diferencial , Fasciite Necrosante/complicações , Humanos , Masculino , Insuficiência de Múltiplos Órgãos/etiologia , Resultado do TratamentoRESUMO
Allogeneic stem cell transplantation is a treatment option for patients with poor risk CLL. We conducted a retrospective analysis of all CLL patients allografted at our institution, the University Hospital of Cologne, Germany. Data was collected on 40 patients from 2004 to 2012. The mean age was 54, and the majority were male (75 %). On average, the patients were diagnosed 6 years (range 2-12) prior to transplant with an average of 4 years (range 1-8) from time of first-line therapy to transplant. The remission states at the time of transplant were complete remission (CR) (n = 4), stable disease (n = 10), partial remission (n = 20) and progressive disease (n = 6). Only reduced intensity conditioning regimens were employed. The average CD34(+) cell dose was 4.16 × 10(6)/kg. Neutrophil engraftment was seen by day +17 (range 10-23) post-transplant, and 88 % achieved 95-100 % donor chimerism by day 100. Overall survival, progression-free survival and non-relapse mortality at 2 years post-transplant were 65, 52.5 and 27.5 %, respectively. A total of 51 % of patients were found to be minimal residual disease (MRD)-negative at 1 year post-transplant. Our single-centre experience confirms the valuable role of allogeneic stem cell transplantation (allo-SCT) in the treatment of poor risk CLL patients with promising long-term survival and acceptable transplant-related mortality. The advent of newer therapeutic agents should not hinder the consideration of allo-SCT for this patient cohort as it remains the only curative option for these patients.
Assuntos
Transplante de Células-Tronco Hematopoéticas/mortalidade , Leucemia Linfocítica Crônica de Células B/mortalidade , Leucemia Linfocítica Crônica de Células B/terapia , Adulto , Idoso , Feminino , Transplante de Células-Tronco Hematopoéticas/tendências , Humanos , Leucemia Linfocítica Crônica de Células B/diagnóstico , Masculino , Pessoa de Meia-Idade , Morbidade , Mortalidade/tendências , Estudos Retrospectivos , Transplante Homólogo/mortalidade , Transplante Homólogo/tendências , Resultado do TratamentoRESUMO
Allogeneic haematopoietic stem cell transplantation is an effective treatment option for chemotherapy-refractory or relapsed haematological malignancies such as leukaemias and lymphomas. After conditioning with chemotherapy with or without total body irradiation, donor cells are infused to reconstitute haematopoiesis. Donor-derived immune cells induce immune reactions to control or eradicate the underlying disease, thereby going beyond the effect of chemotherapy. This graft-versus-tumour effect (GvT) is often accompanied by detrimental graft-versus-host reactions (graft-versus-host disease, GvHD), which substantially influence the mortality and morbidity after transplantation. The balance between GvHD and GvT, implementing various parameters such as donor selection, stem cell source, conditioning, immune reconstitution and immunosuppressive regimens, represents the challenge in the field of allogeneic stem cell transplantation.
Assuntos
Oftalmopatias/imunologia , Doença Enxerto-Hospedeiro/imunologia , Efeito Enxerto vs Tumor/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia/imunologia , Leucemia/terapia , Linfoma/imunologia , Linfoma/terapia , Condicionamento Pré-Transplante/métodos , Aloenxertos , Doença Crônica , Oftalmopatias/prevenção & controle , Oftalmopatias/terapia , Doença Enxerto-Hospedeiro/prevenção & controle , Doença Enxerto-Hospedeiro/terapia , Humanos , Fatores de RiscoRESUMO
Therapy for ocular graft-vs-host disease (ocular GvHD) is challenging for ophthalmologists as progress of the disease often occurs rapidly and is unforeseeable. Primary goal is the preservation or restoration of visual acuity, however, studies on ocular GvHD that have investigated therapeutic concepts are limited. In contrast, most therapeutic recommendations from consensus conferences derive from studies on dry eye diseases other than ocular GvHD. This review demonstrates the available therapies in the following categories: local, systemic, surgical and prophylactic. Primary targets are anti-inflammation, anti-fibrosis and lubrification of the ocular surface. In conclusion, studies strictly on ocular GvHD are needed to enable better evidence-based therapeutic decision-making in the future.
Assuntos
Oftalmopatias/terapia , Doença Enxerto-Hospedeiro/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Crônica , Progressão da Doença , Oftalmopatias/diagnóstico , Oftalmopatias/etiologia , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Humanos , Prognóstico , Acuidade VisualRESUMO
The number of hematopoietic stem cell transplantations is continuously increasing. On the one hand reduced intensity conditioning and improved supportive therapies allow for transplantations in patients with significant comorbidities and up to their eighth decade of life. Due to this development the number of complex and critically ill patients in need of intensive care is constantly growing. Recent developments in general critical care such as sepsis bundles and non-invasive ventilation contribute to a better outcome of these patients. However, treatment algorithms that identify patients potentially benefitting from intensive care but also reduce overtreatment of moribund patients represent a central multidisciplinary challenge not only for the treating transplant physician and intensivist.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/tendências , Insuficiência de Múltiplos Órgãos/terapia , Medicina Baseada em Evidências , Humanos , Resultado do TratamentoRESUMO
The optimal conditioning for patients with higher risk MDS receiving potentially curative allogeneic haematopoietic stem cell transplant(allo-HCT) remains to be defined. This is particularly the case for patients with excess of blasts at time of allo-HCT. Sequential (Seq) conditioning, whereby chemotherapy is followed rapidly by transplant conditioning, offers an opportunity to decrease disease burden, potentially improving outcomes allo-HCT outcomes. Herein we present the only analysis comparing Seq to myeloablative (MAC) and reduced intensity conditioning (RIC) specifically focussed on MDS patients with excess of blasts at allo-HCT. 303 patients were identified in the EBMT registry, receiving RIC (n = 158), Seq (n = 105), and MAC (n = 40). Median follow-up was 67.2 months and median age at allo-HCT was 59.5 years (IQR 53.5-65.6). For the entire cohort, 3 y overall survival (OS) was 50% (95% CI 45-56%) and relapse free survival (RFS) 45% (95% CI 40-51%). No significant differences in OS (log-rank p = 0.13) and RFS (log-rank p = 0.18) were observed between conditioning protocols. On multivariable analysis, lower performance status, worse IPSS-R cytogenetics, sibling donor (compared to 8/8 MUD) and ≥20% blasts at allo-HCT were associated with worse outcomes. In conclusion, the Seq protocol did little to influence the outcome in this high-risk group of patients, with outcomes mostly determined by baseline disease risk and patient characteristics such as performance status.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas , Humanos , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Transplante Homólogo/métodos , Recidiva Local de Neoplasia , Síndromes Mielodisplásicas/terapia , Doença Crônica , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Doença Enxerto-Hospedeiro/etiologiaRESUMO
The objectives of the present study were to elucidate the factors influencing the pharmacokinetics of prophylactically administered posaconazole in allogeneic hematopoietic stem cell transplant (SCT) recipients. Between May 2007 and November 2008, clinical data were obtained from all SCT recipients at the University Hospital of Cologne undergoing therapeutic drug monitoring (TDM) of serum prophylactic posaconazole concentrations. The posaconazole concentrations were determined by high-performance liquid chromatography. We developed a population pharmacokinetic model using nonlinear mixed-effect modeling (NONMEM). The list of covariates tested included age; body weight; body height; gender; posaconazole dose; race; coadministration of antineoplastic chemotherapy; day of stem cell transplantation; concomitant ranitidine, pantoprazole, cyclosporine, or tacrolimus administration; coincident fever; diarrhea; and plasma gamma-glutamyltransferase activity. A total of 149 serum posaconazole concentrations from 32 patients were obtained. A one-compartment model with first-order absorption and elimination as the basic structural model appropriately described the data, with the apparent clearance being 75.8 liters/h (95% confidence interval [CI], 65.2 to 86.4 liters/h) and the apparent volume being distribution of 835 liters (95% CI, 559 to 1,111 liters). Among the covariates tested, significant effects were found for age (decrease in the volume of distribution of 123 liters per year of age) and the presence of diarrhea (59% loss of bioavailability). A basis for prediction of the mean posaconazole concentrations in allogeneic SCT recipients with hematological malignancies is provided for a given dose. Corresponding adjustments of the starting dose according to the presence of diarrhea and according to age appear to be justified before TDM results are available.
Assuntos
Antifúngicos/farmacocinética , Antifúngicos/uso terapêutico , Micoses/prevenção & controle , Transplante de Células-Tronco , Triazóis/farmacocinética , Triazóis/uso terapêutico , Adolescente , Adulto , Idoso , Algoritmos , Antifúngicos/administração & dosagem , Cromatografia Líquida de Alta Pressão , Estudos de Coortes , Interações Medicamentosas , Monitoramento de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , População , Triazóis/administração & dosagem , Adulto JovemRESUMO
Cells derived by trypsinization of neonatal golden hamster pancreas were cultured in modified Eagle's medium for 120 h in the presence of glucose (0.8 mg/ml) and for an additional 48 h in medium containing glucose (0.8 or 3.1 mg/ml) or tolbutamide (1,000 microg/ml) plus glucose (0.8 mg/ml). At day 7, cultures were stained differentially for light microscopy or examined by electron microscopy. Immunoreactive insulin (IRI) and immunoreactive glucagon (IRG) in the culture medium were measured by standard immunoassay procedures. Staining properties and ultrastructural appearance of cultured cells were comparable to those of the intact neonatal hamster pancreas. Cultures consisted predominantly of cells possessing aldehyde fuchsin positive (AF(+)) cytoplasmic granules resembling ultrastructurally those of the intact neonatal pancreatic beta cells and additionally, those of fibroblastoid, acinar, acino-insular, and aldehyde fuchsin negative (AF(-)) argyrophilic cells. IRI release rate by the cultured cells was increased in the presence of elevated glucose or tolbutamide which paralleled the loss of AF(+) granulation, but IRG release rate was suppressed by elevated glucose concentration. These findings indicate that these monolayer cultures consist of most of the cell types occurring in the neonatal pancreas, including endocrinologically competent islet cells.
Assuntos
Pâncreas/citologia , Animais , Animais Recém-Nascidos , Anticorpos , Bovinos , Células Cultivadas , Cricetinae , Estudos de Avaliação como Assunto , Glucagon/análise , Glucose/farmacologia , Histocitoquímica , Insulina/análise , Insulina/metabolismo , Anticorpos Anti-Insulina , Secreção de Insulina , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/metabolismo , Métodos , Microscopia Eletrônica , Pâncreas/efeitos dos fármacos , Radioimunoensaio , Coloração e Rotulagem , Suínos , Fatores de Tempo , Tolbutamida/farmacologia , TripsinaAssuntos
Doença Enxerto-Hospedeiro , Insulina , Soluções Oftálmicas , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Crônica , Oftalmopatias/etiologia , Oftalmopatias/tratamento farmacológico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas , Insulina/administração & dosagem , Soluções Oftálmicas/uso terapêuticoRESUMO
Disruption of intestinal microbial communities appears to underlie many human illnesses, but the mechanisms that promote this dysbiosis and its adverse consequences are poorly understood. In patients who received allogeneic hematopoietic cell transplantation (allo-HCT), we describe a high incidence of enterococcal expansion, which was associated with graft-versus-host disease (GVHD) and mortality. We found that Enterococcus also expands in the mouse gastrointestinal tract after allo-HCT and exacerbates disease severity in gnotobiotic models. Enterococcus growth is dependent on the disaccharide lactose, and dietary lactose depletion attenuates Enterococcus outgrowth and reduces the severity of GVHD in mice. Allo-HCT patients carrying lactose-nonabsorber genotypes showed compromised clearance of postantibiotic Enterococcus domination. We report lactose as a common nutrient that drives expansion of a commensal bacterium that exacerbates an intestinal and systemic inflammatory disease.
Assuntos
Enterococcus/crescimento & desenvolvimento , Microbioma Gastrointestinal , Doença Enxerto-Hospedeiro/microbiologia , Transplante de Células-Tronco Hematopoéticas , Lactose/metabolismo , Idoso , Animais , Disbiose , Enterococcus/genética , Enterococcus/metabolismo , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/genética , Humanos , Intestinos/microbiologia , Masculino , Camundongos , Microbiota , Pessoa de Meia-Idade , RNA Ribossômico 16S , Análise de Sequência de RNA , Transplante HomólogoRESUMO
Recent data link the incidence of intestinal GvHD (iGvHD) after allogeneic haematopoietic stem cell transplantation (aSCT) to exposure with piperacillin-tazobactam or imipenem-cilastatin. To assess relevance of timing, duration, sequence and combination of antibiotic treatment in this setting, we applied a time-dependent model to our aSCT cohort. Patients from the prospective Cologne Cohort of Neutropenic Patients (CoCoNut) undergoing aSCT from January 2007 to April 2013 were included into a time-dependent multivariate Cox proportional hazards regression model with backward-stepwise selection. In 399 eligible patients, cumulative antibiotic exposure (hazard ratio (HR) 2.46; 95% confidence interval (95% CI) 1.59-3.81; P<0.001) and exposure to sequential treatment with penicillin derivatives and carbapenems (HR 6.22, 95% CI 1.27-30.31), but not to the individual classes, were associated with iGvHD at day 100. Glycopeptides were assessed as a risk factor (HR 3.73, 95% CI 1.51-9.19), but not considered independent, since their use was dependent on previous exposure to penicillin derivatives and carbapenems. Patients with iGvHD presented with increased non-relapse mortality at day 365 (HR 3.51; 95% CI 2.10-5.89; P<0.001). We identified sequential exposure to penicillin derivatives and carbapenems as well as overall exposure to antibiotics as independent risk factors for iGVHD. Confirmation of these findings in larger, prospective cohorts is necessary.
Assuntos
Antibacterianos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/métodos , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
The Dutch-Belgian Cooperative Trial Group for Hematology Oncology Group-65/German-speaking Myeloma Multicenter Group-HD4 (HOVON-65/GMMG-HD4) phase III trial compared bortezomib (BTZ) before and after high-dose melphalan and autologous stem cell transplantation (HDM, PAD arm) compared with classical cytotoxic agents prior and thalidomide after HDM (VAD arm) in multiple myeloma (MM) patients aged 18-65 years. Here, the long-term follow-up and data on second primary malignancies (SPM) are presented. After a median follow-up of 96 months, progression-free survival (censored at allogeneic transplantation, PFS) remained significantly prolonged in the PAD versus VAD arm (hazard ratio (HR)=0.76, 95% confidence interval (95% CI) of 0.65-0.89, P=0.001). Overall survival (OS) was similar in the PAD versus VAD arm (HR=0.89, 95% CI: 0.74-1.08, P=0.24). The incidence of SPM were similar between the two arms (7% each, P=0.73). The negative prognostic effects of the cytogenetic aberration deletion 17p13 (clone size ⩾10%) and renal impairment at baseline (serum creatinine >2 mg dl-1) on PFS and OS remained abrogated in the PAD but not VAD arm. OS from first relapse/progression was similar between the study arms (HR=1.02, P=0.85). In conclusion, the survival benefit with BTZ induction/maintenance compared with classical cytotoxic agents and thalidomide maintenance is maintained without an increased risk of SPM.
Assuntos
Bortezomib/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Adolescente , Adulto , Idoso , Aberrações Cromossômicas/efeitos dos fármacos , Feminino , Seguimentos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Melfalan/uso terapêutico , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/patologia , Prognóstico , Intervalo Livre de Progressão , Talidomida/uso terapêutico , Transplante Autólogo/métodos , Adulto JovemRESUMO
The International Prognostic Scoring System has been revised (IPSS-R) to predict prognosis of patients with myelodysplastic syndromes at diagnosis. To validate the use of the IPSS-R assessed before transplant rather than at diagnosis we performed a retrospective analysis of the EBMT database. A total of 579 patients had sufficient information available to calculate IPSS-R at transplant. Median overall survival (OS) from transplant was significantly different according to IPSS-R: very low 23.6 months, low 55.0 months, intermediate 19.7 months, high 13.5 months, very high 7.8 months (P<0.001). In a multivariate Cox model the following parameters were significant risk factors for OS: IPSS-R, graft source, age and prior treatment. Median relapse free survival also showed significant differences according to IPSS-R: very low: 23.6 months, low: 24.8 months, intermediate 10.6 months, high 7.9 months, very high 5.5 months (P<0.001). Multivariate risk factors for relapse-free survival (RFS) were: IPSS-R, reduced intensity conditioning, graft source and prior treatment. A trend for an increased relapse incidence was noted for very high risk IPSS-R. We conclude that the IPSS-R at transplant is a useful prognostic score for predicting OS and RFS after transplantation, capturing both disease evolution and response to prior treatment before transplant.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/diagnóstico , Síndromes Mielodisplásicas/diagnóstico , Prognóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Intervalo Livre de Doença , Feminino , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/terapia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Transplante Homólogo , Adulto JovemRESUMO
A 43-year-old woman with a past medical history of breast cancer and an acute myeloid leukemia (AML) presented with headache over a 3-week period. The clinical examination was completely unremarkable. CT and MRI scans showed a contrast enhancing lesion in the left temporal lobe. Histopathologic examination revealed a malignant, hematopoietic tumor with high mitotic activity, areas of necrosis and diffuse infiltration of the brain parenchyma. Positive staining for Chloroacetateesterase and lysozyme of tumor cells identified its myeloid lineage. The diagnosis was granulocytic sarcoma (GS)/chloroma, a metastatic manifestation of AML. Granulocytic sarcoma (GS) most often occurs in patients with AML, myelodysplastic syndromes and myeloproliferative disorders, and can involve any organ. However intracerebral manifestation of GS is a rare event. In this case histopathological features and differential diagnoses of intracerebral GS are discussed.
Assuntos
Neoplasias Encefálicas/patologia , Sarcoma Mieloide/patologia , Lobo Temporal/patologia , Adulto , Biomarcadores Tumorais , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Imageamento por Ressonância MagnéticaRESUMO
Tyrosine kinase inhibitors represent today's treatment of choice in chronic myeloid leukemia (CML). Allogeneic hematopoietic stem cell transplantation (HSCT) is regarded as salvage therapy. This prospective randomized CML-study IIIA recruited 669 patients with newly diagnosed CML between July 1997 and January 2004 from 143 centers. Of these, 427 patients were considered eligible for HSCT and were randomized by availability of a matched family donor between primary HSCT (group A; N=166 patients) and best available drug treatment (group B; N=261). Primary end point was long-term survival. Survival probabilities were not different between groups A and B (10-year survival: 0.76 (95% confidence interval (CI): 0.69-0.82) vs 0.69 (95% CI: 0.61-0.76)), but influenced by disease and transplant risk. Patients with a low transplant risk showed superior survival compared with patients with high- (P<0.001) and non-high-risk disease (P=0.047) in group B; after entering blast crisis, survival was not different with or without HSCT. Significantly more patients in group A were in molecular remission (56% vs 39%; P=0.005) and free of drug treatment (56% vs 6%; P<0.001). Differences in symptoms and Karnofsky score were not significant. In the era of tyrosine kinase inhibitors, HSCT remains a valid option when both disease and transplant risk are considered.
Assuntos
Antineoplásicos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Inibidores de Proteínas Quinases/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Família , Feminino , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Indução de Remissão , Risco , Análise de Sobrevida , Doadores de Tecidos , Transplante Homólogo , Resultado do TratamentoRESUMO
We describe a technique for examining unidirectional ion movements in suspensions of enzymatically disaggregated smooth muscle cells derived from stomach muscle of the toad. This technique has been used to analyze the movement of 42K across these cells. This analysis was greatly simplified by the finding that the cells were in a steady state with respect to K+ distribution after isolation. The potassium contents of the isolated cells were identical to those of intact smooth muscle (131 mM/liter intracellular fluid) and stable for over 4 h; moreover, the unidirectional influx and efflux rates were equal. An additional simplification was provided by the finding that virtually all the K+ exchanges in a manner predicted for a simple two-compartment system consisting of an extracellular and an intracellular space. Transmembrane K+ flux in these cells averaged 1.2 pmol.cm-2.s-1 at room temperature. A large portion (approximately 80%) of 42K influx appeared to be mediated by a saturable transport system with an apparent Km of 0.6 mM and an apparent Vmax of 1.3 pmol.cm-2.s-1. The calculated resting membrane permeability to K+ in these isolated smooth muscle cells, assuming a membrane potential of -50 mV, was 2.9 X 10(-8) cm/s. The calculated gK+ was 2.7 mumho/cm2 constituting only a small fraction of the total membrane conductance as measured electrophysiologically. The latter finding suggests that the resting membrane potential in the isolated cells must be determined by ions in addition to K+. We propose that these methods for studying ion movements in smooth muscle should aid in unraveling the mechanisms responsible for controlling the distribution of ions both at rest, as in the present study, as well as in response to neurotransmitters.
Assuntos
Eletrofisiologia/métodos , Músculo Liso/metabolismo , Potássio/metabolismo , Animais , Transporte Biológico Ativo , Bufo marinus/fisiologia , Mucosa Gástrica/metabolismo , Técnicas In Vitro , Cinética , Potenciais da Membrana , Músculo Liso/fisiologiaRESUMO
The optimum treatment conditions of interferon (IFN) alpha therapy in chronic myeloid leukemia (CML) are still controversial. To evaluate the role of hydroxyurea (HU) for the outcome of IFN therapy, we conducted a randomized trial to compare the combination of IFN and HU vs HU monotherapy (CML-study II). From February 1991 to December 1994, 376 patients with newly diagnosed CML in chronic phase were randomized. In all, 340 patients were Ph/BCR-ABL positive and evaluable. Randomization was unbalanced 1:2 in favor of the combination therapy, since study conditions were identical to the previous CML-study I and it had been planned in advance to add the HU patients of study I (n=194) to the HU control group. Therefore, a total of 534 patients were evaluable (226 patients with IFN/HU and 308 patients with HU). Analyses were according to intention-to-treat. Median observation time of nontransplanted living patients was 7.6 years (7.9 years for IFN/HU and 7.3 years for HU). The risk profile (new CML score) was available for 532 patients: 200 patients (38%) were low, 239 patients (45%) intermediate, and 93 patients (17%) high risk. Complete hematologic response rates were higher in IFN/HU-treated patients (59 vs 32%). Of 169 evaluable IFN/HU-treated patients (75%), 104 patients (62%) achieved a cytogenetic response that was complete in 12% (n=21), major in 14% (n=24), and at least minimal in 35% (n=59). Of the 534 patients, 105 (20%) underwent allogeneic stem cell transplantation in first chronic phase. In the low-risk group, 65 of 200 patients were transplanted (33%), 30 (13%) in the intermediate-risk group, and nine (10%) in the high-risk group. Duration of chronic phase was 55 months for IFN/HU and 41 months for HU (P<0.0001). Median survival was 64 months for IFN/HU and 53 months for HU-treated patients (P=0.0063). We conclude that IFN in combination with HU achieves a significant long-term survival advantage over HU monotherapy. In view of the data of CML-study I, these results suggest that IFN/HU is also superior to IFN alone. HU should be combined with IFN in IFN-based therapies and for comparisons with new therapies.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Hidroxiureia/administração & dosagem , Interferon-alfa/administração & dosagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Causas de Morte , Criança , Análise Citogenética , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Hidroxiureia/toxicidade , Masculino , Pessoa de Meia-Idade , Indução de Remissão/métodos , Medição de Risco , Análise de Sobrevida , Transplante HomólogoRESUMO
Meibomian gland loss in ocular GvHD was described as a mechanism contributing to dry eye and severe damage to the ocular surface. Infrared images of upper eyelid meibomian glands from 86 ocular GvHD patients, from 10 patients after allogeneic stem cell transplantation (aSCT) without ocular GvHD, from 32 patients prior to aSCT and from 30 healthy controls were analyzed retrospectively and evaluated using two grading schemes. The upper meibomian gland area (uMGA) was calculated and set in relation to the total tarsal area of the lid. Results demonstrate that meibomian gland loss is significantly increased in patients with ocular GvHD as well as in patients prior to aSCT in comparison with controls (P between 0.05 and <0.001). Patients after aSCT without ocular GvHD had no significant difference in uMGA in comparison with controls. This study suggests that meibomian gland loss in GvHD patients is likely to be a multifactorial process that also occurs prior to aSCT, possibly due to underlying diseases and/or secondary to chemotherapy or irradiation. In addition, the question has to be addressed whether meibomian gland loss could serve as a predictor for the development of ocular GvHD. Overall, infrared meibography should be included in routine examination of patients undergoing aSCT and during follow-up.