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High-intensity interval training (HIIT) is an effective alternative to moderate intensity continuous training for improvements in body composition and aerobic capacity; however, there is little work comparing different modalities of HIIT. The purpose of this study was to compare the effects of plyometric- (PLYO) and cycle-oriented (CYC) HIIT on body composition, aerobic capacity, and skeletal muscle size, quality, and function in recreationally trained females. Young (21.7 ± 3.1 yrs), recreationally active females were quasi-randomized (1:1 ratio) to 8 weeks of twice weekly PLYO (n = 15) or CYC (n = 15) HIIT. Body composition (four-compartment model), VO2peak, countermovement jump performance, muscle size, and echo intensity (muscle quality), as well as strength and power of the knee extensors and plantar flexors were measured before and after training. Both groups showed a similar decrease in body fat percentage (p < 0.001; η p 2 = 0.409) and echo intensity (p < 0.001; η p 2 = 0.558), and an increase in fat-free mass (p < 0.001; η p 2 = 0.367) and VO2peak (p = 0.001; η p 2 = 0.318). Muscle size was unaffected (p > 0.05), whereas peak torque was reduced similarly in both groups (p = 0.017; η p 2 = 0.188) and rapid torque capacity was diminished only for the knee extensors after CYC (p = 0.022; d = -0.67). These results suggest that PLYO and CYC HIIT are similarly effective for improving body composition, aerobic capacity, and muscle quality, whereas muscle function may express moderate decrements in recreationally active females. ClinicalTrials.gov (NCT05821504).
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Entrenamiento de Intervalos de Alta Intensidad , Humanos , Femenino , Entrenamiento de Intervalos de Alta Intensidad/métodos , Ejercicio Físico/fisiología , Composición Corporal/fisiología , Músculo Esquelético , Tolerancia al EjercicioRESUMEN
BACKGROUND AND OBJECTIVES: Many hospitals require transfusions to be discontinued when vital signs stray from predetermined ranges, regardless of clinical symptoms. Variations in vital signs may be unrelated to transfusion, however, and needlessly stopping a transfusion may delay medical care while increasing donor exposures and healthcare costs. We hypothesized that a detailed study of vital sign changes associated with transfusion of blood product by component, including those associated with potential reactions (complicated) and those deemed to be uncomplicated, would establish a useful framework of reference for treating clinicians and transfusion services alike. MATERIALS AND METHODS: A retrospective electronic record review of transfusion service and transfusion recipient data was completed on 3852 inpatient transfusion episodes over a 6-month period at four academic tertiary care hospitals across the United States. Vital signs pre- and post-transfusion were recorded by trained clinical research nurses. Serious reactions were adjudicated by a panel of transfusion medicine experts. RESULTS: In both uncomplicated transfusions (n = 3765) and those including an adverse reaction (n = 87), vital sign fluctuations were generally modest. Compared to uncomplicated transfusions, transfusions complicated by febrile reactions were associated with higher pretransfusion temperature and higher pretransfusion pulse rates. Episodes of transfusion circulatory overload were associated with higher pretransfusion respiration rates compared to uncomplicated transfusions. CONCLUSION: Most transfusions are associated with only modest changes in vital signs. Pretransfusion vital signs may be an important yet previously understudied predictor of vital sign changes during transfusion. The optimal role of vital sign assessment during blood transfusion deserves further study.
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Reacción a la Transfusión/diagnóstico , Signos Vitales , Transfusión Sanguínea/métodos , Transfusión Sanguínea/normas , HumanosRESUMEN
The New European Wind Atlas project will create a freely accessible wind atlas covering Europe and Turkey, develop the model chain to create the atlas and perform a series of experiments on flow in many different kinds of complex terrain to validate the models. This paper describes the experiments of which some are nearly completed while others are in the planning stage. All experiments focus on the flow properties that are relevant for wind turbines, so the main focus is the mean flow and the turbulence at heights between 40 and 300 m. Also extreme winds, wind shear and veer, and diurnal and seasonal variations of the wind are of interest. Common to all the experiments is the use of Doppler lidar systems to supplement and in some cases replace completely meteorological towers. Many of the lidars will be equipped with scan heads that will allow for arbitrary scan patterns by several synchronized systems. Two pilot experiments, one in Portugal and one in Germany, show the value of using multiple synchronized, scanning lidar, both in terms of the accuracy of the measurements and the atmospheric physical processes that can be studied. The experimental data will be used for validation of atmospheric flow models and will by the end of the project be freely available.This article is part of the themed issue 'Wind energy in complex terrains'.
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BACKGROUND AND OBJECTIVES: Pathogen reduction technology using amustaline (S-303) was developed to reduce the risk of transfusion-transmitted infection and adverse effects of residual leucocytes. In this study, the viability of red blood cells (RBCs) prepared with a second-generation process and stored for 35 days was evaluated in two different blood centres. MATERIALS AND METHODS: In a single-blind, randomized, controlled, two-period crossover study (n = 42 healthy subjects), amustaline-treated (Test) or Control RBCs were prepared in random sequence and stored for 35 days. On day 35, an aliquot of 51 Cr/99m Tc radiolabeled RBCs was transfused. In a subgroup of 26 evaluable subjects, 24-h RBC post-transfusion recovery, mean life span, median life span (T50 ) and life span area under the curve (AUC) were analysed. RESULTS: The mean 24-h post-transfusion recovery of Test and Control RBCs was comparable (83·2 ± 5·2 and 84·9 ± 5·9%, respectively; P = 0·06) and consistent with the US Food and Drug Administration (FDA) criteria for acceptable RBC viability. There were differences in the T50 between Test and Control RBCs (33·5 and 39·7 days, respectively; P < 0·001), however, these were within published reference ranges of 28-35 days. The AUC (per cent surviving × days) for Test and Control RBCs was similar (22·6 and 23·1 per cent surviving cells × days, respectively; P > 0·05). Following infusion of Test RBCs, there were no clinically relevant abnormal laboratory values or adverse events. CONCLUSION: RBCs prepared using amustaline pathogen reduction meet the FDA criteria for post-transfusion recovery and are metabolically and physiologically appropriate for transfusion following 35 days of storage.
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Acridinas/farmacología , Conservación de la Sangre , Eritrocitos/efectos de los fármacos , Compuestos de Mostaza Nitrogenada/farmacología , Acridinas/química , Adulto , Anciano , Área Bajo la Curva , Supervivencia Celular/efectos de los fármacos , Isótopos de Cromo/química , Estudios Cruzados , Recuento de Eritrocitos , Transfusión de Eritrocitos/efectos adversos , Eritrocitos/química , Eritrocitos/citología , Eritrocitos/metabolismo , Femenino , Semivida , Hematoma/etiología , Humanos , Marcaje Isotópico , Masculino , Viabilidad Microbiana/efectos de los fármacos , Persona de Mediana Edad , Compuestos de Mostaza Nitrogenada/química , Curva ROC , Método Simple Ciego , Tecnecio/química , Factores de Tiempo , Inactivación de Virus/efectos de los fármacos , Adulto JovenRESUMEN
BACKGROUND: The concordance of haemovigilance criteria developed for surveillance of transfusion-associated circulatory overload (TACO) with its clinical diagnosis has not been assessed. In a pilot study to evaluate an electronic screening algorithm, we sought to examine TACO incidence and application of haemovigilance criteria in patients with post-transfusion pulmonary oedema. STUDY DESIGN AND METHODS: From June to September 2014, all transfused adult inpatients at four academic hospitals were screened with an algorithm identifying chest radiographs ordered within 12 h of blood component release. Patients with post-transfusion pulmonary oedema underwent case adjudication by an expert panel. TACO incidence was calculated, and clinical characteristics were compared with other causes of post-transfusion pulmonary oedema. RESULTS: Among 4932 transfused patients, there were 3412 algorithm alerts, 50 cases of TACO and 47 other causes of pulmonary oedema. TACO incidence was 1 case per 100 patients transfused. TACO classification based on two sets of haemovigilance criteria (National Healthcare Safety Network and proposed revised International Society for Blood Transfusion) was concordant with expert panel diagnosis in 57% and 54% of reviewed cases, respectively. Although the majority of clinical parameters did not differentiate expert panel adjudicated TACO from other cases, improved oxygenation within 24 h of transfusion did (P = 0·01). CONCLUSIONS: The incidence of TACO was similar to that observed in prior studies utilizing active surveillance. Case classification by haemovigilance criteria was frequently discordant with clinical diagnoses of TACO in patients with post-transfusion pulmonary oedema. Improvements in oxygenation within 24 h of transfusion merit further evaluation in the diagnosis of TACO.
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Algoritmos , Edema Pulmonar/etiología , Reacción a la Transfusión , Lesión Pulmonar Aguda/epidemiología , Lesión Pulmonar Aguda/etiología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Hospitales Universitarios , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Edema Pulmonar/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
We have previously shown that tolerance of kidney allografts across a full major histocompatibility complex (MHC) barrier can be induced in miniature swine by a 12-day course of high-dose tacrolimus. However, that treatment did not prolong survival of heart allografts across the same barrier. We have now tested the effect of cotransplanting an allogeneic heart and kidney from the same MHC-mismatched donor using the same treatment regimen. Heart allografts (n = 3) or heart plus kidney allografts (n = 5) were transplanted into MHC-mismatched recipients treated with high-dose tacrolimus for 12 days. As expected, all isolated heart allografts rejected by postoperative day 40. In contrast, heart and kidney allografts survived for >200 days with no evidence of rejection on serial cardiac biopsies. Heart/kidney recipients lost donor-specific responsiveness in cell-mediated lympholysis and mixed-lymphocyte reaction assays, were free of alloantibody and exhibited prolonged survival of donor, but not third-party skin grafts. Late (>100 days) removal of the kidney allografts did not cause acute rejection of the heart allografts (n = 2) and did not abrogate donor-specific unresponsiveness in vitro. While kidney-induced cardiac allograft tolerance (KICAT) has previously been demonstrated across a Class I disparity, these data demonstrate that this phenomenon can also be observed across the more clinically relevant full MHC mismatch. Elucidating the renal element(s) responsible for KICAT could provide mechanistic information relevant to the induction of tolerance in recipients of isolated heart allografts as well as other tolerance-resistant organs.
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Rechazo de Injerto/inmunología , Trasplante de Corazón , Trasplante de Riñón , Complejo Mayor de Histocompatibilidad/inmunología , Donantes de Tejidos , Tolerancia al Trasplante , Aloinjertos , Animales , Citometría de Flujo , Rechazo de Injerto/prevención & control , Supervivencia de Injerto , Inmunosupresores , Trasplante de Piel , Porcinos , Porcinos EnanosRESUMEN
BACKGROUND AND OBJECTIVES: Human neutrophil antibodies (HNA) have been associated with severe transfusion-related acute lung injury (TRALI). We identified HNA antibodies in a blood donor population and performed an observational lookback on patients who received products from these donors to determine whether TRALI was associated with these transfusions. MATERIALS AND METHODS: Human neutrophil antibodies were determined in 1171 blood donors (388 non-transfused males, 390 human leucocyte antigen (HLA) antibody-negative females and 393 HLA antibody-positive females) for IgG and IgM antibodies using a flow cytometric assay. Selected positive samples had a monoclonal antibody immobilization of granulocyte antigen (MAIGA) and neutrophil genotyping performed to confirm specificity. Lookback was performed on patients receiving blood from donors with positive samples by extracting recipient data from hospital medical records. An expert panel of three pulmonary critical care physicians reviewed the summarized data and assigned a diagnosis of TRALI, possible TRALI, cannot distinguish between TRALI and TACO, TACO and other. RESULTS: Eight donors had HNA antibodies of which five contributed to this lookback (3-HNA-specific antibodies, 2-HNA non-specific antibodies). Seventy-six blood products were transfused from these donors into individual patients. One patient developed TRALI that was associated with a donor with a non-specific HNA antibody as well as class-I and class-II HLA antibodies. CONCLUSION: The incidence of TRALI in this lookback was low and combined with low frequency of HNA antibodies in the donor population suggests not screening donors for HNA antibodies at this time is acceptable.
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Anticuerpos Anticitoplasma de Neutrófilos/sangre , Donantes de Sangre , Antígenos HLA/sangre , Neutrófilos/inmunología , Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Femenino , Antígenos HLA/inmunología , Humanos , Masculino , Neutrófilos/químicaRESUMEN
The incidence of weak D has been reported to be between 0.23 and 0.5 percent in Europe and 3.0 percent in the United States. All studies were performed before the introduction of monoclonal anti-D reagents. Using current commercial reagents, this study evaluated D+ samples for the presence of weak D. D+ donors, typed by the Olympus PK 7200, using diluted monoclonal blend anti-D and diluted polyclonal anti-D, were selected by sampling batches of 100 to 200 samples from the previous day's collection. Anti-D reagents used on the Olympus PK 7200 are required to detect RBCs with the weak D phenotype which do not agglutinate at immediate spin (IS) when tested with polyclonal anti-D by manual tube methods. More than 95 percent of donors tested were Caucasian. Using tube tests with two different monoclonal blend anti-D reagents and one polyclonal anti-D typing reagent, the presence or absence of the D antigen was evaluated after the IS reading. Donors found negative or weakly positive (< 2+) at IS were further typed for weak D by the IAT. The weak D samples were RHD genotyped by allele-specific PCR. Of 1,005 donors tested, 4 (0.4%) were classified as weak D by one or more anti-D reagents. Polyclonal anti-D reagent demonstrated weaker reactions when compared with the monoclonal blends. All weak D samples were found positive for exon 4, intron 4, and exon 10, a finding consistent with most D+ samples. The incidence of weak D found in this study is not significantly different from that found in earlier studies using polyclonal anti-D reagents.
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Tipificación y Pruebas Cruzadas Sanguíneas , Sistema del Grupo Sanguíneo Rh-Hr/análisis , Alelos , Tipificación y Pruebas Cruzadas Sanguíneas/instrumentación , Tipificación y Pruebas Cruzadas Sanguíneas/normas , Genotipo , Humanos , Incidencia , Indicadores y Reactivos/química , Indicadores y Reactivos/normas , Isoanticuerpos/química , Reacción en Cadena de la Polimerasa , Sistema del Grupo Sanguíneo Rh-Hr/genética , Globulina Inmune rho(D)Asunto(s)
Anestesia por Inhalación , Anestésicos por Inhalación/efectos adversos , Carboxihemoglobina/metabolismo , Hemólisis/fisiología , Isoflurano/análogos & derivados , Isoflurano/efectos adversos , Adulto , Anestésicos por Inhalación/análisis , Monóxido de Carbono/metabolismo , Desflurano , Femenino , Humanos , Isoflurano/análisisRESUMEN
Thrombotic thrombocytopenic purpura (TTP) is a syndrome characterized by microvascular thrombosis with thrombocytopenia and end-organ injury. Evidence suggests that platelet or endothelial cell injury may be initial pathological events in TTP. A number of factors in patient plasma, including immunoglobulins, have been proposed to mediate cellular injury in TTP. However, systematic analyses of TTP patient plasma for the presence of platelet or endothelial cell antibodies are lacking. We, therefore, analyzed 48 TTP patient plasma samples for the presence of platelet and endothelial cell antibodies by using enzyme-linked immunosorbent assay, flow cytometry, and microlymphocytotoxicity. Twelve of 48 TTP patient samples (25%) reacted against purified platelet glycoproteins. Nine (19%) also contained antibodies that bound to allogeneic target platelets in flow-cytometric assays. Nine of 48 samples (19%) contained antibodies to human umbilical vein endothelial cells in flow-cytometric assays, and seven of 48 patient samples (15%) bound to human dermal microvascular endothelial cells. Six of 48 (13%) patient plasma samples contained antibodies that bound to human umbilical vein endothelial cells activated with gamma-interferon and tumor necrosis factor-alpha. Of twenty samples that were reactive in one or more platelet or endothelial cell assay, eight contained human leukocyte antigen antibodies reactive in microlymphocytotoxicity. These studies demonstrate that antibodies reactive against platelet or endothelial cell antigens are not prevalent in TTP, and that more than a third of antibodies detected are human leukocyte antigen alloantibodies. Our findings suggest that autoantibodies against platelets or endothelial cells are not important in the pathogenesis of this syndrome.
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Autoanticuerpos/sangre , Plaquetas/inmunología , Endotelio Vascular/inmunología , Inmunoglobulina G/inmunología , Inmunoglobulina M/inmunología , Glicoproteínas de Membrana Plaquetaria/inmunología , Púrpura Trombocitopénica Trombótica/inmunología , Células Cultivadas , Citotoxicidad Inmunológica , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Humanos , Púrpura Trombocitopénica Trombótica/sangre , Venas UmbilicalesRESUMEN
Thrombotic thrombocytopenic purpura (TTP) is characterized by micro-angiopathic hemolytic anemia (MAHA), thrombocytopenia, neurological symptoms, renal involvement, and fever. We describe our experience in 70 serially encountered TTP patients in the last decade who were treated with a standard therapeutic plasma exchange (TPE) protocol. Seventy percent of the patients were females. The median age of the patients was 43 years (range: 8-80). Sixty patients (85.7%) had a complete response to TPE therapy. This represented 91% of 66 who received at least one TPE. Ten patients died, two patients died before and two during the first plasma exchange. The median number of TPEs performed was nine (range: 1-85). Thirty-five (58%) out of 60 responded to 3-9 TPEs, and 25 (42%) required 10-34 TPEs for the response. The median total plasma volume exchanged was 28 liters (range: 2.7-250 L) and the mean plasma volumes exchanged during each procedure was 3.2 (SD +/- 1.09 L). The patients were classified into early responders (ER) and late responders (LR). ERs had a mean platelet count of 180 x 10(9)/L by Day 5, mean LDH of 643 IU/L by Day 7, and required median of seven TPEs. LRs had a mean platelet count of 122 x 10(9)/L by Day 5, mean LDH of 885 IU/L by Day 7, and required median of 19 TPEs (P = 0.001). The platelet counts were significantly higher (P = 0.01-0.03) in ERs on Days 1, 3, and 5 as compared to LRs but the LDH did not differ significantly. Seventy-seven percent of LRs had exacerbation of TTP and 18% had relapse as compared to 7% each in ERs. Thirteen patients were in coma/semicoma at presentation. Out of these, six died, making coma a bad prognostic indicator. Five of the seven survivors in coma had received two single-plasma volume exchanges on Day 1. In conclusion, 91% of TTP patients had an excellent response to plasma exchange therapy with FFR Coma/ semicoma appears to be a bad prognostic indicator. LRs needed prolonged treatment with a greater number of patients experiencing exacerbation and relapse of TTP as compared to ERs.
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Intercambio Plasmático , Púrpura Trombocitopénica Trombótica/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Coma/etiología , Femenino , Humanos , Hipersensibilidad/etiología , Masculino , Persona de Mediana Edad , Intercambio Plasmático/efectos adversos , Púrpura Trombocitopénica Trombótica/mortalidad , Recurrencia , Estudios Retrospectivos , Factores de Tiempo , Reacción a la Transfusión , Resultado del TratamientoRESUMEN
The development of immune-mediated hemolytic anemia is a well-recognized complication after allogeneic bone marrow transplantation (BMT). The majority of reported cases, however, have been alloimmune in origin due to ABO or minor red blood cell antigen incompatibilities between the donor and recipient. In this study, we report seven adult patients who developed autoimmune hemolytic anemia (AIHA) between June 1985 and January 1993. These patients were identified from a total of 236 adult patients who received T cell-depleted (TCD) grafts as graft-versus-host disease (GVHD) prophylaxis. The onset of AIHA was at a median of 10 months (range 7-25 months) post-transplant and occurred in 5% of all patients transplanted with TCD grafts who survived at least 6 months. Six patients had a warm reacting autoantibody, while one patient had a cold-reacting antibody with a thermal amplitude up to 30 degrees C. All were receiving immunosuppressive treatment for GVHD at the time of diagnosis. Initial treatment in all patients consisted of steroids. Three of the seven had a partial response while the four remaining patients failed to respond to corticosteroids. Splenectomy was performed in three patients with two partial responses. Four patients were treated with additional therapeutic interventions, including plasmapheresis, immunoglobulin infusions, staphylococcus protein A column, or other immunosuppressive agents. In five cases, erythropoietin was administered as adjunctive treatment to maintain adequate hematocrit levels. Two patients are presently in complete remission after prolonged courses of steroids, while a third patient has compensated hemolysis requiring low-dose steroids. Four patients died due to either infectious complications or disseminated intravascular coagulation secondary to cold agglutinin disease. These data indicate that AIHA is a clinically significant and not infrequent complication in allogeneic marrow transplant recipients. The response to conventional treatment is generally unsatisfactory as even patients who ultimately remit require prolonged courses of immunosuppressive therapy.
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Anemia Hemolítica Autoinmune/etiología , Trasplante de Médula Ósea/efectos adversos , Depleción Linfocítica , Linfocitos T/fisiología , Adolescente , Adulto , Anemia Hemolítica Autoinmune/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trasplante HomólogoRESUMEN
Quinine-induced immune thrombocytopenia with hemolytic uremic syndrome (HUS) is a recently defined clinical entity. In this paper we have attempted to characterize the natural history and laboratory abnormalities typical of quinine-induced immune thrombocytopenia associated with hemolytic uremic syndrome in nine patients experiencing ten episodes of the disease. In addition, review of other reported cases of probable quinine-induced HUS is presented. The disease was characterized by the onset of chills, diapheresis, nausea and vomiting, abdominal pain, decreased urine output, and petechiae following quinine exposure. All patients experience significant anemia, severe thrombocytopenia, increased lactate dehydrogenase, elevated serum creatinine, and oliguria. Quinine-dependent platelet-reactive antibodies were identified in eight of nine using flow cytometry. Unexpectedly, drug-dependent antibodies reactive with red cells and granulocytes were identified in four and eight patients, respectively. All patients were treated with plasma exchange (range 1-12 procedures), and seven required hemodialysis. All survive without residual abnormality. Our experience with nine patients with quinine-induced HUS and the nine additional cases reported by others and reviewed in this paper establishes this condition as a distinct clinical entity. Adult patients presenting with HUS should routinely be asked about exposure to quinine in the form of medication or beverages. The mechanism by which quinine-dependent antibodies produce renal failure is uncertain, but preliminary studies (described elsewhere) suggest that drug-induced antibodies reactive with endothelial cells and possibly margination of granulocytes in renal glomeruli may be responsible for this complication. The prognosis in quinine-induced HUS is better than in other forms of adult HUS.
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Síndrome Hemolítico-Urémico/inducido químicamente , Quinina/efectos adversos , Trombocitopenia/inducido químicamente , Adulto , Anciano , Autoanticuerpos/inmunología , Femenino , Síndrome Hemolítico-Urémico/sangre , Síndrome Hemolítico-Urémico/inmunología , Humanos , Masculino , Persona de Mediana Edad , Neutrófilos/inmunología , Glicoproteínas de Membrana Plaquetaria/inmunología , Trombocitopenia/sangre , Trombocitopenia/inmunologíaRESUMEN
Four children with acute lymphocytic leukemia who had disseminated varicella were treated with infusions of apheresed, irradiated lymphocytes from healthy donors who had recently recovered from infection with varicella-zoster virus. Each patient had cessation of new lesion formation and umbilication of old lesions within 24 hours of the first lymphocyte transfusion. There were no side effects attributable to the infusions. A controlled trial of infusions of irradiated lymphocytes should be considered for treatment of disseminated infection with varicella-zoster virus in immunocompromised hosts.
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Varicela/terapia , Transfusión de Linfocitos , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Varicela/etiología , Varicela/inmunología , Niño , Preescolar , Femenino , Humanos , Huésped Inmunocomprometido , Linfocitos/efectos de la radiación , Masculino , Donantes de TejidosRESUMEN
Nutritionally physiological patterns of Pseudallescheria boydii (Microascaceae) and the related species Scedosporium prolificans were established. Differences between the two species were found in assimilation of sucrose, ribitol, xylitol and L-arabinitol. In contrast, no physiological distinction could be made between the three intraspecific variants of P. boydii which have been recognized on the basis of nDNA/DNA homology data and of morphological and clinical differences. Some potential virulence factors were studied in the fungi mentioned above and in some related anamorphs. All species were capable of anaerobic growth, but differed in their temperature relations.
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Pseudallescheria/fisiología , Anaerobiosis , Ecología , Humanos , Especificidad de la Especie , Esporas FúngicasRESUMEN
Eight patients who had hematologic relapse of chronic myelogenous leukemia (CML) after undergoing allogeneic bone marrow transplantation (BMT) were treated with leukocyte infusions from the original bone marrow donors. All patients had previously received marrow grafts from HLA-identical siblings. Six patients were in the accelerated phase of their disease and two were in blast crisis. Each patient received a predetermined T-cell dose within a narrow range of 2.5 to 5.0 x 10(8) T cells/kg. Three patients also received short courses of therapy with alpha interferon to control elevated white blood cell counts within the first several weeks after leukocyte transfusions. Seven of eight evaluable patients developed graft-versus-host disease (GVHD) at a median of 32 days after the initial infusion. One patient had fatal GVHD. A second patient had grade 3 acute GVHD, which has responded to immunosuppressive therapy. The remaining patients all had mild grade I GVHD. Six patients continue to require modest doses of prednisone more than 6 months after infusion. Four patients developed marrow aplasia, which in three patients required marrow boosts from the original donors. Two of these three patients have normal hematopoietic function, whereas the third patient remains growth factor and transfusion dependent. Both patients treated in blast crisis have died, one from GVHD and one from disease progression. All six patients in the accelerated phase are alive and in cytogenetic remission at a median of 42 weeks after infusion. Five of these six patients are in molecular remission. This study demonstrates that leukocyte infusions that administered a defined T-cell dose can exert a profound graft-versus-leukemia effect and are an effective form of salvage immunotherapy in allogeneic marrow transplant recipients. This therapeutic approach appears to be a viable alternative to existing chemotherapeutic and immunomodulatory strategies for the treatment of relapsed CML.
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Trasplante de Médula Ósea , Inmunoterapia Adoptiva , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Terapia Recuperativa , Linfocitos T/inmunología , Adulto , Trasplante de Médula Ósea/efectos adversos , Quimera , Terapia Combinada , Femenino , Enfermedad Injerto contra Huésped/etiología , Humanos , Inmunofenotipificación , Inmunoterapia Adoptiva/efectos adversos , Masculino , Persona de Mediana Edad , Recurrencia , Trasplante HomólogoRESUMEN
Recognition of the seriousness of transfusion-transmitted diseases has been demonstrated by U.S. medical schools through the integration of transfusion medicine (TM) content into their curricula. To evaluate the degree to which these changes in curricula have been reflected in the National Board of Medical Examiners' (NBME) examinations, a study conducted in 1991 evaluated the proportions of TM-related items on Parts I and II of the NBME examinations for 1984-1985 versus 1989-1990. Both Part I (basic sciences) and Part II (clinical sciences) demonstrated significant gains in TM items between the comparison periods (p less than .001), with Part II having the higher gain. An analysis of students' knowledge revealed that students in 1989-1990 tended to perform better on TM items than on examination items generally. The increases in TM content and student performance on TM items on the 1989-1990 examinations suggest that the national effort to expand and improve teaching of TM in U.S. medical schools has been effective.
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Transfusión Sanguínea , Curriculum , Educación de Pregrado en Medicina/normas , Evaluación Educacional/normas , Licencia Médica/normas , Educación de Pregrado en Medicina/tendencias , Estudios de Evaluación como Asunto , Humanos , Licencia Médica/tendenciasRESUMEN
Donor leukocyte infusions were administered to a patient who had relapsed with chronic myelogenous leukemia after having failed two successive HLA-matched allogeneic bone marrow transplants. Serial cytogenetic, restriction fragment length polymorphism, and polymerase chain reaction studies of the patient's marrow and blood after receiving donor leukocyte infusions revealed disappearance of the leukemic clone and the establishment of complete donor chimerism. An antileukemic response in this patient occurred initially in the absence of clinically evident graft-versus-host disease (GVHD), but complete eradication of the leukemic clone did not occur until after the onset of GVHD. The patient is now 48 weeks post infusion and remains in complete remission. This case demonstrates that leukocyte infusions are an effective form of adoptive immunotherapy which can result in a sustained molecular remission.
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Trasplante de Médula Ósea , Leucemia Mielógena Crónica BCR-ABL Positiva/cirugía , Leucemia Mieloide de Fase Acelerada/cirugía , Transfusión de Leucocitos , Adulto , Trasplante de Médula Ósea/inmunología , ADN de Neoplasias/genética , Femenino , Enfermedad Injerto contra Huésped/inmunología , Humanos , Inmunoterapia Adoptiva , Leucemia Mielógena Crónica BCR-ABL Positiva/inmunología , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Leucemia Mieloide de Fase Acelerada/inmunología , Leucemia Mieloide de Fase Acelerada/terapia , Leucocitos/inmunología , Recurrencia , Donantes de Tejidos , Trasplante HomólogoAsunto(s)
Enfermedades Autoinmunes/terapia , Fiebre/inducido químicamente , Técnicas de Inmunoadsorción/efectos adversos , Púrpura Trombocitopénica Idiopática/terapia , Proteína Estafilocócica A/efectos adversos , Urticaria/inducido químicamente , Vasculitis/inducido químicamente , Adulto , Cromatografía de Afinidad , Femenino , Humanos , Hipotensión/inducido químicamente , Incidencia , Prednisona/uso terapéutico , Púrpura Trombocitopénica Idiopática/complicaciones , Enfermedad del Suero , Vasculitis/epidemiologíaRESUMEN
Appropriate postpartum administration of Rh immune globulin relies on sensitive detection and accurate quantitation of fetomaternal hemorrhage (FMH). Recently, the microscopic Du test (micro Du) enhanced with polyethylene glycol (PEG Du) and flow cytometry (FC) have been advocated for this purpose. Three qualitative methods (micro Du, rosette test, and PEG Du) and two quantitative methods (acid elution and FC) for assessing FMH were evaluated with particular attention given to PEG Du and FC. In vitro studies comprised 10 series of dilutions of D+ cord cells in D- adult cells to yield D+ cell concentrations of 0.06, 0.12, 0.25, 0.50, 0.75, 1.0, and 2.0 percent. Additionally, 26 postpartum samples were tested. Of the qualitative techniques, the micro Du test was the least sensitive with 20 percent false-negative results occurring at 0.5 percent fetal cells. The PEG Du test was only slightly more sensitive and offered no clinical advantage. The rosette test was the most sensitive, consistently detecting fetal cells at concentrations of 0.25 percent or greater. FC and acid elution showed similar results, with good correlation obtained between measured and expected quantities of fetal cells (r = 0.99 and 0.96, respectively). One of 26 postpartum samples was positive by all screening techniques; acid elution and FC detected 0.3-percent concentrations of fetal cells and 0.17-percent concentrations of D+ cells, respectively. Although acid elution is a more commonly used method for quantitating FMH, FC offers an acceptable alternative that is capable of analyzing large numbers of cells with objectivity and reproducibility.