RESUMEN
BACKGROUND: GPs detect at best 50c of mental health problems in young people. Barriers to detecting mental health problems include lack of screening tools, limited appointment times and young people's reluctance to report mental health symptoms to GPs. The mobiletype program is a mobile phone mental health assessment and management application which monitors mood, stress and everyday activities then transmits this information to general practitioners (GPs) via a secure website in summary format for medical review. The current aims were to examine: (i) mobiletype as a clinical assistance tool, ii) doctor-patient rapport and, iii) pathways to care. METHODS: We conducted a randomised controlled trial in primary care with patients aged 14 to 24 years recruited from rural and metropolitan general practices. GPs identified and referred eligible participants (those with mild or more mental health concerns) who were randomly assigned to either the intervention group (where mood, stress and daily activities were monitored) or the attention-comparison group (where only daily activities were monitored). Both groups self-monitored for 2 to 4 weeks and reviewed the monitoring data with their GP. GPs, participants and researchers were blind to group allocation at randomisation. GPs assessed the mobiletype program as a clinical assistant tool. Doctor-patient rapport was assessed using the General Practice Assessment Questionnaire Communication and Enablement subscales, and the Trust in Physician Scale (TPS). Pathways to care was measured using The Party Project's Exit Interview. RESULTS: Of the 163 participants assessed for eligibility, 118 were randomised and 114 participants were included in analyses (intervention n = 68, attention-comparison n = 46). T-tests showed that the intervention program increased understanding of patient mental health, assisted in decisions about medication/referral and helped in diagnosis when compared to the attention-comparison program. Mixed model analysis showed no differences in GP-patient rapport nor in pathways to care. CONCLUSIONS: We conducted the first RCT of a mobile phone application in the mental health assessment and management of youth mental health in primary care. This study suggests that mobiletype has much to offer GPs in the often difficult and time-consuming task of assessment and management of youth mental health problems in primary care. TRIAL REGISTRATION: ClinicalTrials.gov NCT00794222.
Asunto(s)
Medicina General/instrumentación , Trastornos Mentales/diagnóstico , Trastornos Mentales/terapia , Aplicaciones Móviles , Atención Primaria de Salud/métodos , Adolescente , Afecto , Consumo de Bebidas Alcohólicas , Comunicación , Dieta , Método Doble Ciego , Femenino , Medicina General/métodos , Humanos , Masculino , Fumar Marihuana , Trastornos Mentales/psicología , Actividad Motora , Relaciones Médico-Paciente , Sueño , Estrés Psicológico/diagnóstico , Adulto JovenRESUMEN
BACKGROUND: Over 75% of mental health problems begin in adolescence and primary care has been identified as the target setting for mental health intervention by the World Health Organisation. The mobiletype program is a mental health assessment and management mobile phone application which monitors mood, stress, coping strategies, activities, eating, sleeping, exercise patterns, and alcohol and cannabis use at least daily, and transmits this information to general practitioners (GPs) via a secure website in summary format for medical review. METHODS: We conducted a randomised controlled trial in primary care to examine the mental health benefits of the mobiletype program. Patients aged 14 to 24 years were recruited from rural and metropolitan general practices. GPs identified and referred eligible participants (those with mild or more mental health concerns) who were randomly assigned to either the intervention group (where mood, stress, and daily activities were monitored) or the attention comparison group (where only daily activities were monitored). Both groups self-monitored for 2 to 4 weeks and reviewed the monitoring data with their GP. GPs, participants, and researchers were blind to group allocation at randomisation. Participants completed pre-, post-, and 6-week post-test measures of the Depression, Anxiety, Stress Scale and an Emotional Self Awareness (ESA) Scale. RESULTS: Of the 163 participants assessed for eligibility, 118 were randomised and 114 participants were included in analyses (intervention group n = 68, comparison group n = 46). Mixed model analyses revealed a significant group by time interaction on ESA with a medium size of effect suggesting that the mobiletype program significantly increases ESA compared to an attention comparison. There was no significant group by time interaction for depression, anxiety, or stress, but a medium to large significant main effect for time for each of these mental health measures. Post-hoc analyses suggested that participation in the RCT lead to enhanced GP mental health care at pre-test and improved mental health outcomes. CONCLUSIONS: Monitoring mental health symptoms appears to increase ESA and implementing a mental health program in primary care and providing frequent reminders, clinical resources, and support to GPs substantially improved mental health outcomes for the sample as a whole. TRIAL REGISTRATION: ClinicalTrials.gov NCT00794222.
Asunto(s)
Teléfono Celular , Trastornos Mentales/diagnóstico , Trastornos Mentales/terapia , Atención Primaria de Salud , Adolescente , Femenino , Humanos , Masculino , Método Simple Ciego , Adulto JovenRESUMEN
The majority of variation in six traits critical to the growth, survival and reproduction of plant species is thought to be organised along just two dimensions, corresponding to strategies of plant size and resource acquisition. However, it is unknown whether global plant trait relationships extend to climatic extremes, and if these interspecific relationships are confounded by trait variation within species. We test whether trait relationships extend to the cold extremes of life on Earth using the largest database of tundra plant traits yet compiled. We show that tundra plants demonstrate remarkably similar resource economic traits, but not size traits, compared to global distributions, and exhibit the same two dimensions of trait variation. Three quarters of trait variation occurs among species, mirroring global estimates of interspecific trait variation. Plant trait relationships are thus generalizable to the edge of global trait-space, informing prediction of plant community change in a warming world.
Asunto(s)
Desarrollo de la Planta , Tundra , Clima , Ecosistema , Plantas/clasificación , Plantas/genéticaRESUMEN
Monocyte esterase activity was studied in 1,000 doctor-attending patients with normal hematological indices and in 56 patients with non-Hodgkin's lymphoma (NHL) or B chronic lymphocytic leukemia (CLL). The incidence of esterase deficiency was significantly greater in the NHL-CLL patients (7.1%) than in the population group (1.7%; p less than 0.05). In the NHL-CLL group, study of the families showed the esterase deficiency to be a familial characteristic. We postulate that the presence of the anomaly may be either a factor predisposing to the development of the NHL or CLL or a factor indicating a predisposition to these disorders.
Asunto(s)
Esterasas/sangre , Trastornos Linfoproliferativos/enzimología , Monocitos/enzimología , Humanos , Isoenzimas/sangre , Leucemia Linfoide/enzimología , Leucemia Linfoide/genética , Linfoma no Hodgkin/enzimología , Linfoma no Hodgkin/genética , Trastornos Linfoproliferativos/genética , LinajeRESUMEN
Pregnancy is often referred to as a hypercoagulable state due to changes in the haemostatic system. Tissue factor (TF) is the initiator of blood clotting in vivo. The effect of pregnancy on monocyte TF expression was determined in a longitudinal case control study (89 pregnant, 39 non-pregnant). Using whole blood flow cytometry and CD14 as a monocyte marker, TF expression was measured on all CD14 positive, CD14Bright and CD14Dim cells. TF expression was significantly lower in pregnant women than in non-pregnant control subjects, on all CD14 positive cells at 20 and 35 weeks, on CD14Bright cells at 12 and 35 weeks and on CD14Dim cells at 20 weeks. Additionally, we report that a higher percentage of CD14Dim than CD14Bright cells express TF. These results suggest that, in order to maintain homeostasis in haemostasis in an otherwise hypercoagulable state, monocyte TF expression is reduced during normal pregnancy.
Asunto(s)
Monocitos/metabolismo , Embarazo/sangre , Tromboplastina/metabolismo , Adulto , Análisis de Varianza , Estudios de Casos y Controles , Femenino , Citometría de Flujo , Humanos , Recuento de Leucocitos , Receptores de Lipopolisacáridos/análisis , Estudios Longitudinales , Monocitos/citología , Embarazo/metabolismoRESUMEN
Cytokines, the central regulators of leucocyte growth and differentiation, are produced by a wide variety of cell types, target various cell subsets and exhibit numerous biological activities. Cytokine dysregulation is believed to play a role in the remodelling of the immune system in old age, however, previous reports of cytokine levels in elderly subjects have been conflicting, possibly due to methodologies employed. We used the relatively new technique of intracellular cytokine detection by flow cytometry to measure cytokine production in CD3+ lymphocytes from young and elderly subjects, but applied it to whole blood, thereby eliminating the need for laborious cell separation techniques and maintaining cells in their normal physiological environment. We found the assay to be very reproducible with acceptable intra- (2.9%) and inter- (6.3%) assay CVs. The percentages of CD3+ cells producing TNF-alpha and IFN-gamma were significantly higher in elderly compared to young people (p=0.0049; p=0.0026, respectively) after stimulation with PMA and ionomycin. Absolute counts of CD3+IFN-gamma+ and CD3+TNF-alpha+ cells were also significantly higher in the elderly group (p=0.039; p=0.051) respectively. There was no significant difference between the age groups for the percentage or numbers of IL-2-producing CD3+ cells on stimulation. CD3+ cells expressing TNF-alpha were highly associated with CD3+ cells expressing IFN-gamma in both elderly and young people. In contrast, IL-2 secreting CD3+ cells were associated with TNF-alpha and IFN-gamma producing CD3+ cells in young but not elderly subjects providing further evidence for the remodelling of the cytokine network associated with old age.
Asunto(s)
Envejecimiento/inmunología , Complejo CD3 , Interferón gamma/biosíntesis , Interleucina-2/biosíntesis , Linfocitos T/inmunología , Factor de Necrosis Tumoral alfa/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Envejecimiento/sangre , Biomarcadores , Femenino , Humanos , Líquido Intracelular/inmunología , Ionomicina/farmacología , Masculino , Linfocitos T/efectos de los fármacos , Acetato de Tetradecanoilforbol/farmacologíaRESUMEN
Aging is associated with changes in lymphocyte subsets and unexplained HLA-DR upregulation on T-lymphocytes. We further investigated this activation, by measuring early (CD69), middle (CD25), and late (HLA-DR) T-lymphocyte activation markers on CD3+ lymphocytes, across subjects (20-100 years) together with serum tumor necrosis factor (TNF-alpha), interferon-gamma (IFN-gamma), and soluble interleukin-2 receptor (sIL-2R). HLA-DR was present as a CD3+ HLA-DR+ subset that constituted 8% of total lymphocytes, increased twofold with age and included CD4+, CD8+, and CD45RA+ phenotypes. HLA-DR was also expressed on a CD8+ CD57+ subset. The CD3+ CD25+ subset constituted 13% of lymphocytes, fell with age but was weakly associated with the CD3+ HLA-DR+ subset especially in older subjects. A small 3-5% CD3+ CD69+ subsets showed no age effect. Serum sIL-2R, TNF-alpha, but not IFN-gamma, were associated with CD3+ HLA-DR+ lymphocytes, TNF-alpha with CD8+ CD57+ count and sIL-2R and IFN-gamma with the CD3+ CD25+/CD3+ CD4+ ratio. The study confirms age-related upregulation of HLA-DR on CD3+ lymphocytes, shows some evidence for associated upregulation of CD25 on CD3+ cells in older subjects, and links serum TNF-alpha, IFN-gamma, and sIL2-R to T-lymphocyte activation.
Asunto(s)
Envejecimiento/inmunología , Antígenos CD/análisis , Antígenos HLA-DR/análisis , Interferón gamma/sangre , Receptores de Interleucina-2/análisis , Factor de Necrosis Tumoral alfa/análisis , Anciano , Anciano de 80 o más Años , Antígenos de Diferenciación de Linfocitos T/análisis , Complejo CD3/análisis , Femenino , Humanos , Lectinas Tipo C , Activación de Linfocitos , MasculinoRESUMEN
ALK-positive diffuse large B-cell lymphoma is a rare, recently characterized lymphoma subtype that shows granular cytoplasmic ALK expression. This report describes a primary gastric ALK-positive B-lineage lymphoma in which a clathrin (CLTC)-ALK fusion was identified by RT-PCR and direct sequencing of the breakpoint. This confirmed the presence of t(2;17)(p23;q23) involving the CLTC gene and is only the 4th report of such a translocation in this lymphoma subtype and the first to describe this tumor within the stomach. As in previous reports, immunophenotyping showed the malignant cell to be a terminally differentiated B-lineage cell characterized by the absence of B-cell antigens and expression of antigens associated with plasma cell differentiation. This case confirms the existence of such a lymphoma subtype arising in extranodal locations and underscores the importance of detailed immunophenotyping and specialized molecular genetic investigations in confirming the diagnosis.
Asunto(s)
Clatrina/genética , Linfoma de Células B/genética , Linfoma de Células B Grandes Difuso/genética , Proteínas Tirosina Quinasas/genética , Neoplasias Gástricas/genética , Adulto , Quinasa de Linfoma Anaplásico , Secuencia de Bases , Humanos , Masculino , Datos de Secuencia Molecular , Proteínas Tirosina Quinasas Receptoras , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Translocación GenéticaRESUMEN
AIMS: To determine if leucocyte volume distribution analysis (LVDA), obtained using a Coulter Counter Model S Plus IV, can be used to aid differentiation of chronic lymphoproliferative disorder (CLPD) subtypes. METHODS: Mean lymphocyte volume and lymphocyte distribution width were measured on each patient (n = 90) using a hard copy of an amplified LVDA histogram. The mean lymphocyte volume was taken as the mean of the values on either side of the peak at half maximum height. The lymphocyte distribution width was taken as the range of cell values between the two values used to calibrate the mean lymphocyte volume. A template showing typical histograms from commonly occurring CLPD was also produced on an acetate sheet. This was used to examine the histogram from each new patient to evaluate its usefulness as an alternative to the calculation of mean lymphocyte volume and lymphocyte distribution width. RESULTS: Mean lymphocyte volume and lymphocyte distribution width were significantly higher in B cell lymphocytic leukaemia of mixed cell type (B CLL/PL), B cell non-Hodgkin's lymphoma with peripheral blood spill, hairy cell leukaemia and T cell prolymphocytic leukaemia than in B cell chronic lymphocytic leukaemia (B CLL). The mean lymphocyte volume, but not the lymphocyte distribution width, was also significantly higher in T cell chronic lymphocytic leukaemia than in B CLL. The template gave an immediate preliminary indication of possible subtype(s) of disorder and could be used as an alternative to measurement of mean lymphocyte volume and lymphocyte distribution width. CONCLUSIONS: Electronic haematology analysers producing an LVDA provide a useful, cost effective cell sizing analysis which can aid the differentiation of subtypes of CLPD.
Asunto(s)
Linfocitos/patología , Tamaño de la Célula , Diagnóstico Diferencial , Humanos , Leucemia de Células B/patología , Leucemia de Células Pilosas/patología , Leucemia Prolinfocítica/patología , Recuento de Leucocitos , Linfoma de Células B/patología , Trastornos Linfoproliferativos/patología , Síndrome de Sézary/patologíaRESUMEN
A 58 year old man presented in 1995 with a swollen testicle. After orchidectomy, a diagnosis of poorly differentiated lymphoma was made. Lymphoid, epithelial, and seminoma markers were all negative. Six months later he developed a buccal lesion, which was biopsied and reported as a high grade non-Hodgkin's lymphoma. It responded completely to chemotherapy but within a year he developed a forearm swelling, which was biopsied and imprints made before fixation of the material. Immunocytochemistry on the imprints showed positivity with antibodies to CD4, CD68, and muramidase, and the non-specific esterase cytochemical stain was strongly positive, leading to a diagnosis of true histiocytic lymphoma. Despite further treatment, the patient entered a terminal acute leukaemic phase, the blasts marking as monoblasts. Review of all the biopsies, including molecular investigations and further immunohistochemistry studies performed retrospectively on the original biopsy, demonstrated that this was the same malignant cell line throughout, and we conclude that this is a case of histiocytic lymphoma, initially presenting as a testicular tumour and terminating in acute monoblastic leukaemia. A diagnosis of histiocytic lymphoma should be considered when lymphoid markers are negative in an apparent lymphoma, but should not be made without recourse to appropriate immunophenotypic and molecular studies.
Asunto(s)
Leucemia Monocítica Aguda/patología , Linfoma de Células B Grandes Difuso/patología , Neoplasias Testiculares/patología , Progresión de la Enfermedad , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana EdadRESUMEN
An indirect immunoperoxidase technique has been used for visualisation of cellular immunoglobulins in chronic lymphocytic leukaemia. Baker's formol calcium was used as fixative. Monoclonal light and heavy chain patterns were demonstrated in 24 out of 27 cases. Only one case did not have any demonstrable immunoglobulins. The presence of alpha or gamma heavy chain immunoglobulin isotypes in leukaemic lymphocytes was found to be related to low mouse rosetting capacity (p less than 0.05).
Asunto(s)
Inmunoglobulinas/análisis , Leucemia Linfoide/inmunología , Adulto , Anciano , Femenino , Humanos , Técnicas para Inmunoenzimas , Cadenas Pesadas de Inmunoglobulina/análisis , Cadenas Ligeras de Inmunoglobulina/análisis , Linfocitos/inmunología , Masculino , Persona de Mediana Edad , Formación de RosetaRESUMEN
AIM: To substantiate the high incidence of monocyte esterase deficiency (MED) in gastrointestinal carcinoma already reported in a small group of patients; to compare the clinical findings in esterase deficient and esterase positive patients. METHODS: Peripheral blood smears (n = 22) or cytocentrifuge preparations (n = 52) of mononuclear cells from the peripheral blood of patients with gastrointestinal carcinoma were stained by the non-specific esterase stain (pH 5.8) using a batch technique. Samples containing > or = 85% esterase negative monocytes were identified at light microscopic examination. RESULTS: Seven of 74 patients were identified as having MED. This correlated exactly with the proportion (five of 46) found before, using an automated method, and was significantly higher than the 0.8% incidence in normal blood donors shown in that study. Comparison of the clinical details of the 12 MED patients with those of 105 esterase positive patients showed a significantly longer disease free survival in the MED cohort and increased occurrence of benign neoplasms--largely colorectal polyps--in this group also. Three patients had a borderline degree of deficiency and were excluded from comparisons, although they showed the same clinical tendencies as the MED group. CONCLUSIONS: There is a strong degree of association between monocyte esterase deficiency and gastrointestinal carcinoma. Further evidence must be sought to prove that the deficiency precedes the disease and therefore may predispose to it, or at least may identify subjects with such a predisposition. This could lead to early diagnosis and effective treatment of gastrointestinal carcinoma in a sizeable proportion of patients.
Asunto(s)
Esterasas/deficiencia , Neoplasias Gastrointestinales/enzimología , Monocitos/enzimología , Anciano , Esterasas/sangre , Femenino , Neoplasias Gastrointestinales/sangre , Humanos , MasculinoRESUMEN
Conventional light and electron microscopic studies, together with cytochemical and immunocytochemical staining procedures, were carried out to ascertain whether the lymphomata of four elderly female patients living within 10 kilometers of each other, who presented within a short space of time with massive splenomegaly and varying cytopenia, belonged to any particular subgroup of lymphoma. In each case the lymphoma had a diffuse pattern and mature B cell phenotype. The malignant cells were of uniform cell type, slightly larger than admixed polymorphonuclear leucocytes, and showed minimal nuclear irregularity and positivity for tartrate resistant acid phosphatase (TRAP) staining. Their clinical and morphological features were compared with those of other lymphoproliferative disorders, but while sharing some features in common with each condition, this small group of patients seemed to have a unique combination of findings. The cytopenias of all four responded well after removal of the spleen and their disease has not been aggressive. It is concluded that these patients have a distinct subgroup of lymphoma, which it is important to recognise so that inappropriate use of aggressive cytotoxic drugs can be avoided.
Asunto(s)
Linfoma de Células B/patología , Linfoma no Hodgkin/patología , Neoplasias del Bazo/patología , Fosfatasa Ácida/análisis , Anciano , Femenino , Humanos , Linfoma de Células B/enzimología , Linfoma de Células B/epidemiología , Linfoma no Hodgkin/enzimología , Linfoma no Hodgkin/epidemiología , Persona de Mediana Edad , Agrupamiento Espacio-Temporal , Neoplasias del Bazo/enzimología , Neoplasias del Bazo/epidemiología , Coloración y Etiquetado , Tartratos/farmacologíaRESUMEN
Breast lymphoma accounts for less than 1% of all non-Hodgkin's lymphomas (NHLs) and approximately 0.1% of all breast neoplasms. Most breast lymphomas are classified as diffuse large B cell or mucosa associated lymphoid tissue (MALT) lymphomas. The case of a 53 year old woman presenting with a breast mass and found to have mantle cell lymphoma is described. Core biopsy of the breast lesion showed a B cell NHL, probably of large cell type and of high grade. Morphological and immunophenotypic analysis of peripheral blood and bone marrow samples suggested a mantle cell lymphoma (MCL). This was confirmed by the detection of a t(11;14) in the bone marrow aspirate and breast tissue by polymerase chain reaction analysis. There have been no previous reports of an MCL presenting as a breast lump. Because a diagnosis of MCL has prognostic and therapeutic implications, this case highlights the need for an awareness of MCL presenting in this way, and the requirement for specialised investigations in its detection.
Asunto(s)
Neoplasias de la Mama/diagnóstico , Linfoma de Células del Manto/diagnóstico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Cromosomas Humanos Par 11 , Cromosomas Humanos Par 14 , Terapia Combinada , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Linfoma de Células del Manto/genética , Linfoma de Células del Manto/terapia , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa/métodos , Prednisona/administración & dosificación , Translocación Genética , Vincristina/administración & dosificaciónRESUMEN
Fourteen cases of breast lymphoma, identified from hospital records between 1990 and 2004, were reclassified according to the World Health Organisation criteria. Primary cases occurred more frequently and all cases were of B cell origin, predominantly involving the right breast. Most primary cases were diffuse large B cell lymphomas, whereas secondary cases were heterogeneous in type and most had a poor prognosis.
Asunto(s)
Neoplasias de la Mama/clasificación , Linfoma/clasificación , Anciano , Anciano de 80 o más Años , Linfocitos B/patología , Neoplasias de la Mama/patología , Neoplasias de la Mama/secundario , Neoplasias de la Mama Masculina/clasificación , Neoplasias de la Mama Masculina/patología , Femenino , Humanos , Linfoma/patología , Linfoma de Células B/clasificación , Linfoma de Células B/patología , Masculino , Persona de Mediana Edad , Pronóstico , Organización Mundial de la SaludRESUMEN
A survey of the incidence of monocyte esterase deficiency in 4000 inpatients (including 808 with malignant neoplastic disease) and 474 normal controls was performed using an automated esterase method. A highly significant excess of patients with malignant disease and the deficiency was evident when compared with normal controls or all other patients. Within the group of patients with malignant disease the demonstrable excess occurred in B chronic lymphocytic leukaemia, non-Hodgkin's and Hodgkin's lymphoma, and carcinoma of the gastrointestinal tract. There was also a significant excess of patients with the deficiency attending the renal unit, both among patients who had had renal transplants and those who had not. A familial incidence of monocyte esterase deficiency was found in 19 (35%) of first degree relatives of those patients in whom family studies were done. It is suggested that the reason for the increased prevalence of the anomaly in these disorders might be that the diminution of esterase activity has a role in their development.
Asunto(s)
Esterasas/deficiencia , Monocitos/enzimología , Neoplasias/enzimología , Esterasas/sangre , Femenino , Neoplasias Gastrointestinales/enzimología , Enfermedad de Hodgkin/enzimología , Humanos , Fallo Renal Crónico/enzimología , Trasplante de Riñón , Leucemia Linfocítica Crónica de Células B/enzimología , Recuento de Leucocitos , Linfoma no Hodgkin/enzimología , Masculino , Neoplasias/genética , LinajeRESUMEN
The refusal of Jehovah's Witnesses to accept blood and blood products often poses a clinical dilemma to present day medicine. We present a case of a Jehovah's Witness who had undergone renal transplantation, only to develop an Epstein-Barr virus associated aggressive lymphoma post-transplant. His condition was further complicated by erythrovirus (parvovirus) B 19 infection resulting in red cell aplasia and severe anemia. The management of this difficult clinical situation is discussed together with a review of recommendations for chemotherapy treatment in Jehovah's Witnesses.
Asunto(s)
Infecciones por Virus de Epstein-Barr/complicaciones , Trasplante de Riñón/efectos adversos , Linfoma de Células B Grandes Difuso/virología , Infecciones por Parvoviridae/complicaciones , Aplasia Pura de Células Rojas/virología , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Manejo de la Enfermedad , Infecciones por Virus de Epstein-Barr/etiología , Humanos , Terapia de Inmunosupresión/efectos adversos , Testigos de Jehová , Linfoma de Células B/virología , Masculino , Infecciones por Parvoviridae/etiología , Parvovirus B19 Humano , Aplasia Pura de Células Rojas/etiologíaRESUMEN
Purine analogs are effective in the treatment of several chronic lymphoproliferative disorders (CLPD) including hairy cell leukemia (HCL). To date, little evidence exists that these drugs are oncogenic. We report a case of HCL in a 66-year-old male treated with 2-deoxycoformycin. Just over 1 year following completion of his treatment, falling platelet and white cell counts were associated with the development of dysplastic features in his bone marrow and a rising blast cell count, culminating in the development of acute myeloid leukemia (AML). To the best of our knowledge only two previous cases of AML have been linked to treatment of HCL with purine analogs, both with 2-chlorodeoxyadenosine. We emphasize the need for long term follow up of patients treated with purine analogs and suggest that even those who are apparently cured be monitored periodically.
Asunto(s)
Antimetabolitos Antineoplásicos/efectos adversos , Leucemia de Células Pilosas/tratamiento farmacológico , Leucemia Mieloide/inducido químicamente , Síndromes Mielodisplásicos/inducido químicamente , Neoplasias Primarias Secundarias/inducido químicamente , Pentostatina/efectos adversos , Enfermedad Aguda , Anciano , Antimetabolitos Antineoplásicos/uso terapéutico , Resultado Fatal , Humanos , Leucemia de Células Pilosas/complicaciones , Recuento de Leucocitos , Masculino , Pentostatina/uso terapéutico , Recuento de PlaquetasRESUMEN
The distribution of circulating CD4 lymphocyte subpopulations determined by reactivity with monoclonal antibodies anti-2H4 (CD45RA), anti-UCHL1 (CD45RO), anti-4B4 (CD29) and anti-Leu8, and analysed by dual colour immunofluorescence flow cytometry is described in a series of patients with B-CLL and in age-matched control subjects. The percentages and absolute numbers of CD4 cells reactive with anti-CD45RA, anti-CD45RO and anti-CD29 reagents were similar in the patient and control groups. In contrast, CD4+ Leu8+ cells (percentages and absolute numbers) were significantly reduced in B-CLL patients resulting in an inversion of the normal CD4+ Leu8+ :CD4+Leu8- ratio. The patients' clinical or therapeutic status did not appear to influence the levels of the respective CD4 subpopulations; nor was evidence of hypogammaglobulinaemia associated with specific numerical alterations in any of the CD4 subpopulations studied. It is proposed that, in B-CLL, the alterations in the CD4Leu8 subpopulations are associated with the disease process, whereas the distributions of CD4+CD45RA+, CD4+ CD45RO+ and CD4+ CD29+ cells reflect the normal physiological levels of these subpopulations in elderly subjects.
RESUMEN
Determination of the biologic potential of lymphoid proliferations in biopsies can be difficult by standard histological or even immunohistochemical examination. Polymerase chain reaction (PCR) has been used with increasing frequency to detect clonal rearrangements of the immunoglobulin heavy chain (IgH) in formaldehyde fixed, paraffin wax embedded tissues. Sensitivity ranges between 50 and 80%, and therefore at least 20% of neoplasms remain undetected by these approaches. Few investigators have attempted to detect immunoglobulin light chain (IgL) gene rearrangements by PCR using paraffin wax embedded samples. We studied 29 cases of B-cell neoplasms, along with 21 cases with equivocal histology and 4 reactive biopsies, using degenerate oligoprimers to amplify Ig(kappa) and Ig(lambda) light chain genes, along with IgH (Fr 1, 2 and 3) gene rearrangement analysis. The combination of these methods detected clonality in 93% of cases (27/29) with histological diagnosis of B-NHL. Fr2 and Fr3 primers detected clonality in 79% (23/29) of cases. IgL chain rearrangements detected 4 cases (14%), negative for IgH rearrangements, improving sensitivity from 79 to 93%. Clonality was detected in 52% (11/21) of histologically equivocal lymphoid proliferations, including one case detected by IgL rearrangements which was negative for IgH rearrangements. Archival material from 4 cases with reactive histology produced polyclonal results. These results confirm that PCR based immunoglobulin gene rearrangement is a sensitive and specific method for demonstrating B-cell clonality in paraffin-wax embedded sections. The addition of IgL analysis to the IgH assay allows the detection of greater than 90% of B-cell lymphoproliferative disorders from routine histological specimens with poor preservation of genomic DNA.